Ralimetinib mesylate | LY2228820 | CAS#862505-00-8 | 862507-23-1 | p38 MAPK inhibitor

MedKoo Cat#: 206737 | Name: Ralimetinib mesylate

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Description:

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

Ralimetinib, also known as LY2228820, is a potent and selective, ATP-competitive inhibitor of the α- and β-isoforms of p38 MAPK in vitro (IC(50) = 5.3 and 3.2 nmol/L, respectively). In cell-based assays, LY2228820 potently and selectively inhibited phosphorylation of MK2 (Thr334) in anisomycin-stimulated HeLa cells (at 9.8 nmol/L by Western blot analysis) and anisomycin-induced mouse RAW264.7 macrophages (IC(50) = 35.3 nmol/L) with no changes in phosphorylation of p38α MAPK, JNK, ERK1/2, c-Jun, ATF2, or c-Myc ≤ 10 μmol/L. LY2228820 enhances bortezomib-induced cytotoxicity and inhibits osteoclastogenesis in multiple myeloma; therapeutic implications.

Chemical Structure

Ralimetinib mesylate

CAS#862507-23-1 (mesylate)

Theoretical Analysis

MedKoo Cat#: 206737

Name: Ralimetinib mesylate

CAS#: 862507-23-1 (mesylate)

Chemical Formula: C26H37FN6O6S2

Exact Mass: 0.0000

Molecular Weight: 612.74

Elemental Analysis: C, 50.97; H, 6.09; F, 3.10; N, 13.72; O, 15.67; S, 10.46

Price and Availability

Size	Price	Availability	Quantity
5mg	USD 300.00	2 Weeks
10mg	USD 550.00	2 Weeks

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Related CAS #

862507-23-1 (mesylate) 862505-00-8 (free base)

Synonym

Ralimetinib mesylate; LY2228820; LY-2228820; LY 2228820; LY2228820 dimesylate.

IUPAC/Chemical Name

5-(2-(tert-butyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)-3-neopentyl-3H-imidazo[4,5-b]pyridin-2-amine dimethanesulfonate

InChi Key

NARMJPIBAXVUIE-UHFFFAOYSA-N

InChi Code

InChI=1S/C24H29FN6.2CH4O3S/c1-23(2,3)13-31-20-17(28-22(31)26)12-11-16(27-20)19-18(14-7-9-15(25)10-8-14)29-21(30-19)24(4,5)6;2*1-5(2,3)4/h7-12H,13H2,1-6H3,(H2,26,28)(H,29,30);2*1H3,(H,2,3,4)

SMILES Code

NC1=NC2=CC=C(C3=C(C4=CC=C(F)C=C4)N=C(C(C)(C)C)N3)N=C2N1CC(C)(C)C.CS(=O)(O)=O.CS(=O)(O)=O

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

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

Related CAS# CAS#862507-23-1 (Ralimetinib mesylate) CAS#862505-00-8 (Ralimetinib free base)

Product Data

Product Data

Instruction

View handling instruction

Biological target:

Ralimetinib dimesylate is a selective, ATP-competitive inhibitor of p38 MAPK α/β with IC50s of 5.3 and 3.2 nM, respectively. Ralimetinib potently and selectively inhibited phosphorylation of MK2 in anisomycin-stimulated HeLa cells and anisomycin-induced mouse RAW264.7 macrophages (IC(50) = 35.3 nmol/L) with no changes in phosphorylation of p38α MAPK, JNK, ERK1/2, c-Jun, ATF2, or c-Myc ≤ 10 μmol/L.

In vitro activity:

Ralimetinib inhibited Rac3-induced cell invasion and migration of lung adenocarcinoma. Following Ralimetinib treatment after silencing of Rac3, E-cadherin expression was increased and vimentin expression was decreased. Reference: J Cancer. 2017 Aug 2;8(13):2511-2522. https://pubmed.ncbi.nlm.nih.gov/28900489/

In vivo activity:

After a single dose, ralimetinib inhibited p38 MAPK-induced phosphorylation of MAPKAP-K2 in peripheral blood mononuclear cells. Ralimetinib demonstrated acceptable safety, tolerability, and pharmacokinetics for patients with advanced cancer. Reference: Clin Cancer Res. 2016 Mar 1;22(5):1095-102. https://pubmed.ncbi.nlm.nih.gov/26581242/

