Recent patents of gene sequences relative to the phosphatidylinositol 3-kinase/Akt pathway and their relevance to drug discovery.
Phosphoinositide 3-kinases (PI3Ks) play an essential role in the signal transduction events initiated by the binding of extracellular signals to their cell surface receptors. There are eight known PI3Ks in humans, which have been subdivided into three classes (I-III). The class I(A) of PI3K comprises the p110alpha, p110beta and p110delta isoforms, which associate with receptor tyrosine kinases (RTKs). On the other hand, the class I(B) PI3K p110gamma is regulated by G-protein-coupled receptors (GPCRs). Gene targeting studies in mice have revealed specific biological functions for the class I(A) p110delta in lymphocyte activation, and the class I(B) p110gamma in inflammatory cell responses. In human cancer, recent reports have described activating mutations in the PIK3CA gene encoding p110alpha, and inactivating mutations in the PTEN gene, a tumor suppressor and antagonist of the PI3K pathway. Thus, individual PI3K isoforms are potential drug targets for a variety of human diseases, including allergies, cancer, rheumatoid arthritis and arterial thrombosis. In this review, we will discuss recent patents relating to class I PI3Ks, including patents on the cDNA sequences of p110gamma and p110delta. Moreover, we will review patents on novel pharmacological PI3K inhibitors and on methods of manipulating T cell responses through PI3K.
Doepfner
Kathrin T
KT
Division of Clinical Chemistry and Biochemistry, University Children's Hospital Zurich, Steinwiesstrasse 75, CH-8032 Zurich, Switzerland.
Boller
Danielle
D
De Laurentiis
Angela
A
Guerreiro
Ana S
AS
Marinov
Marin
M
Arcaro
Alexandre
A
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000378:metabolism; D018076:DNA, Complementary; D055808:Drug Discovery / Q000379:methods*; D018390:Gene Targeting; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D010330:Patents as Topic; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics* / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000276:immunology
D018076:DNA, Complementary; D007527:Isoenzymes; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D020794:Receptor Protein-Tyrosine Kinases; D043562:Receptors, G-Protein-Coupled