研究生論壇抗腫瘤藥物設(shè)計(jì)的新靶點(diǎn)蛋氨酸合成酶催化機(jī)理及抑制劑的研究ppt課件

1、,,抗腫瘤藥物設(shè)計(jì)的新靶點(diǎn)蛋氨酸合成酶催化機(jī)理及抑制劑的研究,1,內(nèi)容,一、抗腫瘤藥物研究的新策略二、抗腫瘤新靶點(diǎn)——蛋氨酸合成酶三、蛋氨酸合成酶結(jié)構(gòu)及催化機(jī)理研究四、蛋氨酸合成酶抑制劑設(shè)計(jì)合成,2,抗腫瘤藥物研究新策略,,預(yù)防藥物、新靶點(diǎn)藥物、多靶點(diǎn)藥物 據(jù)統(tǒng)計(jì)，全世界每年死于癌癥的患者高達(dá)700余萬(wàn)，新發(fā)病例約900萬(wàn)。 化療是癌癥臨床治療的主要手段之一。,3,,,,,,,,1907AACR成立,

2、,1915發(fā)現(xiàn)化學(xué)致癌,1937通過(guò)NCA成立NCI,1940’-------腫瘤化療大發(fā)展,1971 修訂CA消滅癌癥之戰(zhàn),1980’改變策略：攻靶,NCI 篩選中心,2004NCI新計(jì)劃,2007 WCRF,AICR預(yù)防癌癥報(bào)告,制藥業(yè)競(jìng)爭(zhēng)和壟斷，歐美經(jīng)濟(jì)支柱,策略轉(zhuǎn)變—化學(xué)預(yù)防,4,Weinburg, R. A., The biology of cancer,癌的發(fā)展很慢，有時(shí)間來(lái)得及制止,DCIS:Ductal c

3、arcinoma in situ; CIN,cervical intraepithelial neoplasia, PIN, Prostate Intraepithelial Neoplasia,5,一級(jí)預(yù)防 （病因預(yù)防）阻止細(xì)胞轉(zhuǎn)變逆轉(zhuǎn)轉(zhuǎn)變,二級(jí)預(yù)防（臨床前預(yù)防）抑制細(xì)胞增殖抑制細(xì)胞因子阻止細(xì)胞遷移,三級(jí)預(yù)防 （臨床預(yù)防）抑制細(xì)胞增殖阻止腫瘤轉(zhuǎn)移,基于干預(yù)病理全過(guò)程中的關(guān)鍵環(huán)節(jié)階段性、針對(duì)性的干預(yù),6,蛋氨酸合

4、成酶—優(yōu)秀的抗腫瘤靶點(diǎn),7,蛋氨酸合成酶的結(jié)構(gòu)及催化機(jī)理,蛋氨酸合成酶（MS）結(jié)構(gòu)：,8,,,Folic Acid Cycle,9,,,Mechanism of Methionine Synthase,10,,,Structure of Methionine Synthase,11,,12,,13,蛋氨酸合成酶的催化機(jī)理,兩次親核取代過(guò)程,14,,,Study on Mechanism of Methionine Synthase,15

5、,,,16,,,Methyl Configuration of Me-THF,17,,,Methyl Configuration of Methionine,18,,2.蛋氨酸合成酶抑制劑的研究進(jìn)展,,19,,,Design of Methionine Synthase Inhibitors,20,,,Analysis of Synthetic Route,21,,,Synthesis of Methionine Synthase In

6、hibitor,22,,,23,,,24,,,25,,,26,,,Preparation of Aziridine Derivatives,27,,,Biological Testing,28,,,33,31,30,29,,,Biological Testing,,ZZL-18 Inhibition on HL-60, Bel-7402 Cells,Concentration（μmole·L-1）,30,,,Biologica

7、l Testing,,ZZL-20 Inhibition on HL-60, Bel-7402 Cells,Concentration（μmole·L-1）,31,,,Research Workers,,Zhili Zhang Xiaowei Wang Hua YangPeng Han Jie Liu Shouxin ZhouBiao Wang H