LY2784544

SKU: orb1226732

Description

LY2784544 (Gandotinib) is a potent, selective and ATP-competitive inhibitor of JAK2V617F, effectively inhibits JAK2V617F-driven signaling and cell proliferation in Ba/F3 cells (IC50=20 and 55 nM, respectively); inhibits JAK2 and JAK3 in biochemical assays with IC50 of 3 nM and 48 nM, respectively; LY2784544 is much less potent at inhibiting IL-3-stimulated wild-type JAK2-mediated signaling and cell proliferation (IC50=1183 and 1309 nM, respectively); effectively inhibits STAT5 phosphorylation in Ba/F3-JAK2V617F-GFP ascitic tumor cells (TED50=12.7 mg/kg) and significantly reduces Ba/F3-JAK2V617F-GFP tumor burden in the JAK2V617F-induced MPN model; also is a potent GPR39 agonist with pEC50 of 9.36 (at 316 uM ZnCl2).Blood Cancer Phase 2 Clinical(In Vitro):Gandotinib (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, Gandotinib (LY2784544) is much less potent at inhibiting interleukin-3-stimulated wild-type JAK2-mediated signaling and cell proliferation (IC50=1183 and 1309 nM, respectively). Gandotinib (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). Gandotinib (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).\n(In Vivo):Gandotinib (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).

Key Properties

• CAS Number: 1229236-86-5
• MW: 469.9423
• Purity: >98% (HPLC)
• Formula: C₂₃H₂₅ClFN₇O
• SMILES: CC1=NNC(NC2=NN3C(C(CN4CCOCC4)=C2)=NC(C)=C3CC5=CC=C(Cl)C=C5F)=C1
• Target: JAK
• Solubility: 10 mM in DMSO

Bioactivity

• In Vivo:
  Gandotinib (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).
• In Vitro:
  Gandotinib (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, Gandotinib (LY2784544) is much less potent at inhibiting interleukin-3-stimulated wild-type JAK2-mediated signaling and cell proliferation (IC50 = 1183 and 1309 nM, respectively). Gandotinib (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). Gandotinib (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).

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

LY 2784544 | LY-2784544 | Gandotinib

Quick Database Links

Gene Symbol

JAK