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MedKoo Cat#: 319564 | Name: Lixivaptan
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

Lixivaptan, also known as CRTX-080; VPA-985; WAY-VPA-985, is a potent, orally active, non-peptide, selective vasopressin 2 receptor antagonist. Lixivaptan works by reducing the action of the hormone vasopressin that blocks fluid excretion. Lixivaptan acts by blocking vasopressin, an anti-diuretic hormone that causes the kidneys to retain water. When the body needs to remain hydrated under certain conditions, vasopressin can have protective effects.

Chemical Structure

Lixivaptan
CAS#168079-32-1

Theoretical Analysis

MedKoo Cat#: 319564

Name: Lixivaptan

CAS#: 168079-32-1

Chemical Formula: C27H21ClFN3O2

Exact Mass: 473.1306

Molecular Weight: 473.93

Elemental Analysis: C, 68.43; H, 4.47; Cl, 7.48; F, 4.01; N, 8.87; O, 6.75

Price and Availability

Size Price Availability Quantity
5mg USD 110.00 Ready to ship
10mg USD 190.00 Ready to ship
25mg USD 400.00 Ready to ship
50mg USD 650.00 2 Weeks
100mg USD 1,150.00 2 Weeks
200mg USD 1,850.00 2 Weeks
500mg USD 3,250.00 2 Weeks
1g USD 4,650.00 2 Weeks
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Related CAS #
No Data
Synonym
CRTX-080; CRTX080; CRTX 080; VPA-985; VPA985; VPA 985; WAY-VPA-985; WAY-VPA 985; WAY-VPA985; Lixivaptan
IUPAC/Chemical Name
N-(3-chloro-4-(10,11-dihydro-6H-benzo[e]pyrrolo[1,2-a][1,4]diazepine-5-carbonyl)phenyl)-5-fluoro-2-methylbenzamide
InChi Key
UQSWTTDKNJDIRW-UHFFFAOYSA-N
InChi Code
InChI=1S/C27H21ClFN3O2/c1-16-8-9-17(29)13-22(16)27(34)31-18-10-11-20(23(28)14-18)26(33)25-21-6-2-3-7-24(21)30-15-19-5-4-12-32(19)25/h2-5,7-14,30H,6,15H2,1H3,(H,31,34)
SMILES Code
O=C(NC1=CC=C(C(C2=C3C(NCC4=CC=CN42)=CC=CC3)=O)C(Cl)=C1)C5=CC(F)=CC=C5C
Appearance
Solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Product Data
Product Data
Certificate of Analysis
View CoA: current batch, Lot#C24S11C27
Safety Data Sheet (SDS)
View Safety Data Sheet (SDS)
Instruction
View handling instruction
Biological target:
Lixivaptan (VPA-985, WAY-VPA 985) is an orally active and selective vasopressin receptor V2 antagonist, with IC50 values of 1.2 and 2.3 nM for human and rat V2, respectively.
In vitro activity:
Based on preliminary experiments, 100 nM lixivaptan was chosen as the appropriate minimal concentration displaying a clear inhibitory effect on dDAVP-induced increase in cAMP levels in MCD4 cells (data not shown). Treatment with lixivaptan completely abolished the effect of dDAVP on cAMP (dDAVP+LXV = 1.013 ± 0.015, n = 250 cells) (Figure 1B). Reference: Int J Mol Sci. 2019 Dec 26;21(1):183. https://pubmed.ncbi.nlm.nih.gov/31888044/
In vivo activity:
Lixivaptan is expected to have a safer liver profile compared to tolvaptan, the only drug approved to delay PKD progression, based on computational model results and initial clinical evidence. PCK rat and Pkd1RC/RC mouse littermates were fed without or with lixivaptan (0.5%) and R-568 (0.025% for rats and 0.04% for mice), alone or in combination, for 7 (rats) or 13 (mice) weeks. In PCK rats, the combined treatment strongly decreased kidney weight, cyst and fibrosis volumes by 20%, 49%, and 73%, respectively, compared to untreated animals. In Pkd1RC/RC mice, the same parameters were reduced by 20%, 56%, and 69%, respectively. Reference: FASEB J. 2021 Oct;35(10):e21874. https://pubmed.ncbi.nlm.nih.gov/34486176/
