Momelotinib free base

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Description:Momelotinib, also known as CYT387, is an inhibitor of Janus kinases JAK1 and JAK2, acting as an ATP competitor with IC50 values of 11 and 18 nM, respectively. The inhibitor is significantly less active towards other kinases, including JAK3 (IC50 = 0.16 μM). As of 2011, CYT387 is being developed as a drug for myelofibrosis and currently undergoes Phase I/II clinical trials. Additional potential treatment indications for CYT387 include other myeloproliferative neoplasms, cancer (solid and liquid tumors) and inflammatory conditions.

Price and Availability

Momelotinib free base,purity > 98%, is in stock. The same day shipping out after order is received.

Chemical Structure

Theoretical Analysis

MedKoo Cat#: 200786Name: Momelotinib free baseCAS#: 1056634-68-4 (free base)Chemical Formula: C23H22N6O2Exact Mass: 414.18042Molecular Weight: 414.46Elemental Analysis:C, 66.65; H, 5.35; N, 20.28; O, 7.72

Related CAS #:1056634-68-4 (free base)1380317-28-1 (HCl)

Synonym:CTY387; CYT-387; CYT 387; CYT11387; CYT-11387; CYT 11387; Momelotinib; Momelotinib free base

IUPAC/Chemical Name:N-(cyanomethyl)-4-(2-((4-morpholinophenyl)amino)pyrimidin-4-yl)benzamide.

InChi Key:ZVHNDZWQTBEVRY-UHFFFAOYSA-N

InChi Code:InChI=1S/C23H22N6O2/c24-10-12-25-22(30)18-3-1-17(2-4-18)21-9-11-26-23(28-21)27-19-5-7-20(8-6-19)29-13-15-31-16-14-29/h1-9,11H,12-16H2,(H,25,30)(H,26,27,28)

SMILES Code:O=C(NCC#N)C1=CC=C(C2=NC(NC3=CC=C(N4CCOCC4)C=C3)=NC=C2)C=C1

Technical Data

Additional Information

CYT387 is an ATP-competitive small molecule that potently inhibits JAK1/JAK2 kinases (IC(50)=11 and 18 nM, respectively), with significantly less activity against other kinases, including JAK3 (IC(50)=155 nM). CYT387 inhibits growth of Ba/F3-JAK2V617F and human erythroleukemia (HEL) cells (IC(50) approximately 1500 nM) or Ba/F3-MPLW515L cells (IC(50)=200 nM), but has considerably less activity against BCR-ABL harboring K562 cells (IC=58 000 nM). Cell lines harboring mutated JAK2 alleles (CHRF-288-11 or Ba/F3-TEL-JAK2) were inhibited more potently than the corresponding pair harboring mutated JAK3 alleles (CMK or Ba/F3-TEL-JAK3), and STAT-5 phosphorylation was inhibited in HEL cells with an IC(50)=400 nM. Furthermore, CYT387 selectively suppressed the in vitro growth of erythroid colonies harboring JAK2V617F from polycythemia vera (PV) patients, an effect that was attenuated by exogenous erythropoietin. Overall, research data indicate that the JAK1/JAK2 selective inhibitor CYT387 has potential for efficacious treatment of MPN harboring mutated JAK2 and MPL alleles. [source: Pardanani A, Lasho T, Smith G, Burns CJ, Fantino E, Tefferi A. CYT387, a selective JAK1/JAK2 inhibitor: in vitro assessment of kinase selectivity and preclinical studies using cell lines and primary cells from polycythemia vera patients. Leukemia. 2009 Aug;23(8):1441-5. Epub 2009 Mar 19. or http://www.ncbi.nlm.nih.gov/pubmed/19295546]  

References

1: Durmus S, Xu N, Sparidans RW, Wagenaar E, BeijnenJH, Schinkel AH. P-glycoprotein (MDR1/ABCB1) and breast cancerresistance protein (BCRP/ABCG2) restrict brain accumulation of theJAK1/2 inhibitor, CYT387. Pharmacol Res. 2013 Oct;76:9-16. doi:10.1016/j.phrs.2013.06.009. Epub 2013 Jul 1. PubMed PMID: 23827160.

2: Pardanani A, Laborde RR, Lasho TL, Finke C, Begna K, Al-Kali A, HoganWJ, Litzow MR, Leontovich A, Kowalski M, Tefferi A. Safety and efficacyof CYT387, a JAK1 and JAK2 inhibitor, in myelofibrosis. Leukemia. 2013Jun;27(6):1322-7. doi: 10.1038/leu.2013.71. Epub 2013 Mar 5. PubMedPMID: 23459451; PubMed Central PMCID: PMC3677140.

3: Sparidans RW, Durmus S, Xu N, Schinkel AH, Schellens JH, Beijnen JH.Liquid chromatography-tandem mass spectrometric assay for the JAK2inhibitor CYT387 in plasma. J Chromatogr B Analyt Technol Biomed LifeSci. 2012 May 1;895-896:174-7. doi: 10.1016/j.jchromb.2012.03.021. Epub2012 Mar 23. PubMed PMID: 22476054.

4: Monaghan KA, Khong T, Burns CJ, Spencer A. The novel JAK inhibitorCYT387 suppresses multiple signalling pathways, prevents proliferationand induces apoptosis in phenotypically diverse myeloma cells. Leukemia.2011 Dec;25(12):1891-9. doi: 10.1038/leu.2011.175. Epub 2011 Jul 26.PubMed PMID: 21788946.

5: Tyner JW, Bumm TG, Deininger J, Wood L, Aichberger KJ, Loriaux MM,Druker BJ, Burns CJ, Fantino E, Deininger MW. CYT387, a novel JAK2inhibitor, induces hematologic responses and normalizes inflammatorycytokines in murine myeloproliferative neoplasms. Blood. 2010 Jun24;115(25):5232-40. doi: 10.1182/blood-2009-05-223727. Epub 2010 Apr 12.PubMed PMID: 20385788; PubMed Central PMCID: PMC2892953.

6: Pardanani A, Lasho T, Smith G, Burns CJ, Fantino E, Tefferi A.CYT387, a selective JAK1/JAK2 inhibitor: in vitro assessment of kinaseselectivity and preclinical studies using cell lines and primary cellsfrom polycythemia vera patients. Leukemia. 2009 Aug;23(8):1441-5. doi:10.1038/leu.2009.50. Epub 2009 Mar 19. PubMed PMID: 19295546.