NHWD-870 (C007B-378777)

NHWD-870 is a potent, orally active and selective BET family bromodomain inhibitor and only binds bromodomains of BRD2 , BRD3 , BRD4 ( IC 50 =2.7 nM), and BRDT. NHWD-870 has potent tumor suppressive efficacies and suppresses cancer cell-macrophage interaction. NHWD-870 increases tumor apoptosis and inhibits tumor proliferation.In VitroNHWD-870 (0.01-10000 nM) inhibits melanoma cells (A375) with an IC 50 of 2.46 nM. NHWD-870 (0-10000 nM; 5 dys) suppressed cell growth. NHWD-870 (0-50 nM; 24 hours) inhibits BRD4 phosphorylation and c-MYC expression. NHWD-870 exhibits mild inhibition of hERG channel (IC 50 = 5.4 µM)./nNHWD-870 shows robust activities inducing apoptosis and suppressing cell proliferation. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Viability AssayCell Line: H526, A2780, ES-2, and MDA-MB231 cells Concentration: 0-10000 nM Incubation Time: 5 days Result: Showed strong inhibitory activities against these cells in 5-day assays. Western Blot AnalysisCell Line: H526, A2780, ES-2, and MDA-MB231 cells Concentration: 0-50 nM Incubation Time: 24 hours Result: Led to the depletion of phosphorylated BRD4 and c-MYC at 10 nM.In VivoNHWD-870 (0.75-3 mg/kg; p.o.) has strong anti-tumor activities in mouse models . NHWD-870 reduces the number of tumor associated macrophages (TAMs) in subcutaneously implanted H526 and A2780 tumors. NHWD-870 downregulated CSF1 expression in tumor cells to inhibit TAM proliferation . NHWD-870 manifests diverse mechanisms of action in different cancer settings. These include: 1) inhibition of tumor cell growth by downregulating the PDGFRβ, MEK1/2 and STAT1/MYC signaling in tumor cells; 2) inhibition of tumor angiogenesis by decreasing PDGF production in tumor cells and the PDGFRβ and MEK1/2 signaling in endothelial cells. NHWD-870 has potent tumor suppressive efficacies in xenograft mouse models of small cell lung cancer, triple negative breast cancer and ovarian cancer. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: 4-6 weeks old female BALB/c nude mice/6-8 weeks old female C57BL/6 mice were used for B16F10 experiments (bearing NCI-H526, A2780, A375, B16F10, and TMD-8 cells) Dosage: 0.75-3 mg/kg Administration: P.o.; TMD8 and B16F10 melanoma model with once daily for 11-21 days; A375 melanoma and PDX of melanoma with once daily (5 days on, 2 days off) for 21 days. Result: Strongly suppressed the growth of established lung tumor, ovarian tumor, lymphoma, and melanoma in vivo.Form:Solid. Specification: 0.99 Molecular Formula: C29H29N7O Molecular Weight: 491.59