Atrasentan

This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

Identification

Name
Atrasentan
Accession Number
DB06199
Type
Small Molecule
Groups
Investigational
Description

Atrasentan is a substance that is being studied in the treatment of cancer. It belongs to the family of drugs called endothelin-1 protein receptor antagonists. It is a novel, selective endothelin A receptor antagonist (SERA).

Structure
Thumb
Synonyms
Not Available
External IDs
ABT-627
Product Ingredients
IngredientUNIICASInChI Key
Atrasentan HydrochlorideE4G31X93ZA195733-43-8IJFUJIFSUKPWCZ-SQMFDTLJSA-N
International/Other Brands
Xinlay
Categories
UNII
V6D7VK2215
CAS number
173937-91-2
Weight
Average: 510.6218
Monoisotopic: 510.272986958
Chemical Formula
C29H38N2O6
InChI Key
MOTJMGVDPWRKOC-QPVYNBJUSA-N
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
IUPAC Name
(2R,3R,4S)-4-(2H-1,3-benzodioxol-5-yl)-1-[(dibutylcarbamoyl)methyl]-2-(4-methoxyphenyl)pyrrolidine-3-carboxylic acid
SMILES
CCCCN(CCCC)C(=O)CN1C[C@@H]([C@H]([C@@H]1C1=CC=C(OC)C=C1)C(O)=O)C1=CC2=C(OCO2)C=C1

Pharmacology

Indication

Investigated for use/treatment in prostate cancer and cancer/tumors (unspecified).

Pharmacodynamics
Not Available
Mechanism of action
TargetActionsOrganism
UEndothelin-1 receptorNot AvailableHuman
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
Conjugated estrogensThe excretion of Atrasentan can be decreased when combined with Conjugated estrogens.
DiclofenacThe excretion of Atrasentan can be decreased when combined with Diclofenac.
DipyridamoleThe excretion of Atrasentan can be decreased when combined with Dipyridamole.
ErythromycinThe excretion of Atrasentan can be decreased when combined with Erythromycin.
EstradiolThe excretion of Atrasentan can be decreased when combined with Estradiol.
FluvastatinThe excretion of Atrasentan can be decreased when combined with Fluvastatin.
IndinavirThe excretion of Atrasentan can be decreased when combined with Indinavir.
IndomethacinThe excretion of Atrasentan can be decreased when combined with Indomethacin.
IrinotecanThe excretion of Atrasentan can be decreased when combined with Irinotecan.
LovastatinThe excretion of Atrasentan can be decreased when combined with Lovastatin.
Food Interactions
Not Available

References

General References
Not Available
External Links
PubChem Compound
159594
ChemSpider
140321
BindingDB
50051007
ChEBI
135810
ChEMBL
CHEMBL9194
Wikipedia
Atrasentan

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentBrain and Central Nervous System Tumors1
2CompletedOtherDiabetes Mellitus (DM) / Renal Dysfunction1
2CompletedTreatmentAdenocarcinoma of the Prostate / Prostate Cancer1
2CompletedTreatmentChronic Kidney Disease (CKD) / Diabetic Nephropathies3
2CompletedTreatmentProstatic Neoplasms1
2CompletedTreatmentRenal Cancers1
2TerminatedTreatmentCancer of the Ovary / Fallopian Tube Cancer / Peritoneal Cavity Cancer1
2, 3CompletedTreatmentAdenocarcinomas / Prostate Cancer1
3CompletedTreatmentEndothelial Dysfunction1
3CompletedTreatmentMetastatic Cancers / Prostate Cancer1
3CompletedTreatmentProstate Cancer2
3CompletedTreatmentProstatic Neoplasms1
3TerminatedTreatmentDiabetic Nephropathies1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0321 mg/mLALOGPS
logP4.09ALOGPS
logP1.76ChemAxon
logS-4.2ALOGPS
pKa (Strongest Acidic)3.02ChemAxon
pKa (Strongest Basic)8.25ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area88.54 Å2ChemAxon
Rotatable Bond Count12ChemAxon
Refractivity140.14 m3·mol-1ChemAxon
Polarizability55.33 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9485
Blood Brain Barrier+0.6335
Caco-2 permeable-0.5191
P-glycoprotein substrateSubstrate0.836
P-glycoprotein inhibitor IInhibitor0.7581
P-glycoprotein inhibitor IIInhibitor0.8119
Renal organic cation transporterNon-inhibitor0.7707
CYP450 2C9 substrateNon-substrate0.821
CYP450 2D6 substrateNon-substrate0.8057
CYP450 3A4 substrateSubstrate0.7436
CYP450 1A2 substrateNon-inhibitor0.9696
CYP450 2C9 inhibitorNon-inhibitor0.7407
CYP450 2D6 inhibitorNon-inhibitor0.7773
CYP450 2C19 inhibitorInhibitor0.5209
CYP450 3A4 inhibitorInhibitor0.771
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.5707
Ames testNon AMES toxic0.6721
CarcinogenicityNon-carcinogens0.8803
BiodegradationNot ready biodegradable0.962
Rat acute toxicity2.4252 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9465
hERG inhibition (predictor II)Non-inhibitor0.5396
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as phenylpyrrolidines. These are polycyclic aromatic compounds containing a benzene ring linked to a pyrrolidine ring through a CC or CN bond. Pyrrolidine is a five-membered saturated aliphatic heterocycle with one nitrogen atom and four carbon atoms.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Pyrrolidines
Sub Class
Phenylpyrrolidines
Direct Parent
Phenylpyrrolidines
Alternative Parents
Alpha amino acids and derivatives / Benzodioxoles / Anisoles / Pyrrolidine carboxylic acids / Phenoxy compounds / Methoxybenzenes / Alkyl aryl ethers / Aralkylamines / N-alkylpyrrolidines / Pyrroles
show 12 more
Substituents
2-phenylpyrrolidine / Alpha-amino acid or derivatives / Benzodioxole / Phenoxy compound / Anisole / Phenol ether / Pyrrolidine carboxylic acid / Methoxybenzene / Pyrrolidine carboxylic acid or derivatives / Alkyl aryl ether
show 28 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Details
1. Endothelin-1 receptor
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Phosphatidylinositol phospholipase c activity
Specific Function
Receptor for endothelin-1. Mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. The rank order of binding affinities for ET-A is:...
Gene Name
EDNRA
Uniprot ID
P25101
Uniprot Name
Endothelin-1 receptor
Molecular Weight
48721.76 Da
References
  1. Nelson J, Bagnato A, Battistini B, Nisen P: The endothelin axis: emerging role in cancer. Nat Rev Cancer. 2003 Feb;3(2):110-6. [PubMed:12563310]
  2. Cella D, Petrylak DP, Fishman M, Teigland C, Young J, Mulani P: Role of quality of life in men with metastatic hormone-refractory prostate cancer: how does atrasentan influence quality of life? Eur Urol. 2006 May;49(5):781-9. Epub 2006 Jan 19. [PubMed:16458417]
  3. Chichorro JG, Zampronio AR, Souza GE, Rae GA: Orofacial cold hyperalgesia due to infraorbital nerve constriction injury in rats: reversal by endothelin receptor antagonists but not non-steroidal anti-inflammatory drugs. Pain. 2006 Jul;123(1-2):64-74. Epub 2006 Mar 24. [PubMed:16563629]

Drug created on March 19, 2008 10:17 / Updated on August 02, 2018 05:34