MS37452 is a potent inhibitor of CBX7 chromodomain binding to H3K27me3 with Kd of 27.7 μM. MS37452 can inhibit the transcription of the polycomb repressive complex target gene p16/CDKN2A by displacing the binding of CBX7 to the INK4A/ARF locus in prostate cancer/tumor cells.

Physicochemical Properties

Molecular Formula	C22H26N2O5
Molecular Weight	398.45
Exact Mass	398.184
Elemental Analysis	C, 66.32; H, 6.58; N, 7.03; O, 20.08
CAS #	423748-02-1
PubChem CID	1072048
Appearance	Off-white to light yellow solid powder
Density	1.2±0.1 g/cm3
Boiling Point	628.8±55.0 °C at 760 mmHg
Flash Point	334.1±31.5 °C
Vapour Pressure	0.0±1.8 mmHg at 25°C
Index of Refraction	1.575
LogP	2.29
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	6
Heavy Atom Count	29
Complexity	549
Defined Atom Stereocenter Count	0
SMILES	CC1=CC(=CC=C1)OCC(=O)N2CCN(CC2)C(=O)C3=C(C(=CC=C3)OC)OC
InChi Key	LUMCNRKHZRYQOV-UHFFFAOYSA-N
InChi Code	InChI=1S/C22H26N2O5/c1-16-6-4-7-17(14-16)29-15-20(25)23-10-12-24(13-11-23)22(26)18-8-5-9-19(27-2)21(18)28-3/h4-9,14H,10-13,15H2,1-3H3
Chemical Name	1-[4-(2,3-dimethoxybenzoyl)piperazin-1-yl]-2-(3-methylphenoxy)ethanone
Synonyms	MS 37452; MS-37452; MS37452
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

ln Vitro	In comparison to the DMSO control, MS37452 (125-500 μM; 12 hours) significantly elevated INK4A/ARF transcript levels at 250 μM and 500 μM by 25% and 60%, respectively [1]. After two hours of treatment on human PC3 prostate cancer cells, CBX7 occupancy at the INK4A/ARF site is reduced by MS37452 (250 μM) [1]. Compared to DMSO therapy and single drug treatment, the combination of MS37452 (200 µM; 5 days) plus doxorubicin resulted in a prolonged decrease in cell viability [2]. When combined with doxorubicin, MS37452 (200 µM; 5 days)—a CBX7 chromodomain inhibitor (CBX7i)—is a unique treatment approach [2].
Cell Assay	RT-PCR[1] Cell Types: PC3 Cell Tested Concentrations: 125-500 μM Incubation Duration: 12 hrs (hours) Experimental Results: INK4A/ARF expression was up-regulated by up to 25% and 60% at 250 μM and 500 μM, respectively. Cell viability assay [2] Cell Types: Glioblastoma multiforme (GBM) U118MG Cell Tested Concentrations: PRT4165 40 µM, PTC209 200 nM, DZnep 25 µM, GSK343 400 nM, MS37452 200 µM, Doxorubicin 200 nM, Temozolomide 50 µM, SAHA 1 µM Incubation Duration: 5 days Experimental Results: Several combinations were identified that resulted in a sustained decrease in cell viability compared to DMSO treatment and single drug treatment (SAHA/TMZ and MS37452/doxorubicin).
References	[1]. Small-molecule modulators of methyl-lysine binding for the CBX7 chromodomain. Chem Biol. 2015;22(2):161-168. [2]. CBX Chromodomain Inhibition Enhances Chemotherapy Response in Glioblastoma Multiforme. Yale J Biol Med. 2016;89(4):431-440.

Solubility Data

Solubility (In Vitro)

DMSO : ~100 mg/mL (~250.97 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.27 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 25.0 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: ≥ 2.5 mg/mL (6.27 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.5097 mL	12.5486 mL	25.0973 mL
	5 mM	0.5019 mL	2.5097 mL	5.0195 mL
	10 mM	0.2510 mL	1.2549 mL	2.5097 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.