| Identification | Back Directory | [Name]
LY 2784544 | [CAS]
1229236-86-5 | [Synonyms]
CS-13
LY2874544
Tucatinib
LY 2784544
LY2784544/LY-2784544
LY2784544(gandotinib)
Gandotinib (LY2784544)
3-(4-Chloro-2-fluorobenzyl)-2-methyl-N-(5-methyl-1H-pyrazol-3-yl)-8-(morpholinomethyl)imidazo[
3-(4-chloro-2-fluorobenzyl)-2-methyl-N-(5-methyl-1H-pyrazol-3-yl)-8-(morpholinomethyl)imidazo[1,2-b]pyridazin-6-amine
3-(4-chloro-2-fluorobenzyl)-2-Methyl-N-(3-Methyl-1H-pyrazol-5-yl)-8-(MorpholinoMethyl)iMidazo[1,2-b]pyridazin-6-aMine
3-[(4-Chloro-2-fluorophenyl)methyl]-2-methyl-N-(5-methyl-1H-pyrazol-3-yl)-8-(4-morpholinylmethyl)imidazo[1,2-b]pyridazin-6-amine
IMidazo[1,2-b]pyridazin-6-aMine, 3-[(4-chloro-2-fluorophenyl)Methyl]-2-Methyl-N-(5-Methyl-1H-pyrazol-3-yl)-8-(4-MorpholinylMethyl)-
3-[(4-Chloro-2-fluorophenyl)methyl]-2-methyl-N-(5-methyl-1H-pyrazol-3-yl)-8-(4-morpholinylmethyl)imidazo[1,2-b]pyridazin-6-amine LY 2784544 | [Molecular Formula]
C23H25ClFN7O | [MDL Number]
MFCD20482143 | [MOL File]
1229236-86-5.mol | [Molecular Weight]
469.94 |
| Chemical Properties | Back Directory | [density ]
1.45 | [storage temp. ]
Store at -20°C | [solubility ]
≥23.5 mg/mL in DMSO; insoluble in H2O; ≥5.65 mg/mL in EtOH with gentle warming and ultrasonic | [form ]
solid | [pka]
14.12±0.10(Predicted) | [color ]
Light yellow to yellow | [InChIKey]
SQSZANZGUXWJEA-UHFFFAOYSA-N | [SMILES]
C12=NC(C)=C(CC3=CC=C(Cl)C=C3F)N1N=C(NC1C=C(C)NN=1)C=C2CN1CCOCC1 |
| Hazard Information | Back Directory | [Uses]
LY2784544 is a JAK2 inhibitor. LY2784544 may be used as a potential treatment for patients with myeloproliferative neoplasm. | [Definition]
ChEBI: Gandotinib is a member of pyridazines. | [Biological Activity]
LY2784544 is an orally activeATP-competitivepotent and JAK2-selective janus tyrosine kinase inhibitor (IC50/[ATP] = 2.52 nM/5 μM/JAK219.8 nM/20 μM/JAK148.0 nM/2 μM/JAK3) with little activity toward 79 other kinases. LY2784544 selectively inhibits signaling/proliferation driven by oncogenic JAK2V617F (IC50 = 20/55 nM) over those mediated by wt JAK2 upon IL-3 induction (IC50 = 1183/1309 nM) in Ba/F3 cultures and displays in vivo efficacious in a JAK2V617F-induced murine MPN model (10-80 mg/kg bid po.). LY2784544 is also reported to display Zn-dependent (optimal [Zn+2] = 100 μM) GPR39 agonist activitybut not 11 other GPRs. | [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)[1]. | [target]
wild-type JAK2 | [IC 50]
JAK2: 3 nM (IC50); Tyk2: 44 nM (IC50); JAK3: 48 nM (IC50); FGFR2: 32 nM (IC50); FGFR3: 106 nM (IC50); Flt-4: 25 nM (IC50); KDR: 109 nM (IC50); FLT3: 4 nM (IC50); TRKB: 95 nM (IC50); ALK: 138 nM (IC50); MUSK: 147 nM (IC50); AURKA: 168 nM (IC50); MAP3K9: 299 nM (IC50) |
|
|