Gandotinib

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WARNING: This product is for research use only, not for human or veterinary use.

Description:Gandotinib, also known as LY2784544, is a potent and selective JAK inhibitor. LY2784544 in vitro selectivity for JAK2 was found to be equal or superior to known JAK2 inhibitors. LY2784544 effectively inhibited JAK2V617F-driven signaling and cell proliferation in Ba/F3 cells (IC50=20 and 55 nM, respectively). In vivo, LY2784544 effectively inhibited STAT5 phosphorylation in Ba/F3-JAK2V617F-GFP ascitic tumor cells (TED50=12.7 mg/kg) and significantly reduced (P<0.05) Ba/F3-JAK2V617F-GFP tumor burden in the JAK2V617F-induced MPN model (TED50=13.7 mg/kg, twice daily).

Price and Availability

Gandotinib (LY2784544), purity > 98%, is in stock. Current shipping out time is about 2 weeks after order is received. CoA, QC data and MSDS documents are available in one week after order is received.

Chemical Structure

Theoretical Analysis

MedKoo Cat#: 206032Name: GandotinibCAS#: 1229236-86-5Chemical Formula: C23H25ClFN7OExact Mass: 469.17931Molecular Weight: 469.94Elemental Analysis: C, 58.78; H, 5.36; Cl, 7.54; F, 4.04; N, 20.86; O, 3.40

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/h3-4,9,11-12H,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 forthe treatment of myeloproliferative neoplasms. Expert Opin Pharmacother.2014 Jun;15(9):1265-76. doi: 10.1517/14656566.2014.913024. Epub 2014 Apr25. PubMed PMID: 24766055.

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

3: Ma L, Clayton JR, Walgren RA, Zhao B, Evans RJ, Smith MC, Heinz-TahenyKM, 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 andcharacterization of LY2784544, a small-molecule tyrosine kinaseinhibitor 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. ExpertOpin 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 clinicalactivity 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 arethey effective in patients with and without JAK2V617F mutation?Anticancer Agents Med Chem. 2012 Nov;12(9):1098-109. Review. PubMedPMID: 22583424.

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