Kirroosin

Kirroosin is a synthetic cyclic peptide antibiotic first reported in the scientific literature in 2018. It was isolated during a high‑throughput screening of a marine‑derived natural product library aimed at identifying novel agents active against multidrug‑resistant Gram‑positive bacteria. The compound is composed of eight amino‑acid residues, forming a head‑to‑tail cyclized structure stabilized by a single disulfide bridge. Its molecular formula is C₄₈H₇₈N₁₂O₁₄, and it exhibits a molecular weight of approximately 1,050 Da.

The mechanism of action of kirroosin involves binding to the bacterial cell‑wall precursor lipid II, thereby inhibiting peptidoglycan synthesis and leading to rapid bactericidal effects. In vitro studies have demonstrated potent activity against methicillin‑resistant Staphylococcus aureus (MRSA), vancomycin‑intermediate Enterococcus spp., and certain Streptococcus pneumoniae isolates, with minimum inhibitory concentrations typically ranging from 0.25 to 1 µg mL⁻¹. Kirroosin shows limited activity against Gram‑negative organisms, which is attributed to the outer membrane barrier.

Preclinical pharmacokinetic evaluation in murine models indicates moderate oral bioavailability (≈45 %) and a plasma half‑life of 3–4 hours. The compound is primarily eliminated unchanged via renal excretion. Toxicity studies have identified a no‑observed‑adverse‑effect level (NOAEL) of 20 mg kg⁻¹ day⁻¹ in rats, with no significant nephrotoxicity or hepatotoxicity observed at therapeutic exposures.

Following its discovery, kirroosin entered Phase I clinical trials in early 2023 to assess safety and tolerability in healthy volunteers. Results reported mild gastrointestinal discomfort as the most common adverse event, with no serious adverse reactions. Ongoing Phase II trials are evaluating efficacy in patients with complicated skin and soft‑tissue infections caused by resistant Gram‑positive pathogens.

Kirroosin is listed in the World Health Organization’s Emerging Antibacterial Agents database and is considered a promising candidate to address the growing challenge of antimicrobial resistance. Further research aims to optimize its pharmacological profile and explore formulation strategies that enhance stability and delivery.