Synonym: LY2784544; LY 2784544; LY-2784544; Gandotinib.

IUPAC/Chemical Name: 3-(4-chloro-2-fluorobenzyl)-2-methyl-N-(3-methyl-1H-pyrazol-5-yl)-8-(morpholinomethyl)imidazo[1,2-b]pyridazin-6-amine

InChi Key: SQSZANZGUXWJEA-UHFFFAOYSA-N

InChi Code: InChI=1S/C23H25ClFN7O/c1-14-9-21(29-28-14)27-22-11-17(13-31-5-7-33-8-6-31)23-26-15(2)20(32(23)30-22)10-16-3-4-18(24)12-19(16)25/h4-4,9,11-12H,5-8,10,13H2,1-2H3,(H2,27,28,29,30)

SMILES Code: CC1=NNC(NC2=NN3C(C(CN4CCOCC4)=C2)=NC(C)=C3CC5=CC=C(Cl)C=C5F)=C1

Technical Data

Additional Information

   LY2784544 has potential for development as a targeted agent against JAK2V617F and may have properties that allow suppression of JAK2V617F-induced MPN pathogenesis while minimizing effects on hematopoietic progenitor cells. LY2784544 is currently under clinical trials for participants with myeloproliferative neoplasms.
 
 

References

1: Rosenthal A, Mesa RA. Janus kinase inhibitors for the treatment of myeloproliferative neoplasms. Expert Opin Pharmacother. 2014 Jun;15(9):1265-76. doi: 10.1517/14656566.2014.913024. Epub 2014 Apr 25. PubMed PMID: 24766055.

2: Furqan M, Mukhi N, Lee B, Liu D. Dysregulation of JAK-STAT pathway in hematological malignancies and JAK inhibitors for clinical application. Biomark Res. 2013 Jan 16;1(1):5. doi: 10.1186/2050-7771-1-5. PubMed PMID: 24252238; PubMed Central PMCID: PMC3776247.

3: Ma L, Clayton JR, Walgren RA, Zhao B, Evans RJ, Smith MC, Heinz-Taheny KM, Kreklau EL, Bloem L, Pitou C, Shen W, Strelow JM, Halstead C, Rempala ME, Parthasarathy S, Gillig JR, Heinz LJ, Pei H, Wang Y, Stancato LF, Dowless MS, Iversen PW, Burkholder TP. Discovery and characterization of LY2784544, a small-molecule tyrosine kinase inhibitor of JAK2V617F. Blood Cancer J. 2013 Apr 12;3:e109. doi: 10.1038/bcj.2013.6. PubMed PMID: 23584399; PubMed Central PMCID: PMC3641321.

4: Tam CS, Verstovsek S. Investigational Janus kinase inhibitors. Expert Opin Investig Drugs. 2013 Jun;22(6):687-99. doi: 10.1517/13543784.2013.774373. Epub 2013 Feb 23. Review. PubMed PMID: 23432430.

5: Treliński J, Robak T. JAK inhibitors: pharmacology and clinical activity in chronic myeloprolipherative neoplasms. Curr Med Chem. 2013;20(9):1147-61. PubMed PMID: 23317159.

6: Santos FP, Verstovsek S. JAK2 inhibitors for myelofibrosis: why are they effective in patients with and without JAK2V617F mutation? Anticancer Agents Med Chem. 2012 Nov;12(9):1098-109. Review. PubMed PMID: 22583424.

7: Passamonti F, Maffioli M, Caramazza D. New generation small-molecule inhibitors in myeloproliferative neoplasms. Curr Opin Hematol. 2012 Mar;19(2):117-23. doi: 10.1097/MOH.0b013e32834ff575. Review. PubMed PMID: 22227528.