Details of the Drug

General Information of Drug (ID: DMM74PK)

Drug Name
Atrasentan
Synonyms
Xinlay; Atrasentan [INN]; A 127722; A 147627; ABT 627; A-127722; A-147627; ABT-627; Xinlay (TN); A-127722.5; (+)-A 127722; (+)-A-127722; (11C)ABT-627; (2R,3R,4S)-4-(1,3-benzodioxol-5-yl)-1-[2-(dibutylamino)-2-oxoethyl]-2-(4-methoxyphenyl)pyrrolidine-3-carboxylic acid; 2-(4-methoxyphenyl)-4-(1,3-benzodioxol-5-yl)-1-(((dibutylamino)carbonyl)methyl)pyrrolidine-3-carboxylic acid; 2R-(4-methoxyphenyl)-4S(1,3-benzodioxol-5-yl)-1-(N,N-di(n-butyl)aminocarbonyl-methyl)-pyrrolidine-3R-carboxylic acid
Indication
Disease Entry ICD 11 Status REF
Diabetic nephropathy GB61.Z Phase 3 [1]
Prostate cancer 2C82.0 Withdrawn from market [2]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 2 Molecular Weight (mw) 510.6
Logarithm of the Partition Coefficient (xlogp) 2.4
Rotatable Bond Count (rotbonds) 12
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 7
Chemical Identifiers
Formula
C29H38N2O6
IUPAC Name
(2R,3R,4S)-4-(1,3-benzodioxol-5-yl)-1-[2-(dibutylamino)-2-oxoethyl]-2-(4-methoxyphenyl)pyrrolidine-3-carboxylic acid
Canonical SMILES
CCCCN(CCCC)C(=O)CN1C[C@@H]([C@H]([C@@H]1C2=CC=C(C=C2)OC)C(=O)O)C3=CC4=C(C=C3)OCO4
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
InChIKey
MOTJMGVDPWRKOC-QPVYNBJUSA-N
Cross-matching ID
PubChem CID
159594
ChEBI ID
CHEMBL9194
CAS Number
173937-91-2
UNII
V6D7VK2215
DrugBank ID
DB06199
TTD ID
D0Y6UU
VARIDT ID
DR01433
INTEDE ID
DR1899
Drug-Molecule Activity Atlas (DMA)NEW Click to Jump to the Detailed DMA Information of This Drug
Drug Pharmacogenomic Perturbation (DPP)NEW Click to Jump to the Detailed DPP Information of This Drug
Drug ADMET Endpoint Profile (DAE)NEW Click to Jump to the Detailed DAE Information of This Drug
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Endothelin A receptor (EDNRA) TTKRD0G EDNRA_HUMAN Antagonist [3]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
Organic anion transporting polypeptide 1A2 (SLCO1A2) DTE2B1D SO1A2_HUMAN Substrate [4]
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [5]
Organic anion transporting polypeptide 1B3 (SLCO1B3) DT9C1TS SO1B3_HUMAN Substrate [4]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4)
Main DME 		DE4LYSA CP3A4_HUMAN Substrate [6]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Diabetic nephropathy
ICD Disease Classification GB61.Z
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Endothelin A receptor (EDNRA) DTT EDNRA 5.13E-01 -0.82 -0.79
Organic anion transporting polypeptide 1A2 (SLCO1A2) DTP OATP1A2 5.69E-01 -2.39E-02 -2.71E-01
Organic anion transporting polypeptide 1B3 (SLCO1B3) DTP OATP1B3 7.67E-01 0.00E+00 0.00E+00
Organic anion transporting polypeptide 1B1 (SLCO1B1) DTP OATP1B1 7.18E-01 -5.08E-02 -4.53E-01
Cytochrome P450 3A4 (CYP3A4) DME CYP3A4 1.76E-01 -2.60E-02 -3.37E-01
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
2 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 3487).
3 Effects of a selective ET(A)-receptor antagonist, atrasentan (ABT-627), in murine models of allergic asthma: demonstration of mouse strain specificity. Clin Sci (Lond). 2002 Aug;103 Suppl 48:367S-370S.
4 Organic anion transporting polypeptide 1B1 activity classified by SLCO1B1 genotype influences atrasentan pharmacokinetics. Clin Pharmacol Ther. 2006 Mar;79(3):186-96.
5 Organic anion transporting polypeptide 1B1: a genetically polymorphic transporter of major importance for hepatic drug uptake. Pharmacol Rev. 2011 Mar;63(1):157-81.
6 Organic anion transporting polypeptide 1B1 activity classified by SLCO1B1 genotype influences atrasentan pharmacokinetics. Clin Pharmacol Ther. 2006 Mar;79(3):186-96.