Tirbanibulin
Identification
- Summary
Tirbanibulin is a tyrosine kinase and tubulin inhibitor used to treat actinic keratosis on the face or scalp.
- Brand Names
- Klisyri
- Generic Name
- Tirbanibulin
- DrugBank Accession Number
- DB06137
- Background
Tirbanibulin (KX-O1 or KX2–391) is a dual inhibitor of Src Kinase and tubulin.4 On December 14, 2020, tirbanibulin was approved by the FDA for the topical treatment of actinic keratosis on the face or scalp. It is marketed under the brand name Klisyri.12 Actinic keratosis is a chronic condition characterized by lesions, which can potentially transform into invasive squamous cell carcinoma with a risk of 1% over 10 years.3,7 Tirbanibulin blocks the molecular pathways that promote the proliferation, survival, and metastasis of malignant cells. Tirbanibulin exhibits antitumour effects in vitro and in vivo 9 and has been investigated for its antitumor efficacy in the management of various cancers, such as prostate cancer and breast cancer.4,5,6
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
- Weight
- Average: 431.536
Monoisotopic: 431.220891806 - Chemical Formula
- C26H29N3O3
- Synonyms
- Tirbanibulin
- External IDs
- KX-01
- KX-2-391
- KX-2391
- KX2-391
Pharmacology
- Indication
Tirbanibulin is indicated for the topical treatment of actinic keratosis on the face or scalp.11
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Actinic keratoses of the face •••••••••••• •••••••• Treatment of Actinic keratoses of the scalp •••••••••••• •••••••• - Contraindications & Blackbox Warnings
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- Pharmacodynamics
In clinical trials composed comprising patients with actinic keratosis of the face or scalp, tirbanibulin promoted complete clearance of actinic keratosis lesions at day 57 in treated areas in 44-54% of patients compared to 5-13% of patients who received the placebo.11 Actinic keratosis is a chronic, pre-malignant condition characterized by lesions and proliferation of neoplastic keratinocytes.3 Tirbanibulin mediates an anti-proliferative effect by inhibiting tubulin polymerization and Src kinase signalling.1
Tirbanibulin inhibited primary tumour growth and metastasis in many preclinical animal models of cancer.2,4,5,6 In human triple-negative breast cancer, or estrogen receptor (ER)/progesterone receptor (PR)/human epidermal growth factor receptor 2 (HER2)-negative tumour, xenografts, tirbanibulin suppressed tumour growth and metastasis.4 Tirbanibulin was also shown to restore functional ERα expression in ERα-negative breast tumours.10 Tirbanibulin promoted synergistic tumour growth inhibition of breast cancer cell lines when used in combination with tamoxifen 5,10 and paclitaxel.4
In a clinical trial comprising patients with advanced solid tumours, dose-limiting toxicities of tirbanibulin included elevated liver transaminases, neutropenia and fatigue.6
- Mechanism of action
Src tyrosine kinases regulate normal cell growth: the expression of Src kinase is upregulated during the normal hair cycle during the proliferative anagen phase. Additionally, Src tyrosine kinases act as key modulators of cancer cell proliferation, survival, angiogenesis, migration, invasion and metastasis. Src is frequently upregulated in various epithelial tumours including colon, breast and pancreas compared with the adjacent normal tissues. The expression and activity of Src are also enhanced in human actinic keratosis, which is characterized by hyperproliferative premalignant skin lesions.8 The pathogenesis of actinic keratosis commonly involves skin inflammation, oxidative stress, immunosuppression, impaired apoptosis, mutagenesis, dysregulation of keratinocyte growth and proliferation, and tissue remodelling.7 In vitro studies suggest that Src plays a predominant role in the early stages of human skin tumour development, rather than at later stages of tumour progression.8
