Details of the Drug

General Information of Drug (ID: DMYGJQO)

Drug Name
Ponatinib
Synonyms Iclusig (TN)
Indication
Disease Entry ICD 11 Status REF
Acute lymphoblastic leukaemia 2A85 Approved [1]
Chronic myelogenous leukaemia 2A20.0 Approved [2]
Thyroid tumor N.A. Approved [2]
ATC Code
L01EA05: Ponatinib
L01EA: BCR-ABL tyrosine kinase inhibitors
L01E: PROTEIN KINASE INHIBITORS
L01: ANTINEOPLASTIC AGENTS
L: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 1 Molecular Weight (mw) 532.6
Logarithm of the Partition Coefficient (xlogp) 4.1
Rotatable Bond Count (rotbonds) 6
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 8
ADMET Property
Half-life
The concentration or amount of drug in body reduced by one-half in 24 hours (in cancer patients with 45 mg ponatinib once daily) [3]
Metabolism
The drug is metabolized via the esterases and/or amidases []
Vd
The volume of distribution (Vd) of drug is 1223 L []
Chemical Identifiers
Formula
C29H27F3N6O
IUPAC Name
3-(2-imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-N-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]benzamide
Canonical SMILES
CC1=C(C=C(C=C1)C(=O)NC2=CC(=C(C=C2)CN3CCN(CC3)C)C(F)(F)F)C#CC4=CN=C5N4N=CC=C5
InChI
InChI=1S/C29H27F3N6O/c1-20-5-6-22(16-21(20)8-10-25-18-33-27-4-3-11-34-38(25)27)28(39)35-24-9-7-23(26(17-24)29(30,31)32)19-37-14-12-36(2)13-15-37/h3-7,9,11,16-18H,12-15,19H2,1-2H3,(H,35,39)
InChIKey
PHXJVRSECIGDHY-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
24826799
ChEBI ID
CHEMBL1171837
CAS Number
943319-70-8
TTD ID
D0H0EQ
VARIDT ID
DR00204
INTEDE ID
DR1315
ACDINA ID
D00541
Drug-Molecule Activity Atlas (DMA)NEW Click to Jump to the Detailed DMA Information of This Drug
Drug ADMET Endpoint Profile (DAE)NEW Click to Jump to the Detailed DAE Information of This Drug
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Fms-like tyrosine kinase 3 (FLT-3) TTGJCWZ FLT3_HUMAN Modulator [4]
Proto-oncogene c-Ret (RET) TT4DXQT RET_HUMAN Modulator [4]
Tyrosine-protein kinase ABL1 (ABL) TT3PJMV ABL1_HUMAN Modulator [4]
Tyrosine-protein kinase Kit (KIT) TTX41N9 KIT_HUMAN Modulator [4]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [5]
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [5]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4)
Main DME 		DE4LYSA CP3A4_HUMAN Substrate [6]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Substrate [7]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Substrate [8]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Acute lymphoblastic leukaemia
ICD Disease Classification 2A85
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Tyrosine-protein kinase Kit (KIT) DTT KIT 2.06E-01 -0.1 -0.14
Fms-like tyrosine kinase 3 (FLT-3) DTT FLT3 2.11E-01 -0.05 -0.16
P-glycoprotein 1 (ABCB1) DTP P-GP 9.39E-02 1.07E-01 2.80E-01
Breast cancer resistance protein (ABCG2) DTP BCRP 9.45E-01 -5.34E-02 -9.01E-02
Cytochrome P450 3A5 (CYP3A5) DME CYP3A5 9.96E-01 -3.17E-03 -1.84E-02
Cytochrome P450 2D6 (CYP2D6) DME CYP2D6 7.30E-01 -1.91E-02 -1.41E-01
Cytochrome P450 3A4 (CYP3A4) DME CYP3A4 1.04E-02 6.29E-02 3.54E-01
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as Ponatinib
DDI Drug Name DDI Drug ID Severity Mechanism Disease REF
Acalabrutinib DM7GCVW Major Increased risk of bleeding by the combination of Ponatinib and Acalabrutinib. Mature B-cell lymphoma [2A85] [9]
Ibrutinib DMHZCPO Major Increased risk of bleeding by the combination of Ponatinib and Ibrutinib. Mature B-cell lymphoma [2A85] [9]
Coadministration of a Drug Treating the Disease Different from Ponatinib (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Remdesivir DMBFZ6L Moderate Increased risk of hepatotoxicity by the combination of Ponatinib and Remdesivir. 1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019] [10]
