DMP-777

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

一种有效的、选择性的、口服活性的人白细胞弹性蛋白酶 (HLE) 抑制剂，IC50 为 23 nM。

A potent, selective, and orally active human leukocyte elastase (HLE) inhibitor with IC50 of 23 nM; displays >40-fold selectivity over thrombin and chymotrypsin; leads to the rapid emergence of spasmolytic polypeptide/trefoil factor family 2 (TFF2)-expressing metaplasia (SPEM) from the bases of fundic glands in gastrin-deficient mice.Cystic Fibrosis Phase 2 Discontinued.

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DMP-777-treated rats show a marked decrease in H/K-ATPase staining parietal cells. DMP-777-induced loss of parietal cells is significantly ameliorated with coadministration of omeprazole. DMP-777-treated animals demonstrates marked foveolar hyperplasia in the fundus with prominent expansion of diastase-resistant, PAS-positive surface mucous cells. When DMP-777 is coadministeredwith omprazole, there is a significant decrease in BrdUpositive S-phase cells compared with rats thatreceive DMP-777 alone. After oral dosing of monkeys at 40 mg/kg with DMP-777 the only stereoisomer detected in the post-dose plasma samples is the starting material DMP-777, and no inversion of the configuration at positions 'a' and 'b' of DMP-777 has occurred in vivo. Mist1-/- mice treated with DMP-777 show fewer chief cell to SPEM transitions. Mist1-/- mice treated with L635 demonstrates significantly fewer proliferative SPEM cells compared to control mice.

L-694458

Metabolic Enzyme/Protease

Elastase

Elastase

Other Indications

Fibrosis

157341-41-8

564.6725

C31H40N4O6

>98% (HPLC)

10 mM in DMSO

O=C(N1[C@@H](OC2=CC=C(C(N3CCN(C)CC3)=O)C=C2)C(CC)(CC)C1=O)N[C@@H](C4=CC=C(OCO5)C5=C4)CCC

1-Azetidinecarboxamide, N-[(1R)-1-(1,3-benzodioxol-5-yl)butyl]-3,3-diethyl-2-[4-[(4-methyl-1-piperazinyl)carbonyl]phenoxy]-4-oxo-, (2S)-

(-20℃)

With Ice Pack

≥ 2 years