Inositol phospholipid-dependent cellular signalling: opportunities for drug discovery.
In this review, phosphoinositide metabolism is discussed and potential sites for therapeutic intervention are identified. The rapid recent progress in several branches of inositol chemistry has greatly improved our knowledge of the structural requirements for recognition by a variety of key enzymes involved in the pathways, and by the physiological receptor for D-myo-inositol 1,4,5-trisphosphate. Based on existing leads, drug opportunities arise in reducing polarity, in the utilisation of apolar pro-drugs, and in the development of innovative intracellular delivery systems. The identification of novel pharmacophores for future exploration is likely.
Young
R C
RC
Smith Kline & French Research Ltd., Hertfordshire, England.
Downes
C P
CP
D000818:Animals; D002626:Chemistry, Pharmaceutical; D015195:Drug Design; D006801:Humans; D010716:Phosphatidylinositols / Q000502:physiology*; D011355:Prodrugs; D015398:Signal Transduction
D010716:Phosphatidylinositols; D011355:Prodrugs