DDR-TRK-1

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

DDR-TRK-1（DDR1 抑制剂 6j）是一种有效的选择性 DDR1 抑制剂，IC50 为 9.4 nM。

DDR-TRK-1 (DDR1 inhibitor 6j) is a potent, selective selective DDR1 inhibitor with IC50 of 9.4 nM, also potently inhibits TRK family with IC50 of 18-100 nM; DDR-TRK-1 inhibits colony formation and migration of Panc-1 pancreatic cancer cells. In cellular and mouse models of lung fibrosis, DDR-TRK-1 inhibits signaling, expression of fibrotic markers and fibrotic features such as hydroxproline expression; DDR-TRK-1 is selective in KINOMEscan at 1 uM,t he closest off target is CDK11 (370 nM).

DDR-TRK-1 is a promising candidate, with an IC50 value of 9.4 nM against DDR1. DDR-TRK-1 also exhibits reasonable pharmacokinetic (PK) properties, with an oral bioavailability of 66.8% and a T1/2 value of 1.25 h at an oral dose of 20 mg/kg in rats. However, the area under concentration?time curve (AUC) value of DDR-TRK-1 in mice is obviously higher than that in rats, suggesting its good absorption property in mice. The DDR1 inhibition of DDR1-IN-3 is further validated by determining its binding affinity with the DDR1 protein. It is shown that DDR-TRK-1 bounds tightly to DDR1, with a binding constant (Kd) value of 4.7 nM.

DDR-TRK-1 prevents these BLM-induced pathological changes in a dose-dependent manner. These results agree with the expression levels of fibrotic markers in lung tissue lysates, including fibronectin and α-smooth muscle actin (SMA). Further analyses also reveal that the administration of DDR-TRK-1 cause a dose-dependent suppression in the content of hydroxyproline, a unique amino acid found in collagen. The above data collectively indicate the promising therapeutic potential of DDR-TRK-1 against the BLM-induced pulmonary fibrosis.

DDR1 inhibitor 6j

Tyrosine Kinase

DDR

DDR

Cancer

——

1934246-19-1

492.506

C26H23F3N6O

>98% (HPLC)

——

CC1CN(CC2=C1C=CC(=C2)C(=O)NC3=CC(=CC(=C3)C(F)(F)F)N4C=C(N=C4)C)C5=CN=CN=C5

(R)-4-methyl-N-(3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl)-2-(pyrimidin-5-yl)-1,2,3,4-tetrahydroisoquinoline-7-carboxamide

(-20℃)

With Ice Pack

≥ 2 years