Ivosidenib DM8S6T7 Moderate Increased metabolism of Ponatinib caused by Ivosidenib mediated induction of CYP450 enzyme. Acute myeloid leukaemia [2A60] [10]
Arn-509 DMT81LZ Moderate Increased metabolism of Ponatinib caused by Arn-509 mediated induction of CYP450 enzyme. Acute myeloid leukaemia [2A60] [10]
Bedaquiline DM3906J Moderate Increased risk of hepatotoxicity by the combination of Ponatinib and Bedaquiline. Antimicrobial drug resistance [MG50-MG52] [11]
Troleandomycin DMUZNIG Major Decreased metabolism of Ponatinib caused by Troleandomycin mediated inhibition of CYP450 enzyme. Bacterial infection [1A00-1C4Z] [10]
Pexidartinib DMS2J0Z Major Increased risk of hepatotoxicity by the combination of Ponatinib and Pexidartinib. Bone/articular cartilage neoplasm [2F7B] [12]
Talazoparib DM1KS78 Moderate Decreased clearance of Ponatinib due to the transporter inhibition by Talazoparib. Breast cancer [2C60-2C6Y] [13]
Tucatinib DMBESUA Major Decreased metabolism of Ponatinib caused by Tucatinib mediated inhibition of CYP450 enzyme. Breast cancer [2C60-2C6Y] [10]
Levomilnacipran DMV26S8 Moderate Increased risk of bleeding by the combination of Ponatinib and Levomilnacipran. Chronic pain [MG30] [14]
Lumacaftor DMCLWDJ Moderate Increased metabolism of Ponatinib caused by Lumacaftor mediated induction of CYP450 enzyme. Cystic fibrosis [CA25] [10]
MK-8228 DMOB58Q Moderate Decreased metabolism of Ponatinib caused by MK-8228 mediated inhibition of CYP450 enzyme. Cytomegaloviral disease [1D82] [9]
Vortioxetine DM6F1PU Moderate Increased risk of bleeding by the combination of Ponatinib and Vortioxetine. Depression [6A70-6A7Z] [14]
SODIUM CITRATE DMHPD2Y Minor Decreased absorption of Ponatinib due to altered gastric pH caused by SODIUM CITRATE. Discovery agent [N.A.] [10]
Stiripentol DMMSDOY Moderate Decreased metabolism of Ponatinib caused by Stiripentol mediated inhibition of CYP450 enzyme. Epilepsy/seizure [8A61-8A6Z] [9]
Tazemetostat DMWP1BH Moderate Increased metabolism of Ponatinib caused by Tazemetostat mediated induction of CYP450 enzyme. Follicular lymphoma [2A80] [10]
Ripretinib DM958QB Moderate Decreased clearance of Ponatinib due to the transporter inhibition by Ripretinib. Gastrointestinal stromal tumour [2B5B] [10]
Avapritinib DMK2GZX Major Increased risk of bleeding by the combination of Ponatinib and Avapritinib. Gastrointestinal stromal tumour [2B5B] [9]
Cobicistat DM6L4H2 Major Decreased metabolism of Ponatinib caused by Cobicistat mediated inhibition of CYP450 enzyme. Human immunodeficiency virus disease [1C60-1C62] [10]
Aliskiren DM1BV7W Moderate Decreased clearance of Ponatinib due to the transporter inhibition by Aliskiren. Hypertension [BA00-BA04] [15]
Berotralstat DMWA2DZ Moderate Decreased metabolism of Ponatinib caused by Berotralstat mediated inhibition of CYP450 enzyme. Innate/adaptive immunodeficiency [4A00] [9]
Naloxegol DML0B41 Minor Decreased clearance of Ponatinib due to the transporter inhibition by Naloxegol. Large intestine motility disorder [DB32] [16]
Glycerol phenylbutyrate DMDGRQO Moderate Decreased metabolism of Ponatinib caused by Glycerol phenylbutyrate mediated inhibition of CYP450 enzyme. Liver disease [DB90-DB9Z] [17]
Ceritinib DMB920Z Major Decreased metabolism of Ponatinib caused by Ceritinib mediated inhibition of CYP450 enzyme. Lung cancer [2C25] [10]
PF-06463922 DMKM7EW Moderate Increased metabolism of Ponatinib caused by PF-06463922 mediated induction of CYP450 enzyme. Lung cancer [2C25] [10]
Selpercatinib DMZR15V Moderate Decreased metabolism of Ponatinib caused by Selpercatinib mediated inhibition of CYP450 enzyme. Lung cancer [2C25] [18]
