how to choose your PI3K inhibitors

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      I know that many researchers use PI3K inhibitor to block some pathway.
      But there is so many inhibitors of PI3K,how to choose them?

      PI3K is a core target in many pathways and it is related to many diseases.
      PI3K contribute to regulation of normal homeostatic functions, which include the control of cell growth and survival, transcriptional and translational responses,nutrient uptake, proliferation, migration and differentiation.
      The phosphoinositol-3-kinase family is divided into three different classes: Class I, Class II, and Class III.

      The first generation of PI3K inhibitors target the ATP-binding pocket.
      Wortmannin is the first one.
      LY294002,a competitive PI3K inhibitor,appear in 1994.LY294002 is ATP competitive.
      LY294002 has proved useful as a template for pharmacophore searches to discover new PI3K inhibitors.
      p110-δ bound to wortmannin or LY294002 show that these compounds fit into the ATP binding pocket.
      Then IC87114 is discovered , has an IC50 of 100 nM for inhibition of p110-δ.
      TG100–115 which are not chemically derived from LY294002 preferentially target p110-δ and p110-γ.
      TG100–115, which inhibits all four isoforms but displays a 5- 10 fold increased potency against p110-γ and p110-δ.
      PI-103, which was found to have a unique selectivity profile in that it inhibited all four class I PI3Ks and, with near equal potency, mammalian target of rapamycin (mTOR).
      ZSTK474 has a potent inhibition against p110a.

      a rule:
      PI3K inhibitors has revealed some notable trends: inhibitors of p110a often potently inhibit p110-γ whereas inhibitors of p110b often potently inhibit p110-δ.
      compound name

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