LIXIVAPTAN

Details

Stereochemistry	ACHIRAL
Molecular Formula	C27H21ClFN3O2
Molecular Weight	473.926
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1=C(C=C(F)C=C1)C(=O)NC2=CC(Cl)=C(C=C2)C(=O)N3CC4=CC=CN4CC5=C3C=CC=C5

InChI

InChIKey=PPHTXRNHTVLQED-UHFFFAOYSA-N

InChI=1S/C27H21ClFN3O2/c1-17-8-9-19(29)13-23(17)26(33)30-20-10-11-22(24(28)14-20)27(34)32-16-21-6-4-12-31(21)15-18-5-2-3-7-25(18)32/h2-14H,15-16H2,1H3,(H,30,33)

HIDE SMILES / InChI

Molecular Formula	C27H21ClFN3O2
Molecular Weight	473.926
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/CardiovascularandRenalDrugsAdvisoryCommittee/UCM318869.pdf
Curator's Comment: description was created based on several sources, including: http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/CardiovascularandRenalDrugsAdvisoryCommittee/UCM318867.pdf http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/CardiovascularandRenalDrugsAdvisoryCommittee/UCM320601.pdf

Lixivaptan is an orally-active, vasopressin 2 receptor antagonist. It is indicated for the treatment of symptomatic hypervolemic and euvolemic hyponatremia, associated with heart failure (HF) and syndrome of inappropriate antidiuretic hormone (SIADH). Adverse events likely to be result of the pharmacologic action of lixivaptan are: constipation, dry mouth, dizziness, insomnia. Grapefruit juice significantly increased the extent of lixivaptan absorption as compared to lixivaptan administered under fasted conditions but not under fed conditions. Lixivaptan Cmax and AUC∞ increased by 2.4-fold and 3.2-fold, respectively, when lixivaptan was administered with ketoconazole (the same in case of Simvastatin).

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Vasopressin V2 receptor 15 Target ID: CHEMBL1790 Sources: http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/CardiovascularandRenalDrugsAdvisoryCommittee/UCM318869.pdf	Antagonist 2778	0.48 nM [Ki]
Cytochrome P450 3A4 127 Target ID: CHEMBL340 Sources: http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/CardiovascularandRenalDrugsAdvisoryCommittee/UCM318867.pdf	Substrate 661	4.4 µM [IC50]
Cytochrome P450 2C8 18 Target ID: CHEMBL3721 Sources: http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/CardiovascularandRenalDrugsAdvisoryCommittee/UCM318867.pdf	Substrate 661	0.57 µM [IC50]
Cytochrome P450 2C9 50 Target ID: CHEMBL3397 Sources: http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/CardiovascularandRenalDrugsAdvisoryCommittee/UCM318867.pdf	Substrate 661	0.79 µM [IC50]
Vasopressin V1a receptor 17 Target ID: P37288 Gene ID: 552.0 Gene Symbol: AVPR1A Target Organism: Homo sapiens (Human) Sources: Zingg, H.H., Bourque, W.C., Bichet, D.G. (2012) 'Vasopressin and Oxytocin: Molecular, Cellular, and Clinical Advances', p.440 Retrieved from \| https://books.google.ru/books?id=eaXfBwAAQBAJ	Antagonist 2778	55.0 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hyponatremia, associated with heart failure and syndrome of inappropriate antidiuretic hormone 1 Sources: http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/CardiovascularandRenalDrugsAdvisoryCommittee/UCM318869.pdf	Primary		Phase III 656	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
1877 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12395330	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	LIXIVAPTAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
719 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12395330	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	LIXIVAPTAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
183 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12395330	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:	LIXIVAPTAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
1208 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12395330	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	LIXIVAPTAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
210 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12395330	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	LIXIVAPTAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
14884 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12395330	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	LIXIVAPTAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
4391 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12395330	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	LIXIVAPTAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
499 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12395330	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:	LIXIVAPTAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
8775 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12395330	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	LIXIVAPTAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
953 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12395330	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	LIXIVAPTAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
21.62 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12395330	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	LIXIVAPTAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
9.05 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12395330	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	LIXIVAPTAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
14.61 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12395330	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:	LIXIVAPTAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
22.56 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12395330	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	LIXIVAPTAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
12.49 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12395330	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	LIXIVAPTAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FASTED

