Ponatinib hydrochloride potently inhibits proliferation of Ba/F3 cells expressing native BCR-ABL (IC50 = 0.5 nM). Ponatinib hcl (AP24534) inhibits the in vitro kinase activity of FLT3, KIT, FGFR1, and PDGFRα with IC50 values of 13, 13, 2, and 1 nM, respectively. Ponatinib inhibits phosphorylation of all 4 RTKs in a dose-dependent manner, with IC50 values between 0.3 to 20 nM.
In vivo, in a mouse xenograft model of Ba/F3 cells expressing native Bcr-Abl, AP24534 (2.5 mg/kg and 5 mg/kg) prolongs mice median survival. In the xenograft model of Ba/F3 Bcr-AblT315I, Ponatinib hydrochloride (10 mg/kg–50 mg/kg) significantly suppresses tumor growth. AP24534 (30 mg/kg) decreases the phosphorylated Bcr-Abl and phosphorylated CrkL levels in the tumors.
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
Ponatinib (AP24534), a multitargeted pan-FGFR inhibitor with activity in multiple FGFR-amplified or mutated cancer models.
Gozgit JM, et al. Mol Cancer Ther. 2012 Mar;11(3):690-9. PMID: 22238366.
Potent activity of ponatinib (AP24534) in models of FLT3-driven acute myeloid leukemia and other hematologic malignancies.
Gozgit JM, et al. Mol Cancer Ther. 2011 Jun;10(6):1028-35. PMID: 21482694.
AP24534, a pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance.
OHare T, et al. Cancer Cell. 2009 Nov 6;16(5):401-12. PMID: 19878872.
|Related Src-bcr-Abl Products|
Flumatinib mesylate is a selective inhibitor of BCR-ABL/PDGFR/c-Kit with IC50s of 1.2 nM, 307.6 nM and 2662 nM, respectively.
Asciminib, also known as ABL001, is a potent allosteric inhibitor of BCR-ABL, with a Kd value of 0.5-0.8 nM.
TG-100572 hydrochloride is a potent and selective multi-targeted VEGFR2/Src kinase inhibitor.
AMG-47a is a potent inhibitor of Lck and T cell proliferation; exhibits anti-inflammatory activity (ED50 = 11 mg/kg) in the anti-CD3 induced production of IL-2 in mice.
GZD824 Dimesylate is a novel orally bioavailable Bcr-Abl inhibitor for Bcr-Abl(WT) and Bcr-Abl(T315I) with IC50 of 0.34 nM and 0.68 nM, respectively.
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2020 AbMole BioScience. All Rights Reserved.