title: Fluorescent phosphoinositide 3-kinase inhibitors suitable for monitoring of intracellular distribution.
abstract: The monitoring of the drug behavior and distribution in biological system can provide information whether drug reaches its desired target, and a biological rationale for the design of new therapeutics. We have developed a family of potent fluorescent PI3Kα inhibitors in which part of the fluorophore was engineered to be a pharmacophore capable of inhibiting PI3Kα. These xanthine derivatives are characterized by a donor-acceptor molecular structure, and changes in the electronic properties of the two variation points at R(1) and R(2) give rise to notable bathochromic shifts in the λ(em, abs) and increase the value of Φ(F). Further, we illustrated the use of E2 (PI3Kα/IC(50)=0.068 μM, T47D cell viability: IC(50)=0.9 μM) to block cancer cell proliferation and to monitor its subcellular localization by fluorescence microscopy.
authors: Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea.
authors: Donghee
authors: D
authors: Kim
authors: Hyunseung
authors: H
authors: Lee
authors: Hwiseok
authors: H
authors: Jun
authors: Soon-Sun
authors: SS
authors: Hong
authors: Sungwoo
authors: S
authors: Hong
mesh_terms: D019870:1-Phosphatidylinositol 4-Kinase / Q000037:antagonists & inhibitors*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005456:Fluorescent Dyes; D006801:Humans; D020128:Inhibitory Concentration 50; D015336:Molecular Probe Techniques; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000032:analysis* / Q000627:therapeutic use; D019820:Xanthine / Q000737:chemistry / Q000494:pharmacology
chemical_list: D005456:Fluorescent Dyes; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D019820:Xanthine; D019870:1-Phosphatidylinositol 4-Kinase