Talmapimod is a p38 mitogen-activated protein (MAP) kinase inhibitor. Talmapimod reduced human myeloma cell growth in vivo both at early and advanced phases of the disease in mouse xenograft models. Talmapimod that blocks tumor necrosis factor-α, interleukin-1β, and cyclooxygenase-2 synthesis in patients with active rheumatoid arthritis (RA)
ChEBI: An indolecarboxamide obtained by formal condensation of the carboxy group of 6-chloro-3-[(dimethylamino)(oxo)acetyl]-1-methylindole-5-carboxylic acid with the secondary amino group of (2S,5R)-1-[(4-fluorophenyl)methyl]-2,
-dimethylpiperazine. It is a potent inhibitor of MAPK and exhibits anti-cancer properties.
SCIO-469 (Talmapimod) is an orally active, potent and selective mitogen-activated protein kinase (MAPK) p38alpha (p38α, MAPK14) inhibitor (IC50 = 9 nM; 10-fold over p38β, >2000-fold over 20 other kinases) with no significant affinity toward a panel of 70 enzymes and receptors. SCIO-469 inhibits multiple myeloma (MM) growth in mice in vivo (150 or 450 mg/kg powder diet; 5T2MM and 5T33MM) and augments proteasome inhibitor in a murine plasmacytoma model of MM (0.2 mg bortezomib/kg i.v. twice weekly with 30 mg SCIO-469/kg b.i.d. p.o.; RPMI8226).
Targeting p38α MAPK with Talmapimod (SCIO-469) decreases myeloma burden in addition to preventing the development of myeloma bone disease[2].
Talmapimod inhibits multiple myeloma growth and prevents bone disease in the 5T2MM and 5T33MM models[3].
Talmapimod (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: | P.o.; twice daily orally for 14 days |
| Administration: | 10, 30, 90 mg/kg |
| Result: | Dose-dependently reduced tumor growth. |
p38α: 9 nM (IC50); p38β: 90 nM (IC50)
