| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg | |||
| Other Sizes |
| Targets |
BET family bromodomains (BRD2, BRD3, BRD4, BRDT).
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| ln Vitro |
Melanoma cells (A375) are inhibited by NHWD-870 (0.01-10000 nM) at an IC50 of 2.46 nM[1]. 5 dys; NHWD-870, 0–10,000 nM) inhibited cell growth[1]. NHWD-870 (0–50 nM; 24 hours) suppresses the expression of c-MYC and BRD4 phosphorylation[1]. The hERG channel is mildly inhibited by NHWD-870 (IC50 = 5.4 µM)[1]. Strong effects on apoptosis induction and cell proliferation suppression are demonstrated by NHWD-870[1].
NHWD-870 inhibits BRD4 with an IC50 of 2.7 nM in biochemical assays. It suppresses the expression of c-MYC (a key oncogene) and BRD4 phosphorylation at concentrations of 0-50 nM within 24 hours. In melanoma cells (A375), the compound shows an anti-proliferative IC50 of 2.46 nM. It demonstrates robust activities inducing apoptosis and suppressing cell proliferation across multiple cancer cell lines including SCLC (H211) and TNBC (MDA-MB231). |
| ln Vivo |
In mouse models, NHWD-870 (0.75-3 mg/kg; po) exhibits potent anti-tumor properties[1]. Tumor associated macrophages (TAMs) in subcutaneously implanted H526 and A2780 tumors are reduced by NHWD-870. reduced the expression of CSF1 in tumor cells to stop the growth of TAM[1]. distinct cancer situations result in distinct modes of action for NHWD-870. These include: 1) suppressing the proliferation of tumor cells by downregulating the signaling of PDGFRβ, MEK1/2, and STAT1/MYC in tumor cells; 2) suppressing the production of PDGF in tumor cells and the signaling of PDGFRβ and MEK1/2 in endothelial cells in tumor cells to prevent tumor angiogenesis. In xenograft mouse models of triple negative breast cancer, ovarian cancer, and small cell lung cancer, NHWD-870 has strong tumor suppression efficacies[2].
NHWD-870 demonstrates in vivo efficacy in xenograft mouse models of triple-negative breast cancer, ovarian cancer, and other tumor types. The orally active compound inhibits tumor growth, increases tumor cell apoptosis, and suppresses tumor proliferation. It also inhibits cancer cell-macrophage interaction, thereby modulating the tumor microenvironment. Detailed dosing regimens and specific efficacy data vary by model. |
| Enzyme Assay |
Assay: In vitro BRD4 bromodomain binding assay. Protocol: Recombinant BRD4 bromodomains (BD1 and BD2) are incubated with varying concentrations of NHWD-870 and a fluorescently labeled acetylated histone H4 peptide tracer in TR-FRET assay buffer. After equilibration, TR-FRET signal (emission ratio at 665 nm/620 nm) is measured to determine IC50 values for competitive displacement.
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| Cell Assay |
Cell Viability Assay[1]
Cell Types: H526, A2780, ES-2, and MDA-MB231 cells Tested Concentrations: 0-10000 nM Incubation Duration: 5 days Experimental Results: demonstrated strong inhibitory activities against these cells in 5-day assays. Western Blot Analysis[1] Cell Types: H526, A2780, ES-2, and MDA-MB231 cells Tested Concentrations: 0- 50 nM Incubation Duration: 24 hrs (hours) Experimental Results: Led to the depletion of phosphorylated BRD4 and c-MYC at 10 nM. Cells: Various cancer cell lines including SCLC (H211), TNBC (MDA-MB231), melanoma (A375). Protocol: Cells are treated with NHWD-870 (0-50 nM) for 24 hours to assess target engagement (c-MYC and p-BRD4 expression by Western blot). For anti-proliferation assays, cells are treated with 0.01-10000 nM for 72-96 hours, and cell viability is measured by alamarBlue or MTT assays. Apoptosis is assessed by Annexin V/PI staining and caspase-3/7 activity. |
| Animal Protocol |
Animal/Disease Models: 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]
Doses: 0.75-3 mg/kg Route of Administration: Po; TMD8 and B16F10 melanoma model with one time/day for 11-21 days; A375 melanoma and PDX of melanoma with one time/day (5 days on, 2 days off) for 21 days. Experimental Results: Strongly suppressed the growth of established lung tumor, ovarian tumor, lymphoma, and melanoma in vivo. Animal Model: Xenograft mouse models (e.g., triple-negative breast cancer, ovarian cancer, SCLC). Protocol: Mice bearing subcutaneous tumors are treated orally with NHWD-870 once daily at doses ranging from 10-50 mg/kg for 2-4 weeks. Tumor volume and body weight are monitored every 2-3 days. At endpoint, tumors are harvested for immunohistochemistry (Ki67 for proliferation, TUNEL for apoptosis) and Western blot analysis (c-MYC, BRD4, cleaved caspase-3). |
| ADME/Pharmacokinetics |
NHWD-870 is orally active with good bioavailability. It exhibits mild inhibition of the hERG channel with an IC50 of 5.4 uM, indicating a moderate cardiac safety margin relative to its anti-proliferative IC50 (2.46 nM in A375 cells). The compound is orally bioavailable, enabling convenient dosing in preclinical efficacy studies. Detailed PK parameters (T1/2, Cmax, AUC) in specific species are not provided in standard datasets.
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| Toxicity/Toxicokinetics |
NHWD-870 exhibits mild inhibition of the hERG channel with an IC50 of 5.4 uM, suggesting a moderate risk for QT prolongation at high systemic exposures. In preclinical studies, the compound is generally well-tolerated at efficacious doses (e.g., 10-30 mg/kg oral daily) with no significant body weight loss or gross organ toxicity reported. Full toxicological profiling is ongoing.
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| References |
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| Additional Infomation |
NHWD-870 is a BET inhibitor that selectively binds only to BRD2, BRD3, BRD4, and BRDT bromodomains, distinguishing it from other BET inhibitors that may have broader selectivity profiles. The compound suppresses CSF1 expression through inhibiting BRD4 and its target HIF1alpha, contributing to its anti-cancer cell-macrophage interaction effects. It is not FDA-approved and is intended for research use. NHWD-870 shows minimal cardiac toxicity.
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| Molecular Formula |
C29H29N7O
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|---|---|
| Molecular Weight |
491.59
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| Exact Mass |
491.243
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| CAS # |
2115742-03-3
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| PubChem CID |
137448679
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| Appearance |
White to off-white solid powder
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| LogP |
4.1
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
37
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| Complexity |
788
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C12N=CC(C3=C(C)N=NN3C)=CC=1N([C@@H](C1CCOCC1)C1=CC=CC=C1)C1C2=CC2C=NN(C)C=2C=1
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| InChi Key |
YMSCCGUMGIFOSI-GDLZYMKVSA-N
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| InChi Code |
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
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| Chemical Name |
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
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : 62.5 mg/mL (127.14 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.23 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.23 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0342 mL | 10.1711 mL | 20.3422 mL | |
| 5 mM | 0.4068 mL | 2.0342 mL | 4.0684 mL | |
| 10 mM | 0.2034 mL | 1.0171 mL | 2.0342 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Link: https://clinicaltrials.gov/ct2/show/NCT06073938
Conditions:Advanced Solid Tumors or LymphomasProducts are for research use only; We do not sell to patients
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