Table 5 Compounds in phase-I clinical trials (structures in Figs. 8–10)
From: Antibiotics in the clinical pipeline as of December 2022
Name (synonym)a | Compound class (lead source) | Mode of actiona | Administration; indication (developer) |
|---|---|---|---|
SPR206 (43) | polymyxin (NP) | membrane disruption (cell wall) | IV; G-ve (Spero Therapeutics) |
MRX-8b | polymyxin (NP) | membrane disruption (cell wall) | IV; G-ve (MicuRx Pharmaceuticals) |
QPX-9003 (44) | polymyxin (NP) | membrane disruption (cell wall) | IV; G-ve (Qpex Biopharma) |
RG6319b | “arylomycin” (NP) | type I signal peptidase (LepB) inhibitor (cell wall) | not disclosed; G-ve, cUTI (Genentech) |
zifanocycline (45) (KBP-7072) | tetracycline (NP) | protein synthesis inhibition | IV/po; G-ve and G+ve (KBP Biosciences) |
apramycin (46) (EBL-1003) | aminoglycoside (NP) | protein synthesis inhibition | IV; G-ve (Juvabis) |
PLG0206 (47) (WLBU2) | cationic peptide (P) | membrane disruption (cell wall) | topical; G-ve and G+ve, PJI (Peptilogics) / IV administration in phase-I trial |
PL-18 (48) | cationic peptide (P) | membrane disruption (cell wall) | topical (suppository), G-ve and G+ve, bacterial vaginosis (Jiangsu ProteLight Pharmaceutical and Biotechnology) |
murepavadin (49) (POL7080) | protegrin I (P) | β-barrel protein LptD (Imp/OstA) inhibition (cell wall) | inhalation; pseudomonal infections (G-ve) (Spexis) |
TXA709 (50) (prodrug); TXA707 (51) | FtsZ benzamide (S) | FtsZ inhibition (cell wall) | po; G+ve (TAXIS Pharmaceuticals) |
RG6006b (RO7223280) | macrocyclic peptide (S) | unknown | IV, A. baumannii infections (Roche) |
BWC0977 (52) | oxazolidinone containing NBTI (S) | DNA gyrase and topoisomerase IV | IV/po, G-ve and G+ve, but being developed for G-ve (Bugworks Research) |
Mycobacteria | |||
macozinone (53) (PBTZ 169) | benzothiazinone (S) | DprE1 (cell wall) | po; TB (Innovative Medicines for Tuberculosis Foundation / Nearmedic Plus) |
TBI-223 (54) | oxazolidinone (S) | protein synthesis inhibition | po; TB (TB Alliance / Institute of Materia Medica) |
TBAJ-876 (55) | diarylquinoline (S) | mycobacterial ATP synthase inhibition | po; TB (TB Alliance) |
TBAJ-587 (56) | diarylquinoline (S) | mycobacterial ATP synthase inhibition | po; TB (TB Alliance) |
GSK2556286 (57) (GSK-286) | “uracil aryloxypiperidine” (S) | complex pathway related to cholesterol catabolism (adenylyl cyclase Rv1625c) | po, TB (GSK) |
Non-traditional small molecules | |||
BVL-GSK098 (58) + ethionamide (59) | spiroisoxazoline (S) | inactivation of TetR-like repressor (EthR2) – ‘resistance breaker’ | po, TB (BioVersys / GSK) |
GSK3882347b | mannose-derived (S) | Type 1 fimbrin D-mannose specific adhesin (FimH) antagonist – antivirulence | po, G-ve, UTI (GSK / Fimbrion Therapeutics) |
ALS4b | undisclosed (S) | 4,4ʹ-diapophytoene desaturase (CrtN, staphyloxanthin biosynthesis) – antivirulence | po, G+ve, S. aureus infections (Aptorum Therapeutics) |
