Gandotinib (LY2784544)

Catalog No.S2179 Batch:S217903

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Technical Data

Formula

C23H25ClFN7O
Molecular Weight 469.94 CAS No. 1229236-86-5
Solubility (25°C)* In vitro DMSO 94 mg/mL (200.02 mM)
Ethanol 9 mg/mL (19.15 mM)
Water Insoluble
In vivo (Add solvents to the product individually and in order)
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description Gandotinib (LY2784544) is a potent JAK2 inhibitor with IC50 of 3 nM. This compound is effective in JAK2V617F, 8- and 20-fold selective versus JAK1 and JAK3. Phase 2.
Targets
JAK2 (V617F) [1] JAK2 [1] JAK2 [1]
(Cell-free assay)		 FLT3 [2] JAK1 [2] View More
0.245 nM(Ki) 0.288 nM(Ki) 3 nM 4 nM 19.8 nM
In vitro Gandotinib (LY2784544) inhibits IL-3-activated wild type JAK2 with an IC50 of 2.26 μM. Similarly, in the proliferation assay, it shows antiproliferation activity in JAK2 V617F-driven cells with an IC50 of 68 nM, compared to 1.36 μM in wild type JAK2-driven cells and 0.94 μM in JAK3-driven cells. Though biochemical assays do not reveal selectivity of this compound for mutant JAK2V617F, it shows higher selectivity for inhibition of JAK2-mediated signaling and induction of apoptosis in Ba/F3 cells expressing JAK2V617F than wild-type cells.
In vivo Gandotinib (LY2784544) significantly inhibits STAT5 phosphorylation in Ba/F3-JAK2 V617F-GFP xenografts with a Threshold Effective Dose 50 (TED50) of 12.7 mg/kg. It also reduces Ba/F3-JAK2 V617F-GFP tumor burden in the JAK2 V617F-induced MPN model with a TED50 of 13.7 mg/kg after oral treatment. This compound has no effect on CD71/Ter119 positive erythroid progenitors in spleens of SCID mice after oral treatment.

Protocol (from reference)

References

  • https://ash.confex.com/ash/2010/webprogram/Paper26828.html
  • https://pubmed.ncbi.nlm.nih.gov/23584399/

Customer Product Validation

<p>HEL cells were treated for 3 hours with the indicated concentrations of LY2784544. LY2784544 inhibits Jak2-V617F mediated signal transduction at submicromolar concentrations in  intact cells.</p><div><div> </div></div><p> </p>

, , M.Sc. Karoline Gaebler and Dr. Claude Haan of Université du Luxembour

Relative expression of BCLXL, c-MYC, CCND1, MMP2 and VEGF in (A) HL60 cell line. Cells were treated with 1 µM of ruxolitinib, fedratinib, gandotinib or tofacitinib for 6 h. RE=1 for DMSO control. Asterix (*) denotes statistical significance (p<0.05). Error bars denotes±standard deviation. Each relative expression value was obtained from at least two biological experiments run in two technical repeats.

Data from [ , , Eur J Pharmacol, 2015, 765:188-97. ]

(F) SGC-7901 cells were treated with JAK2 specific inhibitor of LY2784544 (5 nM) for 1 h, and then p-JAK2 expressions were measured using western blot analysis. SGC-7901 cells were pretreated with LY2784544 (5 nM) for 1 h, followed by APG (50 mM) incubation for another 24 h. Following, (G) The cell viability and (H) apoptosis were calculated. ***P < 0.001 versus the Con group. ###P < 0.001 versus the IL-6 group; þþþP < 0.001 versus the IL-6/APG group. Data are represented as mean ± SEM (n = 8).

Data from [ , , Biochem Biophys Res Commun, 2018, 498(1):164-170 ]

Selleck's Gandotinib (LY2784544) Has Been Cited by 23 Publications

A panel of janus kinase inhibitors identified with anti-inflammatory effects protect mice from lethal influenza virus infection [ Antimicrob Agents Chemother, 2024, 68(4):e0135023.] PubMed: 38470034
Modulation of the JAK2-STAT3 pathway promotes expansion and maturation of human iPSCs-derived myogenic progenitor cells [ bioRxiv, 2024, 2024.12.09.624203] PubMed: 39713478
A screen of repurposed drugs identifies AMHR2/MISR2 agonists as potential contraceptives [ Proc Natl Acad Sci U S A, 2022, 119(15):e2122512119] PubMed: 35380904
IRF7 expression correlates with HIV latency reversal upon specific blockade of immune activation [ Front Immunol, 2022, 13:1001068] PubMed: 36131914
Establishment and characterization of immortalized sweat gland myoepithelial cells [ Sci Rep, 2022, 12(1):7] PubMed: 34997030
Phenotypic Screening for Small Molecules that Protect β-Cells from Glucolipotoxicity [ ACS Chem Biol, 2022, 10.1021/acschembio.2c00052] PubMed: 35439415
α7-Acetylcholine Receptor Signaling Reduces Neuroinflammation After Subarachnoid Hemorrhage in Mice [ Neurotherapeutics, 2021, 10.1007/s13311-021-01052-3] PubMed: 33970466
JAK2 Inhibition by Fedratinib Reduces Osteoblast Differentiation and Mineralisation of Human Mesenchymal Stem Cells [ Molecules, 2021, 26(3)606] PubMed: 33503825
Dnmt3a is downregulated by Stat5a and mediates G0/G1 arrest by suppressing the miR-17-5p/Cdkn1a axis in Jak2V617F cells [ BMC Cancer, 2021, 21(1):1213] PubMed: 34773997
A novel human colon signet-ring cell carcinoma organoid line: establishment, characterization and application [ Carcinogenesis, 2020, 41(7):993-1004] PubMed: 31740922

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SHIPPING AND STORAGE
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