MS023 free base | CAS#1831110-54-3 | PRMT inhibitor

MedKoo Cat#: 407274 | Name: MS023 free base

Description:

WARNING: This product is for research use only, not for human or veterinary use.

MS023 is a Potent, Selective, and Cell-Active Inhibitor of Human Type I Protein Arginine Methyltransferases. MS023 displayed high potency for type I PRMTs including PRMT1, -3, -4, -6, and -8 but was completely inactive against type II and type III PRMTs, protein lysine methyltransferases and DNA methyltransferases. MS023 is a useful chemical tool for investigating the role of type I PRMTs in health and disease.

Chemical Structure

MS023 free base

CAS#1831110-54-3 (free base)

Theoretical Analysis

MedKoo Cat#: 407274

Name: MS023 free base

CAS#: 1831110-54-3 (free base)

Chemical Formula: C17H25N3O

Exact Mass: 287.1998

Molecular Weight: 287.41

Elemental Analysis: C, 71.04; H, 8.77; N, 14.62; O, 5.57

Price and Availability

Size	Price	Availability
10mg	USD 150.00	Ready to ship
25mg	USD 250.00	Ready to ship
50mg	USD 450.00	Ready to ship
100mg	USD 750.00	Ready to ship
200mg	USD 1,250.00	Ready to ship
500mg	USD 2,150.00	Ready to ship
1g	USD 3,650.00	Ready to ship
2g	USD 6,450.00	Ready to ship

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Related CAS #

1831110-54-3 (free base) 1992047-64-9 (2HCl) 2108631-19-0 (3HCl)

Synonym

MS023; MS-023; MS 023.

IUPAC/Chemical Name

N1-((4-(4-isopropoxyphenyl)-1H-pyrrol-3-yl)methyl)-N1-methylethane-1,2-diamine

InChi Key

FMTVWAGUJRUAKE-UHFFFAOYSA-N

InChi Code

InChI=1S/C17H25N3O/c1-13(2)21-16-6-4-14(5-7-16)17-11-19-10-15(17)12-20(3)9-8-18/h4-7,10-11,13,19H,8-9,12,18H2,1-3H3

SMILES Code

CC(C)OC1=CC=C(C2=CNC=C2CN(C)CCN)C=C1

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot# A21T06K23

QC Data

View QC data: current batch, Lot# A21T06K23

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

MS023 is a potent, selective, and cell-active inhibitor of human type I protein arginine methyltransferases (PRMTs) inhibitor, with IC50s of 30, 119, 83, 4 and 5 nM for PRMT1, PRMT3, PRMT4, PRMT6, and PRMT8, respectively.

In vitro activity:

Entinostat was toxic for normal cells, while its effect on colon cancer cells was stronger (Growth Inhibition of 50% (GI50) was 8.3 µM and 1.2 µM, respectively). The most pronounced ALP-inducing hit was PRMT type 1 inhibitor MS023. Figure 2a shows that MS023 moderately increased ALP activity in comparison to entinostat (e.g. 5-fold increase versus about 30-fold increase respectively at 2.5 µM). Effective concentration of 50% (EC50) of MS023 was 5.8 µM, and it significantly delays HT-29 cell proliferation (GI50 was 2.3 µM). Importantly, MS023 had no effect on either ALP activity or proliferation of CCD-841 cells. Interestingly, MS023 reduced cell growth in four colon cancer cell lines, previously reported as irresponsive to SB treatment25: HCT-116, Colo-205, SW620, and HCT-15 (Table1). This suggests that MS023 effect was not cell line specific. Following formation of established spheroids (5 days), MS023, entinostat or vehicle (DMSO) were added and growth was monitored during 6 additional days. In order to detect dead cells, propidium iodide (PI) staining of the spheroids was perofmed shortly before imaging (Fig. 2b,c). While entinostat rapidly induced cytotoxic effect, MS023 showed reduced growth, but low toxicity. Thus, PRMT type 1 inhibition induces effects associated with cell differentiation in both monolayer and 3D culture. Reference: Sci Rep. 2020; 10: 20030. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7676271/

In vivo activity:

