Unknown

Dataset Information

0

Tetrahydroisoquinoline-7-carboxamide Derivatives as New Selective Discoidin Domain Receptor 1 (DDR1) Inhibitors.

ABSTRACT: Acute lung injury (ALI) is a deadly symptom for serious lung inflammation. Discoidin Domain Receptor 1 (DDR1) is a new potential target for anti-inflammatory drug discovery. A new selective tetrahydroisoquinoline-7-carboxamide based DDR1 inhibitor 7ae was discovered to tightly bind the DDR1 protein and potently inhibit its kinase function with a Kd value of 2.2 nM and an IC50 value of 6.6 nM, respectively. The compound dose-dependently inhibited lipopolysaccharide (LPS)-induced interleukin-6 (IL-6) and tumor necrosis factor-? (TNF-?) release in mouse primary peritoneal macrophages (MPMs). In addition, 7ae also exhibited promising in vivo anti-inflammatory effects in a LPS-induced mouse ALI model. To the best of our knowledge, this is the first "proof of concept" investigation on the potential application of a small molecule DDR1 inhibitor to treat ALI.

SUBMITTER: Wang Z 

PROVIDER: S-EPMC5346979 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

Tetrahydroisoquinoline-7-carboxamide Derivatives as New Selective Discoidin Domain Receptor 1 (DDR1) Inhibitors.

Wang Zhen Z   Zhang Yali Y   Bartual Sergio G SG   Luo Jinfeng J   Xu Tingting T   Du Wenting W   Xun Qiuju Q   Tu Zhengchao Z   Brekken Rolf A RA   Ren Xiaomei X   Bullock Alex N AN   Liang Guang G   Lu Xiaoyun X   Ding Ke K  

ACS medicinal chemistry letters 20170209 3

Acute lung injury (ALI) is a deadly symptom for serious lung inflammation. Discoidin Domain Receptor 1 (DDR1) is a new potential target for anti-inflammatory drug discovery. A new selective tetrahydroisoquinoline-7-carboxamide based DDR1 inhibitor <b>7ae</b> was discovered to tightly bind the DDR1 protein and potently inhibit its kinase function with a <i>K</i><sub>d</sub> value of 2.2 nM and an IC<sub>50</sub> value of 6.6 nM, respectively. The compound dose-dependently inhibited lipopolysaccha  ...[more]

Similar Datasets

Unknown Structure-Based Design of Tetrahydroisoquinoline-7-carboxamides as Selective Discoidin Domain Receptor 1 (DDR1) Inhibitors.
| S-EPMC5053573 | biostudies-literature
Unknown 2-Amino-2,3-dihydro-1<i>H</i>-indene-5-carboxamide-Based Discoidin Domain Receptor 1 (DDR1) Inhibitors: Design, Synthesis, and in Vivo Antipancreatic Cancer Efficacy.
| S-EPMC6985936 | biostudies-literature
Unknown Discovery of VU6015929: A Selective Discoidin Domain Receptor 1/2 (DDR1/2) Inhibitor to Explore the Role of DDR1 in Antifibrotic Therapy.
| S-EPMC6956352 | biostudies-literature
Unknown Periostin interaction with discoidin domain receptor-1 (DDR1) promotes cartilage degeneration.
| S-EPMC7182230 | biostudies-literature
Unknown Discoidin Domain Receptor-1 (DDR1) is Involved in Angiolymphatic Invasion in Oral Cancer.
| S-EPMC7226486 | biostudies-literature
Unknown Discoidin domain receptor 1 (DDR1) kinase as target for structure-based drug discovery.
| S-EPMC4336622 | biostudies-literature
Unknown Glycosylation at Asn211 regulates the activation state of the discoidin domain receptor 1 (DDR1).
| S-EPMC3979393 | biostudies-literature
Unknown Expression and subcellular localization of Discoidin Domain Receptor 1 (DDR1) define prostate cancer aggressiveness.
| S-EPMC8456559 | biostudies-literature
Unknown Silencing of Discoidin Domain Receptor-1 (DDR1) Concurrently Inhibits Multiple Steps of Metastasis Cascade in Gastric Cancer.
| S-EPMC5854925 | biostudies-literature
Unknown Altered Treg Infiltration after Discoidin Domain Receptor 1 (DDR1) Inhibition and Knockout Promotes Tumor Growth in Lung Adenocarcinoma.
| S-EPMC10742023 | biostudies-literature