The exact mechanism of tirbanibulin as a topical treatment of actinic keratosis has not been fully elucidated;11 however, it mainly works by inhibiting fast proliferating cells.3 Tirbanibulin is a non-ATP competitive Src kinase inhibitor and tubulin polymerization inhibitor. It binds to the peptide substrate binding site of Src, a primary target of tirbanibulin, and blocking its downstream signalling pathways that promote cancer cell migration, proliferation, and survival.3,5 Tublin is responsible for cell migration, protein transport, and mitosis: tibranibulin directly binds to the colchicine-binding site of beta-tubulin and causes induces tubulin depolymerization.2 It is also hypothesized that inhibition of Src can also contribute to the inhibitory effects on microtubule polymerization.9 At low nanomolar concentrations, tirbanibulin induces G2/M phase cell cycle arrest in a reversible 2,5 and dose-dependent manner. By inhibiting microtubule polymerization, tirbanibulin also induces mitotic catastrophe.9
Target Actions Organism ATubulin beta chain inhibitorHumans AProto-oncogene tyrosine-protein kinase Src inhibitorHumans - Absorption
Tirbanibulin demonstrates good oral bioavailability.2 Following topical administration of doses ranging from 54 to 295 mg on the face or scalp, the steady-state concentration of tirbanibulin was achieved by 72 hours. At five days following initial administration, the mean Cmax was 0.34±0.30 ng/mL in subjects who received topical treatment on the face and 0.18±0.10 ng/mL in subjects who received topical treatment on the scalp. The mean AUC24 was 5.0±3.9 h x ng/mL in subjects who received topical treatment on the face and 3.2±1.9 h x ng/mL in subjects who received topical treatment on the scalp. The median Tmax was about seven hours.11
- Volume of distribution
There is limited information on the volume of distribution of tirbanibulin. In mouse HT29 xenograft studies, the tissue to plasma ration of tirbanibulin was 1.52.6
- Protein binding
Tirbanibulin is 88% bound to plasma proteins and the extent of plasma protein binding is independent of drug concentrations in the range of 0.01 to 10 µg/mL.11
- Metabolism
In vitro, tirbanibulin is mainly metabolized by CYP3A4, and to a lesser extent, CYP2C8. In adult subjects with actinic keratosis, detected metabolites were KX2-5036 and KX2-5163, which were pharmacologically inactive metabolites with the highest plasma concentrations of 0.09 ng/mL and 0.12 ng/mL, respectively.11
- Route of elimination
There is limited information on the route of elimination of tirbanibulin.
- Half-life
The half-life is about 4 hours.6
- Clearance
There is limited information on the clearance rate of tirbanibulin.
- Adverse Effects
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- Toxicity
The LD50 value of tirbanibulin has not been determined. While there is limited information on overdose from tirbanibulin, it may lead to an increase in the incidence and severity of local skin reactions.11
- 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 softwareEtrasimod The risk or severity of immunosuppression can be increased when Tirbanibulin is combined with Etrasimod. Voriconazole The serum concentration of Tirbanibulin can be increased when it is combined with Voriconazole. - Food Interactions
- No interactions found.
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 Klisyri Ointment 10 mg/1g Topical Almirall, LLC 2020-12-14 Not applicable US Klisyri Ointment 10 mg/g Cutaneous Almirall, S.A. 2021-10-06 Not applicable EU Onakta Ointment 1 % w/w Topical Avir Pharma Inc. Not applicable Not applicable Canada
Categories
- ATC Codes
- D06BX03 — Tirbanibulin
- Drug Categories
- Acetates
- Acids, Acyclic
- Amides
- Antineoplastic Agents
