MS8511 is a selective, covalent, irreversible inhibitor of G9a/GLP that targets cysteine residues in the substrate binding site, with IC50s of 100 nM (G9a) and 140 nM (GLP), and Kds. 44 nM (G9a) and 46 nM (GLP). MS8511 reduces intracellular H3K9me2 levels and increases antiproliferation activity. MS8511 may be utilized to study a variety of cancers (including brain cancer, breast cancer, ovarian cancer, lung cancer, bladder cancer, melanoma, colorectal cancer) and other diseases, such as AD/Alzheimer's disease, sickle cell disease, Prader -Willi syndrome (PWS).

Physicochemical Properties

Molecular Formula	C28H41N5O3
Molecular Weight	495.66
Exact Mass	495.32
CAS #	2866408-21-9
PubChem CID	164512403
Appearance	White to off-white solid powder
LogP	4.5
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	11
Heavy Atom Count	36
Complexity	693
Defined Atom Stereocenter Count	0
SMILES	N(C1CCN(CC1)C(C)C)C1=CC(=NC2C=C(C(=CC=21)OC)OCCCN1CCCC1)NC(=O)C=C
InChi Key	FNRUPVONTWZCGL-UHFFFAOYSA-N
InChi Code	InChI=1S/C28H41N5O3/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)
Chemical Name	N-[6-methoxy-4-[(1-propan-2-ylpiperidin-4-yl)amino]-7-(3-pyrrolidin-1-ylpropoxy)quinolin-2-yl]prop-2-enamide
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
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	G9a 100 nM (IC50) G9a 44 nM (Kd) GLP 140 nM (IC50) GLP 46 nM (Kd)
ln Vitro	MS8511 (Compound 8, 0-100 μM, 10 min) preferentially inhibits G9a and GLP against other PKMTs and PRMTs, with IC50 values of 100 nM (G9a) and 140 nM (GLP)[1]. MS8511 (50 min) prefers covalent modification for G9a over GLP, having Kd values of 44 nM (G9a) and 46 nM (GLP)[1]. MS8511 (0-5 μM, 24-72 h) effectively reduces the H3K9me2 mark in MDA-MB-231 and K562 cellssup>[1]. MS8511 (0.8-25 μM, 3 days) inhibits the growth of MDA-MB-231 cells[1].
Cell Assay	Western Blot Analysis[1] Cell Types: MDA-MB-231, K562 cells. Tested Concentrations: 0.2, 1, 5 μM. Incubation Duration: 24, 48, 72 h. Experimental Results: diminished the H3K9me2 mark in a concentration- and time-dependent manner. Cell Viability Assay[1] Cell Types: MDA-MB-231 cells Tested Concentrations: 0.8, 1.6, 3.1 6.3, 12.5, 25 μM. Incubation Duration: 3 days Experimental Results: Inhibited the growth of MDA-MB-231 cells.
References	[1]. Discovery of the First-in-Class G9a/GLP Covalent Inhibitors. J Med Chem. 2022 Jun 28.

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.0175 mL	10.0876 mL	20.1751 mL
	5 mM	0.4035 mL	2.0175 mL	4.0350 mL
	10 mM	0.2018 mL	1.0088 mL	2.0175 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.