Venetoclax
Identification
- Summary
Venetoclax is a BCL-2 inhibitor used to treat chronic lymphocytic leukemia, small lymphocytic lymphoma, or acute myeloid leukemia.
- Brand Names
- Venclexta
- Generic Name
- Venetoclax
- DrugBank Accession Number
- DB11581
- Background
Venetoclax is a BCL-2 inhibitor that was initially approved by the FDA in April 2016 Label. Proteins in the B cell CLL/lymphoma 2 (BCL-2) family are important regulators of the apoptotic (programmed cell death) process 1, 2. Venetoclax is used to treat chronic lymphocytic leukemia (CLL) and certain types of small lymphocytic lymphoma Label. CLL is the most prevalent leukemia diagnosed in Western countries 7. Venetoclax was developed through reverse engineering of the BCL-2 protein family inhibitor, navitoclax 7. Venetoclax is approximately 10 times more potent than navitoclax with regard to induction of apoptosis in CLL cells 7. A new indication was approved in 2018 for the treatment patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), with or without 17p deletion, who have received at least one prior therapy Label. Previously, this drug was indicated only for patients with 17p gene deletion 11.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
- Weight
- Average: 868.45
Monoisotopic: 867.3180959 - Chemical Formula
- C45H50ClN7O7S
- Synonyms
- 4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)-2-(1H-pyrrolo(2,3-b)pyridin-5-yloxy)benzamide
- 4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl}sulfonyl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide
- 4-{4-[(4'-chloro-5,5-dimethyl[3,4,5,6-tetrahydro[1,1'-biphenyl]]-2-yl)methyl]piperazin-1-yl}-N-(3-nitro-4-{[(oxan-4-yl)methyl]amino}benzene-1-sulfonyl)-2-[(1H-pyrrolo[2,3-b]pyridin-5-yl)oxy]benzamide
- External IDs
- ABT 199
- ABT-199
- ABT199
- GDC 0199
- GDC-0199
- GDC0199
- RG 7601
- RG-7601
- RG7601
Pharmacology
- Indication
Venetoclax is indicated for the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). It is also used in combination with azacitidine, or decitabine, or low-dose cytarabine for the treatment of newly diagnosed acute myeloid leukemia (AML) in adults 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy.9
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 Used in combination to treat Acute myeloid leukemia (aml) Regimen in combination with: Azacitidine (DB00928) •••••••••••• ••••• ••••• •••••••••• ••••••••••••• Used in combination to treat Acute myeloid leukemia (aml) Regimen in combination with: Decitabine (DB01262) •••••••••••• ••••• ••••• •••••••••• ••••••••••••• Used in combination to treat Acute myeloid leukemia (aml) Regimen in combination with: Cytarabine (DB00987) •••••••••••• ••••• •••••••••••••• ••••• ••••••••• Treatment of Chronic lymphocytic leukemia (cll) •••••••••••• ••••• Treatment of Small lymphocytic lymphoma •••••••••••• ••••• - 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
Venetoclax induces rapid and potent onset apoptosis of CLL cells, powerful enough to act within 24h and to lead to tumor lysis syndrome 5, Label, 2. Selective targeting of BCL2 with venetoclax has demonstrated a manageable safety profile and has been shown to induce significant response in patients with relapsed CLL (chronic lymphocytic leukemia) or SLL (small lymphocytic leukemia), including patients with poor prognostic features 6. This drug is not expected to have a significant impact on the cardiac QT interval Label. Venetoclax has demonstrated efficacy in various types of lymphoid malignancies, including relapsed/ refractory CLL harboring deletion 17p, with an overall response rate of approximately 80% 7.
- Mechanism of action
Proteins in the B cell CLL/lymphoma 2 (BCL-2) family are necessary regulators of the apoptotic (anti-cell programmed death) process. This family comprises proapoptotic and prosurvival proteins for various cells. Cancer cells evade apoptosis by inhibiting programmed cell death (apoptosis). The therapeutic potential of directly inhibiting prosurvival proteins was unveiled with the development of navitoclax, a selective inhibitor of both BCL-2 and BCL-2-like 1 (BCL-X(L)), which has demonstrated clinical efficacy in some BCL-2-dependent hematological cancers 1. Selective inhibition of BCL-2 by venetoclax, sparing BCL-xL enables therapeutic induction of apoptosis without the negative effect of thrombocytopenia 7, 1. Venetoclax helps restore the process of apoptosis by binding directly to the BCL-2 protein, displacing pro-apoptotic proteins, leading to mitochondrial outer membrane permeabilization and the activation of caspase enzymes. In nonclinical studies, venetoclax has shown cytotoxic activity in tumor cells that overexpress BCL-2 Label.
