WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 206032
CAS#: 1229236-86-5
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).
MedKoo Cat#: 206032
Name: Gandotinib
CAS#: 1229236-86-5
Chemical Formula: C23H25ClFN7O
Exact Mass: 469.17931
Molecular Weight: 469.94
Elemental 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
Appearance: white solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
| Biological target: | Gandotinib (LY2784544) is a potent JAK2 inhibitor with IC50 of 3 nM. Gandotinib (LY2784544) also inhibits FLT3, FLT4, FGFR2, TYK2, and TRKB with IC50 of 4, 25, 32, 44, and 95 nM. |
| In vitro activity: | As JAK2-STAT5 signaling has a role in MPN cell proliferation, LY2784544 was next evaluated in the MTS cell proliferation assay utilizing the same Ba/F3 cells expressing JAK2V617F or IL-3-activated wild-type JAK2. Consistent with findings from the signaling studies, LY2784544 inhibited the proliferation of JAK2V617F-expressing cells (IC50=55 nM) and was markedly less potent as an inhibitor of the proliferation of IL-3-stimulated wild-type JAK2 expressing Ba/F3 cells (IC50=1309 nM) (Table 3). Reference: Blood Cancer J. 2013 Apr 12;3(4):e109. https://pubmed.ncbi.nlm.nih.gov/23584399/ |
| In vivo activity: | Testing of LY2784544 in SCID mice bearing Ba/F3-JAK2V617F-GFP, ascitic tumors demonstrated potent, dose- and exposuredependent inhibition of STAT5 phosphorylation as demonstrated in Figure 4a (FACS histograms and bar graphs) and Figure 4b, respectively. Reference: Blood Cancer J. 2013 Apr 12;3(4):e109. https://pubmed.ncbi.nlm.nih.gov/23584399/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMF | 30.0 | 63.84 | |
| DMSO | 58.0 | 123.42 | |
| DMSO:PBS (pH 7.2) (1:2) | 0.3 | 0.64 | |
| Ethanol | 9.5 | 20.22 |
The following data is based on the product molecular weight 469.94 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. 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(4):e109. doi: 10.1038/bcj.2013.6. PMID: 23584399; PMCID: PMC3641321 |
| In vitro protocol: | 1. 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(4):e109. doi: 10.1038/bcj.2013.6. PMID: 23584399; PMCID: PMC3641321 |
| In vivo protocol: | 1. 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(4):e109. doi: 10.1038/bcj.2013.6. PMID: 23584399; PMCID: PMC3641321 |
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.
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.
