Thiolactomycin 

Thiolactomycin is an orally active bacterial type II fatty acid synthase (FAS-II) inhibitor with antibacterial and antimalarial activities. Thiolactomycin specifically targets KasA/KasB in mycobacteria and FabB/FabF in bacteria, thereby inhibiting the biosynthesis of fatty acids and mycolic acids. Thiolactomycin can be used in studies related to tuberculosis, systemic bacterial infections, and experimental pyelonephritis^[1][2][3][4].

Thiolactomycin (56-240 μM; 21 days) inhibits growth of Mycobacterium tuberculosis H37Rv with an MIC₅₀ of 56 μM, MIC₉₀ of 125 μM, and MIC₉₉ of 240 μM^[1].
Thiolactomycin (200 μM; 1 h) inhibits mycolic acid biosynthesis in Mycobacterium smegmatis cell wall fractions by 54% at a concentration of 200 μM^[1].
Thiolactomycin (200 μM-1.0 mM) inhibits type II fatty acid synthase activity in Mycobacterium smegmatis cytosolic extracts by 59% at 200 μM and 69% at 1.0 mM^[1].
TlnCACP(apo)-Cy, TlnDA-PCP(holo), and TlnA (10 μM, 10 μM, 2 μM; 4 h) are necessary and sufficient to convert 7-CoA to thiolactomycin, while TlnDTE does not participate in thiolactomycin biosynthesis^[2].
TlnA (2 μM; 2 h) catalyzes the conversion of the unstable thiocarboxylate intermediate 9 to thiolactomycin, with 6 acting as a spontaneous byproduct of 9, not a substrate for TlnA^[2].
TlnCACP-Cy (10 μM; 2 h) mediates sulfur transfer from L-Cys to the polyketide intermediate via a condensation and heterocyclization-dependent mechanism, requiring catalytic residues D140 and D394, but not N352, to generate the thiocarboxylate intermediate 9^[2].
Thiolactomycin inhibits growth of Pseudomonas aeruginosa J-272 with an MIC of 800 μg/mL and Pseudomonas aeruginosa M-57740 with an MIC of 1.56 μg/mL in heart infusion medium^[3].
Thiolactomycin (24 h) exhibits broad-spectrum aerobic antibacterial activity, with particularly potent activity against Salmonella enteritidis T-1 (MIC 6.25-12.5 μg/mL), Serratia marcescens FU-111 (MIC 50-100 μg/mL), and Pseudomonas aeruginosa GMB-75 (MIC 6.25 μg/mL) on NA and ANTI-3 agars^[3].
Thiolactomycin (40 h) exhibits potent activity against Bacteroides fragilis strains (MIC 3.12-12.5 μg/mL) and Fusobacterium necroforum S-45 (MIC 3.25 μg/mL) under anaerobic conditions on Gam agar medium^[3].
Thiolactomycin (25-200 μg/mL) shows moderate in vitro antibacterial activity against S. marcescens 101, S. marcescens 92, S. marcescens 5, K. pneumoniae 3K25, K. pneumoniae 15C, and E. coli 11 with MIC values ranging from 25 to 200 μg/mL^[4].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Thiolactomycin sodium salt (455-1689 mg/kg; i.v., i.p., p.o.; single dose) exhibits weak acute toxicity in ddY male mice, with LD₅₀ values of 455 mg/kg (i.v.), 520 mg/kg (i.p.), and 1689 mg/kg (p.o.)^[3].
Thiolactomycin (≤0.05-12.8 mg/mouse; s.c., p.o.; single dose, two doses at 1 and 3 hours post-challenge) exhibits dose-dependent protective efficacy against multiple bacterial systemic infections in mice, with ED₅₀ values ranging from ≤1.50 to 12.8 mg/mouse, and greater efficacy than carbenicillin against several S. marcescens and K. pneumoniae strains^[4].
Thiolactomycin (0.5-2 mg/mouse; s.c.; 4 doses at 5, 7, 12, 24 hours post-challenge) reduces kidney bacterial counts and abscess formation in mice with experimental pyelonephritis, with significant efficacy at doses of 0.5 to 2 mg/mouse delivered subcutaneously four times post-challenge^[4].
Thiolactomycin (2.83-3.25 mg/mouse; s.c.; two doses at 1 and 3 hours post-challenge) is twice as effective as carbenicillin against S. marcescens systemic infection in cyclophosphamide-induced immunocompromised mice (ED₅₀ 3.25 mg/mouse) and equally effective as carbenicillin in hydrocortisone-induced immunocompromised mice (ED₅₀ 2.83 mg/mouse)^[4].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

210.29

C₁₁H₁₄O₂S

82079-32-1

Solid

C=C/C(C)=C/[C@@]1(C(O)=C(C(S1)=O)C)C

Room temperature in continental US; may vary elsewhere.

• [1]. Douglas JD, et al. Analogues of thiolactomycin: potential drugs with enhanced anti-mycobacterial activity. Microbiology (Reading). 2002;148(Pt 10):3101-3109.

  [2]. Guo J, et al. Deciphering the Thiolactonization Mechanism in Thiolactomycin Biosynthesis. J Am Chem Soc. 2025;147(26):22368-22386.

  [3]. Oishi H, et al. Thiolactomycin, a new antibiotic I. Taxonomy of the producing organism, fermentation and biological properties[J]. The Journal of Antibiotics, 1982, 35(4): 391-395.

  [4]. Miyakawa S, et al. Thiolactomycin, a new antibiotic IV. Biological properties and chemotherapeutic activity in mice[J]. The Journal of antibiotics, 1982, 35(4): 411-419.