Target Actions Organism AApoptosis regulator Bcl-2 antagonistinhibitorHumans - Absorption
Following several oral administrations after a meal, the maximum plasma concentration of venetoclax was reached 5-8 hours after the dose 3. Venetoclax steady state AUC (area under the curve) increased proportionally over the dose range of 150-800 mg. After a low-fat meal, venetoclax mean (± standard deviation) steady-state Cmax was 2.1 ± 1.1 μg/mL and AUC0-24 was 32.8 ± 16.9 μg•h/mL at the 400 mg once daily dose Label.
When compared with the fasted state, venetoclax exposure increased by 3.4 times when ingested with a low-fat meal and 5.2 times with a high-fat meal. When comparing low versus high fat, the Cmax and AUC were both increased by 50% when ingested with a high-fat meal. The FDA label indicataes that venetoclax should be taken with food 7, Label.
- Volume of distribution
The population estimate for apparent volume of distribution (Vdss/F) of venetoclax ranged from 256-321 L Label.
- Protein binding
Venetoclax is highly bound to human plasma protein with unbound fraction in plasma <0.01 across a concentration range of 1-30 µM (0.87-26 µg/mL). The mean blood-to-plasma ratio was 0.57 Label.
- Metabolism
In vitro studies demonstrated that venetoclax is predominantly metabolized as a substrate of CYP3A4/5 Label, 4, 10.
Hover over products below to view reaction partners
- Route of elimination
After single oral administration of 200 mg radiolabeled [14C]-venetoclax dose to healthy subjects, >99.9% of the dose was found in feces and <0.1% of the dose was excreted in urine within 9 days, suggesting that hepatic elimination is responsible for the clearance of venetoclax from systemic circulation. Unchanged venetoclax accounted for 20.8% of the radioactive dose excreted in feces Label.
- Half-life
The half-life of venetoclax is reported to be 19-26 hours, after administration of a single 50-mg dose 7, Label.
- Clearance
Mainly hepatic Label.
- 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
Acute toxicity: oral toxicity (LD50) >2001 mg/kg (mouse) 8.
Venetoclax may cause embryo-fetal harm when administered to a pregnant woman. Patients should avoid pregnancy during treatment. A risk to human male fertility exists based on the results of testicular toxicity (germ cell loss) seen in dogs at exposures as low as 0.5 times the human AUC exposure at the recommended dose Label.
Carcinogenicity studies have not yet been performed with venetoclax Label.
Venetoclax was not shown to be mutagenic in an in vitro bacterial mutagenicity (Ames) assay, did not induce aberrations in an in vitro chromosome aberration assay with human peripheral blood lymphocytes. It was not clastogenic in an in vivo mouse bone marrow micronucleus assay at doses up to 835 mg/kg. The M27 metabolite was negative for genotoxic activity during both in vitro Ames and chromosome aberration assays Label.
- 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 software1,2-Benzodiazepine The metabolism of 1,2-Benzodiazepine can be decreased when combined with Venetoclax. Abametapir The serum concentration of Venetoclax can be increased when it is combined with Abametapir. Abatacept The metabolism of Venetoclax can be increased when combined with Abatacept. Abemaciclib The serum concentration of Abemaciclib can be increased when it is combined with Venetoclax. Abiraterone The metabolism of Abiraterone can be decreased when combined with Venetoclax. - Food Interactions
- Avoid grapefruit products. Grapefruit inhibits CYP3A metabolism, which may increase the serum concentration of venetoclax.
- Avoid St. John's Wort. This herb induces CYP3A metabolism and may reduce serum levels of venetoclax.
- Take at the same time every day.
- Take with a full glass of water.
- Take with food.
