Lixivaptan

Summary

Lixivaptan (CHEMBL49429) is a phase-3 clinical-stage small molecule targeting AVPR2; indicated across 4 conditions including autosomal dominant polycystic kidney disease and polycystic kidney disease.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 1 (AVPR2)
• Indications: 4 conditions
• Clinical trials: 11
• Chemistry: 473.9 Da · C27H21ClFN3O2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL49429
Name	Lixivaptan
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	172997
Molecular formula	C27H21ClFN3O2
Molecular weight	473.9
InChIKey	PPHTXRNHTVLQED-UHFFFAOYSA-N

SMILES: CC1=C(C=C(C=C1)F)C(=O)NC2=CC(=C(C=C2)C(=O)N3CC4=CC=CN4CC5=CC=CC=C53)Cl

IUPAC name: N-[3-chloro-4-(6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepine-5-carbonyl)phenyl]-5-fluoro-2-methylbenzamide

Also known as: CRTX 080, CRTX-080, CRTX080, Lixivaptan, Lixar, VPA 985, Vpa-985, VPA-985, VPA985, WAY-VPA-985, LIXIVAPTAN, LixivaptanÊ

Parent form; salt/anhydrous children: CHEMBL3526685

Patent coverage: 131 distinct patent families (319 SureChEMBL compound mentions), from 4 matched compound structure(s). One matched structure accounts for 250 (78%) of the total. 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
AVPR2	V2 receptor	Inverse agonist	9.2	0%	P30518

Broader ChEMBL bioactivity targets: 5 (assay-derived). Sample: Vasopressin V2 receptor, Vasopressin V1a receptor, Oxytocin receptor, Vasopressin V1a receptor, Vasopressin V2 receptor.

Bioactivity

ChEMBL activities: 33 potent at pChembl ≥ 5 of 33 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
Q00788	9.3	IC50	0.5	nM	CHEMBL_ACT_717014
AVPR2	9	IC50	1	nM	CHEMBL_ACT_1616620
AVPR2	8.92	IC50	1.2	nM	CHEMBL_ACT_1177370
AVPR2	8.92	IC50	1.2	nM	CHEMBL_ACT_1238159
AVPR2	8.92	IC50	1.2	nM	CHEMBL_ACT_1988043
AVPR2	8.92	IC50	1.2	nM	CHEMBL_ACT_217966
AVPR2	8.92	IC50	1.2	nM	CHEMBL_ACT_685575
Q00788	8.64	IC50	2.3	nM	CHEMBL_ACT_1086495
AVPR2	8.64	Ki	2.3	nM	CHEMBL_ACT_1179496
Q00788	8.64	IC50	2.3	nM	CHEMBL_ACT_1238161
Q00788	8.64	IC50	2.3	nM	CHEMBL_ACT_217965
AVPR2	8.3	IC50	5	nM	CHEMBL_ACT_2052383
AVPR2	8.3	IC50	5	nM	CHEMBL_ACT_336919
AVPR2	8.3	IC50	5	nM	CHEMBL_ACT_783600
AVPR2	7.64	Ki	23	nM	CHEMBL_ACT_1179498
AVPR1A	7.36	Ki	44	nM	CHEMBL_ACT_1179495
P30560	7.09	IC50	82	nM	CHEMBL_ACT_717013
AVPR2	7.05	Ki	90	nM	CHEMBL_ACT_336921
AVPR2	7.04	IC50	91	nM	CHEMBL_ACT_2052418
AVPR2	7.04	IC50	91	nM	CHEMBL_ACT_783601
AVPR1A	6.91	IC50	124	nM	CHEMBL_ACT_1988054
AVPR1A	6.82	IC50	150	nM	CHEMBL_ACT_2052352
AVPR1A	6.82	IC50	150	nM	CHEMBL_ACT_336920
AVPR1A	6.82	IC50	150	nM	CHEMBL_ACT_783599
AVPR1A	6.75	IC50	180	nM	CHEMBL_ACT_1616619
AVPR1A	6.64	IC50	230	nM	CHEMBL_ACT_1177369
AVPR1A	6.64	IC50	230	nM	CHEMBL_ACT_1238158
AVPR1A	6.64	IC50	230	nM	CHEMBL_ACT_217964
P30560	6.47	IC50	340	nM	CHEMBL_ACT_1238160
P30560	6.47	IC50	340	nM	CHEMBL_ACT_217963

Target pathways

Aggregated over 1 target gene(s): AVPR2.

