Synonym
LY2784544; LY 2784544; LY-2784544; Gandotinib; Gandotinibum
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
More Info
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.
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 |
mg/mL |
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 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
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.
