Atrasentan

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Atrasentan
Atrasentan.svg
Systematic (IUPAC) name
(2R,3R,4S)-4-(1,3-benzodioxol-5-yl)-1-[2-(dibutylamino)-2-oxoethyl]-2-(4-methoxyphenyl)pyrrolidine-3-carboxylic acid
Clinical data
Legal status
?
Identifiers
CAS number 173937-91-2 N
ATC code None
PubChem CID 159594
ChemSpider 140321 YesY
UNII V6D7VK2215 YesY
ChEMBL CHEMBL9194 YesY
Chemical data
Formula C29H38N2O6 
Mol. mass 510.621 g/mol
 N (what is this?)  (verify)

Atrasentan is an experimental drug that is being studied for the treatment of various types of cancer,[1] including non-small cell lung cancer.[2] It is also being investigated as a therapy for diabetic kidney disease.

Atrasentan failed a phase 3 trial[3] for prostate cancer in patients unresponsive to hormone therapy. A second trial[4] confirmed this finding.

It is an endothelin receptor antagonist selective for subtype A (ETA). While other drugs of this type (sitaxentan, ambrisentan) exploit the vasoconstrictive properties of endothelin and are mainly used for the treatment of pulmonary arterial hypertension, atrasentan blocks endothelin induced cell proliferation.

In April 2014, de Zeeuw et al. showed[5] that 0.5 mg and 1.25 mg of atrasentan reduced urinary albumin by 35 and 38% respectively with modest side effects. Patients also had decreased home blood pressures (but no change in office readings) decrease total cholesterol and LDL. Patients in the 1.25 mg dose group had increased weight gain which was presumably due to increasd edema and had to withdraw from the study more than the placebo or 0.5 mg dose group. Reductions in proteinuria have been associated with beneficial patient outcomes in diabetic kidney disease with other interventions but is not an accepted end-point by the FDA.

The recently initiated SONAR trial[6] will determine if atrasentan reduces kidney failure in diabetic kidney disease.

References[edit]

  1. ^ Atrasentan (entry in the public domain NCI Dictionary of Cancer Terms)
  2. ^ Chiappori, AA; Haura, E; Rodriguez, FA; Boulware, D; Kapoor, R; Neuger, AM; Lush, R; Padilla, B; Burton, M (1 March 2008). "Phase I/II Study of Atrasentan, an Endothelin A Receptor Antagonist, in Combination with Paclitaxel and Carboplatin as First-Line Therapy in Advanced Non–Small Cell Lung Cancer". Clinical Cancer Research 14 (5): 1464–1469. doi:10.1158/1078-0432.CCR-07-1508. PMID 18316570. 
  3. ^ National Cancer Institute News Note
  4. ^ http://www.ncbi.nlm.nih.gov/pubmed/23871417?dopt=Abstract&holding=npg
  5. ^ PubMed link
  6. ^ SONAR Trial at Clinical Trials.gov