Top Reactome pathways

6 total, by targets touching each:

Pathway	Targets	Genes
Vasopressin-like receptors	1	AVPR2
G alpha (s) signalling events	1	AVPR2
Vasopressin regulates renal water homeostasis via Aquaporins	1	AVPR2
Cargo recognition for clathrin-mediated endocytosis	1	AVPR2
Clathrin-mediated endocytosis	1	AVPR2
Defective AVP does not bind AVPR2 and causes neurohypophyseal diabetes insipidus (NDI)	1	AVPR2

Dominant GO biological processes

GO term	Targets
regulation of systemic arterial blood pressure by vasopressin	1
positive regulation of systemic arterial blood pressure	1
renal water retention	1
G protein-coupled receptor signaling pathway	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase-activating G protein-coupled receptor signaling pathway	1
activation of adenylate cyclase activity	1
hemostasis	1
positive regulation of cell population proliferation	1
negative regulation of cell population proliferation	1
positive regulation of gene expression	1
telencephalon development	1
cellular response to hormone stimulus	1
response to cytokine	1
positive regulation of vasoconstriction	1

Indications & clinical

Indications

4 indications (0 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
autosomal dominant polycystic kidney disease	3	MONDO:0004691	EFO:1001496
polycystic kidney disease	3	MONDO:0020642	EFO:0008620
congestive heart failure	2	MONDO:0005009	EFO:0000373

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

Clinical trials

Total trials: 11.

Phase distribution

Phase	Trials
PHASE3	7
PHASE2	2
PHASE1	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00578695	PHASE3	COMPLETED	THE BALANCE Study: Treatment of Hyponatremia Based on Lixivaptan in NYHA Class III/IV Cardiac Patient Evaluation
NCT00660959	PHASE3	COMPLETED	Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Oral Lixivaptan Capsules in Subject With Euvolemic Hyponatremia
NCT00876798	PHASE3	COMPLETED	A Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety and Tolerability of Oral Lixivaptan Capsules in Subjects With Euvolemic Hyponatremia
NCT00876876	PHASE3	WITHDRAWN	International, Multicenter, Open-Label and Randomized Withdrawal Study of Oral Lixivaptan in Heart Failure Patients With Chronic Hyponatremia
NCT04064346	PHASE3	TERMINATED	Efficacy and Safety of Lixivaptan in the Treatment of Autosomal Dominant Polycystic Kidney Disease
NCT04152837	PHASE3	TERMINATED	Safety of Lixivaptan in Subjects Previously Treated With Tolvaptan for Autosomal Dominant Polycystic Kidney Disease
NCT05208866	PHASE3	TERMINATED	Roll-over Study to Assess Safety of Lixivaptan in Participants With ADPKD Who Completed Study PA-ADPKD-303
NCT01055912	PHASE2	COMPLETED	Study to Evaluate the Effects of Oral Administration of Lixivaptan in Patients With Congestive Heart Failure
NCT03487913	PHASE2	COMPLETED	The ELiSA Study - Evaluation of Lixivaptan in Subjects With Autosomal Dominant Polycystic Kidney Disease
NCT00675701	PHASE1	COMPLETED	A Study to Define the ECG Effects of Lixivaptan Compared to Placebo and Moxifloxacin in Healthy Adult Men and Women: A Thorough ECG Study
NCT03717181	Not specified	NO_LONGER_AVAILABLE	Lixivaptan in a Single Subject With Intractable Pain Due to Polycystic Kidney Disease

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

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.

