BX-795

BX-795 is a multi-kinase inhibitor that is an ATP-competitive inhibitor of 3-phosphoinositide-dependent protein kinase 1 (PDK1) and TANK-binding kinase 1 (TBK1, IC50s = 6 and 11 nM, respectively). It also inhibits the CAMK family kinases AMPK-related kinase 5 (NUAK1, IC50 = 5 nM) and microtubule affinity-regulating kinase 1 (MARK1), MARK2, MARK3, and MARK4 (IC50s = 55, 53, 81, and 19 nM, respectively), as well as the MAP3K kinases mixed-lineages kinase 1 (MLK1), MLK2, and MLK3 (IC50s = 50, 46, and 42 nM, respectively). BX-795 is selective for these kinases over five additional kinases (IC50s = >1,100 nM) but does inhibit the receptor tyrosine kinase VEGFR, as well as IkappaB kinase epsilon (I??epsilon) and Aurora B kinase (IC50s = 41 and 31 nM, respectively). It inhibits phosphorylation of Akt at Thr308 and p70 ribosomal S6 kinase 1 (p70S6K1) at Thr389 in PC3 prostate cancer cells (IC50 = 300 nM). BX-795 (1 µM) also inhibits the secretion of IFN-beta induced by LPS or poly(I:C) in RAW 264.7 macrophages. It inhibits the proliferation of PC3 prostate and MDA-MB-468 breast cancer cells (IC50s = 250 and 720 nM, respectively). BX-795 (5 µM) inhibits the proliferation of PDK1-/- murine embryonic stem cells expressing either wild-type PDK1 or PDK1 with an alanine-to-glycine (L159G) mutation.Formal Name: N-[3-[[5-iodo-4-[[3-[(2-thienylcarbonyl)amino]propyl]amino]-2-pyrimidinyl]amino]phenyl]-1-pyrrolidinecarboxamide. CAS Number: 702675-74-9. Molecular Formula: C23H26IN7O2S. Formula Weight: 591.5. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 12.5 mg/ml, DMF:PBS (pH 7.2) (1:4): 0.2 mg/ml, DMSO: 11.1 mg/ml. lambdamax: 247 nm. SMILES: [H]N(CCCN(C(C1=CC=CS1)=O)[H])C2=C(I)C=NC(N([H])C3=CC(N(C(N4CCCC4)=O)[H])=CC=C3)=N2. InChi Code: InChI=1S/C23H26IN7O2S/c24-18-15-27-22(30-20(18)25-9-5-10-26-21(32)19-8-4-13-34-19)28-16-6-3-7-17(14-16)29-23(33)31-11-1-2-12-31/h3-4,6-8,13-15H,1-2,5,9-12H2,(H,26,32)(H,29,33)(H2,25,27,28,30). InChi Key: VAVXGGRQQJZYBL-UHFFFAOYSA-N.