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 Venclexta Tablet 100 mg Oral Abbvie 2016-10-31 Not applicable Canada Venclexta Tablet, film coated 100 mg/1 Oral AbbVie Inc. 2016-04-11 Not applicable US Venclexta Tablet 50 mg Oral Abbvie 2016-10-31 Not applicable Canada Venclexta Tablet, film coated 50 mg/1 Oral AbbVie Inc. 2016-04-11 Not applicable US Venclexta Tablet 10 mg Oral Abbvie 2016-10-31 Not applicable Canada - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Venclexta Venetoclax (10 mg/1) + Venetoclax (50 mg/1) + Venetoclax (100 mg/1) + Venetoclax (100 mg/1) Kit; Tablet, film coated Oral AbbVie Inc. 2016-04-11 Not applicable US Venclexta Venetoclax (10 mg) + Venetoclax (50 mg) + Venetoclax (100 mg) Kit; Tablet Oral Abbvie 2016-10-31 Not applicable Canada Venclexta Venetoclax (10 mg/1) + Venetoclax (50 mg/1) + Venetoclax (100 mg/1) + Venetoclax (100 mg/1) Kit; Tablet, film coated Oral AbbVie Inc. 2016-04-11 Not applicable US Venclexta Venetoclax (10 mg) + Venetoclax (50 mg) + Venetoclax (100 mg) Kit; Tablet Oral Abbvie 2016-10-31 Not applicable Canada Venclexta Venetoclax (10 mg/1) + Venetoclax (50 mg/1) + Venetoclax (100 mg/1) + Venetoclax (100 mg/1) Kit; Tablet, film coated Oral AbbVie Inc. 2016-04-11 Not applicable US
Categories
- ATC Codes
- L01XX52 — Venetoclax
- Drug Categories
- Amides
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- BCL-2 Inhibitor
- BCRP/ABCG2 Inhibitors
- BCRP/ABCG2 Substrates
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (moderate)
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Increased Cellular Death
- Narrow Therapeutic Index Drugs
- OATP1B1/SLCO1B1 Inhibitors
- P-glycoprotein inhibitors
- P-glycoprotein substrates
- P-glycoprotein substrates with a Narrow Therapeutic Index
- Sulfones
- Sulfur Compounds
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as phenylpiperazines. These are compounds containing a phenylpiperazine skeleton, which consists of a piperazine bound to a phenyl group.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Diazinanes
- Sub Class
- Piperazines
- Direct Parent
- Phenylpiperazines
- Alternative Parents
- N-arylpiperazines / Aminobenzenesulfonamides / Diarylethers / Aminobenzoic acids and derivatives / Pyrrolopyridines / Benzenesulfonyl compounds / Nitrobenzenes / Aniline and substituted anilines / Benzoyl derivatives / Dialkylarylamines show 26 more
- Substituents
- Allyl-type 1,3-dipolar organic compound / Amine / Amino acid or derivatives / Aminobenzenesulfonamide / Aminobenzoic acid or derivatives / Aminosulfonyl compound / Aniline or substituted anilines / Aromatic heteropolycyclic compound / Aryl chloride / Aryl halide show 52 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- N54AIC43PW
- CAS number
- 1257044-40-8
- InChI Key
- LQBVNQSMGBZMKD-UHFFFAOYSA-N
- InChI
- InChI=1S/C45H50ClN7O7S/c1-45(2)15-11-33(39(26-45)31-3-5-34(46)6-4-31)29-51-17-19-52(20-18-51)35-7-9-38(42(24-35)60-36-23-32-12-16-47-43(32)49-28-36)44(54)50-61(57,58)37-8-10-40(41(25-37)53(55)56)48-27-30-13-21-59-22-14-30/h3-10,12,16,23-25,28,30,48H,11,13-15,17-22,26-27,29H2,1-2H3,(H,47,49)(H,50,54)
