| Identification | Back Directory | [Name]
Debio-1347 | [CAS]
1265229-25-1 | [Synonyms]
FF284
CS-1637
CH5183284
DCH5183284
Debio-1347
Zoligratinib
CH5183284 (FF-284
Debio-1347:CH5183284
CH5183284 (Debio-1347)
CH5183284;CH-5183284;CH 5183284
[5-amino-1-(2-methyl-1H-benzimidazol-5-yl)-1H-pyrazol-4-yl](1H-indol-2-yl)methanone
Methanone, [5-amino-1-(2-methyl-1H-benzimidazol-6-yl)-1H-pyrazol-4-yl]-1H-indol-2-yl-
(5-amino-1-(2-methyl-3H-benzo[d]imidazol-5-yl)-1H-pyrazol-4-yl)(1H-indol-2-yl)methanone
(5-Amino-1-(2-methyl-1H-benzo[d]imidazol-6-yl)-1H-pyrazol-4-yl)(1H-indol-2-yl)methanone
CH-5183284 (5-amino-1-(2-methyl-1H-benzo[d]imidazol-6-yl)-1H-pyrazol-4-yl)(1H-indol-2-yl)methanone | [Molecular Formula]
C20H16N6O | [MDL Number]
MFCD28502053 | [MOL File]
1265229-25-1.mol | [Molecular Weight]
356.38 |
| Chemical Properties | Back Directory | [Boiling point ]
775.5±55.0 °C(Predicted) | [density ]
1.51±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
≥35.6 mg/mL in DMSO; insoluble in EtOH; insoluble in H2O | [form ]
solid | [pka]
10.51±0.10(Predicted) | [color ]
Off-white to yellow | [CAS DataBase Reference]
1265229-25-1 |
| Hazard Information | Back Directory | [Uses]
CH5183284 is an orally available and selective FGFR (fibroblast growth factor receptor) inhibitor acting on FGFR 1, 2, and 3. | [Biological Activity]
ch5183284 (debio-1347) is a selective and novel inhibitor of fgfr with ic50 value of 9.3, 7.6, 22 and 290 nm for fgfr1, fgfr2, fgfr3 and fgfr4, respectively [1].fibroblast growth factor receptors (fgfrs) are tyrosine kinases and receptors for fibroblast growth factors and consist of fgfr1, fgfr2, fgfr3 and fgfr4. in cancer, fgfr is activated by point mutations, gene amplification or chromosomal translocations/rearrangements and is involved in angiogenesis, cell growth, cell migration, invasion and metastasis [1].ch5183284 (debio-1347) is a selective and novel fgfr inhibitor. in a competitive binding assay, ch5183284 (debio-1347) binding with fgfr1, fgfr2, fgfr3, fgfr4 and kdr with kd values of 20, 20, 25, 740 and 960 nm, respectively. in dms114, snu-16 and kms11 cell lines, ch5183284 (debio-1347) (100-300 nm) inhibited autophosphorylation of fgfr1, fgfr2 and fgfr3. in cancer cell lines with the fgfr genetic alterations, ch5183284 (debio-1347) showed antiproliferative activity [1].in xenograft mouse models, ch5183284 (debio-1347) inhibited tumor growth against xenografts with fgfr genetic alterations such as kg1 (leukemia, fgfr1op-fgfr1 fusion), mfe-280 (endometrial cancer, fgfr2 s252w mutation), snu-16 (gastric cancer, fgfr2 amplification), rt112/84 (bladder cancer, fgfr3-tacc3 fusion) and um-uc-14 (bladder cancer, fgfr3 s249c mutation) by 134%, 100%, 147%, 125% and 116%, respectively [1]. | [Synthesis]
The synthesis of Debio-1347 is as follows:
An aqueous solution (1.67 ml) of 4 M sodium hydroxide was added to an ethanol solution (17 ml) of [5-amino-1-(2-methyl-1H-benzimidazol-5-yl)-1H-pyrazol-4-yl]-(1-benzenesulfonyl-1H-indol-2-yl) methanone (87 mg). The resulting mixture was stirred at room temperature for 2 hours. The reaction mixture was poured into water. The resulting solid was collected by filtration, washed with water, and dried to give Debio-1347 (40 mg, 63%).
 | [in vivo]
Zoligratinib treatment shows a dose-dependent tumor regression (tumor growth inhibition (TGI)=106% at 30 mg/kg and 147% at 100 mg/kg) without apparent body weight loss. Zoligratinib treatment also shows significant in vivo efficacy in xenograft mice models with FGFR genetic alterations, such as KG1 (leukemia, FGFR1OP-FGFR1 fusion), MFE280 (endometrial cancer, FGFR2 S252W mutation), UM-UC-14 (bladder cancer, FGFR3 S249C mutation), and RT112/84 (bladder cancer, FGFR3-TACC3 fusion)[1]. | [IC 50]
FGFR1: 9.3 nM (IC50); FGFR2: 7.6 nM (IC50); FGFR3: 22 nM (IC50); FGFR4: 290 nM (IC50) | [storage]
Store at -20°C | [References]
[1]. nakanishi y, akiyama n, tsukaguchi t, et al. the fibroblast growth factor receptor genetic status as a potential predictor of the sensitivity to ch5183284/debio 1347, a novel selective fgfr inhibitor. mol cancer ther, 2014, 13(11): 2547-2558. |
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