Talmapimod hydrochloride

Talmapimod (SCIO-469) hydrochloride is an orally active, selective, and ATP-competitive p38α inhibitor with an IC50 of 9 nM. Talmapimod hydrochloride shows about 10-fold selectivity over p38β, and at least 2000-fold selectivity over a panel of 20 other kinases, including other MAPKs.

Product information

CAS Number: 309915-12-6

Molecular Weight: 549.46

Formula: C27H31Cl2FN4O3

Synonym:

SCIO-469 hydrochloride

Chemical Name: 2-{6-chloro-5-[(2R, 5S)-4-[(4-fluorophenyl)methyl]-2, 5-dimethylpiperazine-1-carbonyl]-1-methyl-1H-indol-3-yl}-N, N-dimethyl-2-oxoacetamide hydrochloride

Smiles: Cl.CN(C)C(=O)C(=O)C1=CN(C)C2=CC(Cl)=C(C=C21)C(=O)N1C[C@H](C)N(C[C@H]1C)CC1C=CC(F)=CC=1

InChiKey: FOJUFGQLUOOBQP-MCJVGQIASA-N

InChi: InChI=1S/C27H30ClFN4O3.ClH/c1-16-13-33(17(2)12-32(16)14-18-6-8-19(29)9-7-18)26(35)21-10-20-22(25(34)27(36)30(3)4)15-31(5)24(20)11-23(21)28;/h6-11,15-17H,12-14H2,1-5H3;1H/t16-,17+;/m0./s1

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

Talmapimod (SCIO-469) hydrochloride (100-200 nM; 1 hour) inhibits phosphorylation of p38 MAPK in MM cells. Talmapimod hydrochloride inhibits LPS-induced TNF-a production in human whole blood. Talmapimod hydrochloride decreases constitutive p38alpha MAPK phosphorylation of both 5T2MM and 5T33MM cells.

In Vivo:

Talmapimod hydrochloride (10-90 mg/kg; P.o.; twice daily orally for 14 days) dose-dependently reduced tumor growth and also dose-dependently reduced weight of the palpable tumors at termination.

References:

1. Hideshima T et al. p38 MAPK inhibition enhances PS-341 (bortezomib)-induced cytotoxicity against multiple myeloma cells. Oncogene. 2004 Nov 18, 23(54), 8766-76.
2. Navas T, et al. Inhibition of p38alpha MAPK disrupts the pathological loop of proinflammatory factor production in the myelodysplastic syndrome bone marrow microenvironment. Leuk Lymphoma. 2008 Oct;49(10):1963-75.
3. Vanderkerken K et al. Inhibition of p38alpha mitogen-activated protein kinase prevents the development of osteolytic bone disease,reduces tumor burden, and increases survival in murine models of multiple myeloma. Cancer Res. 2007 May 15;67(10):4572-7.

Products are for research use only. Not for human use.