Chemical Properties
Pale Yellow Solid
Usage
AP24534 is a novel potent, orally available small molecule multitargeted kinase inhibitor with IC50 of 0.37, 2, 1.5, 2.2, 1.1, 1and 0.24 nM for native pan-BCR-ABL, mutated form, VEGFR2, FGFR1, PDGFRα, mutant FLT3 phosphorylation and LYN.
Usage
Ponatinib (AP24534) is a novel potent, orally available small molecule multitargeted kinase inhibitor. Ponatinib inhibits both native and mutant BCR-ABL. Ponatinib is used in the treatment of chronic myeloid leukemia (CML) with BCR-ABL kinase inhibitors.
Usage
Ponatinib (AP24534) is a novel, potent multi-target inhibitor of Abl, PDGFRα, VEGFR2, FGFR1 and Src with IC50 of 0.37 nM, 1.1 nM, 1.5 nM, 2.2 nM and 5.4 nM, respectively
Description
Ponatinib (943319-70-8) is a highly potent pan-Bcr-Abl and multikinase inhibitor, suppressing the activity of native Bcr-Abl (IC50=0.37 nM) as well as the mutants T315I (IC50=2 nM), Q252H (IC50=0.44 nM), Y253F (IC50=0.3 nM), M351T (IC50=0.3 nM) and H396P (IC50=0.34 nM).1??Also inhibits PDGFRα, c-Src and c-Kit (IC50=1.1, 5.4 and 12.5 nM respectively)2?as well as FGFR-mediated signaling (IC50<40 nM)3. Protects against influenza A virus-induced death by suppressing cytokine storm in mouse models..4
Uses
AP24534 is a novel potent, orally available small molecule multitargeted kinase inhibitor with IC50 of 0.37, 2, 1.5, 2.2, 1.1, 1and 0.24 nM for native pan-BCR-ABL, mutated form, VEGFR2, FGFR1, PDGFRα, mutant FLT3 phosphorylation and LYN.
Uses
Ponatinib (AP24534) is a novel potent, orally available small molecule multitargeted kinase inhibitor. Ponatinib inhibits both native and mutant BCR-ABL. Ponatinib is used in the treatment of chronic myeloid leukemia (CML) with BCR-ABL kinase inhibitors.
Uses
Ponatinib (AP24534) is a novel, potent multi-target inhibitor of Abl, PDGFRα, VEGFR2, FGFR1 and Src with IC50 of 0.37 nM, 1.1 nM, 1.5 nM, 2.2 nM and 5.4 nM, respectively
Definition
ChEBI: A benzamide obtained by the formal condensation of the carboxy group of 3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methylbenzoic acid with the anilino group of 4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)aniline.
General Description
Ponatinib, a third-generation BCR-ABL tyrosine kinase inhibitor (TKI), was first approved in December 2012 as a third-line treatment for CML patients. However, three months later, its approval was suspended, primarily due to safety concerns arising from the increased incidence of serious vascular occlusive events. Because there was no alternative treatment option at the time for CML patients with the T315I mutation, the suspension was lifted after a couple of months, and ponatinib was reintroduced for adult patients with T315I-postive CML (including accelerated, chronic, or blast phases) or those with T315I-positive Ph+ ALL with multiple safety measures regarding cardiovascular risk.
Class: non-receptor tyrosine kinase
Treatment: CML
Elimination half-life = 24 h
Protein binding = 99%
Clinical Use
Protein kinase inhibitor:
Treatment of chronic myeloid leukaemia (CML)
Treatment of Philadelphia chromosome positive
acute lymphoblastic leukaemia (Ph+ ALL)
Metabolism
Ponatinib is metabolised to an inactive carboxylic acid by
esterases and/or amidases, and metabolised by CYP3A4
to an N-desmethyl metabolite that is 4 times less active
than ponatinib.
Ponatinib is mainly eliminated via faeces. Following a
single oral dose of [14C]-labelled ponatinib, approximately
87% of the radioactive dose is recovered in the faeces and
approximately 5% in the urine.
References
1) O’Hare?et al.?(2009),?AP24534, a pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance; Cancer Cell,?16?401
2) Gozgit?et al.?(2011),?Potent activity of ponatinib (AP24535) in models of FLT3-driven acute myeloid leukemia and other hematologic malignancies; Mol. Cancer Ther.,?10?1028
3) Gozgit?et al.?(2012),?Ponatinib (AP24534), a multitargeted pan-FGFR inhibitor with activity in multiple FGFR-amplified or mutated cancer models; Mol. Cancer Ther.,?11?690
4) Chen?et al.?(2019),?Ponatinib Protects Mice From Lethal Influenza Infection by Suppressing Cytokine Storm; Front. Immunol., 10 1393