Solvent mg/mL mM comments
Solubility
DMF 30.0 63.30
DMSO 91.7 193.42
DMSO:PBS (pH 7.2) (1:2) 0.3 0.70
Ethanol 8.5 17.94
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 473.93 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
1. Di Mise A, Venneri M, Ranieri M, Centrone M, Pellegrini L, Tamma G, Valenti G. Lixivaptan, a New Generation Diuretic, Counteracts Vasopressin-Induced Aquaporin-2 Trafficking and Function in Renal Collecting Duct Cells. Int J Mol Sci. 2019 Dec 26;21(1):183. doi: 10.3390/ijms21010183. PMID: 31888044; PMCID: PMC6981680. 2. Di Mise A, Wang X, Ye H, Pellegrini L, Torres VE, Valenti G. Pre-clinical evaluation of dual targeting of the GPCRs CaSR and V2R as therapeutic strategy for autosomal dominant polycystic kidney disease. FASEB J. 2021 Oct;35(10):e21874. doi: 10.1096/fj.202100774R. PMID: 34486176; PMCID: PMC9290345. 3. Wang X, Constans MM, Chebib FT, Torres VE, Pellegrini L. Effect of a Vasopressin V2 Receptor Antagonist on Polycystic Kidney Disease Development in a Rat Model. Am J Nephrol. 2019;49(6):487-493. doi: 10.1159/000500667. Epub 2019 May 22. PMID: 31117065; PMCID: PMC6647848.
In vitro protocol:
1. Di Mise A, Venneri M, Ranieri M, Centrone M, Pellegrini L, Tamma G, Valenti G. Lixivaptan, a New Generation Diuretic, Counteracts Vasopressin-Induced Aquaporin-2 Trafficking and Function in Renal Collecting Duct Cells. Int J Mol Sci. 2019 Dec 26;21(1):183. doi: 10.3390/ijms21010183. PMID: 31888044; PMCID: PMC6981680.
In vivo protocol:
1. Di Mise A, Wang X, Ye H, Pellegrini L, Torres VE, Valenti G. Pre-clinical evaluation of dual targeting of the GPCRs CaSR and V2R as therapeutic strategy for autosomal dominant polycystic kidney disease. FASEB J. 2021 Oct;35(10):e21874. doi: 10.1096/fj.202100774R. PMID: 34486176; PMCID: PMC9290345. 2. Wang X, Constans MM, Chebib FT, Torres VE, Pellegrini L. Effect of a Vasopressin V2 Receptor Antagonist on Polycystic Kidney Disease Development in a Rat Model. Am J Nephrol. 2019;49(6):487-493. doi: 10.1159/000500667. Epub 2019 May 22. PMID: 31117065; PMCID: PMC6647848.
1: Liamis G, Filippatos TD, Elisaf MS. Treatment of hyponatremia: the role of lixivaptan. Expert Rev Clin Pharmacol. 2014 Jul;7(4):431-41. doi: 10.1586/17512433.2014.911085. Epub 2014 Apr 28. Review. PubMed PMID: 24766294. 2: Bowman BT, Rosner MH. Lixivaptan - an evidence-based review of its clinical potential in the treatment of hyponatremia. Core Evid. 2013;8:47-56. doi: 10.2147/CE.S36744. Epub 2013 Jul 11. PubMed PMID: 23874242; PubMed Central PMCID: PMC3712664. 3: Ring T. Lixivaptan and hyponatremia. Kidney Int. 2013 Jun;83(6):1205-6. doi: 10.1038/ki.2013.39. PubMed PMID: 23728012. 4: Zmily HD, Alani A, Ghali JK. Evaluation of lixivaptan in euvolemic and hypervolemic hyponatremia and heart failure treatment. Expert Opin Drug Metab Toxicol. 2013 May;9(5):645-55. doi: 10.1517/17425255.2013.783566. Epub 2013 Apr 9. Review. PubMed PMID: 23570283. 5: Borne RT, Krantz MJ. Lixivaptan for hyponatremia--the numbers game. JAMA. 2012 Dec 12;308(22):2345-6. doi: 10.1001/jama.2012.54515. PubMed PMID: 23232892. 6: Rosner MH. Lixivaptan: a vasopressin receptor antagonist for the treatment of hyponatremia. Kidney Int. 2012 Dec;82(11):1154-6. doi: 10.1038/ki.2012.317. PubMed PMID: 23151986. 7: Allison SJ. Hyponatraemia: Lixivaptan for euvolaemic hyponatraemia. Nat Rev Nephrol. 2012 Nov;8(11):612. doi: 10.1038/nrneph.2012.204. Epub 2012 Sep 11. PubMed PMID: 22965690. 