SQ-109

SQ-109 is an antibacterial, antifungal, and antiparasitic agent.^1,2,3,4 It is active against M. tuberculosis (MIC = 1.56 µM), several fungi, including various strains of C. albicans, C. kefyr, and C. neoformans (MICs = 0.125-32 µg/ml), and P. falciparum (IC₅₀s = 1.58, 0.38, and 0.14 µM for asexual parasites, immature-stage gametocytes, and late-stage gametocytes, respectively).^1,3,4 SQ-109 induces accumulation of trehalose monomycolate, a cell wall mycolate precursor, in M. tuberculosis in vitro, and mutations in the gene encoding the trehalose monomycolate exporter MmpL3 confer resistance to SQ-109.² In vivo, SQ-109 (1 mg/kg, p.o.) decreases the number of spleen and lung colony-forming units (CFUs) in a mouse model of chronic M. tuberculosis infection.¹

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1. Protopopova, M., Hanrahan, C., Nikonenko, B., et al. Identification of a new antitubercular drug candidate, SQ109, from a combinatorial library of 1,2-ethylenediamines. J. Antimicrob. Chemother. 56(5), 968-974 (2005).

2. Tahlan, K., Wilson, R., Kastrinsky, D.B., et al. SQ109 targets MmpL3, a membrane transporter of trehalose monomycolate involved in mycolic acid donation to the cell wall core of Mycobacterium tuberculosis. Antimicrob Agents Chemother. 56(4), 1797-1809 (2012).

3. Malwal, S.R., Garcia-Rubio, R., Kordalewska, M., et al. Broad-spectrum activity and mechanisms of action of SQ109 on a variety of fungi. ACS Infect. Dis. 11(6), 1662-1672 (2025).

4. Watson, S.J., van der Watt, M.E., Theron, A., et al. The tuberculosis drug candidate SQ109 and its analogs have multistage activity against Plasmodium falciparum. ACS Infect. Dis. 10(9), 3358-3367 (2024).