Atrasentan

Summary

Atrasentan (CHEMBL9194) is a phase-3 clinical-stage small-molecule nephroprotective agent targeting EDNRA and EDNRB; indicated across 5 conditions including diabetic kidney disease and prostate adenocarcinoma.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 2 (EDNRA, EDNRB)
• Indications: 5 conditions
• Clinical trials: 16
• Chemistry: 510.6 Da · C29H38N2O6

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL9194
Name	Atrasentan
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	159594
ChEBI	CHEBI:135810
Molecular formula	C29H38N2O6
Molecular weight	510.6
InChIKey	MOTJMGVDPWRKOC-QPVYNBJUSA-N

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

IUPAC name: (2R,3R,4S)-4-(1,3-benzodioxol-5-yl)-1-[2-(dibutylamino)-2-oxoethyl]-2-(4-methoxyphenyl)pyrrolidine-3-carboxylic acid

ChEBI definition: A member of the class of pyrrolidines that is pyrrolidine substituted by 2-(dibutylamino)-2-oxoethyl, 4-methoxyphenyl, carboxy, and 1,3-benzodioxol-5-yl groups at positions 1, 2, 3, and 4, respectively (the 2R,3R,4S-stereoisomer). It is an endothelin endothelin type A receptor antagonist used to reduce proteinuria in adults with primary immunoglobulin A nephropathy.

Pharmacological roles (ChEBI): nephroprotective agent, endothelin A receptor antagonist.

Also known as: Atrasentan, ATRASENTAN, ABT-627

Parent form; salt/anhydrous children: CHEMBL2106068

Patent coverage: 180 distinct patent families (472 SureChEMBL compound mentions), from 2 matched compound structure(s). Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
EDNRA	ETA receptor	Antagonist	9.2	0.1%	P25101
EDNRB	ETB receptor	Antagonist	6.86	0%	P24530

Broader ChEMBL bioactivity targets: 5 (assay-derived). Sample: Endothelin receptor type B, Endothelin receptor, Endothelin-1 receptor, Endothelin receptor type B, Endothelin-1 receptor.

Bioactivity

ChEMBL activities: 28 potent at pChembl ≥ 5 of 28 total. Top 100 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
P26684	10.47	Ki	0.03	nM	CHEMBL_ACT_147912
EDNRA	10.47	IC50	0.03	nM	CHEMBL_ACT_179977
EDNRA	10.47	Ki	0.03	nM	CHEMBL_ACT_19441199
EDNRA	10.47	Ki	0.03	nM	CHEMBL_ACT_26224377
EDNRA	10.47	Ki	0.03	nM	CHEMBL_ACT_487371
EDNRA	10.47	IC50	0.03	nM	CHEMBL_ACT_560113
P21451	10.4	IC50	0.04	nM	CHEMBL_ACT_487370
P26684	10.33	Ki	0.05	nM	CHEMBL_ACT_668655
EDNRA	10.26	IC50	0.06	nM	CHEMBL_ACT_19441200
EDNRA	10.26	IC50	0.06	nM	CHEMBL_ACT_26224375
EDNRA	10.23	IC50	0.06	nM	CHEMBL_ACT_26224383
EDNRA	10.1	IC50	0.08	nM	CHEMBL_ACT_497915
P26684	10.1	IC50	0.08	nM	CHEMBL_ACT_668653
EDNRA	9.7	IC50	0.2	nM	CHEMBL_ACT_26224380
EDNRA	9.51	IC50	0.31	nM	CHEMBL_ACT_147910
P26684	9.51	IC50	0.31	nM	CHEMBL_ACT_487368
P26684	9.51	IC50	0.31	nM	CHEMBL_ACT_956648
P26684	9.44	IC50	0.36	nM	CHEMBL_ACT_668650
P26684	9.4	IC50	0.4	nM	CHEMBL_ACT_320929
P26684	8.82	IC50	1.5	nM	CHEMBL_ACT_1247558
EDNRB	7.2	Ki	63.3	nM	CHEMBL_ACT_26224378
EDNRB	7.2	IC50	63.3	nM	CHEMBL_ACT_560114
EDNRB	7.07	IC50	84.8	nM	CHEMBL_ACT_26224376
EDNRB	7.06	IC50	88	nM	CHEMBL_ACT_668654
P35463	6.96	IC50	110	nM	CHEMBL_ACT_1247559
P35463	6.72	IC50	191	nM	CHEMBL_ACT_487369
EDNRB	6.29	IC50	515	nM	CHEMBL_ACT_668651
P35463	6.28	IC50	520	nM	CHEMBL_ACT_320930

Target pathways

Aggregated over 2 target gene(s): EDNRA, EDNRB.

