PHA-408

PHA-408 is an inhibitor of IkappaB kinase beta (IKKbeta, IC50 = 0.04 µM). It is selective for IKKbeta over IKKalpha, Pim-1, Pim-2, Tie2, TrkA, and p70S6K (IC50s = 0.6-28.4 µM), as well as a panel of 26 kinases (IC50s = >30 µM for all). PHA-408 inhibits IL-1beta-induced production of prostaglandin E2 (PGE2, Cay-14010) in synovial fibroblasts isolated from patients with rheumatoid arthritis (IC50 = ~0.6 µM). In vivo, PHA-408 (50 mg/kg) reduces serum LPS-induced TNF-alpha production in rats. It inhibits joint swelling and bone destruction in a rat model of streptococcal cell wall-induced arthritis when administered at a dose of 10 mg/kg. PHA-408 (15 and 45 mg/kg) inhibits LPS- or cigarette smoke-induced bronchoalveolar lavage fluid (BALF) neutrophil influx and reduces BALF levels of IL-6, TNF-alpha, and IL-1beta in rats.Formal Name: 8-[[[5-chloro-2-(4-methyl-1-piperazinyl)-4-pyridinyl]carbonyl]amino]-1-(4-fluorophenyl)-4,5-dihydro-1H-benz[g]indazole-3-carboxamide. CAS Number: 503555-55-3. Synonyms: PHA-767408. Molecular Formula: C29H27ClFN7O2. Formula Weight: 560.0. Purity: >98%. Formulation: (Request formulation change), A solid. Solubility: Acetonitrile: Slightly Soluble: 0.1-1 mg/ml, Methanol: Slightly Soluble: 0.1-1 mg/ml. SMILES: O=C(C1=NN(C2=C1CCC3=C2C=C(NC(C4=C(Cl)C=NC(N5CCN(CC5)C)=C4)=O)C=C3)C6=CC=C(C=C6)F)N. InChi Code: InChI=1S/C29H27ClFN7O2/c1-36-10-12-37(13-11-36)25-15-23(24(30)16-33-25)29(40)34-19-6-2-17-3-9-21-26(28(32)39)35-38(27(21)22(17)14-19)20-7-4-18(31)5-8-20/h2,4-8,14-16H,3,9-13H2,1H3,(H2,32,39)(H,34,40). InChi Key: ZLEZHGHFWIHCGU-UHFFFAOYSA-N.