CRS-3123, also known as REP-3123, is a methionyl-tRNA synthetase inhibitor potentially for the treatment of enteric infections. CRS-3123 is in Phase 1 clinical development for the treatment of Clostridium difficile Infection (CDI). CRS-3123 is a small molecule protein synthesis inhibitor that acts on the novel target methionyl-tRNA synthetase (MetRS). REP-3123 has been shown to be active in vitro against clinical isolates of C. difficile including epidemic strains such as B1/ NAP1/027; MIC values of REP-3123 for C. difficile are typically 0.5 -- 1.0 mg/l. REP-3123 is also active against a range of clinically important aerobic Gram-positive bacteria including methicillin-susceptible and -resistant Staphylococcus aureus (MIC90 values of 0.06 and 0.25 mg/l, respectively), Streptococcus pyogenes (MIC90 0.5 mg/l) and enterococci (MIC90 32 mg/l). CRS-3123 has numerous potential advantages over current CDI therapies. In addition to being highly potent against all clinical isolates of C. difficile tested, CRS-3123 has several desirable qualities for the treatment of CDI which include: Narrow spectrum for C. difficile, which may substantially reduce the disruption of normal intestinal flora compared to current therapies; Inhibition of toxin production, potentially leading to lower morbidity and mortality; Inhibition of sporulation, potentially leading to lower rates of transmission and recurrence; A novel mechanism of action, which means that its use will not compromise the utility of systemic antibiotics while maintaining activity against pre-existing resistance mechanisms.

Paeonol (2-hydroxy-4-methoxyacetophenone) is a major phenolic component of the dried root bark of Paeonia suffruticosa Andrews (Paeoniaceae). Paeonol exhibits a wide variety of bioactivities including anti-inflammatory, antioxidative, immunoregulatory, antihypertensive, anti-hyperglycemic, antibacterial, anti-thrombotic, and antitumor effects. Paeonol inhibits anaphylactic reaction by regulating histamine and TNF-α. Paeonol tablets have been used for the treatment of rheumatic arthritis, fever, headache and neuralgia in Chinese clinics.

BN-2629 (also known as SJG-136 and SG2000), a dimeric pyrrolobenzodiazepine that binds in the minor groove of DNA and produces G-G interstrand cross-links via reactive N(10)-C(11)/N(10')-C(ll') imine/carbinolamine moieties. This drug was investigated in phase II clinical trials in patients with epithelial ovarian, primary peritoneal, or fallopian tube cancer, however, these studied were terminated because of the slow accrual. In addition, BN-2629 participated in phase I/II trial in participants with advanced chronic lymphocytic leukemia and acute myeloid leukemia, but Spirogen also terminated these studies.