NHWD-870

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.

Product information

CAS Number: 2115742-03-3

Molecular Weight: 491.59

Formula: C29H29N7O

Chemical Name: 13-(1,4-dimethyl-1H-1,2,3-triazol-5-yl)-5-methyl-10-[(S)-(oxan-4-yl)(phenyl)methyl]-4,5,10,15-tetraazatetracyclo[7.7.0.0²,⁶.0¹¹,¹⁶]hexadeca-1(9),2(6),3,7,11,13,15-heptaene

Smiles: CC1N=NN(C)C=1C1=CN=C2C3C4C=NN(C)C=4C=CC=3N([C@@H](C3CCOCC3)C3C=CC=CC=3)C2=C1

InChiKey: BBKUPPVLTRGWDN-GDLZYMKVSA-N

InChi: InChI=1S/C29H29N7O/c1-18-28(35(3)33-32-18)21-15-25-27(30-16-21)26-22-17-31-34(2)23(22)9-10-24(26)36(25)29(19-7-5-4-6-8-19)20-11-13-37-14-12-20/h4-10,15-17,20,29H,11-14H2,1-3H3/t29-/m1/s1

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO : 125 mg/mL (254.28 mM; Need ultrasonic).

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

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.

Products are for research use only. Not for human use.