Doses

Dose	Population	Adverse events
300 mg single, oral Highest studied dose Dose: 300 mg Route: oral Route: single Dose: 300 mg Sources: https://pubmed.ncbi.nlm.nih.gov/12395330 Page: p.1202	unhealthy, ADULT n = 5 Health Status: unhealthy Condition: Cirrhosis Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 5 Sources: https://pubmed.ncbi.nlm.nih.gov/12395330 Page: p.1202	Sources: https://pubmed.ncbi.nlm.nih.gov/12395330 Page: p.1202
250 mg 2 times / day multiple, oral Studied dose Dose: 250 mg, 2 times / day Route: oral Route: multiple Dose: 250 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/12500203 Page: p.187, 188	unhealthy, ADULT n = 10 Health Status: unhealthy Condition: cirrhosis of liver Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 10 Sources: https://pubmed.ncbi.nlm.nih.gov/12500203 Page: p.187, 188	Disc. AE: Blood sodium increased... AEs leading to discontinuation/dose reduction: Blood sodium increased (50%) Sources: https://pubmed.ncbi.nlm.nih.gov/12500203 Page: p.187, 188

AEs

AE	Significance	Dose	Population
Blood sodium increased	50% Disc. AE	250 mg 2 times / day multiple, oral Studied dose Dose: 250 mg, 2 times / day Route: oral Route: multiple Dose: 250 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/12500203 Page: p.187, 188	unhealthy, ADULT n = 10 Health Status: unhealthy Condition: cirrhosis of liver Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 10 Sources: https://pubmed.ncbi.nlm.nih.gov/12500203 Page: p.187, 188

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P001Y96	https://www.1pchem.com/search?query=1P001Y96
AstaTech	40792	http://astatechinc.com/CPSResult.php?CRNO=40792
BOC Sciences	168079-32-1	http://www.bocsci.com/description.asp?cas=168079-32-1
Chem Scene	CS-7512	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-7512
Debye Scientific	DB-064673	https://www.debyesci.com/index.php?id=product&ext[cno]=DB-064673
Excenen	EX-A1129	http://www.excenen.com/searchresultlist.php?id=EX-A1129
Hairui	HR117073	http://www.hairuichem.com/en/product/search.do?q=HR117073
MedChem Express	HY-14185	https://www.medchemexpress.com/search.html?q=HY-14185&ft=&fa=&fp=
MolPort	MolPort-035-681-616	https://www.molport.com/shop/molecule-link/MolPort-035-681-616
ShangHai Biochempartner	BCP09167	http://www.biochempartner.com/search_BCP09167
Toronto Research Chemicals	L469275	https://www.trc-canada.com/product-detail/?CatNum=L469275
Toronto Research Chemicals	O262005	https://www.trc-canada.com/product-detail/?CatNum=O262005
eMolecules	42853730	https://orderbb.emolecules.com/search/#?query=42853730
eNovation Chemicals	D541728	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D541728&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-4245284872	https://mcule.com/MCULE-4245284872/

PubMed

Title	Date	PubMed
Binding properties of a selective tritiated vasopressin V2 receptor antagonist, [H]-SR 121463.	2000 Oct	11012895

Patents

Sample Use Guides

In Vivo Use Guide

The starting dose for hospitalized patients with hyponatremia is 50 mg once daily (25 mg for outpatients) without regard to meals. The dose may be doubled every 24 hours depending on individual patient response to a maximum of 100 mg once daily (total daily dose 100 mg) in syndrome of inappropriate antidiuretic hormone patients and to a maximum of 100 mg BID (total daily dose 200 mg) in heart failure patients, as needed, to achieve the desired sodium concentration.

Route of Administration: Oral

In Vitro Use Guide

Scatchard analysis of binding to cloned human V2-receptors showed that the dissociation constant (Kd) of [3H]-AVP increased from 0.79 nM in the vehicle-control to 1.04 nM in the presence of 0.5 nM VPA-985, while the maximum binding (B max) remained unchanged (1.14 vs. 1.02 fmole/ug protein, respectively).

Substance Class	Chemical Created by `admin` on `Sat Dec 16 05:04:48 UTC 2023` Edited by `admin` on `Sat Dec 16 05:04:48 UTC 2023`
Record UNII	8F5X4B082E
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

LIXIVAPTAN

Official Name

English

LIXAR

Brand Name

English

lixivaptan [INN]

Common Name

English

LIXIVAPTAN [MI]

Common Name

English

CRTX-080

Code

English

VPA-985

Code

English

LIXIVAPTAN [MART.]

Common Name

English

3'-CHLORO-5-FLUORO-4'-(5H-PYRROLO(2,1-C)(1,4)BENZODIAZEPIN-10(11H)-YLCARBONYL)-O-TOLUANILIDE

Common Name

English

WAY-VPA-985

Code

English

Lixivaptan [WHO-DD]

Common Name

English

CRTX080

Code

English

VPA985

Code

English

BENZAMIDE, N-(3-CHLORO-4-(5H-PYRROLO(2,1-C)(1,4)BENZODIAZEPIN-10(11H)-YLCARBONYL)PHENYL)-5-FLUORO-2-METHYL-

Systematic Name

English

LIXIVAPTAN [USAN]

Common Name

English

LIXIVAPTAN [VANDF]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C2180