PLX647 dihydrochloride

PLX647 dihydrochloride is an orally active, highly specific dual FMS and KIT kinase inhibitor, with IC50s of 28 and 16 nM, reapectively. PLX647 dihydrochloride shows selectivity for FMS and KIT over a panel of 400 kinases at a concentration of 1 μM except FLT3 and KDR (IC50s=91 and 130 nM, respectively).

Product information

CAS Number: 1779796-38-1

Molecular Weight: 455.30

Formula: C21H19Cl2F3N4

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

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

InChiKey: MVMKWLRKACAUTB-UHFFFAOYSA-N

InChi: InChI=1S/C21H17F3N4.2ClH/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);2*1H

Technical Data

Appearance: Solid Power

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

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 dihydrochloride 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 dihydrochloride, with an IC50 of 180 nM. PLX647 dihydrochloride 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 dihydrochloride potently inhibits the growth of FLT3-ITD-expressing MV4-11 cells (IC50=110 nM). PLX647 dihydrochloride displays minimal inhibition of the proliferation of Ba/F3 cells expressing BCR-KDR (IC50=5 μM). PLX647 dihydrochloride inhibits osteoclast differentiation with an IC50 of 0.17 μM.

In Vivo:

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

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