PLX5622 (hemifumarate)

PLX5622 is a brain-penetrant inhibitor of the colony stimulating factor 1 receptor (CSF1R, IC50 = 0.016 µM). It is selective for CSF1R over FMS-related tyrosine kinase 3 (FLT3), Kit, Aurora C, and VEGFR2 (IC50s = 0.39, 0.86, 1, and 1.1 µM, respectively) and is greater than 100-fold selective for CSF1R over a panel of 230 kinases. PLX5622 (65 mg/kg) reduces the number of Iba-1+ cells, a marker of reduced microglia activation, in the dorsal horn of the spinal cord in a mouse model of neuropathic pain induced by partial ligation of the sciatic nerve. It also decreases macrophage levels of TNF-alpha and IL-1beta and infiltration into the sciatic nerve, as well as alleviates mechanical and cold allodynia in the same model. Dietary administration of PLX5622 (1,200 ppm in chow) decreases the number of hippocampal microglia by 90%, as well as reduces the number and volume of retrosplenial and somatosensory cortical amyloid-beta (Abeta) plaques in the 5XFAD transgenic mouse model of Alzheimer's disease.Formal Name: 6-fluoro-N-((5-fluoro-2-methoxypyridin-3-yl)methyl)-5-((5-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)methyl)pyridin-2-amine, hemifumarate. Molecular Formula: C21H19F2N5O . 1/2C4H4O4. Formula Weight: 485.4. Purity: >98%. Formulation: (Request formulation change), A solid. Solubility: DMF: 20 mg/mL, DMSO: 16 mg/mL, Ethanol: Slightly soluble, PBS (pH 7.2): 0.3 mg/mL. lambdamax: 218, 229, 292 nm. SMILES: CC1=CN=C(NC=C2CC3=CC=C(NCC4=C(OC)N=CC(F)=C4)N=C3F)C2=C1.OC(/C=C/C(O)=O)=O.CC5=CN=C(NC=C6CC7=CC=C(NCC8=C(OC)N=CC(F)=C8)N=C7F)C6=C5. InChi Code: InChI=1S/2C21H19F2N5O.C4H4O4/c2*1-12-5-17-14(9-26-20(17)25-8-12)6-13-3-4-18(28-19(13)23)24-10-15-7-16(22)11-27-21(15)29-2,5-3(6)1-2-4(7)8/h2*3-5,7-9,11H,6,10H2,1-2H3,(H,24,28)(H,25,26),1-2H,(H,5,6)(H,7,8)/b,,2-1+. InChi Key: FMEISBYRQFIJPD-WXXKFALUSA-N.