- Cytochrome P-450 CYP1A2 Inhibitors
- Cytochrome P-450 CYP1A2 Inhibitors (weak)
- Cytochrome P-450 CYP2B6 Inhibitors
- Cytochrome P-450 CYP2B6 Inhibitors (weak)
- Cytochrome P-450 CYP2C19 Inhibitors
- Cytochrome P-450 CYP2C19 Inhibitors (weak)
- Cytochrome P-450 CYP2C8 Inhibitors
- Cytochrome P-450 CYP2C8 Inhibitors (weak)
- Cytochrome P-450 CYP2C8 Substrates
- Cytochrome P-450 CYP2C9 Inhibitors
- Cytochrome P-450 CYP2C9 Inhibitors (weak)
- Cytochrome P-450 CYP2D6 Inhibitors
- Cytochrome P-450 CYP2D6 Inhibitors (weak)
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (weak)
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Dermatologicals
- Enzyme Inhibitors
- Fatty Acids
- Fatty Acids, Volatile
- Keratosis, Actinic, drug therapy
- Kinase Inhibitor
- Lipids
- MATE 1 Inhibitors
- MATE 2 Inhibitors
- MATE inhibitors
- Microtubule Inhibitors
- OATP1B1/SLCO1B1 Inhibitors
- OATP1B3 inhibitors
- OCT1 inhibitors
- OCT2 Inhibitors
- Oxazines
- Tubulin Inhibiting Agent
- Tyrosine Kinase Inhibitors
- Classification
- Not classified
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 4V9848RS5G
- CAS number
- 897016-82-9
- InChI Key
- HUNGUWOZPQBXGX-UHFFFAOYSA-N
- InChI
- InChI=1S/C26H29N3O3/c30-26(28-19-21-4-2-1-3-5-21)18-24-9-6-23(20-27-24)22-7-10-25(11-8-22)32-17-14-29-12-15-31-16-13-29/h1-11,20H,12-19H2,(H,28,30)
- IUPAC Name
- N-benzyl-2-(5-{4-[2-(morpholin-4-yl)ethoxy]phenyl}pyridin-2-yl)acetamide
- SMILES
- O=C(CC1=CC=C(C=N1)C1=CC=C(OCCN2CCOCC2)C=C1)NCC1=CC=CC=C1
References
- General References
- Kempers S, DuBois J, Forman S, Poon A, Cutler E, Wang H, Cutler D, Fang J, Kwan R: Tirbanibulin Ointment 1% as a Novel Treatment for Actinic Keratosis: Phase 1 and 2 Results. J Drugs Dermatol. 2020 Nov 1;19(11):1093-1100. doi: 10.36849/JDD.2020.5576. [Article]
- Niu L, Yang J, Yan W, Yu Y, Zheng Y, Ye H, Chen Q, Chen L: Reversible binding of the anticancer drug KXO1 (tirbanibulin) to the colchicine-binding site of beta-tubulin explains KXO1's low clinical toxicity. J Biol Chem. 2019 Nov 29;294(48):18099-18108. doi: 10.1074/jbc.RA119.010732. Epub 2019 Oct 18. [Article]
- Cramer P, Stockfleth E: Actinic keratosis: where do we stand and where is the future going to take us? Expert Opin Emerg Drugs. 2020 Mar;25(1):49-58. doi: 10.1080/14728214.2020.1730810. Epub 2020 Feb 20. [Article]
- Anbalagan M, Ali A, Jones RK, Marsden CG, Sheng M, Carrier L, Bu Y, Hangauer D, Rowan BG: Peptidomimetic Src/pretubulin inhibitor KX-01 alone and in combination with paclitaxel suppresses growth, metastasis in human ER/PR/HER2-negative tumor xenografts. Mol Cancer Ther. 2012 Sep;11(9):1936-47. doi: 10.1158/1535-7163.MCT-12-0146. Epub 2012 Jul 10. [Article]
- Anbalagan M, Carrier L, Glodowski S, Hangauer D, Shan B, Rowan BG: KX-01, a novel Src kinase inhibitor directed toward the peptide substrate site, synergizes with tamoxifen in estrogen receptor alpha positive breast cancer. Breast Cancer Res Treat. 2012 Apr;132(2):391-409. doi: 10.1007/s10549-011-1513-3. Epub 2011 Apr 21. [Article]
- Antonarakis ES, Heath EI, Posadas EM, Yu EY, Harrison MR, Bruce JY, Cho SY, Wilding GE, Fetterly GJ, Hangauer DG, Kwan MF, Dyster LM, Carducci MA: A phase 2 study of KX2-391, an oral inhibitor of Src kinase and tubulin polymerization, in men with bone-metastatic castration-resistant prostate cancer. Cancer Chemother Pharmacol. 2013 Apr;71(4):883-92. doi: 10.1007/s00280-013-2079-z. Epub 2013 Jan 13. [Article]
- Dodds A, Chia A, Shumack S: Actinic keratosis: rationale and management. Dermatol Ther (Heidelb). 2014 Jun;4(1):11-31. doi: 10.1007/s13555-014-0049-y. Epub 2014 Mar 14. [Article]
- Serrels B, Serrels A, Mason SM, Baldeschi C, Ashton GH, Canel M, Mackintosh LJ, Doyle B, Green TP, Frame MC, Sansom OJ, Brunton VG: A novel Src kinase inhibitor reduces tumour formation in a skin carcinogenesis model. Carcinogenesis. 2009 Feb;30(2):249-57. doi: 10.1093/carcin/bgn278. Epub 2008 Dec 5. [Article]