8: Abraham WT, Decaux G, Josiassen RC, Yagil Y, Kopyt N, Thacker HP, Mannelli M, Bichet DG, Orlandi C; HARMONY Study Group. Oral lixivaptan effectively increases serum sodium concentrations in outpatients with euvolemic hyponatremia. Kidney Int. 2012 Dec;82(11):1215-22. doi: 10.1038/ki.2012.274. Epub 2012 Aug 29. PubMed PMID: 22932122. 9: Abraham WT, Hensen J, Gross PA, Bichet DG, Josiassen RC, Chafekar DS, Orlandi C; LIBRA Study Group. Lixivaptan safely and effectively corrects serum sodium concentrations in hospitalized patients with euvolemic hyponatremia. Kidney Int. 2012 Dec;82(11):1223-30. doi: 10.1038/ki.2012.275. Epub 2012 Aug 29. PubMed PMID: 22932119. 10: Dahl E, Gluud LL, Kimer N, Krag A. Meta-analysis: the safety and efficacy of vaptans (tolvaptan, satavaptan and lixivaptan) in cirrhosis with ascites or hyponatraemia. Aliment Pharmacol Ther. 2012 Oct;36(7):619-26. doi: 10.1111/apt.12025. Epub 2012 Aug 21. PubMed PMID: 22908905. 11: Lim GB. Heart failure: Lixivaptan reduces volume overload in patients with heart failure. Nat Rev Cardiol. 2012 May 8;9(7):373. doi: 10.1038/nrcardio.2012.67. PubMed PMID: 22566061. 12: Ghali JK, Orlandi C, Abraham WT; CK-LX2401 Study Investigators. The efficacy and safety of lixivaptan in outpatients with heart failure and volume overload: results of a multicentre, randomized, double-blind, placebo-controlled, parallel-group study. Eur J Heart Fail. 2012 Jun;14(6):642-51. doi: 10.1093/eurjhf/hfs051. Epub 2012 Apr 17. PubMed PMID: 22510424. 13: Zmily HD, Khan NS, Daifallah S, Ghali JK. The potential role for lixivaptan in heart failure and in hyponatremia. Expert Opin Investig Drugs. 2011 Jun;20(6):831-48. doi: 10.1517/13543784.2011.579102. Epub 2011 May 9. Review. PubMed PMID: 21548825. 14: Ghali JK, Zmily HD, Farah JO, Daifallah S. Lixivaptan, a non-peptide vasopressin V2 receptor antagonist for the potential oral treatment of hyponatremia. IDrugs. 2010 Nov;13(11):782-92. Review. PubMed PMID: 21046526. 15: Abraham WT, Aranda JM, Boehmer JP, Elkayam U, Gilbert EM, Gottlieb SS, Hasenfuss G, Kukin M, Lowes BD, O'Connell JB, Tavazzi L, Feldman AM, Ticho B, Orlandi C. Rationale and design of the treatment of hyponatremia based on lixivaptan in NYHA class III/IV cardiac patient evaluation (THE BALANCE) study. Clin Transl Sci. 2010 Oct;3(5):249-53. doi: 10.1111/j.1752-8062.2010.00217.x. PubMed PMID: 20973922. 16: Ku E, Nobakht N, Campese VM. Lixivaptan: a novel vasopressin receptor antagonist. Expert Opin Investig Drugs. 2009 May;18(5):657-62. doi: 10.1517/13543780902889760 . Review. PubMed PMID: 19379124. 17: Molinari AJ, Trybulski EJ, Bagli J, Croce S, Considine J, Qi J, Ali K, Demaio W, Lihotz L, Cochran D. Identification and synthesis of major metabolites of Vasopressin V2-receptor agonist WAY-151932, and antagonist, Lixivaptan. Bioorg Med Chem Lett. 2007 Nov 1;17(21):5796-800. Epub 2007 Aug 28. PubMed PMID: 17855087. 18: Abraham WT, Shamshirsaz AA, McFann K, Oren RM, Schrier RW. Aquaretic effect of lixivaptan, an oral, non-peptide, selective V2 receptor vasopressin antagonist, in New York Heart Association functional class II and III chronic heart failure patients. J Am Coll Cardiol. 2006 Apr 18;47(8):1615-21. Epub 2006 Mar 29. PubMed PMID: 16630999. 19: Martinez-Castelao A. Lixivaptan (American Home Products). Curr Opin Investig Drugs. 2001 Apr;2(4):525-30. Review. PubMed PMID: 11566011.