1. JAK/STAT Signaling
    Epigenetics
    Stem Cell/Wnt
    Protein Tyrosine Kinase/RTK
  2. JAK
    FLT3
    FGFR

LY2784544 (Synonyms: gandotinib)

Cat. No.: HY-13034 Purity: 98.44%
Data Sheet SDS Handling Instructions

LY2784544 is a potent JAK2 inhibitor with IC50 of 3 nM. LY2784544 also inhibits FLT3, FLT4, FGFR2, TYK2, and TRKB with IC50 of 4, 25, 32, 44, and 95 nM.

For research use only. We do not sell to patients.
LY2784544 Chemical Structure

LY2784544 Chemical Structure

CAS No. : 1229236-86-5

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Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO $121 In-stock
5 mg $110 In-stock
10 mg $190 In-stock
50 mg $590 In-stock
100 mg $1000 In-stock
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  • Biological Activity

  • Protocol

  • Technical Information

  • Purity & Documentation

  • References

Description

LY2784544 is a potent JAK2 inhibitor with IC50 of 3 nM. LY2784544 also inhibits FLT3, FLT4, FGFR2, TYK2, and TRKB with IC50 of 4, 25, 32, 44, and 95 nM.

IC50 & Target

IC50: 2.52±0.49 nM (JAK2), 19.8±3 nM (JAK1), 48±14.9 nM (JAK3), 4 nM (FLT3), 32 nM (FGFR2)[1]

In Vitro

LY2784544, a potent, selective and ATP-competitive inhibitor of janus kinase 2 (JAK2) tyrosine kinase. LY2784544 effectively inhibits JAK2V617F-driven signaling and cell proliferation in Ba/F3 cells (IC50=20 and 55 nM, respectively). In comparison, LY2784544 is much less potent at inhibiting interleukin-3-stimulated wild-type JAK2-mediated signaling and cell proliferation (IC50=1183 and 1309 nM, respectively). LY2784544 potently inhibits the JAK2V617F signaling (IC50=20 nM) but, remarkably, shows very minimal activity against the IL-3-activated wild-type JAK2 signaling with an IC50 of 1183 nM. LY2784544 inhibits the proliferation of JAK2V617F-expressing cells (IC50=55 nM) and is markedly less potent as an inhibitor of the proliferation of IL-3-stimulated wild-type JAK2 expressing Ba/F3 cells (IC50=1309 nM). LY2784544 is potent in the cell-based TF-1 JAK2 assay (IC50=45 nM) and had the desired threshold selectivity in the NK-92 JAK3/JAK1 heterodimer assay (942 nM)[1].

In Vivo

LY2784544 effectively inhibits STAT5 phosphorylation in Ba/F3-JAK2V617F-GFP (green fluorescent protein) ascitic tumor cells (TED50=12.7 mg/kg) and significantly reduces (P<0.05) Ba/F3-JAK2V617F-GFP tumor burden in the JAK2V617F-induced MPN model (TED50=13.7 mg/kg, twice daily)[1].

Clinical Trial
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References
Preparing Stock Solutions
Concentration Volume Mass 1 mg 5 mg 10 mg
1 mM 2.1279 mL 10.6397 mL 21.2793 mL
5 mM 0.4256 mL 2.1279 mL 4.2559 mL
10 mM 0.2128 mL 1.0640 mL 2.1279 mL
Please refer to the solubility information to select the appropriate solvent.
Cell Assay
[1]

LY2784544 is dissolved in DMSO and stored, and then diluted with appropriate medium before use[1].

Ba/F3 cells expressing JAK2V617F are placed in RPMI-1640-containing vehicle (DMSO) or LY2784544 (concentration range, 0.001-20 μM) (1×104 cells/96-well). Ba/F3 cells expressing wild-type JAK2 are treated similarly except IL-3 (2 ng/mL) is added. After a 72-hour incubation, cell proliferation is assessed by adding Cell Titer 96 Aqueous One Solution Reagent (20 μL/well). The IC50 for inhibition of cell proliferation is calculated using the GraphPad Prism 4 software[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[1]

LY2784544 is dissolved in DMSO and diluted with PBS or saline[1].

Mice[1]
Dose- and time-dependent in vivo inhibition of JAK2V617F signaling is assessed by measuring inhibition of STAT5 phosphorylation in a mouse ascitic tumor model. Ba/F3-JAK2V617F-GFP cells (1×107) are implanted in the intraperitoneal cavity of severe combined immunodeficiency mice and allowed to develop into ascitic tumors for 7 days. For dose-response studies (six animals/group), LY2784544 is administered once by oral gavage (2.5, 5, 10, 20, 40, or 80 mg/kg), then 30 min later, ascitic tumor cells are collected, fixed, incubated for 2 h with Mouse-anti-pSTAT5 (pY694) Alexa Fluor 647 (1:10 dilution), and analyzed by flow cytometry. Time course studies are performed similarly, except the animals are treated with LY2784544 at 20, 40 or 80 mg/kg and ascitic tumor cells collected at prespecified intervals of 0.25-6 h after dosing. Data are analyzed by the one-way analysis of variance, and Dunnett's test (α=0.05). Dose response data are analyzed with a four-parameter logistic curve-fitting program. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
Molecular Weight

469.94

Formula

C₂₃H₂₅ClFN₇O

CAS No.

1229236-86-5

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

10 mM in DMSO

* "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

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LY2784544
Cat. No.:
HY-13034
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