Search

Your search keyword '"Fred Kohlhapp"' showing total 19 results
Start Over Author "Fred Kohlhapp"
19 results on '"Fred Kohlhapp"'

1. Supplemental figure 14 to 17 from Preclinical Characterization of BET Family Bromodomain Inhibitor ABBV-075 Suggests Combination Therapeutic Strategies

Author

Yu Shen, Warren M. Kati, Keith F. McDaniel, Saul H. Rosenberg, Steven W. Elmore, Guowei Fang, Fred Kohlhapp, Xin Lu, Tamar Uziel, Lisa Hasvold, Dachun Liu, John K. Pratt, Steve Fidanze, Le Wang, George S. Sheppard, Cherrie K. Donawho, Denise Wilcox, Xiaoli Huang, Scott E. Warder, Emily J. Faivre, Lloyd T. Lam, Leiming Li, Daniel H. Albert, Xiaoyu Lin, and Mai H. Bui

Abstract

High level of concomitant Bim and Bcl-2 expression correlates with sensitivity to ABBV-075-induced apoptosis

Published
2023
Full Text
View/download PDF

2. Supplemental table 4 from Preclinical Characterization of BET Family Bromodomain Inhibitor ABBV-075 Suggests Combination Therapeutic Strategies

Author

Yu Shen, Warren M. Kati, Keith F. McDaniel, Saul H. Rosenberg, Steven W. Elmore, Guowei Fang, Fred Kohlhapp, Xin Lu, Tamar Uziel, Lisa Hasvold, Dachun Liu, John K. Pratt, Steve Fidanze, Le Wang, George S. Sheppard, Cherrie K. Donawho, Denise Wilcox, Xiaoli Huang, Scott E. Warder, Emily J. Faivre, Lloyd T. Lam, Leiming Li, Daniel H. Albert, Xiaoyu Lin, and Mai H. Bui

Abstract

Apoptosis induction by MS417 across cancer cell lines

Published
2023
Full Text
View/download PDF

3. Supplemental figure 13 from Preclinical Characterization of BET Family Bromodomain Inhibitor ABBV-075 Suggests Combination Therapeutic Strategies

Author

Yu Shen, Warren M. Kati, Keith F. McDaniel, Saul H. Rosenberg, Steven W. Elmore, Guowei Fang, Fred Kohlhapp, Xin Lu, Tamar Uziel, Lisa Hasvold, Dachun Liu, John K. Pratt, Steve Fidanze, Le Wang, George S. Sheppard, Cherrie K. Donawho, Denise Wilcox, Xiaoli Huang, Scott E. Warder, Emily J. Faivre, Lloyd T. Lam, Leiming Li, Daniel H. Albert, Xiaoyu Lin, and Mai H. Bui

Abstract

Restoration of Myc expression under BET inhibitor treatment failed to rescue cells from apoptosis or cell cycle arrest

Published
2023
Full Text
View/download PDF

4. Data from Preclinical Characterization of BET Family Bromodomain Inhibitor ABBV-075 Suggests Combination Therapeutic Strategies

Author

Yu Shen, Warren M. Kati, Keith F. McDaniel, Saul H. Rosenberg, Steven W. Elmore, Guowei Fang, Fred Kohlhapp, Xin Lu, Tamar Uziel, Lisa Hasvold, Dachun Liu, John K. Pratt, Steve Fidanze, Le Wang, George S. Sheppard, Cherrie K. Donawho, Denise Wilcox, Xiaoli Huang, Scott E. Warder, Emily J. Faivre, Lloyd T. Lam, Leiming Li, Daniel H. Albert, Xiaoyu Lin, and Mai H. Bui

Abstract

ABBV-075 is a potent and selective BET family bromodomain inhibitor that recently entered phase I clinical trials. Comprehensive preclinical characterization of ABBV-075 demonstrated broad activity across cell lines and tumor models, representing a variety of hematologic malignancies and solid tumor indications. In most cancer cell lines derived from solid tumors, ABBV-075 triggers prominent G1 cell-cycle arrest without extensive apoptosis. In this study, we show that ABBV-075 efficiently triggers apoptosis in acute myeloid leukemia (AML), non-Hodgkin lymphoma, and multiple myeloma cells. Apoptosis induced by ABBV-075 was mediated in part by modulation of the intrinsic apoptotic pathway, exhibiting synergy with the BCL-2 inhibitor venetoclax in preclinical models of AML. In germinal center diffuse large B-cell lymphoma, BCL-2 levels or venetoclax sensitivity predicted the apoptotic response to ABBV-075 treatment. In vivo combination studies uncovered surprising benefits of low doses of ABBV-075 coupled with bortezomib and azacitidine treatment, despite the lack of in vitro synergy between ABBV-075 and these agents. The in vitro/in vivo activities of ABBV-075 described here may serve as a useful reference to guide the development of ABBV-075 and other BET family inhibitors for cancer therapy. Cancer Res; 77(11); 2976–89. ©2017 AACR.

