NHWD-870

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

NHWD-870 是 BET 家族溴结构域的有效选择性抑制剂，仅与 BRD2、BRD3、BRD4 (IC50 = 2.7 nM) 和 BRDT 结合。

NHWD-870 is an effective and selective inhibitor of BET family bromodomain only binding to BRD2, BRD3, BRD4 (IC50 = 2.7 nM), and BRDT. NHWD-870 exhibits potent anti-tumor efficacies and suppresses cancer cell-macrophage interaction through the increase of tumor apoptosis and inhibition of tumor proliferation.(In Vitro):NHWD-870 exhibits mild inhibition of the hERG channel (IC50?=?5.4?μM). NHWD-870 shows robust activities inducing apoptosis and suppressing cell proliferation. NHWD-870 (0.01-10000 nM) inhibits melanoma cells (A375) with an IC50 of 2.46 nM. In H526, A2780, ES-2, and MDA-MB231 cells, NHWD-870 (0-10000 nM; 5 days) suppressed cell growth. NHWD-870 (0-50 nM; 24?hours) inhibits BRD4 phosphorylation and c-MYC expression in H526, A2780, ES-2, and MDA-MB231 cells.(In Vivo):NHWD-870 (0.75-3 mg/kg; p.o.) 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 (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. Cell Viability Assay Cell 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 Analysis Cell 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.

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. 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.

——

Apoptosis

Apoptosis

KLF5

——

——

2115742-03-3

491.59

C29H29N7O

>98% (HPLC)

In Vitro:?DMSO : 62.5 mg/mL (127.14 mM)

N/A

——

(-20℃)

With Ice Pack

≥ 2 years