PLX-647

PLX-647 is PLX647 is a potent inhibitors of both FMS and KIT that show strong selectivity compared with other kinases. In the in vitro enzymatic assay, PLX647 inhibits FMS with IC50 = 0.028μM and KIT with IC50 = 0.016 μM. PLX647 represents a unique class of kinase inhibitors with unique dual FMS and KIT specificity.

Product information

CAS Number: 873786-09-5

Molecular Weight: 382.38

Formula: C21H17F3N4

Synonym:

PLX647

PLX 647

PLX-647

Chemical Name: 5-((1H-pyrrolo[2,3-b]pyridin-3-yl)methyl)-N-(4-(trifluoromethyl)benzyl)pyridin-2-amine

Smiles: FC(F)(F)C1=CC=C(CNC2=CC=C(CC3=CNC4=NC=CC=C34)C=N2)C=C1

InChiKey: NODCQQSEMCESEC-UHFFFAOYSA-N

InChi: InChI=1S/C21H17F3N4/c22-21(23,24)17-6-3-14(4-7-17)11-26-19-8-5-15(12-27-19)10-16-13-28-20-18(16)2-1-9-25-20/h1-9,12-13H,10-11H2,(H,25,28)(H,26,27)

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO, not in water

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

In vitro, PLX647 potently inhibits proliferation of BCR-FMS cells, with an IC50 of 92 nM. A corresponding Ba/F3 cell line expressing BCR-KIT is also quite sensitive to PLX647, with an IC50 of 180 nM. PLX647 also inhibits endogenous FMS and KIT, as demonstrated by inhibition of the ligand-dependent cell lines M-NFS-60 (IC50=380 nM) and M-07e (IC50=230 nM), which express FMS and KIT, respectively. PLX647 potently inhibits the growth of FLT3–ITD-expressing MV4-11 cells (IC50=110 nM). PLX647 displayed minimal inhibition of the proliferation of Ba/F3 cells expressing BCR–KDR (IC50=5 μM). PLX647 inhibits osteoclast differentiation with an IC50 of 0.17 μM.

In Vivo:

PLX647 (40 mg/kg; p.o.; twice daily for 7 days) reduces macrophage accumulation in UUO kidney and blood monocytes. PLX647 (40 mg/kg; p.o.; male Swiss Webster mice) reduces LPS-induced TNF-α and IL-6 release. PLX647 (20-80 mg/kg; p.o.; daily or twice daily from 27-41 days) shows effects on collagen-induced arthritis. PLX647 (30 mg/kg) results in significant inhibition of TRAP5b immunostaining and bone osteolysis. PLX647 (30 mg/kg BID) is able to prevent bone damage by the tumor cells.

References:

1. Zhang C, Ibrahim PN, Zhang J, Burton EA, Habets G, Zhang Y, Powell B, West BL, Matusow B, Tsang G, Shellooe R, Carias H, Nguyen H, Marimuthu A, Zhang KY, Oh A, Bremer R, Hurt CR, Artis DR, Wu G, Nespi M, Spevak W, Lin P, Nolop K, Hirth P, Tesch GH, Bollag G. Design and pharmacology of a highly specific dual FMS and KIT kinase inhibitor. Proc Natl Acad Sci U S A. 2013 Apr 2;110(14):5689-94. doi: 10.1073/pnas.1219457110. Epub 2013 Mar 14. PubMed PMID: 23493555; PubMed Central PMCID: PMC3619323.
2. Louvet C, Szot GL, Lang J, Lee MR, Martinier N, Bollag G, Zhu S, Weiss A, Bluestone JA. Tyrosine kinase inhibitors reverse type 1 diabetes in nonobese diabetic mice. Proc Natl Acad Sci U S A. 2008 Dec 2;105(48):18895-900. doi: 10.1073/pnas.0810246105. Epub 2008 Nov 17. PubMed PMID: 19015530; PubMed Central PMCID: PMC2596241.

Products are for research use only. Not for human use.