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| 1mg |
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| 5mg |
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| 10mg | |||
| Other Sizes |
| Targets |
G9a (EHMT2) and GLP (EHMT1), which are histone methyltransferases responsible for the mono- and dimethylation of histone H3 at lysine 9 (H3K9me1/H3K9me2). These enzymes play a crucial role in transcriptional repression and are involved in the pathogenesis of various cancers and neurological disorders.
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| ln Vitro |
MS8511 hydrochloride exhibits potent inhibitory activity against G9a with an IC50 of 100 nM and against GLP with an IC50 of 140 nM. It binds to G9a with a Kd of 44 nM and to GLP with a Kd of 46 nM. The compound effectively reduces intracellular H3K9me2 levels and enhances antiproliferative activity in a concentration-dependent manner at 0-5 uM over 24-72 hours.
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| ln Vivo |
No specific in vivo data is available for MS8511 hydrochloride. The compound is indicated for studying a variety of cancers (including brain, breast, ovarian, lung, bladder, melanoma, colorectal) and diseases such as Alzheimer's, sickle cell disease, and PWS, but detailed animal model studies have not been reported in the available literature.
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| Enzyme Assay |
Typical G9a/GLP inhibition assay (radiolabeled SAM assay): incubate recombinant G9a (0.1-1 ug) with 50 mM Tris-HCl pH 8.5, 10 mM DTT, 0.01% Triton X-100, 1 uM [3H]-SAM (S-adenosylmethionine), and 10 uM H3 peptide substrate (residues 1-21) in a total volume of 50 uL at room temperature for 1-2 hours. MS8511 is added at varying concentrations (1-1000 nM). The reaction is spotted onto P81 filter paper and washed with 10 mM NaHCO3, and radioactivity is counted.
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| Cell Assay |
Standard cell viability protocol: culture cancer cell lines (e.g., U87 glioblastoma or MDA-MB-231 breast) in DMEM+10% FBS in 96-well plates. Treat with MS8511 hydrochloride (0.1-50 uM) for 24-72 hours. Assess H3K9me2 levels by Western blot with specific antibody. Measure anti-proliferative activity by MTT assay. Apoptosis is measured by caspase-3/7 activity or Annexin V/PI staining.
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| Animal Protocol |
No published in vivo data was found for MS8511 hydrochloride. A general protocol for evaluating G9a/GLP inhibitors in vivo would involve establishing subcutaneous xenografts of cancer cell lines in nude mice (e.g., 5×10⁶ U87 cells/injection). When tumors reach ~100 mm3, mice would be randomized to receive MS8511 (e.g., 10-50 mg/kg, IP or oral) or vehicle daily for 3-4 weeks. Tumor volume measured twice weekly, and tumors harvested for H3K9me2 IHC.
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| ADME/Pharmacokinetics |
No PK data were found. As a covalent irreversible inhibitor targeting a cysteine residue, MS8511 hydrochloride would be expected to exhibit prolonged target engagement in vivo. Standard PK studies would involve IV/oral administration in rodents, plasma collection, and LC-MS/MS analysis to determine clearance, half-life, and oral bioavailability.
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| Toxicity/Toxicokinetics |
No specific toxicological data is available. As a covalent inhibitor, off-target toxicity is a potential concern, but no formal evaluations have been reported. Standard preclinical safety assessments would include a 7-day repeat-dose oral toxicity study in rats with histopathological examination of major organs.
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| References | |
| Additional Infomation |
MS8511 hydrochloride (CAS: 3031788-28-7) is supplied as a research-grade compound with molecular formula C28H42ClN5O3 and molecular weight 556.11. It exhibits covalent and irreversible inhibition characteristics. It reduces intracellular H3K9me2 levels and enhances anti-proliferative activity. It is soluble in methanol (~30 mg/mL). Each product in one row, fields tab-separated.
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| Molecular Formula |
C28H42CLN5O3
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|---|---|
| Molecular Weight |
532.12
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| Exact Mass |
531.298
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| CAS # |
3031788-28-7
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| Related CAS # |
MS8511;2866408-21-9
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| PubChem CID |
171360694
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| Appearance |
Off-white to light yellow solid powder
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| Hydrogen Bond Donor Count |
3
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| Rotatable Bond Count |
11
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| Heavy Atom Count |
37
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| Complexity |
693
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC(C)N1CCC(CC1)NC2=CC(=NC3=CC(=C(C=C32)OC)OCCCN4CCCC4)NC(=O)C=C.Cl
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| InChi Key |
JRCSOGLIHWDWKN-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C28H41N5O3.ClH/c1-5-28(34)31-27-19-24(29-21-9-14-33(15-10-21)20(2)3)22-17-25(35-4)26(18-23(22)30-27)36-16-8-13-32-11-6-7-12-32;/h5,17-21H,1,6-16H2,2-4H3,(H2,29,30,31,34);1H
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| Chemical Name |
N-[6-methoxy-4-[(1-propan-2-ylpiperidin-4-yl)amino]-7-(3-pyrrolidin-1-ylpropoxy)quinolin-2-yl]prop-2-enamide;hydrochloride
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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) |
Methanol : ~30 mg/mL (~56.38 mM; with ultrasonication)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8793 mL | 9.3964 mL | 18.7928 mL | |
| 5 mM | 0.3759 mL | 1.8793 mL | 3.7586 mL | |
| 10 mM | 0.1879 mL | 0.9396 mL | 1.8793 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.
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