Novel Anti-CMV Small Molecules

Summary Five structurally diverse small molecules have been discovered that inhibit human cytomegalovirus (CMV) replication with sub- to low micro-molar potency and at concentrations of up to 500-fold lower than those exhibiting cytotoxicity. These molecules represent a distinct departure from contemporary therapy as they inhibit interaction between viral polymerase subunits. In previous studies, it was discovered that specific residues in the connector loop of the UL44 viral subunit were essential for interaction with the catalytic subunit of CMV polymerase, UL54. Highly specific, low-toxicity candidate therapies have been developed to exploit these residues. The compounds discovered may provide treatment for CMV in immunocompromised transplant patients and as prophylaxis during transplant procedures. Additional applications include CMV retinitis in AIDS patient and a potential application for treating congenital CMV.

Applications Nucleoside analogues, including valganciclovir, require high induction and maintenance doses, linked to potential carcinogenic and teratogenic effects, nephrotoxicity, and cytopenia. It is expected that the candidates presented will have lower dosing requirements, better toxicity profiles, and similar or superior oral bioavailability due to their specific mode of action and small molecule structure. Significant markets include an estimated 8,000 to 16,000 patients with CMV pneumonititis caused by transplant procedures, and a broader market for CMV prophylaxis during transplant procedures. In addition, CMV retinitis affects approximately 45,000 AIDS patients in the US, while congenital CMV affects approximately 1% of newborns, making CMV the most common congenital infection. For Further Information Please Contact the Director of Business Development Katie Gordon Email: katherine_gordon@hms.harvard.edu Telephone: (617) 432-0920

Inventor(s): Coen, Donald M.

Type of Offer: Licensing



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