Identification
- Summary
Zanubrutinib is a kinase inhibitor used to treat mantle cell lymphoma, a type of B-cell non-Hodgkin lymphoma, in adults who previously received therapy.
- Brand Names
- Brukinsa
- Generic Name
- Zanubrutinib
- DrugBank Accession Number
- DB15035
- Background
Zanubrutinib is a novel Bruton's tyrosine kinase (BTK) inhibitor used for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy.7 Mantle cell lymphoma is an aggressive mature B-cell non-Hodgkin lymphoma associated with early relapse, poor clinical outcomes, and long-term survival.5 BTK is an enzyme that plays a role in oncogenic signalling pathways, promoting the survival and proliferation of malignant B cells.6 Compared to the first-generation BTK inhibitor ibrutinib, zanubrutinib displays higher potency and selectivity for BTK with fewer off-target effects.4 Due to this enhanced selectivity towards BTK, zanubrutinib belongs to the second-generation BTK inhibitor drug group that also includes acalabrutinib, which was approved by the FDA in 2017.
Zanubrutinib was granted accelerated approval by the FDA in November 2019 based on clinical trial results that demonstrated an 84% overall response rate from zanubrutinib therapy in patients with MCL,8 which measures the proportion of patients in a trial whose tumour is entirely or partially destroyed by a drug.9 It is currently marketed under the trade name BRUKINSA™ and is available as oral capsules. In August 2021, the FDA granted accelerated approval to zanubrutinib for the treatment of adults with Waldenström’s macroglobulinemia.11 This indication is valid in the US, Europe, and Canada.12 In September 2021, zanubrutinib was granted another accelerated approval for the treatment of relapsed or refractory marginal zone lymphoma who have received at least one anti-CD20-based regimen.10 In October 2022, the EMA's Committee for Medicinal Products for Human Use (CHMP) recommended zanubrutinib be granted marketing authorization for the treatment of chronic lymphocytic leukemia.14
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Zanubrutinib (DB15035)
- Weight
- Average: 471.561
Monoisotopic: 471.227039814 - Chemical Formula
- C27H29N5O3
- Synonyms
- Zanubrutinib
- External IDs
- BGB-3111
Pharmacology
- Indication
Zanubrutinib is indicated for the treatment of:
- Mantle cell lymphoma (MCL) in adults who have received at least one prior therapy.7,13
- Waldenström’s macroglobulinemia in adults.7,13,19
- Relapsed or refractory marginal zone lymphoma (MZL) in adults who have received at least one anti-CD20-based regimen.7,13,19
- Chronic lymphocytic leukemia (CLL) 15,19 or small lymphocytic lymphoma (SLL) in adults.15
- Refractory or relapsed follicular lymphoma, in combination with obinutuzumab, in adults who have received at least two prior systemic therapies.18,19
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Chronic lymphocytic leukemia •••••••••••• ••••• ••••••• Treatment of Chronic lymphocytic leukemia •••••••••••• ••••• ••••••• Treatment of Mantle cell lymphoma (mcl) •••••••••••• ••••• •• ••••• ••• ••••• ••••••• ••••••• Treatment of Mantle cell lymphoma (mcl) •••••••••••• ••••• ••• ••••• ••••••• ••••••• Treatment of Marginal zone lymphoma (mzl) •••••••••••• ••••• •••••••• •• ••••• ••• ••••• ••••••••••••••• ••••••• ••••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Zanubrutinib is an immunomodulating agent that decreases the survival of malignant B cells. It inhibits BTK by binding to its active site. It works to inhibit the proliferation and survival of malignant B cells to reduce the tumour size in mantle cell lymphoma.7
- Mechanism of action
Bruton's tyrosine kinase (BTK) is a non-receptor kinase and a signalling molecule for the B cell receptors expressed on the peripheral B cell surface.6 The BCR signalling pathway plays a crucial role in normal B-cell development but also the proliferation and survival of malignant B cells in many B cell malignancies, including mantle-cell lymphoma (MCL).6,4 Once activated by upstream Src-family kinases, BTK phosphorylates phospholipase-Cγ (PLCγ), leading to Ca2+ mobilization and activation of NF-κB and MAP kinase pathways. These downstream cascades promote the expression of genes involved in B cell proliferation and survival.2 The BCR signalling pathway also induces the anti-apoptotic protein Bcl-xL and regulates the integrin α4β1 (VLA-4)-mediated adhesion of B cells to vascular cell adhesion molecule-1 (VCAM-1) and fibronectin via BTK. Apart from the direct downstream signal transduction pathway of B cells, BTK is also involved in chemokine receptor, Toll-like receptor (TLR) and Fc receptor signalling pathways.6
Zanubrutinib inhibits BTK by forming a covalent bond with cysteine 481 residue in the adenosine triphosphate (ATP)–binding pocket of BTK, which is the enzyme's active site. This binding specificity is commonly seen with other BTK inhibitors. Due to this binding profile, zanubrutinib may also bind with varying affinities to related and unrelated ATP-binding kinases that possess a cysteine residue at this position.4 By blocking the BCR signalling pathway, zanubrutinib inhibits the proliferation, trafficking, chemotaxis, and adhesion of malignant B cells, ultimately leading to reduced tumour size.7 Zanubrutinib was also shown to downregulate programmed death-ligand 1 (PD-1) expression and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) on CD4+ T cells.1
Target Actions Organism ATyrosine-protein kinase BTK inhibitorHumans UEpidermal growth factor receptor inhibitorHumans UReceptor tyrosine-protein kinase erbB-2 inhibitorHumans UReceptor tyrosine-protein kinase erbB-4 inhibitorHumans UTyrosine-protein kinase ITK/TSK inhibitorHumans UCytoplasmic tyrosine-protein kinase BMX inhibitorHumans UTyrosine-protein kinase JAK2 inhibitorHumans UTyrosine-protein kinase Tec inhibitorHumans UTyrosine-protein kinase Blk inhibitorHumans UTyrosine-protein kinase JAK3 inhibitorHumans UProtein-tyrosine kinase 6 inhibitorHumans UTyrosine-protein kinase Fgr inhibitorHumans UTyrosine-protein kinase FRK inhibitorHumans UTyrosine-protein kinase Lck inhibitorHumans UTyrosine-protein kinase TXK inhibitorHumans - Absorption
Following oral administration of zanubrutinib 160 mg twice daily and 320 mg once daily, the mean (%CV) zanubrutinib steady-state concentrations were 2,295 (37%) ng·h/mL and 2,180 (41%) ng·h/mL, respectively. The mean Cmax (%CV) was 314 (46%) ng/mL following 160 mg twice daily and 543 (51%) ng/mL following 320 mg once daily.7
The Cmax and AUC of zanubrutinib increase in a dose-proportional manner and there is minimal systemic accumulation after repeated dosing. The median Tmax is 2 hours.7
- Volume of distribution
The geometric mean (%CV) apparent steady-state Vd is 881 (95%) L. The blood-to plasma ratio is about 0.7 to 0.8.7
- Protein binding
The plasma protein binding of zanubrutinib is approximately 94%.7
- Metabolism
Zanubrutinib is predominantly metabolized by CYP3A4.7 Its metabolites have not been characterized.
