J.P. Morgan Chase的問題，透過圖書和論文來找解法和答案更準確安心。 我們找到下列各種有用的問答集和懶人包

JPMorgan’’s Fall and Revival: How the Wave of Consolidation Changed America’’s Premier Bank

為了解決J.P. Morgan Chase的問題，作者Sargen, Nicholas P. 這樣論述：

Uncovers Morgan’s transformation with detailed interviews from former senior executivesOffers an insider account of what transpired before J.P. Morgan merged with ChaseTells the story of JPMorgan against the backdrop of a larger U.S. banking consolidation era in the 1980s and 90s

Thriving in a Global Pandemic and Beyond: More Than 100 Real-Life Lessons

為了解決J.P. Morgan Chase的問題，作者Schrock, Saundra 這樣論述：

For over 30 years, Saundra held various executive positions within the financial services industry. One of her most rewarding and challenging roles was to manage J. P. Morgan Chase’s branch banking network of 3,000 branches and over 30,000 employees. From her career beginnings as a bank teller to he

r role as Executive Vice President of J.P. Morgan Chase, Saundra credits much of her success to embracing the main tenets and practices of mindfulness. The dramatic impact these practices have had on her life ignited her passion for sharing the benefits of mindfulness with as many people as possible

. Today, Saundra is the founder and CEO of Levelhead an organization that offers a mindfulness-based program designed for the workplace and higher education delivered via a digital engagement platform. This book reflects her extensive work in a wide variety of industries and her work with higher edu

cation. Her programs have been empirically validated to reduce stress and anxiety and offer busy people choices in how and when they practice mindfulness. For more information see getlevelhead.com and getlevelheaded.com. Saundra holds an MBA from Arizona State University and a doctorate in Industria

l and Organizational Psychology from Grand Canyon University, Phoenix, Arizona.

Designing and Synthesis of HDAC inhibitors as Anti-cancer agents

為了解決J.P. Morgan Chase的問題，作者ARSHDEEP SINGH 這樣論述：

Contents Page No.Abstract……………………………………………………………………………………….1Chinese Abstract ……………………………………………………………………………3List of Figures…………………………………………………………………………………5List of Tables………………………………………………………………………………….6List of Schemes………………………………………………………………………………..7Chapter 1. Cancer & Epigenetics1.1 Cancer………………………

…………………………………………………………….81.1.1 Introduction…………………………………………………………………………..81.1.2 Epidemiology…………………………………………………………………………91.1.3 Risk Factors…………………………………………………………………………...91.1.4 Biomarkers: Diagnostic Tool for Cancer…………………………………………101.1.5 Hallmarks of Cancer………………………………………………………………..131.1.6 Treatmen

ts of Cancer……………………………………………………………….141.1.7 Cytotoxic Therapy ………………………………………………………………….151.1.8 Targeted therapy……………………………………………………………………151.2 Epigenetics………………………………………………………………………………171.2.1 Introduction…………………………………………………………………………171.2.2 Epigenetic Dysregulation in Cancer………………………………………………..20Ch

apter 2. Designing and synthesis of benzamide based HDAC inhibitors as anti-canceragents2.1 Histone deacetylases (HDACs)………………………………………………………….242.1.1 Classes of HDAC………………………………………………………………………252.1.2 Non-histone substrates of HDACs……………………………………………………262.1.3 Role of HDACs in different cancers………………

…………………………………..272.1.4 HDAC inhibitors………………………………………………………………………342.2 Rationale……...………..………………………………………………………………...392.3 Designing Strategy………………………………………………………………………402.4 Results and Discussion…………………………………………………………………..412.4.1 Chemistry……………………………………………………………………………...412.4.2 Biological Evaluatio

n………………………………………………………………….452.4.2.1 In vitro cytotoxicity study…………………………………………………………...452.4.2.2 HDAC inhibition study of compounds 7 and 15……………………………………462.4.2.3 Cytotoxicity of 15 and 7 in HDACi-resistant cell lines…………………………….472.4.2.4 Compound 15 and 7 exhibit potent anti-proliferative activi

ty and triggersapoptosis……………………………………………………………………………..482.4.2.5 Cytotoxicity of 15 and 7 in leukemia cell lines……………………………………...492.4.2.6 HDAC inhibitory activities of 15 and 7 in cells…………………………………….502.4.2.7 Compounds 15 and 7 impair tubulin assembly in-vitro and in cells……………...512.4.2.8 Compoun

d 15 and 7 trigger the cell-cycle arrest in mitosis……………………….532.4.2.9 Cytotoxicity of 15 and 7 in non-small cell lung cancer cell lines…………………..552.4.2.10 Cytotoxicity of 7 in multiple-drug resistant uterine cancer cell lines……552.4.2.11 Docking study of compound 7………………………………………………572.5 Conclusion

