WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H205941
CAS#: 244133-31-1
Description: VRT-043198, the active metabolite of VX-765 (Belnacasan), is a Caspase inhibitor. VRT-043198 exhibits 100- to 10,000-fold selectivity against other caspase-3 and -6 to -9. VRT-043198 inhibited the release of interleukin (IL)-1beta and IL-18, but it had little effect on the release of several other cytokines, including IL-1alpha, tumor necrosis factor-alpha, IL-6 and IL-8.
Hodoodo Cat#: H205941
Name: VRT-043198
CAS#: 244133-31-1
Chemical Formula: C22H29ClN4O6
Exact Mass: 480.18
Molecular Weight: 480.940
Elemental Analysis: C, 54.94; H, 6.08; Cl, 7.37; N, 11.65; O, 19.96
Synonym: VRT043198, VRT-043198, VRT 043198; mitabolite of VX-765 (Belnacasan);
IUPAC/Chemical Name: 1. (2S)-1-((S)-2-(4-amino-3-chlorobenzamido)-3,3-dimethylbutanoyl)-N-((3S)-2-hydroxy-5-oxotetrahydrofuran-3-yl)pyrrolidine-2-carboxamide (ring-close) 2. (S)-3-((S)-1-((S)-2-(4-amino-3-chlorobenzamido)-3,3-dimethylbutanoyl)pyrrolidine-2-carboxamido)-4-oxobutanoic acid (ring open)
InChi Key: GGAMPJOZFRKVQR-CIWGKMQQSA-N; SOZONDBMOYWSRW-QANKJYHBSA-N.
InChi Code: InChI=1S/C22H29ClN4O6/c1-22(2,3)17(26-18(29)11-6-7-13(24)12(23)9-11)20(31)27-8-4-5-15(27)19(30)25-14-10-16(28)33-21(14)32/h6-7,9,14-15,17,21,32H,4-5,8,10,24H2,1-3H3,(H,25,30)(H,26,29)/t14-,15-,17+,21?/m0/s1; InChI=1S/C22H29ClN4O6/c1-22(2,3)18(26-19(31)12-6-7-15(24)14(23)9-12)21(33)27-8-4-5-16(27)20(32)25-13(11-28)10-17(29)30/h6-7,9,11,13,16,18H,4-5,8,10,24H2,1-3H3,(H,25,32)(H,26,31)(H,29,30)/t13-,16-,18+/m0/s1
SMILES Code: 1. O=C([C@H]1N(C([C@H](C(C)(C)C)NC(C2=CC=C(N)C(Cl)=C2)=O)=O)CCC1)N[C@@H](C3)C(O)OC3=O (ring-close) 2. 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](CC(O)=O)C=O (ring-open)
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: 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: >5 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:
Biological target: | VRT-043198 is an inhibitor of IL-converting enzyme (ICE)/caspase-1 with Kis of 0.8 nM and less than 0.6 nM for caspase-1 and caspase-4, respectively. |
In vitro activity: | In cultures of peripheral blood mononuclear cells and whole blood from healthy subjects stimulated with bacterial products, VRT-043198 inhibited the release of interleukin (IL)-1beta and IL-18, but it had little effect on the release of several other cytokines, including IL-1alpha, tumor necrosis factor-alpha, IL-6 and IL-8. In contrast, VRT-043198 had little or no demonstrable activity in cellular models of apoptosis, and it did not affect the proliferation of activated primary T cells or T-cell lines. Reference: J Pharmacol Exp Ther. 2007 May;321(2):509-16. https://jpet.aspetjournals.org/content/321/2/509.long |
In vivo activity: | VX-765 was efficiently converted to VRT-043198 when administered orally to mice, and it inhibited lipopolysaccharide-induced cytokine secretion. In addition, VX-765 reduced disease severity and the expression of inflammatory mediators in models of rheumatoid arthritis and skin inflammation. These data suggest that VX-765 is a novel cytokine inhibitor useful for treatment of inflammatory diseases. Reference: J Pharmacol Exp Ther. 2007 May;321(2):509-16. https://jpet.aspetjournals.org/content/321/2/509.long |
Solvent | Max Conc. mg/mL | Max Conc. mM | |
---|---|---|---|
Solubility | |||
DMSO | 50.0 | 103.96 |
The following data is based on the product molecular weight 480.94 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.