- Route of elimination
Following oral administration of 320 mg radiolabelled zanubrutinib, approximately 87% of the dose was excreted in the feces and about 8% of the dose was recovered in the urine, where less than 1% of the recovered drug comprised of unchanged parent drug.7
- Half-life
Following administration of a single oral dose of 160 mg or 320 mg of zanubrutinib, the mean half-life is approximately 2 to 4 hours.7
- Clearance
The mean (%CV) apparent oral clearance (CL/F) of zanubrutinib is 182 (37%) L/h.7
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
There is limited data on zanubrutinib overdose.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbametapir The serum concentration of Zanubrutinib can be increased when it is combined with Abametapir. Abatacept The metabolism of Zanubrutinib can be increased when combined with Abatacept. Acalabrutinib The metabolism of Zanubrutinib can be decreased when combined with Acalabrutinib. Acetaminophen The metabolism of Zanubrutinib can be increased when combined with Acetaminophen. Acetazolamide The serum concentration of Zanubrutinib can be increased when it is combined with Acetazolamide. - Food Interactions
- Avoid grapefruit products. Grapefruit inhibits CYP3A metabolism, which may increase the serum concentration of zanubrutinib. Dose adjustment may be necessary if coadministered.
- Avoid St. John's Wort. This herb induces CYP3A metabolism and may reduce serum levels of zanubrutinib.
- Take with a full glass of water.
- Take with or without food. Food does not significantly affect drug concentrations.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Brukinsa Capsule 80 mg Oral Beigene Switzerland Gmbh 2021-03-30 Not applicable Canada 
Brukinsa Capsule 80 mg/1 Oral Beigene Usa, Inc. 2019-11-14 Not applicable US 
Brukinsa Capsule 80 mg Oral Bei Gene Ireland Ltd 2022-01-21 Not applicable EU 
Categories
- ATC Codes
- L01EL03 — Zanubrutinib
- Drug Categories
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- Bruton's tyrosine kinase (BTK) inhibitors
- Bruton's Tyrosine Kinase Inhibitors
- Cytochrome P-450 CYP2B6 Inducers
- Cytochrome P-450 CYP2B6 Inducers (strength unknown)
- Cytochrome P-450 CYP2B6 Substrates
- Cytochrome P-450 CYP2B6 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 Enzyme Inducers
- Cytochrome P-450 Substrates
- Enzyme Inhibitors
- Hematologic Agents
- Kinase Inhibitor
- Narrow Therapeutic Index Drugs
- P-glycoprotein substrates
- P-glycoprotein substrates with a Narrow Therapeutic Index
- Protein Kinase Inhibitors
- Teratogens
- Tyrosine Kinase Inhibitors
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as diphenylethers. These are aromatic compounds containing two benzene rings linked to each other through an ether group.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Benzene and substituted derivatives
- Sub Class
- Diphenylethers
- Direct Parent
- Diphenylethers
- Alternative Parents
- Phenylpyrazoles / Diarylethers / Pyrimidinecarboxamides / Pyrazolopyrimidines / N-acylpiperidines / Pyrazole-4-carboxamides / Phenoxy compounds / Phenol ethers / Secondary alkylarylamines / Vinylogous amides show 10 more
- Substituents
- Acrylic acid or derivatives / Amine / Amino acid or derivatives / Aromatic heteropolycyclic compound / Azacycle / Azole / Carbonyl group / Carboxamide group / Carboxylic acid derivative / Diaryl ether show 26 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- AG9MHG098Z
- CAS number
- 1691249-45-2
- InChI Key
- RNOAOAWBMHREKO-QFIPXVFZSA-N
- InChI
- InChI=1S/C27H29N5O3/c1-2-23(33)31-16-13-18(14-17-31)22-12-15-29-27-24(26(28)34)25(30-32(22)27)19-8-10-21(11-9-19)35-20-6-4-3-5-7-20/h2-11,18,22,29H,1,12-17H2,(H2,28,34)/t22-/m0/s1
- IUPAC Name
- (7S)-2-(4-phenoxyphenyl)-7-[1-(prop-2-enoyl)piperidin-4-yl]-4H,5H,6H,7H-pyrazolo[1,5-a]pyrimidine-3-carboxamide
- SMILES
- NC(=O)C1=C2NCC[C@@H](C3CCN(CC3)C(=O)C=C)N2N=C1C1=CC=C(OC2=CC=CC=C2)C=C1
References
- Synthesis Reference
Guo Y, Liu Y, Hu N, et al. Discovery of Zanubrutinib (BGB-3111), a Novel, Potent, and Selective Covalent Inhibitor of Bruton’s Tyrosine Kinase. JOURNAL OF MEDICINAL CHEMISTRY. 62(17):7923-7940. doi:10.1021/acs.jmedchem.9b00687.
