NHWD-870
Based on 1 publication(s) in Google Scholar
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.
For research use only. We do not sell to patients.
- Purity : 99.36%
- CAS No.: 2115742-03-3
- Formula: C29H29N7O
- Molecular Weight:491.59
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Storage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Protocols
- Purity & Documentation
- References
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Help & FAQs
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Publications Citing Use of MedChemExpress (MCE) NHWD-870
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Biological Activity
Description
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| MDA-MB-231 | IC50 |
1.58 nM
Compound: 5; NWHD-870
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Antiproliferative activity against human MDA-MB-231 cells assessed as reduction in cell viability by MTS assay
Antiproliferative activity against human MDA-MB-231 cells assessed as reduction in cell viability by MTS assay
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[PMID: 36893627] |
| MDA-MB-231 | IC50 |
1.58 nM
Compound: 57; NHWD-870
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Antiproliferative activity against human MDA-MB-231 cells assessed as reduction in cell viability incubated for 72 hrs by MTS assay
Antiproliferative activity against human MDA-MB-231 cells assessed as reduction in cell viability incubated for 72 hrs by MTS assay
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[PMID: 37209450] |
| NCI-H211 | IC50 |
1.99 nM
Compound: 5; NWHD-870
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Antiproliferative activity against human NCI-H211 cells assessed as reduction in cell viability by MTS assay
Antiproliferative activity against human NCI-H211 cells assessed as reduction in cell viability by MTS assay
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[PMID: 36893627] |
| NCI-H211 | IC50 |
1.99 nM
Compound: 57; NHWD-870
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Antiproliferative activity against human NCI-H211 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay
Antiproliferative activity against human NCI-H211 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay
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[PMID: 37209450] |
In Vitro
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].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:H526, A2780, ES-2, and MDA-MB231 cells
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Concentration:0-10000 nM
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Incubation Time:5 days
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Result:Showed strong inhibitory activities against these cells in 5-day assays.
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Cell Line:H526, A2780, ES-2, and MDA-MB231 cells
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Concentration:0-50 nM
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Incubation Time:24 hours
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Result:Led to the depletion of phosphorylated BRD4 and c-MYC at 10 nM.
In Vivo
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].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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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]
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Dosage:0.75-3 mg/kg
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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.
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Result:Strongly suppressed the growth of established lung tumor, ovarian tumor, lymphoma, and melanoma in vivo.
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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CAS No. 2115742-03-3
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Appearance Solid
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Molecular Weight 491.59
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Formula C29H29N7O
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Color White to off-white
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SMILES
CN1N=CC2=CC3=C(N([C@H](C4=CC=CC=C4)C5CCOCC5)C6=CC(C7=C(C)N=NN7C)=CN=C63)C=C12
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Publications (1)
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Journal Impact Factor
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Most Recent
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J Nanobiotechnology
A combination of a TLR7/8 agonist and an epigenetic inhibitor suppresses triple-negative breast cancer through triggering anti-tumor immune. [Abstract]2024 May 29;22(1):296. PMID: 38811964
Solvent & Solubility
In Vitro:
DMSO : 62.5 mg/mL (127.14 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
In Vivo:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.08 mg/mL (4.23 mM); Clear solution
This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Protocols
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Apoptosis
Apoptosis, also called programmed cell death, is generally characterized by distinct morphological characteristics.
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TUNEL staining for apoptotic DNA fragmentation
TUNEL staining detects DNA strand breaks by using terminal deoxynucleotidyl transferase to add labeled nucleotides to exposed 3′-OH DNA termini, generating either microscopic staining in fixed cells or tissue sections, or fluorescence/cytometric signal in cell suspensions. TUNEL positivity reflects DNA fragmentation but should not be interpreted alone as definitive apoptosis, because TUNEL can also label necrotic, autolytic, mechanically damaged, or DNA-repair-associated DNA breaks.
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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
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Annexin V plus membrane-impermeant dye apoptosis staining
Annexin V-based apoptosis assays rely on the detection of phosphatidylserine (PS) externalization from the inner leaflet of the plasma membrane to the outer leaflet, an early biochemical hallmark of apoptosis. Fluorescently labeled Annexin V binds PS in a calcium-dependent manner, enabling identification of early apoptotic cells by flow cytometry or fluorescence microscopy. When combined with a membrane-impermeant DNA-binding dye (e. g. , propidium iodide), this approach allows discrimination between viable (Annexin V−/dye−), early apoptotic (Annexin V+/dye−), and late apoptotic or necrotic (Annexin V+/dye+) cell populations by assessing membrane integrity and PS exposure.
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Apoptosis Solutions
Apoptosis is a regulated, generally non-lytic cell-death pathway that removes unwanted, damaged, infected, or abnormal cells through coordinated morphological changes, caspase activation, DNA fragmentation, and membrane remodeling. The intrinsic apoptosis pathway is controlled mainly by mitochondrial outer membrane permeabilization, BCL-2 family proteins, cytochrome c release, apoptosome formation, caspase-9 activation, and downstream executioner caspase-3/7 activation. The extrinsic apoptosis pathway is initiated by death receptors such as Fas, TNFR, and TRAIL receptors, which recruit adaptor proteins and activate caspase-8 before engaging executioner caspases or mitochondrial amplification through BID cleavage. Apoptosis is linked to many phenotypes, including cancer cell killing, tissue homeostasis, immune regulation, neurodegeneration, infection response, and treatment-induced cytotoxicity; unresolved questions include how apoptosis interacts with necroptosis, pyroptosis, ferroptos
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Cell Viability Determination by MTT Colorimetric Assay
The following protocol uses the MTT colorimetric assay as a classic literature-established method for assessing cell viability/metabolic activity in cultured mammalian cells. MTT[3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] is reduced by metabolically active cells to a colored formazan product; the amount of formazan is quantified spectrophotometrically and provides an indirect measure of metabolically active viable cells. Importantly, MTT reduction reflects cellular oxidoreductase/metabolic activity rather than an absolute direct count of living cells, so changes in cellular metabolism can alter the signal independently of cell number.
Purity & Documentation
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Data Sheet (283 KB)
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SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Korean - KR (393 KB)
- Portuguese - PT (393 KB)
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Handling Instructions (2659 KB)
References
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.0342 mL | 10.1711 mL | 20.3422 mL | 50.8554 mL |
| 5 mM | 0.4068 mL | 2.0342 mL | 4.0684 mL | 10.1711 mL | |
| 10 mM | 0.2034 mL | 1.0171 mL | 2.0342 mL | 5.0855 mL | |
| 15 mM | 0.1356 mL | 0.6781 mL | 1.3561 mL | 3.3904 mL | |
| 20 mM | 0.1017 mL | 0.5086 mL | 1.0171 mL | 2.5428 mL | |
| 25 mM | 0.0814 mL | 0.4068 mL | 0.8137 mL | 2.0342 mL | |
| 30 mM | 0.0678 mL | 0.3390 mL | 0.6781 mL | 1.6952 mL | |
| 40 mM | 0.0509 mL | 0.2543 mL | 0.5086 mL | 1.2714 mL | |
| 50 mM | 0.0407 mL | 0.2034 mL | 0.4068 mL | 1.0171 mL | |
| 60 mM | 0.0339 mL | 0.1695 mL | 0.3390 mL | 0.8476 mL | |
| 80 mM | 0.0254 mL | 0.1271 mL | 0.2543 mL | 0.6357 mL | |
| 100 mM | 0.0203 mL | 0.1017 mL | 0.2034 mL | 0.5086 mL |
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