……………………………………………………………………………59Chapter 3. Designing and Synthesis of abiraterone based dual CYP17A1/HDACinhibitors to treat Glioblastoma (GBM)3.1 Introduction……………………………………………………………………………..603.1.1 Classification of CYPs………………………………………………………………...613.1.2 Cytochrome P450 17A1 (CYP17A1) enzyme………………………

………………...613.1.3 CYP17A1 inhibitors…………………………………………………………………...633.1.4 Implication of CYP17A1 in Glioblastoma (GBM)…………………………………...653.1.5 Role of HDACs in Glioblastomas……………………………………………………..673.2 Rationale…………………………………………………………………………………683.3 Designing Strategy………………………………………………………………………703.4 Result

s and Discussion…………………………………………………………………..723.4.1 Chemistry……………………………………………………………………………...723.4.2 Biological Evaluation………………………………………………………………….753.4.2.1 HDAC inhibition activity……………………………………………………………753.4.2.2 In vitro cytotoxicity study of amide linkage containing abiraterone hydroxamateson gli

oblastoma cell lines……………………………………………………………………763.4.2.3 CYP17A1 inhibition study…………………………………………………………..763.4.2.4 Cell viability assay using P3-R GBM cell lines……………………………………..773.4.2.5 Inhibition of survival of TMZ-resistant glioblastoma by compound 41………….783.4.2.6 Compound 41 increases ROS in Pt#

3-R……………………………………………793.4.2.7 Inhibition of TMZ-resistant tumor growth in-vivo by Compound 41 exertedthrough CYP17A1 inhibition……………………………………………………………….803.5 Conclusion……………………………………………………………………………….81Chapter 4. Synthesis of selective class IIa HDAC inhibitors for various cancers4.1 Introduction…………

…………………………………………………………………..834.1.1 Structural characteristics of class IIa HDACs……………………………………….834.1.2 Expression of class IIa HDACs in various tissues……………………………………854.1.3 Interaction partners of class IIa HDACs……………………………………………..854.1.4 Subcellular localization of class IIa HDACs…………………………………………8

74.1.5 Catalytic activity of class IIa HDACs………………………………………………...874.1.6 Role of class IIa HDACs in cancer……………………………………………………884.1.7 Selective class IIa HDAC inhibitors…………………………………………………914.2 Rationale…………………………………………………………………………………934.3 Designing Strategy………………………………………………………………………944.4 Results a

nd Discussion…………………………………………………………………..954.4.1 Chemistry……………………………………………………………………………...954.4.2 Biological Evaluation………………………………………………………………….974.4.2.1 HDAC inhibition activity……………………………………………………………974.4.2.2 In-vitro cytotoxicity of compounds (156, 158 and 160) against various cancer celllines………

…………………………………………………………………………………..984.5 Conclusion……………………………………………………………………………….995. Index of Appendix……………………………………………………………………1005.1 Appendix 1: Instruments, equipment, and reagents…………………………………1005.1.1 Experimental instrument and equipment………………………………………1005.1.2 Experimental solvent and reagent……

……………………………………………..1005.1.3 Experimental reagent abbreviation………………………………………………...1025.1.4 Experimental……………………………………………………………………….1045.1.5 Biological Procedures……………………………………………………………...1456. References……………………………………………………………………………...1497. 1H NMR of Final Compounds…………………………………………………………1818. 13C NM

R spectras of Final Compounds……………………………………………...2269. HRMS of Final Compounds…………………………………………………………..268List of Figures Page No.Figure 1. Processes involved in tumorigenesis and sites to identify biomarkers……………..9Figure 2. Risk factors of cancer (Black boxes represents Non-intrinsic risk factors)…

…….10Figure 3. Hallmarks of cancer……………………………………………………………….14Figure 4. Structures of cytotoxic agents……………………………………………………..16Figure 5. Structures of small molecule inhibitors…………………………………………...17Figure 6. Representation of various epigenetic processes involved in regulation of chromatinarchitecture

and gene expression along with their targeting to cure cancer………………….19Figure 7. Layout of Epigenetic tools consisting of epigenetic writers, readers and erasers…20Figure 8. Regulation of gene-expression switch by HATs and HDACs…………………….25Figure 9. Non-histone protein substrates of HDACs with the sp

ecific HDACs involved…..27Figure 10. HDAC inhibitors structures……………………………………………………...36Figure 11. Designing strategy and structures of final compounds…………………………..41Figure 12. Antiproliferative activity of MS-275, 7 and 15 against HDACi-sensitive andresistant cell lines…………………………………………………………………………….

