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VNI (molecule)

VNI (molecule)

VNI is an experimental drug for treating Chagas disease currently being studied at Vanderbilt University. The molecule acts by inhibiting Trypanosoma cruzi sterol 14α-desmethylase activity in vitro. It exhibits no toxicity in mouse cells and unlike the related compounds posaconazole and fluconazole, increasing the dose is not required to maintain anti-parasitic activity.[1][2][3]

According to the researchers, "VNI cures the acute and chronic forms of Chagas disease in mice, with 100% survival and no observable side effects. Low cost (<$0.10/mg [4]), oral bioavailability, favorable pharmacokinetics, and low toxicity make this compound an exceptional candidate for clinical trials. The efficacy of VNI provides additional compelling support for efficacious antiparasitic treatment of chronic Chagas disease, further validating CYP51 as a viable drug targeting T. cruzi, and it opens a new opportunity for therapeutic cure of patients. Although widespread searches for other new drugs that target T. cruzi are surely being pursued, there are millions of patients with this debilitating illness who need immediate therapy, and VNI or a derivative might fulfill this need."[1]

VNI
Names
IUPAC name
N-[(1R)-1-(2,4-dichlorophenyl)-2-imidazol-1-yl-ethyl]-4-(5-phenyl-1,3,4-oxadiazol-2-yl)benzamide
Identifiers
CAS Number
  • 1246770-52-4 [8]☑Y
3D model (JSmol)
  • Interactive image [9]
ChemSpider
Properties
C26H19Cl2N5O2
Molar mass504.37 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

References

[1]
Citation Link//www.ncbi.nlm.nih.gov/pubmed/23372180Villalta, F; Dobish, MC; Nde, PN; Kleshchenko, YY; Hargrove, TY; Johnson, CA; Waterman, JN; Johnston, MR; Lepesheva, GI (2013). "VNI Cures Acute and Chronic Experimental Chagas Disease". The Journal of Infectious Diseases. 208 (3): 504–11. doi:10.1093/infdis/jit042. PMC 3698996. PMID 23372180.
Sep 29, 2019, 10:35 AM
[2]
Citation Link//www.ncbi.nlm.nih.gov/pubmed/23504044Hargrove, TY; Kim, K; de Nazaré Correia Soeiro M; Da Silva, CF; Da Gama Jaen Batista, DD; Batista, MM; Yazlovitskaya, EM; Waterman, MR; Sulikowski, GA; Lepesheva, GI (2012). "CYP51 structures and structure-based development of novel, pathogen-specific inhibitory scaffolds". International journal for parasitology, drugs and drug resistance. 2: 178–186. doi:10.1016/j.ijpddr.2012.06.001. PMC 3596085. PMID 23504044.
Sep 29, 2019, 10:35 AM
[3]
Citation Link//www.ncbi.nlm.nih.gov/pubmed/19923211Lepesheva, GI; Park, HW; Hargrove, TY; Vanhollebeke, B; Wawrzak, Z; Harp, JM; Sundaramoorthy, M; Nes, WD; Pays, E; Chaudhuri, M; Villalta, F; Waterman, MR (2010). "Crystal structures of Trypanosoma brucei sterol 14alpha-demethylase and implications for selective treatment of human infections". The Journal of Biological Chemistry. 285 (3): 1773–80. doi:10.1074/jbc.M109.067470. PMC 2804335. PMID 19923211.
Sep 29, 2019, 10:35 AM
[4]
Citation Link//www.ncbi.nlm.nih.gov/pubmed/23214987Dobish, Mark C.; Villalta, Fernando; Waterman, Michael R.; Lepesheva, Galina I.; Johnston, Jeffrey N. (2012). "Organocatalytic, Enantioselective Synthesis of VNI: A Robust Therapeutic Development Platform for Chagas, a Neglected Tropical Disease". Organic Letters. 14 (24): 6322–5. doi:10.1021/ol303092v. PMC 3528807. PMID 23214987.
Sep 29, 2019, 10:35 AM
[5]
Citation Linkwww.commonchemistry.org1246770-52-4
Sep 29, 2019, 10:35 AM
[6]
Citation Linkchemapps.stolaf.eduInteractive image
Sep 29, 2019, 10:35 AM
[7]
Citation Linkwww.chemspider.com25060282
Sep 29, 2019, 10:35 AM
[8]
Citation Linkwww.commonchemistry.org1246770-52-4
Sep 29, 2019, 10:35 AM
[9]
Citation Linkchemapps.stolaf.eduInteractive image
Sep 29, 2019, 10:35 AM
[10]
Citation Linkwww.chemspider.com25060282
Sep 29, 2019, 10:35 AM
[11]
Citation Linkwww.ncbi.nlm.nih.gov"VNI Cures Acute and Chronic Experimental Chagas Disease"
Sep 29, 2019, 10:35 AM
[12]
Citation Linkdoi.org10.1093/infdis/jit042
Sep 29, 2019, 10:35 AM
[13]
Citation Linkwww.ncbi.nlm.nih.gov3698996
Sep 29, 2019, 10:35 AM
[14]
Citation Linkwww.ncbi.nlm.nih.gov23372180
Sep 29, 2019, 10:35 AM
[15]
Citation Linkwww.ncbi.nlm.nih.gov"CYP51 structures and structure-based development of novel, pathogen-specific inhibitory scaffolds"
Sep 29, 2019, 10:35 AM
[16]
Citation Linkdoi.org10.1016/j.ijpddr.2012.06.001
Sep 29, 2019, 10:35 AM
[17]
Citation Linkwww.ncbi.nlm.nih.gov3596085
Sep 29, 2019, 10:35 AM
[18]
Citation Linkwww.ncbi.nlm.nih.gov23504044
Sep 29, 2019, 10:35 AM
[19]
Citation Linkwww.ncbi.nlm.nih.gov"Crystal structures of Trypanosoma brucei sterol 14alpha-demethylase and implications for selective treatment of human infections"
Sep 29, 2019, 10:35 AM
[20]
Citation Linkdoi.org10.1074/jbc.M109.067470
Sep 29, 2019, 10:35 AM