XL019

• CAT Number: I005630
• CAS Number: 945755-56-6
• Molecular Formula: C₂₅H₂₈N₆O₂
• Molecular Weight: 444.53
• Purity: ≥95%
• Target: JAK
• Solubility: in DMSO > 10 mM
• Storage: Store at -20°C
• IC50: 2.2 nM (JAK2); 214.2 nM (JAK3) [1]
• IUPAC Name: (2S)-N-[4-[2-(4-morpholin-4-ylanilino)pyrimidin-4-yl]phenyl]pyrrolidine-2-carboxamide
• InChI: InChI=1S/C25H28N6O2/c32-24(23-2-1-12-26-23)28-19-5-3-18(4-6-19)22-11-13-27-25(30-22)29-20-7-9-21(10-8-20)31-14-16-33-17-15-31/h3-11,13,23,26H,1-2,12,14-17H2,(H,28,32)(H,27,29,30)/t23-/m0/s1
• InChIKey: ISOCDPQFIXDIMS-QHCPKHFHSA-N
• SMILES: C1CC(NC1)C(=O)NC2=CC=C(C=C2)C3=NC(=NC=C3)NC4=CC=C(C=C4)N5CCOCC5

XL019 (Cat.No:I005630) is a potent and selective JAK2 inhibitor with IC50 of 2.2 nM, 100 fold selectivity over JAK1; shows good biochemical and cellular potency against JAK2 with good selectivity against the Janus Kinase family as well as a broad kinase panel.

Reference

1:Leuk Res. 2014 Mar;38(3):316-22. doi: 10.1016/j.leukres.2013.12.006. Epub 2013 Dec 11. Phase I evaluation of XL019, an oral, potent, and selective JAK2 inhibitor.Verstovsek S,Tam CS,Wadleigh M,Sokol L,Smith CC,Bui LA,Song C,Clary DO,Olszynski P,Cortes J,Kantarjian H,Shah NP, PMID: 24374145 PMCID: PMC4414320 DOI: 10.1016/j.leukres.2013.12.006 Abstract: This phase I study evaluated selective JAK2 inhibitor XL019 in 30 patients with myelofibrosis. The initial dose cohorts were 100, 200, and 300 mg orally on days 1-21 of a 28-day cycle. Central and/or peripheral neurotoxicity developed in all patients. Subsequently, patients were treated on lower doses; neurotoxicity was again observed, leading to study termination. Peripheral neuropathy resolved in 50%, and central neurotoxicity in all patients within months after therapy cessation. Myelosuppression was minimal. The terminal half-life of XL019 was approximately 21 h, with steady state reached by Day 8. International Working Group defined responses were seen in three (10%) patients.Copyright © 2013 Elsevier Ltd. All rights reserved.