- Kim S, Min A, Lee KH, Yang Y, Kim TY, Lim JM, Park SJ, Nam HJ, Kim JE, Song SH, Han SW, Oh DY, Kim JH, Kim TY, Hangauer D, Lau JY, Im K, Lee DS, Bang YJ, Im SA: Antitumor Effect of KX-01 through Inhibiting Src Family Kinases and Mitosis. Cancer Res Treat. 2017 Jul;49(3):643-655. doi: 10.4143/crt.2016.168. Epub 2016 Oct 6. [Article]
- Anbalagan M, Sheng M, Fleischer B, Zhang Y, Gao Y, Hoang V, Matossian M, Burks HE, Burow ME, Collins-Burow BM, Hangauer D, Rowan BG: Dual Src Kinase/Pretubulin Inhibitor KX-01, Sensitizes ERalpha-negative Breast Cancers to Tamoxifen through ERalpha Reexpression. Mol Cancer Res. 2017 Nov;15(11):1491-1502. doi: 10.1158/1541-7786.MCR-16-0297-T. Epub 2017 Jul 27. [Article]
- FDA Approved Drug Products: KLISYRI (tirbanibulin) ointment, for topical use [Link]
- Drugs.com: Klisyri FDA Approval History [Link]
- Cayman Chemical: KX2-391 Safety Data Sheet [Link]
- External Links
- ChemSpider
- 24633341
- BindingDB
- 50303801
- 2471078
- ChEMBL
- CHEMBL571546
- ZINC
- ZINC000043152787
- PDBe Ligand
- DN0
- Wikipedia
- Tirbanibulin
- PDB Entries
- 6knz
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 Completed Treatment Actinic Keratosis (AK) 2 4 Not Yet Recruiting Treatment Actinic Keratosis (AK) 1 4 Recruiting Treatment Actinic Keratosis (AK) 1 3 Completed Treatment Actinic Keratosis (AK) 3 3 Not Yet Recruiting Treatment Actinic Keratosis (AK) 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Ointment Cutaneous 10 mg/g Ointment Topical 10 mg/1g Ointment Topical 1 % w/w - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US7851470 No 2010-12-14 2029-02-02 US US10617693 No 2020-04-14 2038-03-12 US US8980890 No 2015-03-17 2025-12-28 US US7300931 No 2007-11-27 2026-02-06 US US10323001 No 2019-06-18 2027-12-28 US US8236799 No 2012-08-07 2025-12-28 US US10669236 No 2020-06-02 2038-09-07 US US11497750 No 2018-03-12 2038-03-12 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.0248 mg/mL ALOGPS logP 3.26 ALOGPS logP 3.21 Chemaxon logS -4.2 ALOGPS pKa (Strongest Acidic) 15.36 Chemaxon pKa (Strongest Basic) 6.63 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 63.69 Å2 Chemaxon Rotatable Bond Count 9 Chemaxon Refractivity 124.86 m3·mol-1 Chemaxon Polarizability 48.49 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes 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 splash10-0059-0319600000-7659c0d6da6d08ea0947 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-0059-0269400000-d38d9b741932838fdc9b Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-01tc-1379000000-26b7ac1b5c35eb33a071 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-01t9-0397000000-113ccf59b5b3bea306dc Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-03yi-3921300000-63dfc6ae3ad5045660ea Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-008a-3962100000-c9f4f8a18a0bfde2b44f Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 223.4084223 predictedDarkChem Lite v0.1.0 [M+H]+ 224.3539223 predictedDarkChem Lite v0.1.0 [M+Na]+ 223.4505223 predictedDarkChem Lite v0.1.0
Targets
![](https://go.drugbank.com/assets/locked/DrugTargets2-682eb846d210ae4bf33ca03febccfb57bb1c61318e699b729e5df4dfab2c5b67.png)
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- Curator comments
- Tirbanibulin binds to the colchicine-binding site of β-tubulin. Antonarakis et al. (2013) showed that IC50 for tubulin polymerization inhibition in human tumour cells is about 125 nM in the absence of plasma and about 500 nM in the presence of plasma. An approximate 4-fold reduction in potency for tubulin polymerization inhibition is attributed to extensive plasma protein binding of tirbanibulin (88%).
- General Function
- Ubiquitin protein ligase binding
- Specific Function
- Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain.