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. Wannamaker W, Davies R, Namchuk M, Pollard J, Ford P, Ku G, Decker C, Charifson P, Weber P, Germann UA, Kuida K, Randle JC. (S)-1-((S)-2-{[1-(4-amino-3-chloro-phenyl)-methanoyl]-amino}-3,3-dimethyl-butanoyl)-pyrrolidine-2-carboxylic acid ((2R,3S)-2-ethoxy-5-oxo-tetrahydro-furan-3-yl)-amide (VX-765), an orally available selective interleukin (IL)-converting enzyme/caspase-1 inhibitor, exhibits potent anti-inflammatory activities by inhibiting the release of IL-1beta and IL-18. J Pharmacol Exp Ther. 2007 May;321(2):509-16. doi: 10.1124/jpet.106.111344. Epub 2007 Feb 8. PMID: 17289835. |
In vitro protocol: | 1. Wannamaker W, Davies R, Namchuk M, Pollard J, Ford P, Ku G, Decker C, Charifson P, Weber P, Germann UA, Kuida K, Randle JC. (S)-1-((S)-2-{[1-(4-amino-3-chloro-phenyl)-methanoyl]-amino}-3,3-dimethyl-butanoyl)-pyrrolidine-2-carboxylic acid ((2R,3S)-2-ethoxy-5-oxo-tetrahydro-furan-3-yl)-amide (VX-765), an orally available selective interleukin (IL)-converting enzyme/caspase-1 inhibitor, exhibits potent anti-inflammatory activities by inhibiting the release of IL-1beta and IL-18. J Pharmacol Exp Ther. 2007 May;321(2):509-16. doi: 10.1124/jpet.106.111344. Epub 2007 Feb 8. PMID: 17289835. |
In vivo protocol: | 1. Wannamaker W, Davies R, Namchuk M, Pollard J, Ford P, Ku G, Decker C, Charifson P, Weber P, Germann UA, Kuida K, Randle JC. (S)-1-((S)-2-{[1-(4-amino-3-chloro-phenyl)-methanoyl]-amino}-3,3-dimethyl-butanoyl)-pyrrolidine-2-carboxylic acid ((2R,3S)-2-ethoxy-5-oxo-tetrahydro-furan-3-yl)-amide (VX-765), an orally available selective interleukin (IL)-converting enzyme/caspase-1 inhibitor, exhibits potent anti-inflammatory activities by inhibiting the release of IL-1beta and IL-18. J Pharmacol Exp Ther. 2007 May;321(2):509-16. doi: 10.1124/jpet.106.111344. Epub 2007 Feb 8. PMID: 17289835. |
1: Adriaenssens Y, Jiménez Fernández D, Vande Walle L, Elvas F, Joossens J, Lambeir A, Augustyns K, Lamkanfi M, Van der Veken P. Carboxylate isosteres for caspase inhibitors: the acylsulfonamide case revisited. Org Biomol Chem. 2017 Sep 13;15(35):7456-7473. doi: 10.1039/c7ob01403a. PubMed PMID: 28837200.
2: Wannamaker W, Davies R, Namchuk M, Pollard J, Ford P, Ku G, Decker C, Charifson P, Weber P, Germann UA, Kuida K, Randle JC. (S)-1-((S)-2-{[1-(4-amino-3-chloro-phenyl)-methanoyl]-amino}-3,3-dimethyl-butanoy l)-pyrrolidine-2-carboxylic acid ((2R,3S)-2-ethoxy-5-oxo-tetrahydro-furan-3-yl)-amide (VX-765), an orally available selective interleukin (IL)-converting enzyme/caspase-1 inhibitor, exhibits potent anti-inflammatory activities by inhibiting the release of IL-1beta and IL-18. J Pharmacol Exp Ther. 2007 May;321(2):509-16. Epub 2007 Feb 8. PubMed PMID: 17289835.
1. Bassil F, Fernagut PO, Bezard E, Pruvost A, Leste-Lasserre T, Hoang QQ, Ringe D, Petsko GA, Meissner WG. Reducing C-terminal truncation mitigates synucleinopathy and neurodegeneration in a transgenic model of multiple system atrophy. Proc Natl Acad Sci U S A. 2016 Aug 23;113(34):9593-8. doi: 10.1073/pnas.1609291113. Epub 2016 Aug 1. PMID: 27482103; PMCID: PMC5003293.