- General References
- Zou YX, Zhu HY, Li XT, Xia Y, Miao KR, Zhao SS, Wu YJ, Wang L, Xu W, Li JY: The impacts of zanubrutinib on immune cells in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma. Hematol Oncol. 2019 Oct;37(4):392-400. doi: 10.1002/hon.2667. Epub 2019 Sep 13. [Article]
- Guo Y, Liu Y, Hu N, Yu D, Zhou C, Shi G, Zhang B, Wei M, Liu J, Luo L, Tang Z, Song H, Guo Y, Liu X, Su D, Zhang S, Song X, Zhou X, Hong Y, Chen S, Cheng Z, Young S, Wei Q, Wang H, Wang Q, Lv L, Wang F, Xu H, Sun H, Xing H, Li N, Zhang W, Wang Z, Liu G, Sun Z, Zhou D, Li W, Liu L, Wang L, Wang Z: Discovery of Zanubrutinib (BGB-3111), a Novel, Potent, and Selective Covalent Inhibitor of Bruton's Tyrosine Kinase. J Med Chem. 2019 Sep 12;62(17):7923-7940. doi: 10.1021/acs.jmedchem.9b00687. Epub 2019 Aug 19. [Article]
- Tarantelli C, Zhang L, Curti E, Gaudio E, Spriano F, Priebe V, Cascione L, Arribas AJ, Zucca E, Rossi D, Stathis A, Bertoni F: The Bruton tyrosine kinase inhibitor zanubrutinib (BGB-3111) demonstrated synergies with other anti-lymphoma targeted agents. Haematologica. 2019 Jul;104(7):e307-e309. doi: 10.3324/haematol.2018.214759. Epub 2019 Jan 24. [Article]
- Tam CS, Trotman J, Opat S, Burger JA, Cull G, Gottlieb D, Harrup R, Johnston PB, Marlton P, Munoz J, Seymour JF, Simpson D, Tedeschi A, Elstrom R, Yu Y, Tang Z, Han L, Huang J, Novotny W, Wang L, Roberts AW: Phase 1 study of the selective BTK inhibitor zanubrutinib in B-cell malignancies and safety and efficacy evaluation in CLL. Blood. 2019 Sep 12;134(11):851-859. doi: 10.1182/blood.2019001160. Epub 2019 Jul 24. [Article]
- Schieber M, Gordon LI, Karmali R: Current overview and treatment of mantle cell lymphoma. F1000Res. 2018 Jul 25;7. doi: 10.12688/f1000research.14122.1. eCollection 2018. [Article]
- Pal Singh S, Dammeijer F, Hendriks RW: Role of Bruton's tyrosine kinase in B cells and malignancies. Mol Cancer. 2018 Feb 19;17(1):57. doi: 10.1186/s12943-018-0779-z. [Article]
- FDA Approved Drug Products: Brukinsa (zanubrutinib) capsules [Link]
- FDA grants accelerated approval to zanubrutinib for mantle cell lymphoma [Link]
- Clinical Trial Endpoints in Cancer Research: Four Terms You Should Know [Link]
- FDA.gov: FDA approvals of Brukinsa (zanubrutinib), for adult patients with relapsed or refractory marginal zone lymphoma, and Exkivity (mobocertinib) for adult patients with locally advanced or metastatic non-small cell lung cancer with epidermal growth factor receptor exon 20 insertion mutations [Link]
- FDA.gov: FDA approves zanubrutinib for Waldenström’s macroglobulinemia [Link]
- Businesswire: BeiGene Announces Approval of BRUKINSA (zanubrutinib) in the European Union for Treatment of Adults with Waldenström’s Macroglobulinemia [Link]
- Health Canada Product Monograph: BRUKINSA (zanubrutinib) Oral Capsules [Link]
- EMA Summary of Opinion: Brukinsa (zanubrutinib) [Link]
- FDA Approved Drug Products: BRUKINSA (zanubrutinib) capsules, for oral use (January 2023) [Link]
- Health Canada Product Monograph: BRUKINSA (zanubrutinib) Oral Capsules (May 2023) [Link]
- FDA Approved Drug Products: BRUKINSA® (zanubrutinib) capsules, for oral use (Jan 2024) [Link]
- Health Canada Approved Drug Proucts: BRUKINSA (zanubrutinib) capsules for oral use (Feb 2024) [Link]
- EMA Approved Drug Products: BRUKINSA (zanubrutinib) Oral Capsules [Link]
- External Links
- Human Metabolome Database
- HMDB0304875
- ChemSpider
- 64835237
- BindingDB
- 250082
- 2262435
- ChEMBL
- CHEMBL3936761
- ZINC
- ZINC000584641430
- Wikipedia
- Zanubrutinib
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 3 Active Not Recruiting Treatment Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma 2 3 Active Not Recruiting Treatment Mantle Cell Lymphoma (MCL) 1 3 Completed Treatment Waldenström's Macroglobulinemia (WM) 1 3 Enrolling by Invitation Treatment B-cell Malignancy 1 3 Not Yet Recruiting Treatment Splenic Marginal Zone Lymphoma 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Capsule Oral 80 mg Capsule Oral 80 mg/1 - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US9447106 No 2016-09-20 2034-04-22 US US10570139 No 2020-02-25 2034-04-22 US US10927117 No 2021-02-23 2037-08-15 US US11142528 No 2021-10-12 2034-04-22 US US11591340 No 2017-08-15 2037-08-15 US US11786531 No 2023-01-19 2043-01-19 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.0103 mg/mL ALOGPS logP 3.27 ALOGPS logP 3.42 Chemaxon logS -4.7 ALOGPS pKa (Strongest Acidic) 13.81 Chemaxon pKa (Strongest Basic) 2.68 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 102.48 Å2 Chemaxon Rotatable Bond Count 6 Chemaxon Refractivity 146.25 m3·mol-1 Chemaxon Polarizability 51.75 Å3 Chemaxon Number of Rings 5 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-00di-0000900000-5d2814456f7202241973 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0zfr-0000900000-20ff9292804d788af3cc Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-00di-0000900000-6c67c0dd55024ec59542 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0pe9-0617900000-4432e2d1b07c2e9c54d3 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-00fr-2007900000-47ea8bde7abdd6e7ca5b Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-006x-5119600000-12675677e715f7d5db2f Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Not Available
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Protein tyrosine kinase activity
- Specific Function
- Non-receptor tyrosine kinase indispensable for B lymphocyte development, differentiation and signaling. Binding of antigen to the B-cell antigen receptor (BCR) triggers signaling that ultimately le...