Top Reactome pathways

3 total, by targets touching each:

Pathway	Targets	Genes
Peptide ligand-binding receptors	2	EDNRA, EDNRB
G alpha (q) signalling events	2	EDNRA, EDNRB
Transcriptional and post-translational regulation of MITF-M expression and activity	1	EDNRB

Dominant GO biological processes

GO term	Targets
regulation of heart rate	2
signal transduction	2
G protein-coupled receptor signaling pathway	2
phospholipase C-activating G protein-coupled receptor signaling pathway	2
positive regulation of cytosolic calcium ion concentration	2
regulation of blood pressure	2
gene expression	2
heparin proteoglycan metabolic process	2
vasoconstriction	2
positive regulation of canonical NF-kappaB signal transduction	2
developmental pigmentation	2
enteric nervous system development	2
sodium ion homeostasis	2
canonical Wnt signaling pathway	2
establishment of endothelial barrier	2

Indications & clinical

Indications

4 diseases in clinical trials (phase 1–3, investigational — not approved indications). Highest ChEMBL trial phase per disease; a non-cancer approved use is occasionally logged at phase 3 here.

Disease (in trials)	Phase	MONDO	EFO
diabetic kidney disease	3	MONDO:0005016	EFO:0000401
prostate adenocarcinoma	3	MONDO:0005082	EFO:0000673
IgA glomerulonephritis	3	MONDO:0005342	EFO:0004194
chronic kidney disease	2	MONDO:0005300	EFO:0003884

1 further indication record had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 16.

Phase distribution

Phase	Trials
PHASE2	7
PHASE3	6
Not specified	2
PHASE2/PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04573478	PHASE3	ACTIVE_NOT_RECRUITING	Atrasentan in Patients With IgA Nephropathy
NCT07498335	PHASE3	NOT_YET_RECRUITING	Study to Assess the Efficacy, Pharmacokinetics, Safety and Tolerability of Atrasentan in Pediatric Patients With Primary IgAN
NCT00036543	PHASE3	COMPLETED	A Study of Atrasentan in Men With Metastatic, Hormone-Refractory Prostate Cancer
NCT00036556	PHASE3	COMPLETED	Study of Atrasentan in Men With Non-Metastatic, Hormone-Refractory Prostate Cancer
NCT00127478	PHASE2/PHASE3	COMPLETED	A Long Term Safety Study With Atrasentan
NCT00271492	PHASE3	COMPLETED	Correlation of Endothelial Function and Early Coronary Artery Disease in Humans
NCT01858532	PHASE3	TERMINATED	Study Of Diabetic Nephropathy With Atrasentan
NCT04573920	PHASE2	ACTIVE_NOT_RECRUITING	Atrasentan in Patients With Proteinuric Glomerular Diseases
NCT00038662	PHASE2	COMPLETED	Safety and Efficacy of Atrasentan in Men With Hormone Naive Prostate Cancer Exhibiting Early Signs of Biochemical Failure
NCT00181558	PHASE2	COMPLETED	Atrasentan and Zometa for Men With Prostate Cancer Metastatic to Bone
NCT01356849	PHASE2	COMPLETED	Evaluate the Efficacy and Safety of Once Daily Administration of Atrasentan Tablets (Low and High) Compared to Placebo in Reducing Residual Albuminuria in Type 2 Diabetic Patients With Nephropathy Who Are Treated With the Maximum Tolerated Labeled Dose of a Renin Angiotensin System (RAS) Inhibitor
NCT01399580	PHASE2	COMPLETED	A Prospective, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate Efficacy and Safety of Atrasentan, Including Thoracic Bioimpedance, in Type 2 Diabetic Subjects With Nephropathy
NCT02118714	PHASE2	COMPLETED	Atrasentan Spermatogenesis and Testicular Function
NCT05834738	PHASE2	COMPLETED	Randomized, Double-blind, Placebo-controlled, Crossover Study of Atrasentan in Subjects With IgA Nephropathy
NCT06952426	Not specified	RECRUITING	A Mobile App-Based Study to Evaluate Disease Burden and Treatment Patterns in Immunoglobulin A Nephropathy (IgAN) in the US
NCT07319585	Not specified	AVAILABLE	Managed Access Programs for EXV811, Atrasentan