- IUPAC Name
- 4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-(3-nitro-4-{[(oxan-4-yl)methyl]amino}benzenesulfonyl)-2-{1H-pyrrolo[2,3-b]pyridin-5-yloxy}benzamide
- SMILES
- CC1(C)CCC(CN2CCN(CC2)C2=CC=C(C(=O)NS(=O)(=O)C3=CC=C(NCC4CCOCC4)C(=C3)[N+]([O-])=O)C(OC3=CN=C4NC=CC4=C3)=C2)=C(C1)C1=CC=C(Cl)C=C1
References
- General References
- Souers AJ, Leverson JD, Boghaert ER, Ackler SL, Catron ND, Chen J, Dayton BD, Ding H, Enschede SH, Fairbrother WJ, Huang DC, Hymowitz SG, Jin S, Khaw SL, Kovar PJ, Lam LT, Lee J, Maecker HL, Marsh KC, Mason KD, Mitten MJ, Nimmer PM, Oleksijew A, Park CH, Park CM, Phillips DC, Roberts AW, Sampath D, Seymour JF, Smith ML, Sullivan GM, Tahir SK, Tse C, Wendt MD, Xiao Y, Xue JC, Zhang H, Humerickhouse RA, Rosenberg SH, Elmore SW: ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. Nat Med. 2013 Feb;19(2):202-8. doi: 10.1038/nm.3048. Epub 2013 Jan 6. [Article]
- Cang S, Iragavarapu C, Savooji J, Song Y, Liu D: ABT-199 (venetoclax) and BCL-2 inhibitors in clinical development. J Hematol Oncol. 2015 Nov 20;8:129. doi: 10.1186/s13045-015-0224-3. [Article]
- Salem AH, Agarwal SK, Dunbar M, Enschede SL, Humerickhouse RA, Wong SL: Pharmacokinetics of Venetoclax, a Novel BCL-2 Inhibitor, in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia or Non-Hodgkin's Lymphoma. J Clin Pharmacol. 2016 Aug 25. doi: 10.1002/jcph.821. [Article]
- Agarwal SK, Hu B, Chien D, Wong SL, Salem AH: Evaluation of Rifampin's Transporter Inhibitory and CYP3A Inductive Effects on the Pharmacokinetics of Venetoclax, a Bcl-2 Inhibitor: Results of a Single- and Multiple-dose Study. J Clin Pharmacol. 2016 Mar 7. doi: 10.1002/jcph.730. [Article]
- Anderson MA, Deng J, Seymour JF, Tam C, Kim SY, Fein J, Yu L, Brown JR, Westerman D, Si EG, Majewski IJ, Segal D, Heitner Enschede SL, Huang DC, Davids MS, Letai A, Roberts AW: The BCL2 selective inhibitor venetoclax induces rapid onset apoptosis of CLL cells in patients via a TP53-independent mechanism. Blood. 2016 Jun 23;127(25):3215-24. doi: 10.1182/blood-2016-01-688796. Epub 2016 Apr 11. [Article]
- Roberts AW, Davids MS, Pagel JM, Kahl BS, Puvvada SD, Gerecitano JF, Kipps TJ, Anderson MA, Brown JR, Gressick L, Wong S, Dunbar M, Zhu M, Desai MB, Cerri E, Heitner Enschede S, Humerickhouse RA, Wierda WG, Seymour JF: Targeting BCL2 with Venetoclax in Relapsed Chronic Lymphocytic Leukemia. N Engl J Med. 2016 Jan 28;374(4):311-22. doi: 10.1056/NEJMoa1513257. Epub 2015 Dec 6. [Article]
- King AC, Peterson TJ, Horvat TZ, Rodriguez M, Tang LA: Venetoclax: A First-in-Class Oral BCL-2 Inhibitor for the Management of Lymphoid Malignancies. Ann Pharmacother. 2017 May;51(5):410-416. doi: 10.1177/1060028016685803. Epub 2017 Jan 6. [Article]
- Venetoclax, Safety Sheet [Link]
- FDA Approved Drug Products: Venclexta (venetoclax) oral tablets [Link]
- Australian Product Information: Venetoclax [File]
- Venetoclax, Previous FDA label [File]
- External Links
- Human Metabolome Database
- HMDB0247760
- KEGG Drug
- D10679
- PubChem Compound
- 49846579
