KW-2478

KW-2478 is an HSP90 inhibitor (IC₅₀ = 3.8 nM). KW-2478 inhibits the growth and induces apoptosis in chronic myeloid leukemia (CML) cells and liver cancer cells. KW-2478 weakens the BCR/ABL and MAPK signaling pathways, leading to increased p27 and p21 expression and decreased cyclin B1 expression. KW-2478 downregulates STAT3 expression. KW-2478 may be used in research on cancers such as CML and liver cancer^[1][2]. IC50 & Target:IC50: 3.8 nM (Hsp90α)^[1] In Vitro:KW-2478 is an inhibitor of Hsp90, with an IC₅₀ of 3.8 nM for Hsp90α. KW-2478 shows anti-proliferative activity against multiple myeloma (MM) and non-Hodgkin’s lymphoma (NHL), with GI₅₀s of 0.30 μM (OPM-2/GFP), 0.34 μM (KMS-11), 0.39 μM (RPMI 8226), 0.12 μM (NCI-H929), 0.36 μM (Raji), 0.098 μM (SR), and 0.33 μM μM (SC-1). KW-2478 also inhibits the transcription of c-Maf and Cyclin D1 genes by mainly suppressing the function of Cdk9^[1]. In Vivo:KW-2478 (25-200 mg/kg, i.v.) inhibits tumor growth in combined immunodeficiency (SCID) mice bearing NCI-H929 cells, without body weight loss. KW-2478 (100 mg/kg, i.v.) causes degradation of the Hsp90 client proteins (IGF-1Rβ, c-Raf-1, Cdk9) levels and dephosphorylated Erk1/2 proteins in NCI-H929 tumors of mice^[1].