CH5183284

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

CH5183284是一种选择性口服FGFR抑制剂，分别针对FGFR1（IC50 = 9.3 nM）、FGFR2（IC50 = 7.6 nM）、FGFR3（IC50 = 290）和FGFR4（IC50 = 22 nM）。

Debio-1347, also known as FF284 and CH5183284, is an orally bioavailable inhibitor of the fibroblast growth factor receptor subtypes 1 (FGFR-1), 2 (FGFR-2) and 3 (FGFR-3), with potential antineoplastic activity. FGFR inhibitor debio 1347 binds to and inhibits FGFR-1, -2, and -3, which result in the inhibition of FGFR-mediated signal transduction pathways. This leads to the inhibition of both tumor cell proliferation and angiogenesis, and causes cell death in FGFR-overexpressing tumor cells.(In Vitro):Zoligratinib is well balanced in cellular antiproliferative activity against SNU-16 and stability in human liver microsome. The selectivity of 8 to inhibit FGFR over KDR is suggested to be caused by the difference in the interaction with M535 in FGFR1 and L889 in KDR. The IC50 of Zoligratinib is 29 nM for FGF-dependent proliferation and 780 nM for VEGF-dependent proliferation.(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).

Zoligratinib is well balanced in cellular antiproliferative activity against SNU-16 and stability in human liver microsome. The selectivity of 8 to inhibit FGFR over KDR is suggested to be caused by the difference in the interaction with M535 in FGFR1 and L889 in KDR. The IC50 of Zoligratinib is 29 nM for FGF-dependent proliferation and 780 nM for VEGF-dependent proliferation.

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).

Debio-1347 | Debio 1347 | Debio1347 | CH5183284

Endocrinology/Hormones

Estrogen Receptor/ERR

FGFR1| FGFR2| FGFR3| FGFR4

Cancer

——

1265229-25-1

356.38

C20H16N6O

>98% (HPLC)

DMSO : 25 mg/mL. 70.15 mM;

Cc1nc2c([nH]1)cc(cc2)n1c(c(cn1)C(=O)c1cc2ccccc2[nH]1)N

(5-amino-1-(2-methyl-1H-benzo[d]imidazol-6-yl)-1H-pyrazol-4-yl)(1H-indol-2-yl)methanone

(-20℃)

With Ice Pack

≥ 2 years