- Gene Name
- TUBB
- Uniprot ID
- P07437
- Uniprot Name
- Tubulin beta chain
- Molecular Weight
- 49670.515 Da
References
- Niu L, Yang J, Yan W, Yu Y, Zheng Y, Ye H, Chen Q, Chen L: Reversible binding of the anticancer drug KXO1 (tirbanibulin) to the colchicine-binding site of beta-tubulin explains KXO1's low clinical toxicity. J Biol Chem. 2019 Nov 29;294(48):18099-18108. doi: 10.1074/jbc.RA119.010732. Epub 2019 Oct 18. [Article]
- Anbalagan M, Ali A, Jones RK, Marsden CG, Sheng M, Carrier L, Bu Y, Hangauer D, Rowan BG: Peptidomimetic Src/pretubulin inhibitor KX-01 alone and in combination with paclitaxel suppresses growth, metastasis in human ER/PR/HER2-negative tumor xenografts. Mol Cancer Ther. 2012 Sep;11(9):1936-47. doi: 10.1158/1535-7163.MCT-12-0146. Epub 2012 Jul 10. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- Curator comments
- Tirbanibulin binds to the substrate-binding site of Src kinase. Antonarakis et al. (2013) showed that the IC50 for Src inhibition in human tumour cells is about 25 nM in the absence of human plasma and about 100 nM in the presence of human plasma. An approximate 4-fold reduction in potency for Src inhibition is attributed to extensive plasma protein binding of tirbanibulin (88%).
- General Function
- Sh3/sh2 adaptor activity
- Specific Function
- Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion recept...
- Gene Name
- SRC
- Uniprot ID
- P12931
- Uniprot Name
- Proto-oncogene tyrosine-protein kinase Src
- Molecular Weight
- 59834.295 Da
References
- Anbalagan M, Carrier L, Glodowski S, Hangauer D, Shan B, Rowan BG: KX-01, a novel Src kinase inhibitor directed toward the peptide substrate site, synergizes with tamoxifen in estrogen receptor alpha positive breast cancer. Breast Cancer Res Treat. 2012 Apr;132(2):391-409. doi: 10.1007/s10549-011-1513-3. Epub 2011 Apr 21. [Article]
- Antonarakis ES, Heath EI, Posadas EM, Yu EY, Harrison MR, Bruce JY, Cho SY, Wilding GE, Fetterly GJ, Hangauer DG, Kwan MF, Dyster LM, Carducci MA: A phase 2 study of KX2-391, an oral inhibitor of Src kinase and tubulin polymerization, in men with bone-metastatic castration-resistant prostate cancer. Cancer Chemother Pharmacol. 2013 Apr;71(4):883-92. doi: 10.1007/s00280-013-2079-z. Epub 2013 Jan 13. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- SubstrateInhibitor
- Curator comments
- In vitro, tirbanibulin and the metabolite KX2-5036 directly or time-dependently inhibited CYP3A4 with an IC50 value of >17 µM.
- 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: KLISYRI (tirbanibulin) ointment, for topical use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- SubstrateInhibitor
- Curator comments
- In vitro, tirbanibulin and the metabolite KX2-5036 directly or time-dependently inhibited CYP2C8 with an IC50 value of >17 µM.
- 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
- CYP2C8
- Uniprot ID
- P10632
- Uniprot Name
- Cytochrome P450 2C8
- Molecular Weight
- 55824.275 Da
References
- FDA Approved Drug Products: KLISYRI (tirbanibulin) ointment, for topical use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- Curator comments
- In vitro, tirbanibulin and the metabolite KX2-5036 directly or time-dependently inhibited CYP1A2 with an IC50 value of >17 µM.
- General Function
- Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
- 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
- CYP1A2
- Uniprot ID
- P05177
- Uniprot Name
- Cytochrome P450 1A2
- Molecular Weight
- 58293.76 Da
References
- FDA Approved Drug Products: KLISYRI (tirbanibulin) ointment, for topical use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- Curator comments
- In vitro, tirbanibulin and the metabolite KX2-5036 directly or time-dependently inhibited CYP2B6 with an IC50 value of >17 µM.
- 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: KLISYRI (tirbanibulin) ointment, for topical use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- Curator comments
- In vitro, tirbanibulin and the metabolite KX2-5036 directly or time-dependently inhibited CYP2C9 with an IC50 value of >17 µM.
- 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
- CYP2C9
- Uniprot ID
- P11712
- Uniprot Name
- Cytochrome P450 2C9
- Molecular Weight
- 55627.365 Da
References
- FDA Approved Drug Products: KLISYRI (tirbanibulin) ointment, for topical use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- Curator comments
- In vitro, tirbanibulin and the metabolite KX2-5036 directly or time-dependently inhibited CYP2C19 with an IC50 value of >17 µM.
