These are preliminary reports that have not been peer-reviewed. They should not be regarded as conclusive, guide clinical practice/health-related behavior, or be reported in news media as established information. For more information, please see our FAQs.

Nicotinamide-Ponatinib, HSN748, a Potent Anti-CML and Anti-AML Compound with Better Kinase Selectivity than Ponatinib

submitted on 10.11.2018 and posted on 13.11.2018 by Elizabeth Larocque, Nimmashetti Naganna, Herman Sintim

Ponatinib is a multikinase inhibitor that is used to treat chronic myeloid leukemia patients harboring mutated ABL1(T315I) kinase. Due to the potent inhibition of FLT3, RET and FGFRs, it is also being evaluated against AML, biliary and lung cancers. The multikinase inhibition profile of ponatinib may also account for its toxicity, thus analogs with improved kinase selectivity could be better tolerated. A nicotinamide analog of ponatinib, HSN748, retains activity against FLT3, ABL1, VEGFRs and PDGFRa/b but losses activity against c-Src, FGFRs and P38a. Since Src or FGFR inhibitions are known to lead to platelet disfunction or cardiovascular toxicities respectively, HSN748 might have a better safety profile than ponatinib and deserves further evaluation as a possible CML or AML therapeutic.


Email Address of Submitting Author


Purdue University



ORCID For Submitting Author


Declaration of Conflict of Interest

HOS is a co-founder of KinaRx LLC, a start-up company interested in developing therapies for malignant neoplastic diseases.