Small-molecule inhibitors of Chlamydia cell growth

Summary Small molecule inhibitors of CopN for the treatment of Chlamydia pneumoniae associated pneumonia and vascular disease. See Huang et al. Nature 01 Oct 2008.

CopN is a member of a family of proteins common to pathogenic organisms including C. pneumoniae, C. psittaci B577 (C. abortus), C. trachomatis, Yersinia species and P. aeruginosa. CopN, in addition to CP1062 and CP0833, are putative substrates of a specialized secretion system that directly translocates proteins from the bacterial cytosol into the host cells. This protein acts on the host cell by disrupting spindle integrity and inducing G2/M cell cycle arrest.

Harvard investigators have exploited this feature of CopN to screen for inhibitors of CopN function in S. cerevisiae. Inhibitors of CopN were predicted to relieve the cell cycle arrest and allow for cell division and growth. This approach of screening for “functional knockouts” circumvented challenges associated with the genetic intractability of Chlamydia, and allowed for the identification of two unrelated small molecule inhibitors. These compounds were then tested in primate cells and confirmed as inhibitors of C. pneumoniae inclusions. No overt cellular toxicity was observed in the primate cells and the potency of both inhibitors was comparable to chloramphenicol, an antibiotic active against Chlamydia.

Applications Small molecule therapeutics for the treatment of Chlamydia pneumoniae induced pneumonia or therapeutics for the treatment of patients with antibodies against C. pneumoniae and previous histories, either personal or familial, with atherosclerosis or stroke. For Further Information Please Contact the Director of Business Development Alex Szidon Email: [email protected] Telephone: (617) 495-3067

Inventor(s): Lory, Stephen

Type of Offer: Licensing



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