Calaspargase pegol DMQZBXI Moderate Increased risk of hepatotoxicity by the combination of Ponatinib and Calaspargase pegol. Malignant haematopoietic neoplasm [2B33] [19]
Idelalisib DM602WT Moderate Increased risk of hepatotoxicity by the combination of Ponatinib and Idelalisib. Mature B-cell leukaemia [2A82] [20]
GDC-0199 DMH0QKA Major Decreased clearance of Ponatinib due to the transporter inhibition by GDC-0199. Mature B-cell leukaemia [2A82] [10]
IPI-145 DMWA24P Moderate Decreased metabolism of Ponatinib caused by IPI-145 mediated inhibition of CYP450 enzyme. Mature B-cell leukaemia [2A82] [21]
Arry-162 DM1P6FR Major Increased risk of bleeding by the combination of Ponatinib and Arry-162. Melanoma [2C30] [9]
LGX818 DMNQXV8 Major Increased risk of bleeding by the combination of Ponatinib and LGX818. Melanoma [2C30] [9]
Dabrafenib DMX6OE3 Moderate Increased metabolism of Ponatinib caused by Dabrafenib mediated induction of CYP450 enzyme. Melanoma [2C30] [10]
Ubrogepant DM749I3 Moderate Decreased clearance of Ponatinib due to the transporter inhibition by Ubrogepant. Migraine [8A80] [22]
Rimegepant DMHOAUG Moderate Decreased clearance of Ponatinib due to the transporter inhibition by Rimegepant. Migraine [8A80] [23]
Tecfidera DM2OVDT Moderate Additive immunosuppressive effects by the combination of Ponatinib and Tecfidera. Multiple sclerosis [8A40] [24]
Siponimod DM2R86O Major Additive immunosuppressive effects by the combination of Ponatinib and Siponimod. Multiple sclerosis [8A40] [10]
Ocrelizumab DMEZ2KH Moderate Additive immunosuppressive effects by the combination of Ponatinib and Ocrelizumab. Multiple sclerosis [8A40] [25]
Fedratinib DM4ZBK6 Major Increased risk of bleeding by the combination of Ponatinib and Fedratinib. Myeloproliferative neoplasm [2A20] [9]
Vorapaxar DMA16BR Major Increased risk of bleeding by the combination of Ponatinib and Vorapaxar. Myocardial infarction [BA41-BA43] [9]
Netupitant DMEKAYI Moderate Decreased metabolism of Ponatinib caused by Netupitant mediated inhibition of CYP450 enzyme. Nausea/vomiting [MD90] [9]
Rucaparib DM9PVX8 Moderate Decreased metabolism of Ponatinib caused by Rucaparib mediated inhibition of CYP450 enzyme. Ovarian cancer [2C73] [26]
Abametapir DM2RX0I Moderate Decreased metabolism of Ponatinib caused by Abametapir mediated inhibition of CYP450 enzyme. Pediculosis [1G00] [27]
Lefamulin DME6G97 Moderate Decreased metabolism of Ponatinib caused by Lefamulin mediated inhibition of CYP450 enzyme. Pneumonia [CA40] [28]
Voxelotor DMCS6M5 Moderate Decreased metabolism of Ponatinib caused by Voxelotor mediated inhibition of CYP450 enzyme. Sickle-cell disorder [3A51] [9]
Telotristat ethyl DMDIYFZ Moderate Increased metabolism of Ponatinib caused by Telotristat ethyl mediated induction of CYP450 enzyme. Small intestine developmental anomaly [DA90] [17]
LEE011 DMMX75K Moderate Decreased metabolism of Ponatinib caused by LEE011 mediated inhibition of CYP450 enzyme. Solid tumour/cancer [2A00-2F9Z] [9]
Lusutrombopag DMH6IKO Moderate Decreased clearance of Ponatinib due to the transporter inhibition by Lusutrombopag. Thrombocytopenia [3B64] [26]
Elagolix DMB2C0E Moderate Increased metabolism of Ponatinib caused by Elagolix mediated induction of CYP450 enzyme. Uterine fibroid [2E86] [10]
Betrixaban DM2C4RF Major Increased risk of bleeding by the combination of Ponatinib and Betrixaban. Venous thromboembolism [BD72] [9]
⏷ Show the Full List of 49 DDI Information of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG
DIG Name DIG ID PubChem CID Functional Classification
Lactose monohydrate E00393 104938 Binding agent; Diluent; Dry powder inhaler carrier; Lyophilization aid
Magnesium stearate E00208 11177 lubricant
