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. 2016 Mar 25;60(4):2528-31.
doi: 10.1128/AAC.02770-15. Print 2016 Apr.

The Investigational Fungal Cyp51 Inhibitor VT-1129 Demonstrates Potent In Vitro Activity against Cryptococcus neoformans and Cryptococcus gattii

Shawn R Lockhart  1 , Annette W Fothergill  2 , Naureen Iqbal  1 , Carol B Bolden  1 , Nina T Grossman  1 , Edward P Garvey  3 , Stephen R Brand  3 , William J Hoekstra  3 , Robert J Schotzinger  3 , Elizabeth Ottinger  4 , Thomas F Patterson  5 , Nathan P Wiederhold  6
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The Investigational Fungal Cyp51 Inhibitor VT-1129 Demonstrates Potent In Vitro Activity against Cryptococcus neoformans and Cryptococcus gattii

Shawn R Lockhart et al. Antimicrob Agents Chemother. .

Abstract

Thein vitroactivities of the novel fungal Cyp51 inhibitor VT-1129 were evaluated against a large panel ofCryptococcus neoformansandCryptococcus gattiiisolates. VT-1129 demonstrated potent activities against bothCryptococcusspecies as demonstrated by low MIC50and MIC90values. ForC. gattii, thein vitropotency was maintained against all genotypes. In addition, significantly lower geometric mean MICs were observed for VT-1129 than for fluconazole againstC. neoformans, including isolates with reduced fluconazole susceptibility.

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Figures

FIG 1
FIG 1
Chemical structure of VT-1129.
FIG 2
FIG 2
MIC distributions of VT-1129 and fluconazole against Cryptococcus neoformans and C. gattii isolates. (A) Percentage of isolates at different VT-1129 and fluconazole MIC levels against 180 C. neoformans isolates. (B) Percentage of isolates at different MIC levels for VT-1129 at the lower concentration range tested against 54 C. neoformans isolates. (C) Percentage of isolates at different VT-1129 MIC levels against 321 C. gattii isolates. VT-1129 MICs using the 50% inhibition of growth endpoint are shown by the gray bars and 100% inhibition by the white bars, and fluconazole MICs at 50% inhibition are shown by the black bars.
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References

    1. Perfect JR, Dismukes WE, Dromer F, Goldman DL, Graybill JR, Hamill RJ, Harrison TS, Larsen RA, Lortholary O, Nguyen MH, Pappas PG, Powderly WG, Singh N, Sobel JD, Sorrell TC. 2010. Clinical practice guidelines for the management of cryptococcal disease: 2010 update by The Infectious Diseases Society of America. Clin Infect Dis 50:291–322. doi:10.1086/649858. - DOI - PMC - PubMed
    1. Chayakulkeeree M, Perfect JR. 2006. Cryptococcosis. Infect Dis Clin North Am 20:507−544, v−vi. doi:10.1016/j.idc.2006.07.001. - DOI - PubMed
    1. Li SS, Mody CH. 2010. Cryptococcus. Proc Am Thorac Soc 7:186−196. doi:10.1513/pats.200907-063AL. - DOI - PubMed
    1. Park BJ, Wannemuehler KA, Marston BJ, Govender N, Pappas PG, Chiller TM. 2009. Estimation of the current global burden of cryptococcal meningitis among persons living with HIV/AIDS. AIDS 23:525–530. doi:10.1097/QAD.0b013e328322ffac. - DOI - PubMed
    1. Hoekstra WJ, Garvey EP, Moore WR, Rafferty SW, Yates CM, Schotzinger RJ. 2014. Design and optimization of highly-selective fungal CYP51 inhibitors. Bioorg Med Chem Lett 24:3455–3458. doi:10.1016/j.bmcl.2014.05.068. - DOI - PubMed

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