Reversible Inhibitors of Cytosine-C5 DNA Methyltransferase

BACKGROUND: In eukaryotes, the methylation state of a gene specifically affects its transcription. Proper function of the methylation enzyme is crucial for viable development and normal cellular activity. Increased activity of the enzyme cytosine-C5 DNA methyltransferase (DCMTase) has been directly associated with neoplastic development and excess methylation by DCMTase may constitute a key step in carcinogenesis. Currently, the drugs available for inhibiting DCMTase bind irreversibly to the enzyme and have toxic side effects.

DESCRIPTION: Scientists at the University of California have discovered synthetic ligands that inhibit DCMTase activity by binding to an allosteric site. These modulators bind reversibly, permitting greater therapeutic versatility. In one embodiment, the inhibition constant, 20 nanomolar, is suitably tight for drug design.

APPLICATIONS: Recent reports indicate that degenerative conditions such as cancer and aging may be halted by inhibition of DCMTase. It is also perceivable that regeneration of healthy tissues may be stimulated. The modulators are likely to be useful tools for basic research as well.

ADVANTAGES: By binding to an allosteric site, the UC modulators have the potential to either up- or down-regulate DCMTase activity. As inhibitors, the UC compounds offer superior characteristics over the currently used inhibitors, including:

* Noncovalent, reversible inhibition;
* Strong inhibition constant of 20 nanomolar;
* Likely to have fewer side effects due to their high specificity for DCMTase.

Patents:
US 7,138,384   [MORE INFO]
US 7,125,857   [MORE INFO]

Type of Offer: Licensing



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