	Solvent	mg/mL	mM
Solubility
	DMSO	61.0	99.55

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 612.74 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. Zhang C, Liu T, Wang G, Wang H, Che X, Gao X, Liu H. Rac3 Regulates Cell Invasion, Migration and EMT in Lung Adenocarcinoma through p38 MAPK Pathway. J Cancer. 2017 Aug 2;8(13):2511-2522. doi: 10.7150/jca.18161. PMID: 28900489; PMCID: PMC5595081. 2. Patnaik A, Haluska P, Tolcher AW, Erlichman C, Papadopoulos KP, Lensing JL, Beeram M, Molina JR, Rasco DW, Arcos RR, Kelly CS, Wijayawardana SR, Zhang X, Stancato LF, Bell R, Shi P, Kulanthaivel P, Pitou C, Mulle LB, Farrington DL, Chan EM, Goetz MP. A First-in-Human Phase I Study of the Oral p38 MAPK Inhibitor, Ralimetinib (LY2228820 Dimesylate), in Patients with Advanced Cancer. Clin Cancer Res. 2016 Mar 1;22(5):1095-102. doi: 10.1158/1078-0432.CCR-15-1718. Epub 2015 Nov 18. Erratum in: Clin Cancer Res. 2016 May 15;22(10 ):2596. PMID: 26581242. 3. Tate CM, Blosser W, Wyss L, Evans G, Xue Q, Pan Y, Stancato L. LY2228820 dimesylate, a selective inhibitor of p38 mitogen-activated protein kinase, reduces angiogenic endothelial cord formation in vitro and in vivo. J Biol Chem. 2013 Mar 1;288(9):6743-53. doi: 10.1074/jbc.M112.425553. Epub 2013 Jan 18. PMID: 23335506; PMCID: PMC3585111.

In vitro protocol:

In vivo protocol:

1. Patnaik A, Haluska P, Tolcher AW, Erlichman C, Papadopoulos KP, Lensing JL, Beeram M, Molina JR, Rasco DW, Arcos RR, Kelly CS, Wijayawardana SR, Zhang X, Stancato LF, Bell R, Shi P, Kulanthaivel P, Pitou C, Mulle LB, Farrington DL, Chan EM, Goetz MP. A First-in-Human Phase I Study of the Oral p38 MAPK Inhibitor, Ralimetinib (LY2228820 Dimesylate), in Patients with Advanced Cancer. Clin Cancer Res. 2016 Mar 1;22(5):1095-102. doi: 10.1158/1078-0432.CCR-15-1718. Epub 2015 Nov 18. Erratum in: Clin Cancer Res. 2016 May 15;22(10 ):2596. PMID: 26581242. 2. Tate CM, Blosser W, Wyss L, Evans G, Xue Q, Pan Y, Stancato L. LY2228820 dimesylate, a selective inhibitor of p38 mitogen-activated protein kinase, reduces angiogenic endothelial cord formation in vitro and in vivo. J Biol Chem. 2013 Mar 1;288(9):6743-53. doi: 10.1074/jbc.M112.425553. Epub 2013 Jan 18. PMID: 23335506; PMCID: PMC3585111.

Arend, R. C., Jackson-Fisher, A., Jacobs, I. A., Chou, J., & Monk, B. J. (2021). Ovarian cancer: new strategies and emerging targets for the treatment of patients with advanced disease. Cancer biology & therapy, 22(2), 89-105. Alam, A., Yildirim, O., Siddiqui, F., & Imam, N. and Sadik Bay. Biological Networks in Human Health and Disease, 75. Bakowski, M. A., Beutler, N., Wolff, K. C., Kirkpatrick, M. G., Chen, E., Nguyen, T. T. H., ... & Rogers, T. F. (2021). Drug repurposing screens identify chemical entities for the development of COVID-19 interventions. Nature communications, 12(1), 3309. Balkrishna, A., Kumar, S., Hazari, P., Sahu, R., & Arya, V. (2023). Computational analysis depicting potency of phytochemicals to target MAPK signalling pathway in breast cancer.