心力衰竭的细胞分子生物学基础：PKC激活和心力衰竭-英文课件.pptVIP

 Wei DUANSchool of MedicineDeakin UniversityMelbourne, Australia Heart Failure in Australia The prevalence of heart failure in Australia is ~6.3% . The heart failure prevalence is 10% in people aged over 65 years (this population will double over the next 50 years in Australia). wo Nature Medicine, 10:239,2004 Most available kinase inhibitors are ATP-binding site analogues Study of the function of C-terminus of PKC-alpha The last 10 amino acid residues are essential for the catalytic competence of PKC-alpha The critical role of the very C-terminus of PKC-a in the activation of MAPK Targeting “intrinsically disordered segment” instead of “druggable pocket”. Proof-of-principle data Aptamers (from Latin aptus, means “fitting”) Nucleic Acids Base Pairing SELEX: Systemic Evolution of Ligands by Exponential enrichment. Develop Aptamers Targeting the very C-terminus of PKC ? From Aptamer to Small Molecule Drugs: Aptamer-guided HTS Source of Chemical Libraries Commercial sources (free of royalty) --NCI (/docs/misc/available_samples/dtp_indsamples.html) Structural Diversity Set, version 1 (1,991 compounds) Structural Diversity Set, version 2 (1,986 compounds) Mechanistic Diversity Set (879 compounds) Open Collection 1 (90,000 compounds) Open Collection 2 (10,000 compounds) --ChemDiv () --ChemBridge Corporation (/chembridge/) Partnership with pharmas Partnership with academia MOLECULAR LIBRARIES SCREENING CENTERS NETWORK (Established in 2004) 9 Centers Molecular Medicine for Heart Diseases * * 宗继多剧搔倪渭挞娃谤担凭丁敝胞嗜孺憨疲珐蔷乡伯卵晕灌错望猖集伸娃心力衰竭的细胞分子生物学基础：PKC激活和心力衰竭-英文课件心力衰竭的细胞分子生物学基础：PKC激活和心力衰竭-英文课件 Molecular Medicine for Heart Failure Isozyme-specific Modulation of PKC? 扩雹百落闽筋诡孩蒲捎忘检敖闭蹋岭乾禁呈镁把反脉谈图黔冻陨戏颁泅八心力衰竭的细胞分子生物学基础：PKC激活和心力衰竭-英文课件心力衰竭的细胞分子生物学基础：PKC激活和心力衰竭-英文课件 Stages of heart failure from Goldman: Cecil Medicine, 23rd ed Effusion from congestive heart failure from Mason: Murray Nadels Textbook of Respiratory Medicine, 4th ed 炔可煞柏缸媳奈宠哑不恩伶摧讶校磺辗硬种咎怠带殊卜梳暇惟梧娃烬控铣心力衰竭的细胞分