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Biomedical subjects

David Cavalla

Publications and source records attributed to David Cavalla.

18 recordsLinked to original sources
PubMed2005

Therapeutic switching: a new strategic approach to enhance R&D productivity.

New chemical entity discovery and development is a long, expensive and risky way of producing new therapeutics. An alternative approach, namely finding new uses for existing drugs, offers substantial advantages in terms of cost, time and risk, and represents a highly attractive strategy to drug discovery. Patents protecting the new use may also be obtained. There are multiple different classes of such R and D programs, depending on whether the original development is still protected by composition of matter patents, and whether the compound was ever fully developed/marketed for its original indication. There are also shortened R and D programs for new uses for stereoisomers and metabolites of existing drugs. Case histories in all areas are presented.

Drug Design↗
PubMed2003

The extended pharmaceutical enterprise.

The availability of widespread contractual services led to the birth of the virtual company in the 1990s. As the concept has matured, and the biotechnology sector diversified, interchange of intellectual property in the form of collaborative and license arrangements opens up still further the opportunities for outsourced forms of pharmaceutical R&D.

Contracts↗
PubMed2003

Pharmacology of a new cyclic nucleotide phosphodiesterase type 4 inhibitor, V11294.

V11294 is a new cyclic nucleotide phosphodiesterase type 4 (PDE4) inhibitor of the rolipram class. In this report we present the pharmacological profile of V11294. V11294 inhibited PDE4 isolated from human lung with IC(50) 405 nM, compared to 3700 nM for rolipram. In contrast, V11294 inhibition of human PDE3 and PDE5 occurred only at concentrations greater than 100,000 nM. Like rolipram, V11294 inhibited PDE4D more potently than other PDE4 subtypes. V11294, when incubated with human anticoagulated whole blood in vitro, or administered to mice, caused increased cAMP concentration, consistent with inhibition of PDE4. V11294 inhibited lectin-induced proliferation and lipopolysaccharide-induced TNFalpha synthesis by human adherent monocytes in vitro and inhibited lipopolysaccharide-induced TNFalpha synthesis in mice. V11294 caused relaxation of guinea pig isolated trachea and inhibited allergen-induced bronchoconstriction and eosinophilia in guinea pigs at doses of 1 and 3 mg/kg, p.o. In ferrets, V11294 was not emetogenic at doses up to 30 mg/kg, p.o., despite plasma concentration reaching 10-fold the IC(50) for PDE4. In contrast, rolipram induced severe retching and vomiting at 10 mg/kg, p.o. In conclusion, V11294 is an orally active PDE4 inhibitor that exhibits antiinflammatory activity in vitro, and in vivo at doses that are not emetogenic.

3',5'-Cyclic-AMP Phosphodiesterases↗