NHWD-870 是一种高效、口服活性和选择性的 BET family bromodomain 抑制剂，仅与 BRD2、BRD3、BRD4 (IC50=2.7 nM) 和 BRDT 结合。NHWD-870 具有较强的抑癌作用，并能抑制癌细胞与巨噬细胞的相互作用。
货号:ajcx34084
CAS:2115742-03-3
分子式:C29H29N7O
分子量：491.59
溶解度:DMSO : 125 mg/mL (254.28 mM; Need ultrasonic)
纯度：98%
存储：Store at -20°C
库存：现货

Background:

NHWD-870 is a potent, orally active and selective BET family bromodomain inhibitor and only binds bromodomains of BRD2, BRD3, BRD4 (IC50=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[1].

NHWD-870 (0.01-10000 nM) inhibits melanoma cells (A375) with an IC50 of 2.46 nM[1].NHWD-870 (0-10000 nM; 5 dys) suppressed cell growth[1].NHWD-870 (0-50 nM; 24 hours) inhibits BRD4 phosphorylation and c-MYC expression[1].NHWD-870 exhibits mild inhibition of hERG channel (IC50 = 5.4 µM)[1].NHWD-870 shows robust activities inducing apoptosis and suppressing cell proliferation[1].

NHWD-870 (0.75-3 mg/kg; p.o.) has strong anti-tumor activities in mouse models[1].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[1].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[2].

[1]. Yin M, et al. Potent BRD4 inhibitor suppresses cancer cell-macrophage interaction. Nat Commun. 2020;11(1):1833. Published 2020 Apr 14.
[2]. Nenghui Wang, et al. Abstract 1382: A novel BET family bromodomain inhibitor NHWD-870 represents a promising therapeutic agent for a broad spectrum of cancers. Molecular and Cellular Biology, Genetics.