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NHWD-870

產(chǎn)品活性：NHWD-870 是一種高效、口服活性和選擇性的 BET family bromodomain 抑制劑,，僅與 BRD2,、BRD3、BRD4 (IC₅₀=2.7 nM) 和 BRDT 結(jié)合,。NHWD-870 具有較強的抑癌作用,，并能抑制癌細胞與巨噬細胞的相互作用,。

研究領(lǐng)域：Epigenetics  |  Apoptosis

作用靶點：Epigenetic Reader Domain  |  Apoptosis

In Vitro: NHWD-870 (0.01-10000 nM) inhibits melanoma cells (A375) with an IC₅₀ 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 (IC₅₀?=?5.4?µM).NHWD-870 shows robust activities inducing apoptosis and suppressing cell proliferation.

In Vivo: NHWD-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.

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