VX 765

Cas：273404-37-8

Product Information：

VX 765, is designed to inhibit Caspase, which is an enzyme that controls the generation of two cytokines, IL-1b and IL-18. VX-765 has been shown to inhibit acute seizures in preclinical models. In addition, VX-765 has shown activity in preclinical models of chronic epilepsy. VX-765 had been dosed in over 100 patients in phase-I and phase-IIa clinical trials relating to other diseases, including a 28-day phase-IIa clinical trial in patients with psoriasis. It has completed the treatment phase of a phase-IIa clinical trial of VX-765 that enrolled approximately 75 patients with treatment-resistant epilepsy. The double-blind, randomized, placebo-controlled clinical trial was designed to evaluate the safety, tolerability and clinical activity of VX-765.

Chemical Formula: C24H33ClN4O6

Exact Mass: 508.20886

Molecular Weight: 508.99

Elemental Analysis: C, 56.63; H, 6.53; Cl, 6.97; N, 11.01; O, 18.86

Synonym: 

VX 765

VX765

VX-765

Belnacasan

Chemical Name: (S)-1-((S)-2-(4-amino-3-chlorobenzamido)-3,3-dimethylbutanoyl)-N-((2R,3S)-2-ethoxy-5-oxotetrahydrofuran-3-yl)pyrrolidine-2-carboxamide

InChi Key:

SJDDOCKBXFJEJB-MOKWFATOSA-N

InChi Code: InChI=1S/C24H33ClN4O6/c1-5-34-23-16(12-18(30)35-23)27-21(32)17-7-6-10-29(17)22(33)19(24(2,3)4)28-20(31)13-8-9-15(26)14(25)11-13/h8-9,11,16-17,19,23H,5-7,10,12,26H2,1-4H3,(H,27,32)(H,28,31)/t16-,17-,19+,23+/m0/s1

Smiles Code:

O=C([C@H]1N(C([C@@H](NC(C2=CC=C(N)C(Cl)=C2)=O)C(C)(C)C)=O)CCC1)N[C@@H](C3)[C@H](OCC)OC3=O

Technical Data：

Appearance: White to off-white 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: 0 A– 4 o C for short term (weeks to 1 month) or -20 o C for long terms (months to years).

Solubility: soluble in DMSO, not soluble 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

In Vivo:

Belnacasan reduces inflammatory response in murine models of inflammatory disease.

Belnacasan (50-200 mg/kg) significantly reduces serum IL-1β levels by as much as 60%. It is noteworthy that the effect of Belnacasan on the release of IL-1β induced by LPS reached a plateau at 100 mg/kg. Belnacasan (25-100 mg/kg × 2) significantly reduces ear edema. Belnacasan also dose-dependently reduces the concentrations of cytokines, chemokines, and inflammatory mediators in the ear biopsy samples.

Belnacasan (25-200 mg/kg) significantly delays the time to seizure onset by 1.5- to twofold (p<0.01), reduces the number of seizures by 40% (p<0.01) and the total time spent in EEG seizure activity by 30 to 50% (p<0.01).

References：

1. Bialer M, Johannessen SI, Levy RH, Perucca E, Tomson T, White HS. Progress report on new antiepileptic drugs: a summary of the Eleventh Eilat Conference (EILAT XI). Epilepsy Res. 2013 Jan;103(1):2-30. doi: 10.1016/j.eplepsyres.2012.10.001. Epub 2012 Dec 4. Review. PubMed PMID: 23219031.

2. Boxer MB, Shen M, Auld DS, Wells JA, Thomas CJ. A small molecule inhibitor of Caspase 1. 2010 Feb 25 [updated 2011 Mar 3]. Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010-. Available from http://www.ncbi.nlm.nih.gov/books/NBK56241/ PubMed PMID: 21735610.

3. Akin D, Ravizza T, Maroso M, Carcak N, Eryigit T, Vanzulli I, Aker RG, Vezzani A, Onat FY. IL-1β is induced in reactive astrocytes in the somatosensory cortex of rats with genetic absence epilepsy at the onset of spike-and-wave discharges, and contributes to their occurrence. Neurobiol Dis. 2011 Dec;44(3):259-69. doi: 10.1016/j.nbd.2011.05.015. Epub 2011 May 30. PubMed PMID: 21645619.

4. Maroso M, Balosso S, Ravizza T, Iori V, Wright CI, French J, Vezzani A. Interleukin-1β biosynthesis inhibition reduces acute seizures and drug resistant chronic epileptic activity in mice. Neurotherapeutics. 2011 Apr;8(2):304-15. doi: 10.1007/s13311-011-0039-z. PubMed PMID: 21431948; PubMed Central PMCID: PMC3101825.

Products are for research use only. Not for human use.