| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 50mg | |||
| Other Sizes |
| Targets |
BRD4 (bromodomain-containing protein 4), specifically the tandem BD1 and BD2 bromodomains. MS645 is a bivalent inhibitor that simultaneously engages both bromodomains of BRD4, providing enhanced binding affinity and sustained target inhibition compared to monovalent inhibitors.
|
|---|---|
| ln Vitro |
On mouse macrophage RAW cells and non-lymphoid cell lines of non-tumorigenic mammary epithelial cells MCF10A, MS645 has a growth-inhibiting effect. The triple-negative breast cancer (TNBC) cell lines HS5878T, BT549, and MCF 10A had IC50 values of 15, 30, and 60 nM, respectively. In HCC1806 cells, MS645 significantly reduced c-Myc expression and increased p21, a tumor suppressor and cell cycle factor. 4.1, 6.8, and 7.9 nanometers[1]. [1].
MS645 inhibits BRD4-BD1/BD2 with a Ki of 18.4 nM. The bivalent binding mode provides high potency and prolonged target engagement. MS645 downregulates pro-inflammatory cytokines and genes for cell-cycle control and DNA damage repair that are largely unaffected by monovalent BRD inhibition. The compound inhibits proliferation of TNBC cells. |
| ln Vivo |
In vivo, MS645 demonstrates antitumor efficacy in solid tumor models, including triple-negative breast cancer (TNBC). The compound's bivalent binding mechanism results in sustained repression of BRD4 transcriptional activity, providing durable pharmacodynamic effects. MS645 represents a novel approach to targeting BET proteins in cancer.
|
| Enzyme Assay |
Bromodomain binding assays typically employ AlphaScreen or TR-FRET technology. Biotinylated histone H4 peptide (acetylated at K5, K8, K12, K16) is incubated with recombinant BRD4-BD1 or BD2 domains and test compound. Binding is detected by donor and acceptor beads, and IC₅0 or Ki values are calculated from displacement curves. Surface plasmon resonance (SPR) can also be used to measure binding kinetics.
|
| Cell Assay |
TNBC and other solid tumor cell lines are treated with MS645 at various concentrations for 24-72 hours. Cell viability is assessed by MTT or CellTiter-Glo assays. BRD4 target engagement and downstream effects are evaluated by Western blotting for BRD4 target genes (e.g., MYC). Gene expression profiling by RNA-seq or qPCR is performed to assess the unique transcriptional effects of bivalent BRD4 inhibition.
|
| Animal Protocol |
Mice bearing TNBC xenografts are administered MS645 via intraperitoneal or intravenous injection. Tumor growth is monitored by caliper measurements. Tumors are harvested for pharmacodynamic analysis of BRD4 target engagement, gene expression changes, and apoptosis markers. Efficacy is determined by tumor growth inhibition and survival extension.
|
| ADME/Pharmacokinetics |
MS645 has a molecular weight of 938.04 g/mol and formula C4₈H₅4Cl2N10O2S2. As a large bivalent molecule, it may have distinct PK properties with potentially limited oral bioavailability. PK parameters would be determined in rodent studies following IV administration. The compound is typically formulated in suitable vehicles containing DMSO and co-solvents for in vivo administration.
|
| Toxicity/Toxicokinetics |
Toxicology data for MS645 are not publicly available. Standard preclinical safety assessment would include cytotoxicity assays, hERG inhibition testing, and repeat-dose toxicology studies in rodents. The compound's bivalent binding mode may provide improved therapeutic index by enabling lower doses and reduced off-target effects.
|
| References | |
| Additional Infomation |
MS645 is a research compound for studying BET bromodomain biology and developing novel cancer therapeutics. It is not clinically approved. The bivalent inhibition strategy represents an innovative approach to targeting BRD4 with enhanced potency and sustained activity. MS645 is a valuable tool for investigating the role of BRD4 in cancer and other diseases.
|
| Molecular Formula |
C48H54CL2N10O2S2
|
|---|---|
| Molecular Weight |
938.04416513443
|
| Exact Mass |
936.324
|
| CAS # |
2250091-96-2
|
| PubChem CID |
137349088
|
| Appearance |
Light yellow to yellow solid powder
|
| LogP |
10
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
10
|
| Rotatable Bond Count |
17
|
| Heavy Atom Count |
64
|
| Complexity |
1520
|
| Defined Atom Stereocenter Count |
2
|
| SMILES |
ClC1C=CC(=CC=1)C1C2C(C)=C(C)SC=2N2C(C)=NN=C2[C@H](CC(NCCCCCCCCCCNC(C[C@H]2C3=NN=C(C)N3C3=C(C(C)=C(C)S3)C(C3C=CC(=CC=3)Cl)=N2)=O)=O)N=1
|
| InChi Key |
VFGPQYYCEGAFLY-UWXQCODUSA-N
|
| InChi Code |
InChI=1S/C48H54Cl2N10O2S2/c1-27-29(3)63-47-41(27)43(33-15-19-35(49)20-16-33)53-37(45-57-55-31(5)59(45)47)25-39(61)51-23-13-11-9-7-8-10-12-14-24-52-40(62)26-38-46-58-56-32(6)60(46)48-42(28(2)30(4)64-48)44(54-38)34-17-21-36(50)22-18-34/h15-22,37-38H,7-14,23-26H2,1-6H3,(H,51,61)(H,52,62)/t37-,38-/m0/s1
|
| Chemical Name |
2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]-N-[10-[[2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]acetyl]amino]decyl]acetamide
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO : ~200 mg/mL (~213.21 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (5.33 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 50.0 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: ≥ 5 mg/mL (5.33 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 50.0 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 | 1.0661 mL | 5.3303 mL | 10.6605 mL | |
| 5 mM | 0.2132 mL | 1.0661 mL | 2.1321 mL | |
| 10 mM | 0.1066 mL | 0.5330 mL | 1.0661 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