- Gene Name
- BTK
- Uniprot ID
- Q06187
- Uniprot Name
- Tyrosine-protein kinase BTK
- Molecular Weight
- 76280.71 Da
References
- Guo Y, Liu Y, Hu N, Yu D, Zhou C, Shi G, Zhang B, Wei M, Liu J, Luo L, Tang Z, Song H, Guo Y, Liu X, Su D, Zhang S, Song X, Zhou X, Hong Y, Chen S, Cheng Z, Young S, Wei Q, Wang H, Wang Q, Lv L, Wang F, Xu H, Sun H, Xing H, Li N, Zhang W, Wang Z, Liu G, Sun Z, Zhou D, Li W, Liu L, Wang L, Wang Z: Discovery of Zanubrutinib (BGB-3111), a Novel, Potent, and Selective Covalent Inhibitor of Bruton's Tyrosine Kinase. J Med Chem. 2019 Sep 12;62(17):7923-7940. doi: 10.1021/acs.jmedchem.9b00687. Epub 2019 Aug 19. [Article]
- Tarantelli C, Zhang L, Curti E, Gaudio E, Spriano F, Priebe V, Cascione L, Arribas AJ, Zucca E, Rossi D, Stathis A, Bertoni F: The Bruton tyrosine kinase inhibitor zanubrutinib (BGB-3111) demonstrated synergies with other anti-lymphoma targeted agents. Haematologica. 2019 Jul;104(7):e307-e309. doi: 10.3324/haematol.2018.214759. Epub 2019 Jan 24. [Article]
- Tam CS, Trotman J, Opat S, Burger JA, Cull G, Gottlieb D, Harrup R, Johnston PB, Marlton P, Munoz J, Seymour JF, Simpson D, Tedeschi A, Elstrom R, Yu Y, Tang Z, Han L, Huang J, Novotny W, Wang L, Roberts AW: Phase 1 study of the selective BTK inhibitor zanubrutinib in B-cell malignancies and safety and efficacy evaluation in CLL. Blood. 2019 Sep 12;134(11):851-859. doi: 10.1182/blood.2019001160. Epub 2019 Jul 24. [Article]
- Bond DA, Woyach JA: Targeting BTK in CLL: Beyond Ibrutinib. Curr Hematol Malig Rep. 2019 Jun;14(3):197-205. doi: 10.1007/s11899-019-00512-0. [Article]
- Castillo JJ, Treon SP: What is new in the treatment of Waldenstrom macroglobulinemia? Leukemia. 2019 Nov;33(11):2555-2562. doi: 10.1038/s41375-019-0592-8. Epub 2019 Oct 7. [Article]
- Kaliamurthi S, Selvaraj G, Selvaraj C, Singh SK, Wei DQ, Peslherbe GH: Structure-Based Virtual Screening Reveals Ibrutinib and Zanubrutinib as Potential Repurposed Drugs against COVID-19. Int J Mol Sci. 2021 Jun 30;22(13). pii: ijms22137071. doi: 10.3390/ijms22137071. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Ubiquitin protein ligase binding
- Specific Function
- Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses. Known ligands include EGF, TG...
- Gene Name
- EGFR
- Uniprot ID
- P00533
- Uniprot Name
- Epidermal growth factor receptor
- Molecular Weight
- 134276.185 Da
References
- Tam CS, Trotman J, Opat S, Burger JA, Cull G, Gottlieb D, Harrup R, Johnston PB, Marlton P, Munoz J, Seymour JF, Simpson D, Tedeschi A, Elstrom R, Yu Y, Tang Z, Han L, Huang J, Novotny W, Wang L, Roberts AW: Phase 1 study of the selective BTK inhibitor zanubrutinib in B-cell malignancies and safety and efficacy evaluation in CLL. Blood. 2019 Sep 12;134(11):851-859. doi: 10.1182/blood.2019001160. Epub 2019 Jul 24. [Article]
- Guo Y, Liu Y, Hu N, Yu D, Zhou C, Shi G, Zhang B, Wei M, Liu J, Luo L, Tang Z, Song H, Guo Y, Liu X, Su D, Zhang S, Song X, Zhou X, Hong Y, Chen S, Cheng Z, Young S, Wei Q, Wang H, Wang Q, Lv L, Wang F, Xu H, Sun H, Xing H, Li N, Zhang W, Wang Z, Liu G, Sun Z, Zhou D, Li W, Liu L, Wang L, Wang Z: Discovery of Zanubrutinib (BGB-3111), a Novel, Potent, and Selective Covalent Inhibitor of Bruton's Tyrosine Kinase. J Med Chem. 2019 Sep 12;62(17):7923-7940. doi: 10.1021/acs.jmedchem.9b00687. Epub 2019 Aug 19. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Transmembrane signaling receptor activity
- Specific Function
- Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding. Essential component of a neuregulin-receptor complex, alt...
- Gene Name
- ERBB2
- Uniprot ID
- P04626
- Uniprot Name
- Receptor tyrosine-protein kinase erbB-2
- Molecular Weight
- 137909.27 Da
References
- Tam CS, Trotman J, Opat S, Burger JA, Cull G, Gottlieb D, Harrup R, Johnston PB, Marlton P, Munoz J, Seymour JF, Simpson D, Tedeschi A, Elstrom R, Yu Y, Tang Z, Han L, Huang J, Novotny W, Wang L, Roberts AW: Phase 1 study of the selective BTK inhibitor zanubrutinib in B-cell malignancies and safety and efficacy evaluation in CLL. Blood. 2019 Sep 12;134(11):851-859. doi: 10.1182/blood.2019001160. Epub 2019 Jul 24. [Article]
- Guo Y, Liu Y, Hu N, Yu D, Zhou C, Shi G, Zhang B, Wei M, Liu J, Luo L, Tang Z, Song H, Guo Y, Liu X, Su D, Zhang S, Song X, Zhou X, Hong Y, Chen S, Cheng Z, Young S, Wei Q, Wang H, Wang Q, Lv L, Wang F, Xu H, Sun H, Xing H, Li N, Zhang W, Wang Z, Liu G, Sun Z, Zhou D, Li W, Liu L, Wang L, Wang Z: Discovery of Zanubrutinib (BGB-3111), a Novel, Potent, and Selective Covalent Inhibitor of Bruton's Tyrosine Kinase. J Med Chem. 2019 Sep 12;62(17):7923-7940. doi: 10.1021/acs.jmedchem.9b00687. Epub 2019 Aug 19. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Transmembrane receptor protein tyrosine kinase activity
- Specific Function
- Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins and EGF family members and regulates development of the heart, the central nervous system and the mamma...
