HSN608 / Purdue University, KinaRx - LARVOL DELTA

Identification of alkynyl nicotinamide HSN748 as a RET solvent-front mutant inhibitor with intracranial efficacy. (PubMed, RSC Med Chem) - "RET solvent-front G810C/R/S mutations confer resistance to the currently approved RET protein tyrosine kinase inhibitors (TKIs) selpercatinib and pralsetinib. Among three compounds (HSN748, HSND19, and HSN608) evaluated for B/KR(G810C) brain tumors, HSN748 exhibited significant intracranial tumor inhibition. PK analysis indicated that HSN748 has a brain/plasma partition coefficient (K p) of 0.4, demonstrating its capability to penetrate the central nervous system (CNS)."

Journal • Brain Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CCDC6 • KIF5B • RET

Alkynyl nicotinamides show antileukemic activity in drug-resistant acute myeloid leukemia. (PubMed, J Clin Invest) - "AML patients treated with investigational drugs targeting mutant FLT3, including Quizartinib and Crenolanib, develop resistance to these drugs...We have identified 2 novel nicotinamide-based FLT3 inhibitors (HSN608 and HSN748) that target FLT3 mutations at subnanomolar concentrations and are potently effective against drug-resistant secondary mutations of FLT3. These compounds show antileukemic activity against FLT3ITD in drug-resistant AML, relapsed/refractory AML, and in AML bearing a combination of epigenetic mutations of TET2 along with FLT3ITD. We demonstrate that HSN748 outperformed the FDA-approved FLT3 inhibitor Gilteritinib in terms of inhibitory activity against FLT3ITD in vivo."

Journal • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • FLT3 • TET2