- PubChem Substance
- 347827991
- ChemSpider
- 29315017
- BindingDB
- 60828
- 1747556
- ChEBI
- 133021
- ChEMBL
- CHEMBL3137309
- ZINC
- ZINC000150338755
- PharmGKB
- PA166153473
- PDBe Ligand
- LBM
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Venetoclax
- PDB Entries
- 6o0k / 6o0l / 6o0m / 6o0p
- FDA label
- Download (1.31 MB)
- MSDS
- Download (230 KB)
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 4 Active Not Recruiting Treatment Acute Myeloid Leukemia 1 4 Not Yet Recruiting Treatment Chronic Lymphocytic Leukemia 1 3 Active Not Recruiting Treatment Acute Lymphoblastic Leukaemias (ALL) / Acute Myeloid Leukemia / Cancer / Chronic Lymphocytic Leukemia / Multiple Myeloma (MM) / Non-Hodgkin's Lymphoma (NHL) / Non-Hodgkin's Lymphomas 1 3 Active Not Recruiting Treatment Acute Myeloid Leukemia 5 3 Active Not Recruiting Treatment Acute Myeloid Leukemia / Cancer 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Kit; tablet Oral Kit; tablet, film coated Oral Tablet Oral 10 mg Tablet Oral 100 mg Tablet Oral 50 mg Tablet, coated Oral 10 mg Tablet, film coated Oral 10 mg/1 Tablet, film coated Oral 100 mg/1 Tablet, film coated Oral 50 mg/1 Tablet, film coated Oral 100.0 mg Tablet, film coated Oral 10.0 mg Tablet, film coated Oral 50.0 mg Tablet, film coated Oral Tablet, film coated Oral 100 mg Tablet, film coated Oral 10 mg Tablet, film coated Oral 50 mg - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US9174982 No 2015-11-03 2030-05-26 US US8546399 No 2013-10-01 2031-06-27 US US9539251 No 2017-01-10 2033-09-06 US US8722657 No 2014-05-13 2032-01-29 US US10730873 No 2020-08-04 2031-11-21 US US10993942 No 2021-05-04 2033-09-06 US US11110087 No 2021-09-07 2033-09-06 US US11369599 No 2012-05-23 2032-05-23 US US11413282 No 2013-09-06 2033-09-06 US US11590128 No 2013-09-06 2033-09-06 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source logP 99 MSDS - Predicted Properties
Property Value Source Water Solubility 0.000933 mg/mL ALOGPS logP 6.92 ALOGPS logP 6.76 Chemaxon logS -6 ALOGPS pKa (Strongest Acidic) 4.19 Chemaxon pKa (Strongest Basic) 7.96 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 10 Chemaxon Hydrogen Donor Count 3 Chemaxon Polar Surface Area 172.03 Å2 Chemaxon Rotatable Bond Count 12 Chemaxon Refractivity 238.59 m3·mol-1 Chemaxon Polarizability 93.95 Å3 Chemaxon Number of Rings 8 Chemaxon Bioavailability 0 Chemaxon Rule of Five No 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
- Not Available
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 272.3913 predictedDeepCCS 1.0 (2019) [M+H]+ 274.2867 predictedDeepCCS 1.0 (2019) [M+Na]+ 280.43314 predictedDeepCCS 1.0 (2019)
Targets
![](https://go.drugbank.com/assets/locked/DrugTargets2-682eb846d210ae4bf33ca03febccfb57bb1c61318e699b729e5df4dfab2c5b67.png)
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- AntagonistInhibitor
- General Function
- Ubiquitin protein ligase binding
- Specific Function
- Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells. Regulates cell death by controlling the mitochondrial membrane permeability. Appea...