MS023 efficacy in-vivo was examined using HT-29 xenograft model in nude mice. In order to calculate desirable frequency of MS023 injection, a preliminary experiment was performed, where cell growth medium containing MS023 was replaced 5 days later with a fresh one containing or not a second dose of MS023. The absence of MS023 led to restoration of the proliferative potential, while addition of a second dose kept the cells in low-proliferating status (data not shown). Therefore, the animals received 2 doses of the compound/week. The treatment started when tumors reached 6–7 mm diameter. MS023 treatment significantly delayed tumor growth (Fig. 8a) without any signs of toxicity. This data shows that MS023 was able to reduce tumor growth and proliferation in vivo through differentiation of malignant cells, demonstrating a tractable model of pharmacological manipulation of colon cancer differentiation, with clinical implications. Reference: Sci Rep. 2020; 10: 20030. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7676271/

	Solvent	mg/mL	mM
Solubility
	DMSO	62.0	215.72
	H2O	39.0	135.70

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 287.41 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Plotnikov A, Kozer N, Cohen G, Carvalho S, Duberstein S, Almog O, Solmesky LJ, Shurrush KA, Babaev I, Benjamin S, Gilad S, Kupervaser M, Levin Y, Gershovits M, Ben-Avraham D, Barr HM. PRMT1 inhibition induces differentiation of colon cancer cells. Sci Rep. 2020 Nov 18;10(1):20030. doi: 10.1038/s41598-020-77028-8. PMID: 33208761; PMCID: PMC7676271. 2. Cai T, Yu Z, Wang Z, Liang C, Richard S. Arginine methylation of SARS-Cov-2 nucleocapsid protein regulates RNA binding, its ability to suppress stress granule formation, and viral replication. J Biol Chem. 2021 May 23;297(1):100821. doi: 10.1016/j.jbc.2021.100821. Epub ahead of print. PMID: 34029587; PMCID: PMC8141346. 3. Zhu Y, He X, Lin YC, Dong H, Zhang L, Chen X, Wang Z, Shen Y, Li M, Wang H, Sun J, Nguyen LX, Zhang H, Jiang W, Yang Y, Chen J, Müschen M, Chen CW, Konopleva MY, Sun W, Jin J, Carlesso N, Marcucci G, Luo Y, Li L. Targeting PRMT1-mediated FLT3 methylation disrupts maintenance of MLL-rearranged acute lymphoblastic leukemia. Blood. 2019 Oct 10;134(15):1257-1268. doi: 10.1182/blood.2019002457. PMID: 31395602; PMCID: PMC6788006

In vitro protocol:

In vivo protocol:

1. Plotnikov A, Kozer N, Cohen G, Carvalho S, Duberstein S, Almog O, Solmesky LJ, Shurrush KA, Babaev I, Benjamin S, Gilad S, Kupervaser M, Levin Y, Gershovits M, Ben-Avraham D, Barr HM. PRMT1 inhibition induces differentiation of colon cancer cells. Sci Rep. 2020 Nov 18;10(1):20030. doi: 10.1038/s41598-020-77028-8. PMID: 33208761; PMCID: PMC7676271. 2. Zhu Y, He X, Lin YC, Dong H, Zhang L, Chen X, Wang Z, Shen Y, Li M, Wang H, Sun J, Nguyen LX, Zhang H, Jiang W, Yang Y, Chen J, Müschen M, Chen CW, Konopleva MY, Sun W, Jin J, Carlesso N, Marcucci G, Luo Y, Li L. Targeting PRMT1-mediated FLT3 methylation disrupts maintenance of MLL-rearranged acute lymphoblastic leukemia. Blood. 2019 Oct 10;134(15):1257-1268. doi: 10.1182/blood.2019002457. PMID: 31395602; PMCID: PMC6788006.

1: Eram MS, Shen Y, Szewczyk MM, Wu H, Senisterra G, Li F, Butler KV, Kaniskan HÜ, Speed BA, Dela Seña C, Dong A, Zeng H, Schapira M, Brown PJ, Arrowsmith CH, Barsyte-Lovejoy D, Liu J, Vedadi M, Jin J. A Potent, Selective, and Cell-Active Inhibitor of Human Type I Protein Arginine Methyltransferases. ACS Chem Biol. 2015 Dec 8. [Epub ahead of print] PubMed PMID: 26598975.