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5mg |
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10mg |
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25mg |
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50mg |
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100mg |
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250mg |
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500mg |
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Purity: ≥98%
Lixivaptan (formerly known as VPA-985, WAY-VPA 985) is a novel, potent, selective and orally bioactive non-peptide antagonist of vasopressin receptor V2 with IC50 values of 1.2 and 2.3 nM for human and rat V2, respectively. Lixivaptan functions by inhibiting the function of the vasopressin hormone, which prevents the excretion of fluid. Vasopressin is an anti-diuretic hormone that causes the kidneys to retain water, and lixivaptan works by blocking it. Vasopressin can provide protective effects when the body needs to stay hydrated under specific circumstances.
Targets |
human V2 receptor ( IC50 = 1.2 nM ); rat V2 receptor ( IC50 = 2.3 nM )
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ln Vitro |
Lixivaptan exhibits competitive antagonist activity on V2 absorption [1].
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ln Vivo |
In conscious dogs, lixivaptan (1, 3, and 10 mg/kg po) was administered with 30 mL/kg (po) and arginine vasopressin (AVP)-treated water (0.4 μg/kg in oil, subcutaneously) ) ) relative to the AVP-treated vehicle group increased Uvol by 438, 1018, and 1133%, respectively, while Uosm decreased from 1222 mOsm/kg (water-loaded and AVP-treated vehicle) to 307, 221, and 175 mOsm/kg, respectively. In AVP-deficient homozygous Brattleboro, lixivaptan at 10 mg/kg po (i.e., 10 times the dose that produced V2 multiantagonist activity) bid for 5 days showed sustained multiantagonist effects without evidence of agonist effects. In a randomized, double-blind, gradient-controlled ascending single-dose study, patients (fasted overnight before formulation) and mice received 30, 75, or 150 mg of lixivaptan. All of these increased doses increase urine flow and serum sodium concentrations and produce significant dose-related decreases in urine osmolality [1]. Phase II clinical trials in patients with congestive heart failure, liver tumor ascites, or inappropriate antidiuretic metabolic syndrome showed that lixivaptan increased water clearance rather than affecting renal sodium excretion or activating the neurohormonal system [2].
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References |
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Molecular Formula |
C27H21CLFN3O2
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Molecular Weight |
473.92594
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Exact Mass |
473.13
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Elemental Analysis |
C, 68.43; H, 4.47; Cl, 7.48; F, 4.01; N, 8.87; O, 6.75
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CAS # |
168079-32-1
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Appearance |
Solid powder
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SMILES |
CC1=C(C=C(C=C1)F)C(=O)NC2=CC(=C(C=C2)C(=O)N3CC4=CC=CN4CC5=CC=CC=C53)Cl
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InChi Key |
PPHTXRNHTVLQED-UHFFFAOYSA-N
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InChi Code |
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)
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Chemical Name |
N-[3-chloro-4-(6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepine-5-carbonyl)phenyl]-5-fluoro-2-methylbenzamide
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Synonyms |
VPA-985; VPA985; VPA 985; WAY-VPA-985; WAY VPA-985; WAY-VPA 985; WAY VPA 985; CRTX-080; CRTX080; CRTX 080; Lixivaptan
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HS Tariff Code |
2934.99.9001
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vitro) |
DMSO: ~95 mg/mL (~200.5 mM)
Ethanol: ~7 mg/mL |
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Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.39 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.39 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.) |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.1100 mL | 10.5501 mL | 21.1002 mL | |
5 mM | 0.4220 mL | 2.1100 mL | 4.2200 mL | |
10 mM | 0.2110 mL | 1.0550 mL | 2.1100 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
NCT01055912 | Completed | Drug: Lixivaptan Drug: Placebo |
Congestive Heart Failure | CardioKine Inc. | January 2010 | Phase 2 |
NCT00876798 | Completed | Drug: Lixivaptan Drug: Placebo |
Euvolemic Hyponatremia | CardioKine Inc. | June 2009 | Phase 3 |
NCT00578695 | Completed | Drug: lixivaptan Drug: Placebo |
Hyponatremia | CardioKine Inc. | January 2007 | Phase 3 |
NCT00675701 | Completed | Drug: placebo Drug: lixivaptan Drug: moxifloxacin |
Healthy | CardioKine Inc. | May 2008 | Phase 1 |
NCT03487913 | Completed | Drug: Lixivaptan | Autosomal Dominant Polycystic Kidney Disease |
Palladio Biosciences | September 14, 2018 | Phase 2 |