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[1][2][3].

Research Areas >> Cancer

Signaling Pathways >> MAPK/ERK Pathway >> p38 MAPK

p38α:9 nM (IC50)

p38β:90 nM (IC50)

Talmapimod (SCIO-469) hydrochloride (100-200 nM; 1 hour) inhibits phosphorylation of p38 MAPK in MM cells[1]. Talmapimod hydrochloride inhibits LPS-induced TNF-a production in human whole blood[2]. Talmapimod hydrochloride decreases constitutive p38alpha MAPK phosphorylation of both 5T2MM and 5T33MM cells[3]. Western Blot Analysis[1] Cell Line: MM.1S, U266, RPMI8226, MM.1R, and RPMI-Dox40 cell lines Concentration: 100, 200 nM Incubation Time: 1 hour Result: Strongly inhibits phosphorylation of p38 MAPK.

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[4]. Animal Model: Six-week-old male triple immune-deficient BNX mice (RPMI-8226 MM palpable tumors)[4] Dosage: 10, 30, 90 mg/kg Administration: P.o.; twice daily orally for 14 days Result: Dose-dependently reduced tumor growth.

[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.

[4]. Medicherla S, et al. p38alpha-selective MAP kinase inhibitor reduces tumor growth in mouse xenograft models of multiple myeloma. Anticancer Res. 2008 Nov-Dec;28(6A):3827-33.