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 1 clinical and 6 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

50 molecules share ≥1 primary target. Top 50 by shared-target count:

Molecule	Source	Status	Shared targets
BOSENTAN	ChEMBL + PubChem	Phase 4 (approved)	EDNRA, EDNRB
AMBRISENTAN	ChEMBL	Phase 4 (approved)	EDNRA, EDNRB
APROCITENTAN	ChEMBL	Phase 4 (approved)	EDNRA, EDNRB
MACITENTAN	ChEMBL	Phase 4 (approved)	EDNRA, EDNRB
SITAXENTAN	ChEMBL	Phase 4 (approved)	EDNRA, EDNRB
SULFISOXAZOLE	ChEMBL	Phase 4 (approved)	EDNRA, EDNRB
AVOSENTAN	ChEMBL	Phase 3	EDNRA, EDNRB
CLAZOSENTAN	ChEMBL	Phase 3	EDNRA, EDNRB
DARUSENTAN	ChEMBL	Phase 3	EDNRA, EDNRB
TEZOSENTAN	ChEMBL	Phase 3	EDNRA, EDNRB
ENDOTHELIN	ChEMBL	Phase 2	EDNRA, EDNRB
ENRASENTAN	ChEMBL	Phase 2	EDNRA, EDNRB
FELOPRENTAN	ChEMBL	Phase 2	EDNRA, EDNRB
Dihydroergotamine	PubChem	Approved	EDNRA, EDNRB
Fidaxomicin	PubChem	Approved	EDNRA, EDNRB
Propoxyphene	PubChem	Approved	EDNRA, EDNRB
Pyrazinamide	PubChem	Approved	EDNRA, EDNRB
SPARSENTAN	ChEMBL + PubChem	Phase 4 (approved)	EDNRA
ACYCLOVIR	ChEMBL	Phase 4 (approved)	EDNRA
AMIODARONE	ChEMBL	Phase 4 (approved)	EDNRA
ENOXACIN	ChEMBL	Phase 4 (approved)	EDNRA
FLUOXETINE	ChEMBL	Phase 4 (approved)	EDNRA
GRAMICIDIN	ChEMBL	Phase 4 (approved)	EDNRA
IRBESARTAN	ChEMBL	Phase 4 (approved)	EDNRA
MAZINDOL	ChEMBL	Phase 4 (approved)	EDNRB
MELOXICAM	ChEMBL	Phase 4 (approved)	EDNRA
MODAFINIL	ChEMBL	Phase 4 (approved)	EDNRB
NITAZOXANIDE	ChEMBL	Phase 4 (approved)	EDNRA
PIOGLITAZONE	ChEMBL	Phase 4 (approved)	EDNRA
SULFATHIAZOLE	ChEMBL	Phase 4 (approved)	EDNRA
SUNITINIB	ChEMBL	Phase 4 (approved)	EDNRA
EXISULIND	ChEMBL	Phase 3	EDNRA
ZIBOTENTAN	ChEMBL	Phase 3	EDNRA
BQ-123	ChEMBL	Phase 2	EDNRA
EDONENTAN	ChEMBL	Phase 2	EDNRA
FANDOSENTAN	ChEMBL	Phase 2	EDNRA
Aclidinium Bromide	PubChem	Approved	EDNRB
Afatinib	PubChem	Approved	EDNRA
Alogliptin	PubChem	Approved	EDNRB
Apixaban	PubChem	Approved	EDNRA
Belzutifan	PubChem	Approved	EDNRB
Binimetinib	PubChem	Approved	EDNRA
chenodiol	PubChem	Approved	EDNRA
Desloratadine	PubChem	Approved	EDNRB
Fulvestrant	PubChem	Approved	EDNRA
Imipenem	PubChem	Approved	EDNRA
Methotrexate	PubChem	Approved	EDNRB
Olmesartan Medoxomil	PubChem	Approved	EDNRB
Tafamidis	PubChem	Approved	EDNRA
Tiotropium Bromide Monohydrate	PubChem	Approved	EDNRB