“Upcycling” known molecules and targets for drug-resistant TB
Despite reinvigorated efforts in Tuberculosis (TB) drug discovery over the past 20 years, relatively few new drugs and candidates have emerged with clear utility against drug resistant TB. Over the same period, significant technological advances and learnings around target value have taken place. Th...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-10-01
|
| Series: | Frontiers in Cellular and Infection Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2022.1029044/full |
| _version_ | 1811196312739119104 |
|---|---|
| author | Christine Roubert Evelyne Fontaine Anna M Upton |
| author_facet | Christine Roubert Evelyne Fontaine Anna M Upton |
| author_sort | Christine Roubert |
| collection | DOAJ |
| description | Despite reinvigorated efforts in Tuberculosis (TB) drug discovery over the past 20 years, relatively few new drugs and candidates have emerged with clear utility against drug resistant TB. Over the same period, significant technological advances and learnings around target value have taken place. This has offered opportunities to re-assess the potential for optimization of previously discovered chemical matter against Mycobacterium tuberculosis (M.tb) and for reconsideration of clinically validated targets encumbered by drug resistance. A re-assessment of discarded compounds and programs from the “golden age of antibiotics” has yielded new scaffolds and targets against TB and uncovered classes, for example beta-lactams, with previously unappreciated utility for TB. Leveraging validated classes and targets has also met with success: booster technologies and efforts to thwart efflux have improved the potential of ethionamide and spectinomycin classes. Multiple programs to rescue high value targets while avoiding cross-resistance are making progress. These attempts to make the most of known classes, drugs and targets complement efforts to discover new chemical matter against novel targets, enhancing the chances of success of discovering effective novel regimens against drug-resistant TB. |
| first_indexed | 2024-04-12T00:57:29Z |
| format | Article |
| id | doaj.art-114794c09691476e8321f3938850da66 |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-04-12T00:57:29Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-114794c09691476e8321f3938850da662022-12-22T03:54:35ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882022-10-011210.3389/fcimb.2022.10290441029044“Upcycling” known molecules and targets for drug-resistant TBChristine RoubertEvelyne FontaineAnna M UptonDespite reinvigorated efforts in Tuberculosis (TB) drug discovery over the past 20 years, relatively few new drugs and candidates have emerged with clear utility against drug resistant TB. Over the same period, significant technological advances and learnings around target value have taken place. This has offered opportunities to re-assess the potential for optimization of previously discovered chemical matter against Mycobacterium tuberculosis (M.tb) and for reconsideration of clinically validated targets encumbered by drug resistance. A re-assessment of discarded compounds and programs from the “golden age of antibiotics” has yielded new scaffolds and targets against TB and uncovered classes, for example beta-lactams, with previously unappreciated utility for TB. Leveraging validated classes and targets has also met with success: booster technologies and efforts to thwart efflux have improved the potential of ethionamide and spectinomycin classes. Multiple programs to rescue high value targets while avoiding cross-resistance are making progress. These attempts to make the most of known classes, drugs and targets complement efforts to discover new chemical matter against novel targets, enhancing the chances of success of discovering effective novel regimens against drug-resistant TB.https://www.frontiersin.org/articles/10.3389/fcimb.2022.1029044/fulldrug resistancetargetantibioticsphenotypic screeninggolden age of antibiotics |
| spellingShingle | Christine Roubert Evelyne Fontaine Anna M Upton “Upcycling” known molecules and targets for drug-resistant TB Frontiers in Cellular and Infection Microbiology drug resistance target antibiotics phenotypic screening golden age of antibiotics |
| title | “Upcycling” known molecules and targets for drug-resistant TB |
| title_full | “Upcycling” known molecules and targets for drug-resistant TB |
| title_fullStr | “Upcycling” known molecules and targets for drug-resistant TB |
| title_full_unstemmed | “Upcycling” known molecules and targets for drug-resistant TB |
| title_short | “Upcycling” known molecules and targets for drug-resistant TB |
| title_sort | upcycling known molecules and targets for drug resistant tb |
| topic | drug resistance target antibiotics phenotypic screening golden age of antibiotics |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2022.1029044/full |
| work_keys_str_mv | AT christineroubert upcyclingknownmoleculesandtargetsfordrugresistanttb AT evelynefontaine upcyclingknownmoleculesandtargetsfordrugresistanttb AT annamupton upcyclingknownmoleculesandtargetsfordrugresistanttb |