- General Function
- Steroid hydroxylase activity
- Specific Function
- Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
- Gene Name
- CYP2C19
- Uniprot ID
- P33261
- Uniprot Name
- Cytochrome P450 2C19
- Molecular Weight
- 55930.545 Da
References
- FDA Approved Drug Products: KLISYRI (tirbanibulin) ointment, for topical use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- Curator comments
- In vitro, tirbanibulin and the metabolite KX2-5036 directly or time-dependently inhibited CYP2D6 with an IC50 value of >17 µM.
- General Function
- Steroid hydroxylase activity
- Specific Function
- Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
- Gene Name
- CYP2D6
- Uniprot ID
- P10635
- Uniprot Name
- Cytochrome P450 2D6
- Molecular Weight
- 55768.94 Da
References
- FDA Approved Drug Products: KLISYRI (tirbanibulin) ointment, for topical use [Link]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- Curator comments
- In vitro, tirbanibulin and the metabolite KX2-5036 inhibited MATE1, MATE2-K, OATP1B1, OATP1B3, OCT1 and/or OCT2 with an IC50 value of >1 µM.
- General Function
- Monovalent cation:proton antiporter activity
- Specific Function
- Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide (NMN), metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfat...
- Gene Name
- SLC47A1
- Uniprot ID
- Q96FL8
- Uniprot Name
- Multidrug and toxin extrusion protein 1
- Molecular Weight
- 61921.585 Da
References
- FDA Approved Drug Products: KLISYRI (tirbanibulin) ointment, for topical use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- Curator comments
- In vitro, tirbanibulin and the metabolite KX2-5036 inhibited MATE1, MATE2-K, OATP1B1, OATP1B3, OCT1 and/or OCT2 with an IC50 value of >1 µM.
- General Function
- Drug transmembrane transporter activity
- Specific Function
- Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide, metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfate, acy...
- Gene Name
- SLC47A2
- Uniprot ID
- Q86VL8
- Uniprot Name
- Multidrug and toxin extrusion protein 2
- Molecular Weight
- 65083.915 Da
References
- FDA Approved Drug Products: KLISYRI (tirbanibulin) ointment, for topical use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- Curator comments
- In vitro, tirbanibulin and the metabolite KX2-5036 inhibited MATE1, MATE2-K, OATP1B1, OATP1B3, OCT1 and/or OCT2 with an IC50 value of >1 µM.
- 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
- FDA Approved Drug Products: KLISYRI (tirbanibulin) ointment, for topical use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- Curator comments
- In vitro, tirbanibulin and the metabolite KX2-5036 inhibited MATE1, MATE2-K, OATP1B1, OATP1B3, OCT1 and/or OCT2 with an IC50 value of >1 µM.
- General Function
- Sodium-independent organic anion transmembrane transporter activity
- Specific Function
- Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotre...
- Gene Name
- SLCO1B3
- Uniprot ID
- Q9NPD5
- Uniprot Name
- Solute carrier organic anion transporter family member 1B3
- Molecular Weight
- 77402.175 Da
References
- FDA Approved Drug Products: KLISYRI (tirbanibulin) ointment, for topical use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- Curator comments
- In vitro, tirbanibulin and the metabolite KX2-5036 inhibited MATE1, MATE2-K, OATP1B1, OATP1B3, OCT1 and/or OCT2 with an IC50 value of >1 µM.
- General Function
- Secondary active organic cation transmembrane transporter activity
- Specific Function
- Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnico...
- Gene Name
- SLC22A1
- Uniprot ID
- O15245
- Uniprot Name
- Solute carrier family 22 member 1
- Molecular Weight
- 61153.345 Da
References
- FDA Approved Drug Products: KLISYRI (tirbanibulin) ointment, for topical use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- Curator comments
- In vitro, tirbanibulin and the metabolite KX2-5036 inhibited MATE1, MATE2-K, OATP1B1, OATP1B3, OCT1 and/or OCT2 with an IC50 value of >1 µM.
- General Function
- Quaternary ammonium group transmembrane transporter activity
- Specific Function
- Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creat...
- Gene Name
- SLC22A2
- Uniprot ID
- O15244
- Uniprot Name
- Solute carrier family 22 member 2
- Molecular Weight
- 62579.99 Da
References
- FDA Approved Drug Products: KLISYRI (tirbanibulin) ointment, for topical use [Link]
Drug created at November 18, 2007 18:30 / Updated at February 21, 2021 18:51