NHWD-870

• CAT Number: I045298
• CAS Number: 2115742-03-3
• Molecular Formula: C29H29N7O
• Molecular Weight: 491.59
• Purity: ≥95%
• Synonyms: 5-(3,5-dimethyltriazol-4-yl)-12-methyl-8-[(S)-oxan-4-yl(phenyl)methyl]-3,8,12,13-tetrazatetracyclo[7.7.0.02,7.011,15]hexadeca-1(9),2(7),3,5,10,13,15-heptaene
• InChI: InChI=1S/C29H29N7O/c1-18-28(35(3)33-32-18)22-14-26-27(30-16-22)23-13-21-17-31-34(2)24(21)15-25(23)36(26)29(19-7-5-4-6-8-19)20-9-11-37-12-10-20/h4-8,13-17,20,29H,9-12H2,1-3H3/t29-/m1/s1
• InChIKey: YMSCCGUMGIFOSI-GDLZYMKVSA-N
• SMILES: CC1=C(N(N=N1)C)C2=CC3=C(C4=C(N3C(C5CCOCC5)C6=CC=CC=C6)C=C7C(=C4)C=NN7C)N=C2

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].

Reference

[1]. Yin M, et al. Potent BRD4 inhibitor suppresses cancer cell-macrophage interaction. Nat Commun. 2020;11(1):1833. Published 2020 Apr 14.
 [Content Brief]

[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.