48Figure 13. Compounds 7 and 15 trigger apoptosis…………………………………………..49Figure 14. HDAC-inhibitory activity of MS-275, 7 and 15 in cells…………………………51Figure 15. Compounds 7 and 15 impair tubulin assembly in vitro and in cells……………..52Figure 16. Compounds 7 and 15 induce the cell-cycle arrest in mitosis a

nd trigger DNAfragmentation at low concentration…………………………………………………………..54Figure 17. Multiple drug-resistant cells are vulnerable to 7…………………………………56Figure 18. Compound 7 docked in active sites of HDAC1 and tubulin……………………..58Figure 19. The role of CYP17A1 in adrenal steroidogenesis………………………………..63F

igure 20. Structures of CYP17A1 inhibitors……………………………………………….65Figure 21. Overexpression of CYP17A1 induced by Sp1 based inhibition of DNMT3amediatedDNA methylation results in increased expression of DHEA and glioma resistance toTMZ………………………………………………………………………………………….66Figure 22. Role of HDAC 1/2 in

TMZ resistant glioblastoma………………………………67Figure 23. Pathways leading to drug resistance in GBM. A. Involvement of CYP17A1 andHDAC 1/2/6 in Glioblastoma (GBM) along with induction of drug resistance. B. Complex ofCYP17A1 and SAR1a/b maintains ER health and increased SAR1 expression escapes cellfrom an

y damage induced by Abiraterone…………………………………………………...70Figure 24. Designing of dual CYP17A1/HDAC inhibitors based on Abiraterone………….716Figure 25. Effect of compounds 41-44, 47, 52-55, 58-62, 65-66 on glioblastoma celllines…………………………………………………………………………………………..76Figure 26. CYP17A1 inhibitory activity

of abiraterone based HDAC inhibitors…………...77Figure 27. A. Cytotoxicity of ester-based abiraterone derivatives in P3-R cells after 72 hrs oftreatment. B. Cytotoxicity of compound 41 in P3-R GBM cell line after 96 hrs oftreatment……………………………………………………………………………………...78Figure 28. Growth inhibition of TMZ

-resistant glioblastoma cell lines by compound 41 after96 hrs of treatment……………………………………………………………………………79Figure 29. Analysis of ROS levels in Pt#3-R cells by dihydrorhodamine 123 (DHR) usingflow cytometry after 48h of treatment………………………………………………………..80Figure 30. Effect of compound 41 on GBMs in-vivo

. A. Effect of compound 41 on U87MGRcells xenografted in mice Excised tumors were photographed and weighed. B. Compound41 reduced the growth of Pt#3R cells inoculated in mice……………………………………81Figure 31. Classes of HDACs……………………………………………………………….83Figure 32. General structure of class IIa HDACs………………………

……………………84Figure 33. Comparison of Structural features of class I and class IIa HDAC catalyticdomains with inhibitors and bound peptides…………………………………………………85Figure 34. Association of class IIa HDACs with various interaction partners through distinctdomains………………………………………………………………………………………86Figure 35

. FDA-approved HDAC inhibitors………………………………………………...92Figure 36. A. Structures of class II and class IIa selective HDAC inhibitors……………….93Figure 37. Designing of selective HDAC IIa inhibitors……………………………………..95List of Tables Page No.Table 1. Classification of different biomarkers with their respectiv

e cancers………………11Table 2. Mutations involved in epigenetic modifiers in various human cancers……………21Table 3. Various classes of HDACs…………………………………………………………25Table 4. Role of different HDACs in various cancers……………………………………….28Table 5. HDAC inhibitors currently under clinical studies………………………………….36T

able 6. Cytotoxicity of compounds (7-15) in solid tumor cell lines………………………..46Table 7. HDAC inhibitory activity of compounds 7 and 15………………………………...47Table 8. Cytotoxicity of compounds 7 and 15 in leukemic cell lines. ………………………50Table 9. Antiproliferative activity of 7, 15, MS-275 and vinorelbine a

gainst lung cancer celllines…………………………………………………………………………………………..557Table 10. Major substrate-based classification of human P450s…………………………….60Table 11. Inhibition of the activities (IC50, μM) Of HDAC isoforms 1, 2, 6, and 8………...75Table 12. Alterations in class IIa HDACs in various cancers…………………………

…….90Table 13. HDAC inhibitory activity of compounds (148-168)……………………………...98Table 14. Cytotoxicity of 156, 158 and 160 against cancer cell lines……………………….99List of Schemes Page No.Scheme 1. Synthetic Approaches to Compounds 7-14………………………………………43Scheme 2. Synthetic Approach to Compound 15…………………………

…………………45Scheme 3. Synthesis of compounds (41-44)…………………………………………………72Scheme 4. Synthesis of compounds (52-55)…………………………………………………73Scheme 5. Synthesis of compounds (58-62)…………………………………………………74Scheme 6. Synthesis of compounds (65-66)…………………………………………………74Scheme 7. Synthesis of carboxylic acid derivati

ve (69)……………………………………..95Scheme 8. Synthesis of compounds (148-168)………………………………………………96