- Gene Name
- ERBB4
- Uniprot ID
- Q15303
- Uniprot Name
- Receptor tyrosine-protein kinase erbB-4
- Molecular Weight
- 146806.865 Da
References
- Tam CS, Trotman J, Opat S, Burger JA, Cull G, Gottlieb D, Harrup R, Johnston PB, Marlton P, Munoz J, Seymour JF, Simpson D, Tedeschi A, Elstrom R, Yu Y, Tang Z, Han L, Huang J, Novotny W, Wang L, Roberts AW: Phase 1 study of the selective BTK inhibitor zanubrutinib in B-cell malignancies and safety and efficacy evaluation in CLL. Blood. 2019 Sep 12;134(11):851-859. doi: 10.1182/blood.2019001160. Epub 2019 Jul 24. [Article]
- Guo Y, Liu Y, Hu N, Yu D, Zhou C, Shi G, Zhang B, Wei M, Liu J, Luo L, Tang Z, Song H, Guo Y, Liu X, Su D, Zhang S, Song X, Zhou X, Hong Y, Chen S, Cheng Z, Young S, Wei Q, Wang H, Wang Q, Lv L, Wang F, Xu H, Sun H, Xing H, Li N, Zhang W, Wang Z, Liu G, Sun Z, Zhou D, Li W, Liu L, Wang L, Wang Z: Discovery of Zanubrutinib (BGB-3111), a Novel, Potent, and Selective Covalent Inhibitor of Bruton's Tyrosine Kinase. J Med Chem. 2019 Sep 12;62(17):7923-7940. doi: 10.1021/acs.jmedchem.9b00687. Epub 2019 Aug 19. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Non-membrane spanning protein tyrosine kinase activity
- Specific Function
- Tyrosine kinase that plays an essential role in regulation of the adaptive immune response. Regulates the development, function and differentiation of conventional T-cells and nonconventional NKT-c...
- Gene Name
- ITK
- Uniprot ID
- Q08881
- Uniprot Name
- Tyrosine-protein kinase ITK/TSK
- Molecular Weight
- 71830.405 Da
References
- Tam CS, Trotman J, Opat S, Burger JA, Cull G, Gottlieb D, Harrup R, Johnston PB, Marlton P, Munoz J, Seymour JF, Simpson D, Tedeschi A, Elstrom R, Yu Y, Tang Z, Han L, Huang J, Novotny W, Wang L, Roberts AW: Phase 1 study of the selective BTK inhibitor zanubrutinib in B-cell malignancies and safety and efficacy evaluation in CLL. Blood. 2019 Sep 12;134(11):851-859. doi: 10.1182/blood.2019001160. Epub 2019 Jul 24. [Article]
- Guo Y, Liu Y, Hu N, Yu D, Zhou C, Shi G, Zhang B, Wei M, Liu J, Luo L, Tang Z, Song H, Guo Y, Liu X, Su D, Zhang S, Song X, Zhou X, Hong Y, Chen S, Cheng Z, Young S, Wei Q, Wang H, Wang Q, Lv L, Wang F, Xu H, Sun H, Xing H, Li N, Zhang W, Wang Z, Liu G, Sun Z, Zhou D, Li W, Liu L, Wang L, Wang Z: Discovery of Zanubrutinib (BGB-3111), a Novel, Potent, and Selective Covalent Inhibitor of Bruton's Tyrosine Kinase. J Med Chem. 2019 Sep 12;62(17):7923-7940. doi: 10.1021/acs.jmedchem.9b00687. Epub 2019 Aug 19. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Non-receptor tyrosine kinase that plays central but diverse modulatory roles in various signaling processes involved in the regulation of actin reorganization, cell migration, cell proliferation and survival, cell adhesion, and apoptosis. Participates in signal transduction stimulated by growth factor receptors, cytokine receptors, G-protein coupled receptors, antigen receptors and integrins. Induces tyrosine phosphorylation of BCAR1 in response to integrin regulation. Activation of BMX by integrins is mediated by PTK2/FAK1, a key mediator of integrin signaling events leading to the regulation of actin cytoskeleton and cell motility. Plays a critical role in TNF-induced angiogenesis, and implicated in the signaling of TEK and FLT1 receptors, 2 important receptor families essential for angiogenesis. Required for the phosphorylation and activation of STAT3, a transcription factor involved in cell differentiation. Also involved in interleukin-6 (IL6) induced differentiation. Plays also a role in programming adaptive cytoprotection against extracellular stress in different cell systems, salivary epithelial cells, brain endothelial cells, and dermal fibroblasts. May be involved in regulation of endocytosis through its interaction with an endosomal protein RUFY1. May also play a role in the growth and differentiation of hematopoietic cells; as well as in signal transduction in endocardial and arterial endothelial cells.
