Mycobacterium tuberculosis DprE1 Inhibitor OPC-167832 Is Active against Mycobacterium abscessus In Vitro

Jickky Palmae Sarathy; Matthew D. Zimmerman; Martin Gengenbacher; Véronique Dartois; Thomas Dick

doi:10.1128/aac.01237-22

Mycobacterium tuberculosis DprE1 Inhibitor OPC-167832 Is Active against Mycobacterium abscessus In Vitro

Center for Discovery and Innovation

Hackensack Meridian Health

Research output: Contribution to journal › Article › peer-review

19 Scopus citations

Abstract

The antituberculosis candidate OPC-167832, an inhibitor of DprE1, was active against Mycobacterium abscessus. Resistance mapped to M. abscessus dprE1, suggesting target retention. OPC-167832 was bactericidal and did not antagonize activity of clinical anti-M. abscessus antibiotics. Due to its moderate potency compared to that against Mycobacterium tuberculosis, the compound lacked efficacy in a mouse model and is thus not a repurposing candidate. These results identify OPC-167832–DprE1 as a lead-target couple for a M. abscessus-specific optimization program.

Original language	English
Journal	Antimicrobial Agents and Chemotherapy
Volume	66
Issue number	12
DOIs	https://doi.org/10.1128/aac.01237-22
State	Published - Dec 2022

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

DprE1
Mycobacterium abscessus
NTM
OPC-167832
SigA
nontuberculous mycobacteria

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10.1128/aac.01237-22

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title = "Mycobacterium tuberculosis DprE1 Inhibitor OPC-167832 Is Active against Mycobacterium abscessus In Vitro",

abstract = "The antituberculosis candidate OPC-167832, an inhibitor of DprE1, was active against Mycobacterium abscessus. Resistance mapped to M. abscessus dprE1, suggesting target retention. OPC-167832 was bactericidal and did not antagonize activity of clinical anti-M. abscessus antibiotics. Due to its moderate potency compared to that against Mycobacterium tuberculosis, the compound lacked efficacy in a mouse model and is thus not a repurposing candidate. These results identify OPC-167832{\textendash}DprE1 as a lead-target couple for a M. abscessus-specific optimization program.",

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author = "Sarathy, \{Jickky Palmae\} and Zimmerman, \{Matthew D.\} and Martin Gengenbacher and V{\'e}ronique Dartois and Thomas Dick",

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year = "2022",

month = dec,

doi = "10.1128/aac.01237-22",

language = "English",

volume = "66",

journal = "Antimicrobial Agents and Chemotherapy",

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AU - Sarathy, Jickky Palmae

AU - Zimmerman, Matthew D.

AU - Gengenbacher, Martin

AU - Dartois, Véronique

AU - Dick, Thomas

PY - 2022/12

Y1 - 2022/12

N2 - The antituberculosis candidate OPC-167832, an inhibitor of DprE1, was active against Mycobacterium abscessus. Resistance mapped to M. abscessus dprE1, suggesting target retention. OPC-167832 was bactericidal and did not antagonize activity of clinical anti-M. abscessus antibiotics. Due to its moderate potency compared to that against Mycobacterium tuberculosis, the compound lacked efficacy in a mouse model and is thus not a repurposing candidate. These results identify OPC-167832–DprE1 as a lead-target couple for a M. abscessus-specific optimization program.

AB - The antituberculosis candidate OPC-167832, an inhibitor of DprE1, was active against Mycobacterium abscessus. Resistance mapped to M. abscessus dprE1, suggesting target retention. OPC-167832 was bactericidal and did not antagonize activity of clinical anti-M. abscessus antibiotics. Due to its moderate potency compared to that against Mycobacterium tuberculosis, the compound lacked efficacy in a mouse model and is thus not a repurposing candidate. These results identify OPC-167832–DprE1 as a lead-target couple for a M. abscessus-specific optimization program.

KW - DprE1

KW - Mycobacterium abscessus

KW - NTM

KW - OPC-167832

KW - SigA

KW - nontuberculous mycobacteria

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M3 - Article

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AN - SCOPUS:85144372874

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JO - Antimicrobial Agents and Chemotherapy

JF - Antimicrobial Agents and Chemotherapy

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ER -

Mycobacterium tuberculosis DprE1 Inhibitor OPC-167832 Is Active against Mycobacterium abscessus In Vitro

Abstract

UN SDGs

Keywords

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