120 molecules share ≥1 primary target. Top 60 by shared-target count:

Molecule	Source	Status	Shared targets
CINACALCET	ChEMBL + PubChem	Phase 4 (approved)	AVPR2
PIMOZIDE	ChEMBL + PubChem	Phase 4 (approved)	AVPR2
RIFAMPIN	ChEMBL + PubChem	Phase 4 (approved)	AVPR2
TEGASEROD	ChEMBL + PubChem	Phase 4 (approved)	AVPR2
AMIODARONE	ChEMBL	Phase 4 (approved)	AVPR2
AMOXAPINE	ChEMBL	Phase 4 (approved)	AVPR2
ATOSIBAN	ChEMBL	Phase 4 (approved)	AVPR2
BALSALAZIDE	ChEMBL	Phase 4 (approved)	AVPR2
BOSUTINIB	ChEMBL	Phase 4 (approved)	AVPR2
CARBETOCIN	ChEMBL	Phase 4 (approved)	AVPR2
CHLORHEXIDINE	ChEMBL	Phase 4 (approved)	AVPR2
CLOTRIMAZOLE	ChEMBL	Phase 4 (approved)	AVPR2
CONIVAPTAN	ChEMBL	Phase 4 (approved)	AVPR2
DESMOPRESSIN	ChEMBL	Phase 4 (approved)	AVPR2
FLUSPIRILENE	ChEMBL	Phase 4 (approved)	AVPR2
IDEBENONE	ChEMBL	Phase 4 (approved)	AVPR2
IPRINDOLE	ChEMBL	Phase 4 (approved)	AVPR2
ITRACONAZOLE	ChEMBL	Phase 4 (approved)	AVPR2
LASOFOXIFENE	ChEMBL	Phase 4 (approved)	AVPR2
MEFLOQUINE	ChEMBL	Phase 4 (approved)	AVPR2
MOZAVAPTAN	ChEMBL	Phase 4 (approved)	AVPR2
NEBIVOLOL	ChEMBL	Phase 4 (approved)	AVPR2
NERATINIB	ChEMBL	Phase 4 (approved)	AVPR2
NIMESULIDE	ChEMBL	Phase 4 (approved)	AVPR2
NITAZOXANIDE	ChEMBL	Phase 4 (approved)	AVPR2
OXYTOCIN	ChEMBL	Phase 4 (approved)	AVPR2
PYRVINIUM	ChEMBL	Phase 4 (approved)	AVPR2
RIFAXIMIN	ChEMBL	Phase 4 (approved)	AVPR2
SERTINDOLE	ChEMBL	Phase 4 (approved)	AVPR2
SERTRALINE	ChEMBL	Phase 4 (approved)	AVPR2
SUNITINIB	ChEMBL	Phase 4 (approved)	AVPR2
TERFENADINE	ChEMBL	Phase 4 (approved)	AVPR2
THIOTHIXENE	ChEMBL	Phase 4 (approved)	AVPR2
TOLVAPTAN	ChEMBL	Phase 4 (approved)	AVPR2
TRIFLUOPERAZINE	ChEMBL	Phase 4 (approved)	AVPR2
VASOPRESSIN	ChEMBL	Phase 4 (approved)	AVPR2
BALOVAPTAN	ChEMBL	Phase 3	AVPR2
OTILONIUM BROMIDE	ChEMBL	Phase 3	AVPR2
PYRONARIDINE	ChEMBL	Phase 3	AVPR2
QUERCETIN	ChEMBL	Phase 3	AVPR2
RETOSIBAN	ChEMBL	Phase 3	AVPR2
BENZETHONIUM	ChEMBL	Phase 2	AVPR2
DOMIPHEN	ChEMBL	Phase 2	AVPR2
EPELSIBAN	ChEMBL	Phase 2	AVPR2
FEDOVAPAGON	ChEMBL	Phase 2	AVPR2
NELIVAPTAN	ChEMBL	Phase 2	AVPR2
ORNIPRESSIN	ChEMBL	Phase 2	AVPR2
PECAVAPTAN	ChEMBL	Phase 2	AVPR2
RELCOVAPTAN	ChEMBL	Phase 2	AVPR2
SELEPRESSIN	ChEMBL	Phase 2	AVPR2
Abiraterone	PubChem	Approved	AVPR2
Acetylcholine	PubChem	Approved	AVPR2
acetylcysteine	PubChem	Approved	AVPR2
Aclidinium Bromide	PubChem	Approved	AVPR2
Acyclovir	PubChem	Approved	AVPR2
Adenine	PubChem	Approved	AVPR2
Afatinib	PubChem	Approved	AVPR2
Allopurinol	PubChem	Approved	AVPR2
Almotriptan	PubChem	Approved	AVPR2
Alogliptin	PubChem	Approved	AVPR2