- Specific Function
- Atp binding
- Gene Name
- BMX
- Uniprot ID
- P51813
- Uniprot Name
- Cytoplasmic tyrosine-protein kinase BMX
- Molecular Weight
- 78010.17 Da
References
- Tam CS, Trotman J, Opat S, Burger JA, Cull G, Gottlieb D, Harrup R, Johnston PB, Marlton P, Munoz J, Seymour JF, Simpson D, Tedeschi A, Elstrom R, Yu Y, Tang Z, Han L, Huang J, Novotny W, Wang L, Roberts AW: Phase 1 study of the selective BTK inhibitor zanubrutinib in B-cell malignancies and safety and efficacy evaluation in CLL. Blood. 2019 Sep 12;134(11):851-859. doi: 10.1182/blood.2019001160. Epub 2019 Jul 24. [Article]
- Guo Y, Liu Y, Hu N, Yu D, Zhou C, Shi G, Zhang B, Wei M, Liu J, Luo L, Tang Z, Song H, Guo Y, Liu X, Su D, Zhang S, Song X, Zhou X, Hong Y, Chen S, Cheng Z, Young S, Wei Q, Wang H, Wang Q, Lv L, Wang F, Xu H, Sun H, Xing H, Li N, Zhang W, Wang Z, Liu G, Sun Z, Zhou D, Li W, Liu L, Wang L, Wang Z: Discovery of Zanubrutinib (BGB-3111), a Novel, Potent, and Selective Covalent Inhibitor of Bruton's Tyrosine Kinase. J Med Chem. 2019 Sep 12;62(17):7923-7940. doi: 10.1021/acs.jmedchem.9b00687. Epub 2019 Aug 19. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Sh2 domain binding
- Specific Function
- Non-receptor tyrosine kinase involved in various processes such as cell growth, development, differentiation or histone modifications. Mediates essential signaling events in both innate and adaptiv...
- Gene Name
- JAK2
- Uniprot ID
- O60674
- Uniprot Name
- Tyrosine-protein kinase JAK2
- Molecular Weight
- 130672.475 Da
References
- Tam CS, Trotman J, Opat S, Burger JA, Cull G, Gottlieb D, Harrup R, Johnston PB, Marlton P, Munoz J, Seymour JF, Simpson D, Tedeschi A, Elstrom R, Yu Y, Tang Z, Han L, Huang J, Novotny W, Wang L, Roberts AW: Phase 1 study of the selective BTK inhibitor zanubrutinib in B-cell malignancies and safety and efficacy evaluation in CLL. Blood. 2019 Sep 12;134(11):851-859. doi: 10.1182/blood.2019001160. Epub 2019 Jul 24. [Article]
- Guo Y, Liu Y, Hu N, Yu D, Zhou C, Shi G, Zhang B, Wei M, Liu J, Luo L, Tang Z, Song H, Guo Y, Liu X, Su D, Zhang S, Song X, Zhou X, Hong Y, Chen S, Cheng Z, Young S, Wei Q, Wang H, Wang Q, Lv L, Wang F, Xu H, Sun H, Xing H, Li N, Zhang W, Wang Z, Liu G, Sun Z, Zhou D, Li W, Liu L, Wang L, Wang Z: Discovery of Zanubrutinib (BGB-3111), a Novel, Potent, and Selective Covalent Inhibitor of Bruton's Tyrosine Kinase. J Med Chem. 2019 Sep 12;62(17):7923-7940. doi: 10.1021/acs.jmedchem.9b00687. Epub 2019 Aug 19. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Non-receptor tyrosine kinase that contributes to signaling from many receptors and participates as a signal transducer in multiple downstream pathways, including regulation of the actin cytoskeleton. Plays a redundant role to ITK in regulation of the adaptive immune response. Regulates the development, function and differentiation of conventional T-cells and nonconventional NKT-cells. Required for TCR-dependent IL2 gene induction. Phosphorylates DOK1, one CD28-specific substrate, and contributes to CD28-signaling. Mediates signals that negatively regulate IL2RA expression induced by TCR cross-linking. Plays a redundant role to BTK in BCR-signaling for B-cell development and activation, especially by phosphorylating STAP1, a BCR-signaling protein. Required in mast cells for efficient cytokine production. Involved in both growth and differentiation mechanisms of myeloid cells through activation by the granulocyte colony-stimulating factor CSF3, a critical cytokine to promoting the growth, differentiation, and functional activation of myeloid cells. Participates in platelet signaling downstream of integrin activation. Cooperates with JAK2 through reciprocal phosphorylation to mediate cytokine-driven activation of FOS transcription. GRB10, a negative modifier of the FOS activation pathway, is another substrate of TEC. TEC is involved in G protein-coupled receptor- and integrin-mediated signalings in blood platelets. Plays a role in hepatocyte proliferation and liver regeneration and is involved in HGF-induced ERK signaling pathway. TEC regulates also FGF2 unconventional secretion (endoplasmic reticulum (ER)/Golgi-independent mechanism) under various physiological conditions through phosphorylation of FGF2 'Tyr-215'. May also be involved in the regulation of osteoclast differentiation.
- Specific Function
- Atp binding
- Gene Name
- TEC
- Uniprot ID
- P42680
- Uniprot Name
- Tyrosine-protein kinase Tec
- Molecular Weight
- 73580.73 Da
References
- Tam CS, Trotman J, Opat S, Burger JA, Cull G, Gottlieb D, Harrup R, Johnston PB, Marlton P, Munoz J, Seymour JF, Simpson D, Tedeschi A, Elstrom R, Yu Y, Tang Z, Han L, Huang J, Novotny W, Wang L, Roberts AW: Phase 1 study of the selective BTK inhibitor zanubrutinib in B-cell malignancies and safety and efficacy evaluation in CLL. Blood. 2019 Sep 12;134(11):851-859. doi: 10.1182/blood.2019001160. Epub 2019 Jul 24. [Article]
- Guo Y, Liu Y, Hu N, Yu D, Zhou C, Shi G, Zhang B, Wei M, Liu J, Luo L, Tang Z, Song H, Guo Y, Liu X, Su D, Zhang S, Song X, Zhou X, Hong Y, Chen S, Cheng Z, Young S, Wei Q, Wang H, Wang Q, Lv L, Wang F, Xu H, Sun H, Xing H, Li N, Zhang W, Wang Z, Liu G, Sun Z, Zhou D, Li W, Liu L, Wang L, Wang Z: Discovery of Zanubrutinib (BGB-3111), a Novel, Potent, and Selective Covalent Inhibitor of Bruton's Tyrosine Kinase. J Med Chem. 2019 Sep 12;62(17):7923-7940. doi: 10.1021/acs.jmedchem.9b00687. Epub 2019 Aug 19. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Non-receptor tyrosine kinase involved in B-lymphocyte development, differentiation and signaling. B-cell receptor (BCR) signaling requires a tight regulation of several protein tyrosine kinases and phosphatases, and associated coreceptors. Binding of antigen to the B-cell antigen receptor (BCR) triggers signaling that ultimately leads to B-cell activation. Signaling through BLK plays an important role in transmitting signals through surface immunoglobulins and supports the pro-B to pre-B transition, as well as the signaling for growth arrest and apoptosis downstream of B-cell receptor. Specifically binds and phosphorylates CD79A at 'Tyr-188'and 'Tyr-199', as well as CD79B at 'Tyr-196' and 'Tyr-207'. Phosphorylates also the immunoglobulin G receptors FCGR2A, FCGR2B and FCGR2C. With FYN and LYN, plays an essential role in pre-B-cell receptor (pre-BCR)-mediated NF-kappa-B activation. Contributes also to BTK activation by indirectly stimulating BTK intramolecular autophosphorylation. In pancreatic islets, acts as a modulator of beta-cells function through the up-regulation of PDX1 and NKX6-1 and consequent stimulation of insulin secretion in response to glucose.
