Table 4 Compounds in, or that have recently completed, phase-II clinical trials (structures in Figs. 5–7)
From: Antibiotics in the clinical pipeline as of December 2022
Name (synonym)a | Compound class (lead source) | Mode of action | Administration; indication (Developer) |
|---|---|---|---|
sanfetrinem cilexetil (14) (prodrug, GV-104326); sanfetrinem (15) | trinem (β-lactam) (NP) | PBP (cell wall) | po; TB (GSK) |
MGB-BP-3 (16) | distamycin A (NP) | DNA minor groove binding | po topical; CDI (MGB Biopharma) |
exeporfinium chloride (17) (XF-73) | porphyrin (NP) | membrane-perturbing activity | topical; post-surgical nasal decolonization (Destiny Pharma) |
cannabidiol (18) (BTX 1801) | cannabidiol (NP) | membrane disruption (cell wall) | topical, S. aureus infections (Botanix Pharmaceuticals) |
TNP-2092 (19) (CBR 2092) | rifamycin -quinolizinone (ABT719) hybridb (NP-S) | RNA polymerase, DNA gyrase (GyrA) and Topo IV (ParC) | IV (po topical); ABSSSI, PJI, encephalopathy (TenNor Therapeutics) |
TNP-2198 (20) | rifamycin-nitroimidazole hybridb (NP-S) | RNA polymerase | po topical; CDI (TenNor Therapeutics) |
afabicin (21) (prodrug, Debio-1450); afabicin desphosphono (22) (Debio 1452, AFN-1252) | benzofuran naphthyridine (S) | FabI inhibition (cell wall, fatty acid biosynthesis) | IV/po; ABSSSI (Debiopharm) |
peceleganan (23) (PL-5, V681) | cationic peptide (P) | membrane disruption (cell wall) | topical, wound infections (Jiangsu ProteLight Pharmaceutical and Biotechnology) |
Recce-327c (R327) | acrolein polymer (S) | disruption of cellular bioenergetics via membrane potential and/or ATP synthesis | topical, burn wound infections (Recce Pharmaceuticals); IV administration in Phase-I trial |
pravibismane (24) (MBN-101) | bismuth thiol (S) | disruption of cellular bioenergetics via membrane potential | topical; diabetic foot infections and orthopedic-implant infection (Microbion Corporation) |
DNV-3837 (25) (prodrug, MCB-3837); DNV-3681 (26) | oxazolidinone-quinolone hybridb (S-S) | protein synthesis inhibition, DNA gyrase (GyrA) and topo IV (ParC) | IV; CDI (Deinove) |
ibezapolstat (27) (ACX-362E)a | dichlorobenzyl guanine (DCBG) (S) | DNA polymerase IIIC | po topical; CDI (Acurx Pharmaceuticals) |
CRS3123 (28) (REP3123) | “diaryldiamine” (S); | methionyl-tRNA synthetase (protein synthesis) | po topical, CDI (Crestone) |
Mycobacteria | |||
delpazolid (29) (RMX2001, LCB01-0371) | oxazolidinone (S) | protein synthesis inhibition | po; TB and MRSA bacteremia (LegoChem Biosciences) |
sutezolid (30) (PF-2341272, PNU-100480) | oxazolidinone (S) | protein synthesis inhibition | po; TB (European and Developing Countries Clinical Trials Partnership / TB Alliance / Sequella) |
telacebec (31) (Q203) | imidazo[1,2-a]pyridine amide (S) | respiratory cytochrome bc1 complex | po; TB (Qurient Co) |
fobrepodacin (32) (prodrug, SPR720, pVXc-486); SPR719 (33) | “ethyl urea benzimidazole” (S) | DNA gyrase (GyrB) and Topo IV (ParE) | po; TB (Spero Therapeutics) |
BTZ-043 (34) | benzothiazinone (S) | DprE1 (cell wall) | po; TB (European and Developing Countries Clinical Trials Partnership) |
quabodepistat (35) (OPC-167832) | 3,4-dihydrocarbostyril (S) | DprE1 (cell wall) | po; TB (Otsuka Pharmaceutical) |
GSK3036656 (36) | oxaborole (S) | leucyl-tRNA synthetase (protein synthesis) | po; TB (GSK) |
TBA-7371 (37) | azaindole (S) | DprE1 (cell wall) | po; TB (TB Alliance / Foundation for Neglected Disease Research / Bill & Melinda Gates Medical Research Institute) |
sudapyridine (38) (WX-081) | diarylquinoline (S) | mycobacterial ATP synthase inhibition | po; TB (Shanghai Jiatan Biotech) |
pyrifazimine (39) (TBI-166) | riminophenazine (clofazimine) (S) | DNA binding leading to cell cycle disruption | po; TB (Institute of Materia Medica / Chinese Academy of Medical Sciences / Peking Union Medical College) |
Non-traditional small molecules | |||
fluorothiazinon (40) + cefepime (41) | thyazinone (S) + cephalosporin (NP) | bacterial type III secretion system (T3SS) | po; G-ve virulence (Gamaleya Research Institute of Epidemiology and Microbiology) |
dovramilast (42) (CC-11050, AMR-634) | “3-oxo-1H-isoindol-4-yl” (S) | phosphodiesterase 4 (PDE4) inhibitor (host immune response) | po, Leprosy and TB (Medicines Development for Global Health) |