- Gene Name
- BCL2
- Uniprot ID
- P10415
- Uniprot Name
- Apoptosis regulator Bcl-2
- Molecular Weight
- 26265.66 Da
References
- Davids MS, Letai A: ABT-199: taking dead aim at BCL-2. Cancer Cell. 2013 Feb 11;23(2):139-41. doi: 10.1016/j.ccr.2013.01.018. [Article]
- Souers AJ, Leverson JD, Boghaert ER, Ackler SL, Catron ND, Chen J, Dayton BD, Ding H, Enschede SH, Fairbrother WJ, Huang DC, Hymowitz SG, Jin S, Khaw SL, Kovar PJ, Lam LT, Lee J, Maecker HL, Marsh KC, Mason KD, Mitten MJ, Nimmer PM, Oleksijew A, Park CH, Park CM, Phillips DC, Roberts AW, Sampath D, Seymour JF, Smith ML, Sullivan GM, Tahir SK, Tse C, Wendt MD, Xiao Y, Xue JC, Zhang H, Humerickhouse RA, Rosenberg SH, Elmore SW: ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. Nat Med. 2013 Feb;19(2):202-8. doi: 10.1038/nm.3048. Epub 2013 Jan 6. [Article]
- King AC, Peterson TJ, Horvat TZ, Rodriguez M, Tang LA: Venetoclax: A First-in-Class Oral BCL-2 Inhibitor for the Management of Lymphoid Malignancies. Ann Pharmacother. 2017 May;51(5):410-416. doi: 10.1177/1060028016685803. Epub 2017 Jan 6. [Article]
- Castillo JJ, Treon SP: Management of Waldenstrom macroglobulinemia in 2020. Hematology Am Soc Hematol Educ Program. 2020 Dec 4;2020(1):372-379. doi: 10.1182/hematology.2020000121. [Article]
- Pallis M, Burrows F, Ryan J, Grundy M, Seedhouse C, Abdul-Aziz A, Montero J, Letai A, Russell N: Complementary dynamic BH3 profiles predict co-operativity between the multi-kinase inhibitor TG02 and the BH3 mimetic ABT-199 in acute myeloid leukaemia cells. Oncotarget. 2017 Mar 7;8(10):16220-16232. doi: 10.18632/oncotarget.8742. [Article]
- Emadi A, Kapadia B, Bollino D, Bhandary B, Baer MR, Niyongere S, Strovel ET, Kaizer H, Chang E, Choi EY, Ma X, Tighe KM, Carter-Cooper B, Moses BS, Civin CI, Mahurkar A, Shetty AC, Gartenhaus RB, Kamangar F, Lapidus RG: Venetoclax and pegcrisantaspase for complex karyotype acute myeloid leukemia. Leukemia. 2021 Jul;35(7):1907-1924. doi: 10.1038/s41375-020-01080-6. Epub 2020 Nov 16. [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]
- Wang L, Lin N: Double remission of chronic lymphocytic leukemia and secondary acute myeloid leukemia after venetoclax monotherapy: A case report. Medicine (Baltimore). 2021 Feb 12;100(6):e24703. doi: 10.1097/MD.0000000000024703. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- SubstrateInhibitor
- 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
- Agarwal SK, Hu B, Chien D, Wong SL, Salem AH: Evaluation of Rifampin's Transporter Inhibitory and CYP3A Inductive Effects on the Pharmacokinetics of Venetoclax, a Bcl-2 Inhibitor: Results of a Single- and Multiple-dose Study. J Clin Pharmacol. 2016 Mar 7. doi: 10.1002/jcph.730. [Article]
- Weiss J, Gajek T, Kohler BC, Haefeli WE: Venetoclax (ABT-199) Might Act as a Perpetrator in Pharmacokinetic Drug-Drug Interactions. Pharmaceutics. 2016 Feb 24;8(1). pii: pharmaceutics8010005. doi: 10.3390/pharmaceutics8010005. [Article]
- Freise KJ, Hu B, Salem AH: Impact of ritonavir dose and schedule on CYP3A inhibition and venetoclax clinical pharmacokinetics. Eur J Clin Pharmacol. 2018 Apr;74(4):413-421. doi: 10.1007/s00228-017-2403-3. Epub 2018 Jan 4. [Article]
- Venclexta FDA label [File]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- SubstrateInhibitor
- 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
References
- Agarwal SK, Hu B, Chien D, Wong SL, Salem AH: Evaluation of Rifampin's Transporter Inhibitory and CYP3A Inductive Effects on the Pharmacokinetics of Venetoclax, a Bcl-2 Inhibitor: Results of a Single- and Multiple-dose Study. J Clin Pharmacol. 2016 Mar 7. doi: 10.1002/jcph.730. [Article]
- Australian Product Information, Venetoclax [File]
- Venclexta FDA label [File]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
- Gene Name
- ABCG2
- Uniprot ID
- Q9UNQ0
- Uniprot Name
- ATP-binding cassette sub-family G member 2
- Molecular Weight
- 72313.47 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- Data supported only by in vitro evidence.
- General Function
- Sodium-independent organic anion transmembrane transporter activity
- Specific Function
- Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
- Gene Name
- SLCO1B1
- Uniprot ID
- Q9Y6L6
- Uniprot Name
- Solute carrier organic anion transporter family member 1B1
- Molecular Weight
- 76447.99 Da
References
Drug created at April 18, 2016 16:22 / Updated at February 20, 2024 23:54