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Details

Stereochemistry ACHIRAL
Molecular Formula C29H27F3N6O
Molecular Weight 532.5595
Optical Activity UNSPECIFIED
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PONATINIB

SMILES

CN1CCN(CC2=C(C=C(NC(=O)C3=CC=C(C)C(=C3)C#CC4=CN=C5C=CC=NN45)C=C2)C(F)(F)F)CC1

InChI

InChIKey=PHXJVRSECIGDHY-UHFFFAOYSA-N
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)

HIDE SMILES / InChI

Molecular Formula C29H27F3N6O
Molecular Weight 532.5595
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

Ponatinib (trade name Iclusig, previously AP24534) is developed by ARIAD Pharmaceuticals for the treatment of chronic myeloid leukemia (CML) and Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia (ALL). Ponatinib has been designed to be effective against these types of tumors. The United States Food and Drug Administration approved the drug as a candidate in 2012, but temporarily suspended sales on 31 October 2013 because of "the risk of life-threatening blood clots and severe narrowing of blood vessels". This suspension was partially lifted on Dec. 20, 2013 with ponatinib being issued revised prescribing information, a new "Black Box Warning" and a "Risk Evaluation and Mitigation Strategy" in place to better evaluate the risks and benefits of using the drug. Ponatinib is an orally bioavailable multitargeted receptor tyrosine kinase (RTK) inhibitor with potential antiangiogenic and antineoplastic activities. Ponatinib inhibits unmutated and all mutated forms of Bcr-Abl, including T315I, the highly drug therapy-resistant missense mutation of Bcr-Abl. This agent also inhibits other tyrosine kinases including those associated with vascular endothelial growth factor receptors (VEGFRs) and fibroblast growth factor receptors (FGFRs); in addition, it inhibits the tyrosine kinase receptor TIE2 and FMS-related tyrosine kinase receptor-3 (Flt3). RTK inhibition by ponatinib may result in the inhibition of cellular proliferation and angiogenesis and may induce cell death. Bcr-Abl is a fusion tyrosine kinase encoded by the Philadelphia chromosome.

CNS Activity

Originator

Approval Year

PubMed

PubMed

TitleDatePubMed
Inhibitors of ABL and the ABL-T315I mutation.
2008
Discovery of 5-(arenethynyl) hetero-monocyclic derivatives as potent inhibitors of BCR-ABL including the T315I gatekeeper mutant.
2011 Jun 15
Discovery of 5-(arenethynyl) hetero-monocyclic derivatives as potent inhibitors of BCR-ABL including the T315I gatekeeper mutant.
2011 Jun 15
The BCR-ABL35INS insertion/truncation mutant is kinase-inactive and does not contribute to tyrosine kinase inhibitor resistance in chronic myeloid leukemia.
2011 Nov 10
The BCR-ABL35INS insertion/truncation mutant is kinase-inactive and does not contribute to tyrosine kinase inhibitor resistance in chronic myeloid leukemia.
2011 Nov 10
Ponatinib is active against imatinib-resistant mutants of FIP1L1-PDGFRA and KIT, and against FGFR1-derived fusion kinases.
2012 Jul
Ponatinib is active against imatinib-resistant mutants of FIP1L1-PDGFRA and KIT, and against FGFR1-derived fusion kinases.
2012 Jul
The ins and outs of bcr-abl inhibition.
2012 May
Ponatinib may overcome resistance of FLT3-ITD harbouring additional point mutations, notably the previously refractory F691I mutation.
2012 May
Ponatinib as targeted therapy for FGFR1 fusions associated with the 8p11 myeloproliferative syndrome.
2013 Jan
Ponatinib suppresses the development of myeloid and lymphoid malignancies associated with FGFR1 abnormalities.
2013 Jan
Ponatinib as targeted therapy for FGFR1 fusions associated with the 8p11 myeloproliferative syndrome.
2013 Jan
Ponatinib suppresses the development of myeloid and lymphoid malignancies associated with FGFR1 abnormalities.
2013 Jan
Ponatinib is a potent inhibitor of wild-type and drug-resistant gatekeeper mutant RET kinase.
2013 Sep 5
A selective chemical probe for exploring the role of CDK8 and CDK19 in human disease.
2015 Dec
Patents

