atrasentan   Click here for help

GtoPdb Ligand ID: 3487

Synonyms: A-127722 | A-147627 | ABT-627
Compound class: Synthetic organic
Comment: Atrasentan (ABT-627) is an orally available, nonpeptide endothelin receptor antagonist. The stereochemistry represented here matches that defined in the INN record for atrasentan.
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species

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2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 5
Hydrogen bond donors 1
Rotatable bonds 13
Topological polar surface area 88.54
Molecular weight 510.27
XLogP 4.23
No. Lipinski's rules broken 1
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES CCCCN(C(=O)CN1CC(C(C1c1ccc(cc1)OC)C(=O)O)c1ccc2c(c1)OCO2)CCCC
Isomeric SMILES CCCCN(C(=O)CN1C[C@@H]([C@H]([C@@H]1c1ccc(cc1)OC)C(=O)O)c1ccc2c(c1)OCO2)CCCC
InChI InChI=1S/C29H38N2O6/c1-4-6-14-30(15-7-5-2)26(32)18-31-17-23(21-10-13-24-25(16-21)37-19-36-24)27(29(33)34)28(31)20-8-11-22(35-3)12-9-20/h8-13,16,23,27-28H,4-7,14-15,17-19H2,1-3H3,(H,33,34)/t23-,27-,28+/m1/s1
InChI Key MOTJMGVDPWRKOC-QPVYNBJUSA-N
References
1. Chiappori AA, Haura E, Rodriguez FA, Boulware D, Kapoor R, Neuger AM, Lush R, Padilla B, Burton M, Williams C et al.. (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.
Clin Cancer Res, 14 (5): 1464-9. [PMID:18316570]
2. Heerspink HJL, Parving HH, Andress DL, Bakris G, Correa-Rotter R, Hou FF, Kitzman DW, Kohan D, Makino H, McMurray JJV et al.. (2019)
Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial.
Lancet, 393 (10184): 1937-1947. [PMID:30995972]
3. Nelson JB, Chan-Tack K, Hedican SP, Magnuson SR, Opgenorth TJ, Bova GS, Simons JW. (1996)
Endothelin-1 production and decreased endothelin B receptor expression in advanced prostate cancer.
Cancer Res, 56 (4): 663-8. [PMID:8630991]
4. Opgenorth TJ, Adler AL, Calzadilla SV, Chiou WJ, Dayton BD, Dixon DB, Gehrke LJ, Hernandez L, Magnuson SR, Marsh KC et al.. (1996)
Pharmacological characterization of A-127722: an orally active and highly potent ETA-selective receptor antagonist.
J Pharmacol Exp Ther, 276 (2): 473-81. [PMID:8632312]
5. Salani D, Rosanò L, Di Castro V, Spinella F, Venuti A, Padley RJ, Nicotra MR, Natali PG, Bagnato A. (2002)
ABT-627, a potent endothelin receptor A antagonist, inhibits ovarian carcinoma growth in vitro.
Clin Sci, 103 Suppl 48: 318S-321S. [PMID:12193113]
6. Sasser JM, Sullivan JC, Hobbs JL, Yamamoto T, Pollock DM, Carmines PK, Pollock JS. (2007)
Endothelin A receptor blockade reduces diabetic renal injury via an anti-inflammatory mechanism.
J Am Soc Nephrol, 18 (1): 143-54. [PMID:17167119]
7. Smeijer JD, Kohan DE, Rossing P, Correa-Rotter R, Liew A, Tang SCW, de Zeeuw D, Gansevoort RT, Ju W, Lambers Heerspink HJ. (2023)
Insulin resistance, kidney outcomes and effects of the endothelin receptor antagonist atrasentan in patients with type 2 diabetes and chronic kidney disease.
Cardiovasc Diabetol, 22 (1): 251. [PMID:37716952]
8. Waijer SW, Gansevoort RT, Bakris GL, Correa-Rotter R, Hou FF, Kohan DE, Kitzman DW, Makino H, McMurray JJV, Perkovic V et al.. (2021)
The Effect of Atrasentan on Kidney and Heart Failure Outcomes by Baseline Albuminuria and Kidney Function: A Post Hoc Analysis of the SONAR Randomized Trial.
Clin J Am Soc Nephrol, 16 (12): 1824-1832. [PMID:34853062]
9. Winn M, von Geldern TW, Opgenorth TJ, Jae HS, Tasker AS, Boyd SA, Kester JA, Mantei RA, Bal R, Sorensen BK et al.. (1996)
2,4-Diarylpyrrolidine-3-carboxylic acids--potent ETA selective endothelin receptor antagonists. 1. Discovery of A-127722.
J Med Chem, 39 (5): 1039-48. [PMID:8676339]