- Specific Function
- Atp binding
- Gene Name
- BLK
- Uniprot ID
- P51451
- Uniprot Name
- Tyrosine-protein kinase Blk
- Molecular Weight
- 57706.01 Da
References
- Tam CS, Trotman J, Opat S, Burger JA, Cull G, Gottlieb D, Harrup R, Johnston PB, Marlton P, Munoz J, Seymour JF, Simpson D, Tedeschi A, Elstrom R, Yu Y, Tang Z, Han L, Huang J, Novotny W, Wang L, Roberts AW: Phase 1 study of the selective BTK inhibitor zanubrutinib in B-cell malignancies and safety and efficacy evaluation in CLL. Blood. 2019 Sep 12;134(11):851-859. doi: 10.1182/blood.2019001160. Epub 2019 Jul 24. [Article]
- Guo Y, Liu Y, Hu N, Yu D, Zhou C, Shi G, Zhang B, Wei M, Liu J, Luo L, Tang Z, Song H, Guo Y, Liu X, Su D, Zhang S, Song X, Zhou X, Hong Y, Chen S, Cheng Z, Young S, Wei Q, Wang H, Wang Q, Lv L, Wang F, Xu H, Sun H, Xing H, Li N, Zhang W, Wang Z, Liu G, Sun Z, Zhou D, Li W, Liu L, Wang L, Wang Z: Discovery of Zanubrutinib (BGB-3111), a Novel, Potent, and Selective Covalent Inhibitor of Bruton's Tyrosine Kinase. J Med Chem. 2019 Sep 12;62(17):7923-7940. doi: 10.1021/acs.jmedchem.9b00687. Epub 2019 Aug 19. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Protein tyrosine kinase activity
- Specific Function
- Non-receptor tyrosine kinase involved in various processes such as cell growth, development, or differentiation. Mediates essential signaling events in both innate and adaptive immunity and plays a...
- Gene Name
- JAK3
- Uniprot ID
- P52333
- Uniprot Name
- Tyrosine-protein kinase JAK3
- Molecular Weight
- 125097.565 Da
References
- Guo Y, Liu Y, Hu N, Yu D, Zhou C, Shi G, Zhang B, Wei M, Liu J, Luo L, Tang Z, Song H, Guo Y, Liu X, Su D, Zhang S, Song X, Zhou X, Hong Y, Chen S, Cheng Z, Young S, Wei Q, Wang H, Wang Q, Lv L, Wang F, Xu H, Sun H, Xing H, Li N, Zhang W, Wang Z, Liu G, Sun Z, Zhou D, Li W, Liu L, Wang L, Wang Z: Discovery of Zanubrutinib (BGB-3111), a Novel, Potent, and Selective Covalent Inhibitor of Bruton's Tyrosine Kinase. J Med Chem. 2019 Sep 12;62(17):7923-7940. doi: 10.1021/acs.jmedchem.9b00687. Epub 2019 Aug 19. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Receptor binding
- Specific Function
- Non-receptor tyrosine-protein kinase implicated in the regulation of a variety of signaling pathways that control the differentiation and maintenance of normal epithelia, as well as tumor growth. F...
- Gene Name
- PTK6
- Uniprot ID
- Q13882
- Uniprot Name
- Protein-tyrosine kinase 6
- Molecular Weight
- 51833.72 Da
References
- Guo Y, Liu Y, Hu N, Yu D, Zhou C, Shi G, Zhang B, Wei M, Liu J, Luo L, Tang Z, Song H, Guo Y, Liu X, Su D, Zhang S, Song X, Zhou X, Hong Y, Chen S, Cheng Z, Young S, Wei Q, Wang H, Wang Q, Lv L, Wang F, Xu H, Sun H, Xing H, Li N, Zhang W, Wang Z, Liu G, Sun Z, Zhou D, Li W, Liu L, Wang L, Wang Z: Discovery of Zanubrutinib (BGB-3111), a Novel, Potent, and Selective Covalent Inhibitor of Bruton's Tyrosine Kinase. J Med Chem. 2019 Sep 12;62(17):7923-7940. doi: 10.1021/acs.jmedchem.9b00687. Epub 2019 Aug 19. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Protein tyrosine kinase activity
- Specific Function
- Non-receptor tyrosine-protein kinase that transmits signals from cell surface receptors devoid of kinase activity and contributes to the regulation of immune responses, including neutrophil, monocy...
- Gene Name
- FGR
- Uniprot ID
- P09769
- Uniprot Name
- Tyrosine-protein kinase Fgr
- Molecular Weight
- 59478.11 Da
References
- Guo Y, Liu Y, Hu N, Yu D, Zhou C, Shi G, Zhang B, Wei M, Liu J, Luo L, Tang Z, Song H, Guo Y, Liu X, Su D, Zhang S, Song X, Zhou X, Hong Y, Chen S, Cheng Z, Young S, Wei Q, Wang H, Wang Q, Lv L, Wang F, Xu H, Sun H, Xing H, Li N, Zhang W, Wang Z, Liu G, Sun Z, Zhou D, Li W, Liu L, Wang L, Wang Z: Discovery of Zanubrutinib (BGB-3111), a Novel, Potent, and Selective Covalent Inhibitor of Bruton's Tyrosine Kinase. J Med Chem. 2019 Sep 12;62(17):7923-7940. doi: 10.1021/acs.jmedchem.9b00687. Epub 2019 Aug 19. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Receptor binding
- Specific Function
- Non-receptor tyrosine-protein kinase that negatively regulates cell proliferation. Positively regulates PTEN protein stability through phosphorylation of PTEN on 'Tyr-336', which in turn prevents i...