Sample Use Guides

In Vivo Use Guide
45 mg taken orally once daily with or without food
Route of Administration: Oral
In Vitro Use Guide
Ponatinib inhibited the in vitro tyrosine kinase activity of ABL and T315I mutant ABL with IC50 concentrations of 0.4 and 2.0 nM, respectively. Ponatinib inhibited the in vitro activity of additional kinases with IC50 concentrations between 0.1 and 20 nM, including members of the VEGFR, PDGFR, FGFR, EPH receptors and SRC families of kinases, and KIT, RET, TIE2, and FLT3. Ponatinib inhibited the in vitro viability of cells expressing native or mutant BCR-ABL, including T315I.
Substance Class Chemical
Created
by admin
on Mon Oct 21 23:34:15 UTC 2019
Edited
by admin
on Mon Oct 21 23:34:15 UTC 2019
Record UNII
4340891KFS
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
PONATINIB
DASH   INN   USAN   VANDF   WHO-DD  
INN   USAN  
Official Name English
PONATINIB [WHO-DD]
Common Name English
PONATINIB [VANDF]
Common Name English
PONATINIB [INN]
Common Name English
3-(2-(IMIDAZO(1,2-B)PYRIDAZIN-3-YL)ETHYNYL)-4-METHYL-N-(4-((4-METHYLPIPERAZIN-1- YL)METHYL)-3-(TRIFLUOROMETHYL)PHENYL)BENZAMIDE
Systematic Name English
PONATINIB [MI]
Common Name English
AP24534
Code English
AP-24534
Code English
BENZAMIDE, 3-(2-IMIDAZO(1,2-B)PYRIDAZIN-3-YLETHYNYL)-4-METHYL-N-(4-((4-METHYL-1- PIPERAZINYL)METHYL)-3-(TRIFLUOROMETHYL)PHENYL)-
Systematic Name English
PONATINIB [USAN]
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 466714
Created by admin on Mon Oct 21 23:34:16 UTC 2019 , Edited by admin on Mon Oct 21 23:34:16 UTC 2019
NCI_THESAURUS C155700
Created by admin on Mon Oct 21 23:34:16 UTC 2019 , Edited by admin on Mon Oct 21 23:34:16 UTC 2019
LIVERTOX 786
Created by admin on Mon Oct 21 23:34:16 UTC 2019 , Edited by admin on Mon Oct 21 23:34:16 UTC 2019
FDA ORPHAN DRUG 294809
Created by admin on Mon Oct 21 23:34:16 UTC 2019 , Edited by admin on Mon Oct 21 23:34:16 UTC 2019
FDA ORPHAN DRUG 294709
Created by admin on Mon Oct 21 23:34:16 UTC 2019 , Edited by admin on Mon Oct 21 23:34:16 UTC 2019
NCI_THESAURUS C1742
Created by admin on Mon Oct 21 23:34:16 UTC 2019 , Edited by admin on Mon Oct 21 23:34:16 UTC 2019
WHO-ATC L01XE24
Created by admin on Mon Oct 21 23:34:16 UTC 2019 , Edited by admin on Mon Oct 21 23:34:16 UTC 2019
NDF-RT N0000175605
Created by admin on Mon Oct 21 23:34:16 UTC 2019 , Edited by admin on Mon Oct 21 23:34:16 UTC 2019
WHO-VATC QL01XE24
Created by admin on Mon Oct 21 23:34:16 UTC 2019 , Edited by admin on Mon Oct 21 23:34:16 UTC 2019
EMA ASSESSMENT REPORTS ICLUSING (AUTHORIZED: LEUKEMIA, MYELOID)
Created by admin on Mon Oct 21 23:34:16 UTC 2019 , Edited by admin on Mon Oct 21 23:34:16 UTC 2019
Code System Code Type Description
WIKIPEDIA
PONATINIB
Created by admin on Mon Oct 21 23:34:16 UTC 2019 , Edited by admin on Mon Oct 21 23:34:16 UTC 2019
PRIMARY
PUBCHEM
24826799
Created by admin on Mon Oct 21 23:34:16 UTC 2019 , Edited by admin on Mon Oct 21 23:34:16 UTC 2019
PRIMARY
NCI_THESAURUS
C95777
Created by admin on Mon Oct 21 23:34:16 UTC 2019 , Edited by admin on Mon Oct 21 23:34:16 UTC 2019
PRIMARY
IUPHAR
5890
Created by admin on Mon Oct 21 23:34:16 UTC 2019 , Edited by admin on Mon Oct 21 23:34:16 UTC 2019
PRIMARY
LactMed
943319-70-8
Created by admin on Mon Oct 21 23:34:16 UTC 2019 , Edited by admin on Mon Oct 21 23:34:16 UTC 2019
PRIMARY
MESH
C545373
Created by admin on Mon Oct 21 23:34:16 UTC 2019 , Edited by admin on Mon Oct 21 23:34:16 UTC 2019
PRIMARY
INN
9362
Created by admin on Mon Oct 21 23:34:16 UTC 2019 , Edited by admin on Mon Oct 21 23:34:16 UTC 2019
PRIMARY
EPA CompTox
943319-70-8
Created by admin on Mon Oct 21 23:34:16 UTC 2019 , Edited by admin on Mon Oct 21 23:34:16 UTC 2019
PRIMARY
ChEMBL
CHEMBL1171837
Created by admin on Mon Oct 21 23:34:16 UTC 2019 , Edited by admin on Mon Oct 21 23:34:16 UTC 2019
PRIMARY
MERCK INDEX
M11700
Created by admin on Mon Oct 21 23:34:16 UTC 2019 , Edited by admin on Mon Oct 21 23:34:16 UTC 2019
PRIMARY
EVMPD
SUB91901
Created by admin on Mon Oct 21 23:34:16 UTC 2019 , Edited by admin on Mon Oct 21 23:34:16 UTC 2019
PRIMARY
DRUG BANK
DB08901
Created by admin on Mon Oct 21 23:34:16 UTC 2019 , Edited by admin on Mon Oct 21 23:34:16 UTC 2019
PRIMARY
CAS
943319-70-8
Created by admin on Mon Oct 21 23:34:16 UTC 2019 , Edited by admin on Mon Oct 21 23:34:16 UTC 2019
PRIMARY
HSDB
943319-70-8
Created by admin on Mon Oct 21 23:34:16 UTC 2019 , Edited by admin on Mon Oct 21 23:34:16 UTC 2019
PRIMARY
RXCUI
1364347
Created by admin on Mon Oct 21 23:34:16 UTC 2019 , Edited by admin on Mon Oct 21 23:34:16 UTC 2019
PRIMARY RxNorm
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Name Property Type Amount Referenced Substance Defining Parameters References
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