atrasentan

Ligand id: 3487

Name: atrasentan

Structure and Physico-chemical Properties

2D Structure
Calculated Physico-chemical Properties
Hydrogen bond acceptors 5
Hydrogen bond donors 1
Rotatable bonds 13
Topological polar surface area 88.54
Molecular weight 510.27
XLogP 4.69
No. Lipinski's rules broken 1

Molecular properties generated using the CDK

No information available.
Summary of Clinical Use
Atrasentan was assessed in a Phase I/II clinical trial as a potential anti-cancer treatment (in combination with paclitaxel and carboplatin) but the compound did not show improved efficacy compared to chemotherapy alone in NSCLC [1]. Phase III trial in prostate cancer also failed. Development of atrasentan as a novel monotherapy for diabetic nephropathy has continued and reached Phase III (NCT01858532 is ongoing as of May 2015).
Mechanism Of Action and Pharmacodynamic Effects
Atrasentan is an antagonist of the endothelin A (ETA) receptor. The molecular machanism underlying anti-cancer effects are attributed to atrasentan's ability to inhibit endothelin-induced cell proliferation [4]. This effect is particularly relevant in prostate cancer where endothelin levels are elevated [2]. As a treatment for diabetic nephropathy, atrasentan is reported to reduce renal injury via an anti-inflammatory mechanism involving inhibition of superoxide production [5].