| Identification | Back Directory | [Name]
Pyrido[2',3':4,5]pyrrolo[3,2-f]indazole, 7-(1,4-dimethyl-1H-1,2,3-triazol-5-yl)-1,9-dihydro-1-methyl-9-[(S)-phenyl(tetrahydro-2H-pyran-4-yl)methyl]- | [CAS]
2115742-03-3 | [Synonyms]
NHWD-870
Pyrido[2',3':4,5]pyrrolo[3,2-f]indazole, 7-(1,4-dimethyl-1H-1,2,3-triazol-5-yl)-1,9-dihydro-1-methyl-9-[(S)-phenyl(tetrahydro-2H-pyran-4-yl)methyl]- | [Molecular Formula]
C29 H29 N7 O | [MDL Number]
MFCD33402167 | [MOL File]
2115742-03-3.mol | [Molecular Weight]
491.59 |
| Chemical Properties | Back Directory | [Boiling point ]
687.3±65.0 °C(Predicted) | [density ]
1.38±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO : 125 mg/mL (254.28 mM; Need ultrasonic) | [form ]
Solid | [pka]
5.31±0.50(Predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Uses]
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]. | [Biological Activity]
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]. | [in vivo]
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]. | 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)[1] | | 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.
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| [storage]
Store at -20°C | [References]
[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. |
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