Polyethylene glycol 4000 E00654 Not Available Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Polyvinyl alcohol E00666 Not Available Coating agent; Emulsion stabilizing agent; Film/Membrane-forming agent
Silicon dioxide E00670 Not Available Anticaking agent; Opacifying agent; Viscosity-controlling agent
Talc E00520 16211421 Anticaking agent; Diluent; Glidant; lubricant
Titanium dioxide E00322 26042 Coating agent; Colorant; Opacifying agent
Hydrophobic colloidal silica E00285 24261 Anticaking agent; Emulsion stabilizing agent; Glidant; Suspending agent; Viscosity-controlling agent
Cellulose microcrystalline E00698 Not Available Adsorbent; Suspending agent; Diluent
⏷ Show the Full List of 9 Pharmaceutical Excipients of This Drug
Pharmaceutical Formulation
Formulation Name Drug Dosage Dosage Form Route
Ponatinib Hydrochloride eq 10mg base tablet eq 10mg base Tablet Oral
Ponatinib Hydrochloride eq 15mg base tablet eq 15mg base Tablet Oral
Ponatinib Hydrochloride eq 30mg base tablet eq 30mg base Tablet Oral
Ponatinib Hydrochloride eq 45mg base tablet eq 45mg base Tablet Oral
Ponatinib 15 mg tablet 15 mg Oral Tablet Oral
Ponatinib 30 mg tablet 30 mg Oral Tablet Oral
Ponatinib 45 mg tablet 45 mg Oral Tablet Oral
Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5890).
2 Ponatinib FDA Label
3 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
4 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
5 DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. (ID: DB08901)
6 Evaluation of the effect of multiple doses of rifampin on the pharmacokinetics and safety of ponatinib in healthy subjects. Clin Pharmacol Drug Dev. 2015 Sep;4(5):354-60.
7 Novel pathways of ponatinib disposition catalyzed by CYP1A1 involving generation of potentially toxic metabolites. J Pharmacol Exp Ther. 2017 Oct;363(1):12-19.
8 Potential of ponatinib to treat chronic myeloid leukemia and acute lymphoblastic leukemia. Onco Targets Ther. 2013 Aug 20;6:1111-8.
9 Product Information. Iclusig (ponatinib). Ariad Pharmaceuticals Inc, Cambridge, MA.
10 Cerner Multum, Inc. "Australian Product Information.".
11 Product Information. Sirturo (bedaquiline). Janssen Pharmaceuticals, Titusville, NJ.
12 Product Information. Turalio (pexidartinib). Daiichi Sankyo, Inc., Parsippany, NJ.
13 Product Information. Talzenna (talazoparib). Pfizer U.S. Pharmaceuticals Group, New York, NY.
14 Alderman CP, Moritz CK, Ben-Tovim DI "Abnormal platelet aggregation associated with fluoxetine therapy." Ann Pharmacother 26 (1992): 1517-9. [PMID: 1482806]
15 Canadian Pharmacists Association.
16 Product Information. Movantik (naloxegol). Astra-Zeneca Pharmaceuticals, Wilmington, DE.
17 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
18 Product Information. Retevmo (selpercatinib). Lilly, Eli and Company, Indianapolis, IN.
19 Al-Nawakil C, Willems L, Mauprivez C, et.al "Successful treatment of l-asparaginase-induced severe acute hepatotoxicity using mitochondrial cofactors." Leuk Lymphoma 55 (2014): 1670-4. [PMID: 24090500]
20 Product Information. Zydelig (idelalisib). Gilead Sciences, Foster City, CA.
21 Product Information. Copiktra (duvelisib). Verastem, Inc., Needham, MA.
22 Product Information. Ubrelvy (ubrogepant). Allergan Inc, Irvine, CA.
23 Product Information. Nurtec ODT (rimegepant). Biohaven Pharmaceuticals, New Haven, CT.
24 Product Information. Vumerity (diroximel fumarate). Alkermes, Inc, Cambridge, MA.
25 Product Information. Ocrevus (ocrelizumab). Genentech, South San Francisco, CA.
26 EMA. European Medicines Agency. European Union "EMA - List of medicines under additional monitoring.".
27 Product Information. Xeglyze (abametapir topical). Dr. Reddy's Laboratories Inc, Upper Saddle River, NJ.
28 Product Information. Xenleta (lefamulin). Nabriva Therapeutics US, Inc., King of Prussia, PA.