- Gene Name
- FRK
- Uniprot ID
- P42685
- Uniprot Name
- Tyrosine-protein kinase FRK
- Molecular Weight
- 58253.61 Da
References
- Guo Y, Liu Y, Hu N, Yu D, Zhou C, Shi G, Zhang B, Wei M, Liu J, Luo L, Tang Z, Song H, Guo Y, Liu X, Su D, Zhang S, Song X, Zhou X, Hong Y, Chen S, Cheng Z, Young S, Wei Q, Wang H, Wang Q, Lv L, Wang F, Xu H, Sun H, Xing H, Li N, Zhang W, Wang Z, Liu G, Sun Z, Zhou D, Li W, Liu L, Wang L, Wang Z: Discovery of Zanubrutinib (BGB-3111), a Novel, Potent, and Selective Covalent Inhibitor of Bruton's Tyrosine Kinase. J Med Chem. 2019 Sep 12;62(17):7923-7940. doi: 10.1021/acs.jmedchem.9b00687. Epub 2019 Aug 19. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Sh2 domain binding
- Specific Function
- Non-receptor tyrosine-protein kinase that plays an essential role in the selection and maturation of developing T-cells in the thymus and in the function of mature T-cells. Plays a key role in T-ce...
- Gene Name
- LCK
- Uniprot ID
- P06239
- Uniprot Name
- Tyrosine-protein kinase Lck
- Molecular Weight
- 58000.15 Da
References
- Guo Y, Liu Y, Hu N, Yu D, Zhou C, Shi G, Zhang B, Wei M, Liu J, Luo L, Tang Z, Song H, Guo Y, Liu X, Su D, Zhang S, Song X, Zhou X, Hong Y, Chen S, Cheng Z, Young S, Wei Q, Wang H, Wang Q, Lv L, Wang F, Xu H, Sun H, Xing H, Li N, Zhang W, Wang Z, Liu G, Sun Z, Zhou D, Li W, Liu L, Wang L, Wang Z: Discovery of Zanubrutinib (BGB-3111), a Novel, Potent, and Selective Covalent Inhibitor of Bruton's Tyrosine Kinase. J Med Chem. 2019 Sep 12;62(17):7923-7940. doi: 10.1021/acs.jmedchem.9b00687. Epub 2019 Aug 19. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Non-receptor tyrosine kinase that plays a redundant role with ITK in regulation of the adaptive immune response. Regulates the development, function and differentiation of conventional T-cells and nonconventional NKT-cells. When antigen presenting cells (APC) activate T-cell receptor (TCR), a series of phosphorylation lead to the recruitment of TXK to the cell membrane, where it is phosphorylated at Tyr-420. Phosphorylation leads to TXK full activation. Contributes also to signaling from many receptors and participates in multiple downstream pathways, including regulation of the actin cytoskeleton. Like ITK, can phosphorylate PLCG1, leading to its localization in lipid rafts and activation, followed by subsequent cleavage of its substrates. In turn, the endoplasmic reticulum releases calcium in the cytoplasm and the nuclear activator of activated T-cells (NFAT) translocates into the nucleus to perform its transcriptional duty. With PARP1 and EEF1A1, TXK forms a complex that acts as a T-helper 1 (Th1) cell-specific transcription factor and binds the promoter of IFNG to directly regulate its transcription, and is thus involved importantly in Th1 cytokine production. Phosphorylates both PARP1 and EEF1A1. Phosphorylates also key sites in LCP2 leading to the up-regulation of Th1 preferred cytokine IL-2. Phosphorylates 'Tyr-201' of CTLA4 which leads to the association of PI-3 kinase with the CTLA4 receptor.
- Specific Function
- Atp binding
- Gene Name
- TXK
- Uniprot ID
- P42681
- Uniprot Name
- Tyrosine-protein kinase TXK
- Molecular Weight
- 61257.9 Da
References
- Guo Y, Liu Y, Hu N, Yu D, Zhou C, Shi G, Zhang B, Wei M, Liu J, Luo L, Tang Z, Song H, Guo Y, Liu X, Su D, Zhang S, Song X, Zhou X, Hong Y, Chen S, Cheng Z, Young S, Wei Q, Wang H, Wang Q, Lv L, Wang F, Xu H, Sun H, Xing H, Li N, Zhang W, Wang Z, Liu G, Sun Z, Zhou D, Li W, Liu L, Wang L, Wang Z: Discovery of Zanubrutinib (BGB-3111), a Novel, Potent, and Selective Covalent Inhibitor of Bruton's Tyrosine Kinase. J Med Chem. 2019 Sep 12;62(17):7923-7940. doi: 10.1021/acs.jmedchem.9b00687. Epub 2019 Aug 19. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- FDA Approved Drug Products: Brukinsa (zanubrutinib) capsules [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inducer
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2B6
- Uniprot ID
- P20813
- Uniprot Name
- Cytochrome P450 2B6
- Molecular Weight
- 56277.81 Da
References
- FDA Approved Drug Products: Brukinsa (zanubrutinib) capsules [Link]
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Components:
| Name | UniProt ID |
|---|---|
| Cytochrome P450 3A4 | P08684 |
| Cytochrome P450 3A43 | Q9HB55 |
| Cytochrome P450 3A5 | P20815 |
| Cytochrome P450 3A7 | P24462 |
References
- FDA Approved Drug Products: Brukinsa (zanubrutinib) capsules [Link]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- Curator comments
- The FDA Label suggests that zanubrutinib is likely to be a substrate of P-gp, although this drug-transporter interaction is not confirmed.
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- Multidrug resistance protein 1
- Molecular Weight
- 141477.255 Da
Drug created at May 20, 2019 14:44 / Updated at February 20, 2024 23:54