NMS-0963 / Nerviano Medical Sciences - LARVOL DELTA

Discovery and optimization of 4-pyrazolyl-2-aminopyrimidine derivatives as potent spleen tyrosine kinase (SYK) inhibitors. (PubMed, Eur J Med Chem) - "Extensive study of structure-activity relationships led to the identification of 1 (NMS-0963), a highly potent Syk inhibitor (IC50 = 3 nM) endowed with high selectivity within a panel of tested kinases and high antiproliferative activity in SYK-dependent BaF3-TEL/SYK cells and in other BCR-dependent hematological tumor cell lines...In in vivo pharmacokinetics studies, 1, displayed good pharmacokinetics properties, with linear exposure with dose and excellent oral bioavailability. These findings suggest that 1 is a promising new Syk inhibitor for treating BCR-dependent hematological cancers."

Journal • Hematological Disorders • Hematological Malignancies • Oncology • SYK

NMS-0963 is a novel potent, selective and orally available Syk inhibitor with promising preclinical activity in diffuse large B-cell lymphoma (AACR 2023) - "Small molecule inhibitors of key signaling kinases involved in the BCR pathway, such as the Btk inhibitor ibrutinib and the PI3Kdelta inhibitor idelalisib, have already demonstrated significant clinical activity. Furthermore, NMS-963 demonstrated striking in vivo efficacy in tumor models of CD79/Myd88 mutated DLBCL, superior to competitors. Together with a permissive preclinical safety profile, these results support a rational for clinical development of NMS-0963 in DLBCL."

Preclinical • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • MYD88 • SYK