Published
2023
Full Text
View/download PDF

5. Supplemental figure 10 & 11 from Preclinical Characterization of BET Family Bromodomain Inhibitor ABBV-075 Suggests Combination Therapeutic Strategies

Author

Yu Shen, Warren M. Kati, Keith F. McDaniel, Saul H. Rosenberg, Steven W. Elmore, Guowei Fang, Fred Kohlhapp, Xin Lu, Tamar Uziel, Lisa Hasvold, Dachun Liu, John K. Pratt, Steve Fidanze, Le Wang, George S. Sheppard, Cherrie K. Donawho, Denise Wilcox, Xiaoli Huang, Scott E. Warder, Emily J. Faivre, Lloyd T. Lam, Leiming Li, Daniel H. Albert, Xiaoyu Lin, and Mai H. Bui

Abstract

ABBV-075 inhibits Bcl-XL transcription and displace BRD4 from Bcl-XL regulatory regions

Published
2023
Full Text
View/download PDF

6. Supplemental table 3 from Preclinical Characterization of BET Family Bromodomain Inhibitor ABBV-075 Suggests Combination Therapeutic Strategies

Author

Yu Shen, Warren M. Kati, Keith F. McDaniel, Saul H. Rosenberg, Steven W. Elmore, Guowei Fang, Fred Kohlhapp, Xin Lu, Tamar Uziel, Lisa Hasvold, Dachun Liu, John K. Pratt, Steve Fidanze, Le Wang, George S. Sheppard, Cherrie K. Donawho, Denise Wilcox, Xiaoli Huang, Scott E. Warder, Emily J. Faivre, Lloyd T. Lam, Leiming Li, Daniel H. Albert, Xiaoyu Lin, and Mai H. Bui

Abstract

Apoptosis induction by ABBV-075 across cancer cell lines

Published
2023
Full Text
View/download PDF

7. 'Supplemental figure 2 from Preclinical Characterization of BET Family Bromodomain Inhibitor ABBV-075 Suggests Combination Therapeutic Strategies

Author

Yu Shen, Warren M. Kati, Keith F. McDaniel, Saul H. Rosenberg, Steven W. Elmore, Guowei Fang, Fred Kohlhapp, Xin Lu, Tamar Uziel, Lisa Hasvold, Dachun Liu, John K. Pratt, Steve Fidanze, Le Wang, George S. Sheppard, Cherrie K. Donawho, Denise Wilcox, Xiaoli Huang, Scott E. Warder, Emily J. Faivre, Lloyd T. Lam, Leiming Li, Daniel H. Albert, Xiaoyu Lin, and Mai H. Bui

Abstract

Induction of apoptosis across cancer cell lines and CD34 normal cells

Published
2023
Full Text
View/download PDF

8. Supplemental table 1 from Preclinical Characterization of BET Family Bromodomain Inhibitor ABBV-075 Suggests Combination Therapeutic Strategies

Author

Yu Shen, Warren M. Kati, Keith F. McDaniel, Saul H. Rosenberg, Steven W. Elmore, Guowei Fang, Fred Kohlhapp, Xin Lu, Tamar Uziel, Lisa Hasvold, Dachun Liu, John K. Pratt, Steve Fidanze, Le Wang, George S. Sheppard, Cherrie K. Donawho, Denise Wilcox, Xiaoli Huang, Scott E. Warder, Emily J. Faivre, Lloyd T. Lam, Leiming Li, Daniel H. Albert, Xiaoyu Lin, and Mai H. Bui

Abstract

Anti-proliferative activity of ABBV-075 across cancer cell lines

Published
2023
Full Text
View/download PDF

9. Supplemental figure 7 & 8 from Preclinical Characterization of BET Family Bromodomain Inhibitor ABBV-075 Suggests Combination Therapeutic Strategies

Author

Yu Shen, Warren M. Kati, Keith F. McDaniel, Saul H. Rosenberg, Steven W. Elmore, Guowei Fang, Fred Kohlhapp, Xin Lu, Tamar Uziel, Lisa Hasvold, Dachun Liu, John K. Pratt, Steve Fidanze, Le Wang, George S. Sheppard, Cherrie K. Donawho, Denise Wilcox, Xiaoli Huang, Scott E. Warder, Emily J. Faivre, Lloyd T. Lam, Leiming Li, Daniel H. Albert, Xiaoyu Lin, and Mai H. Bui

Abstract

BET inhibitor causes cell cycle arrest and triggers senescence in solid tumor cells

Published
2023
Full Text
View/download PDF

10. Supplemental figure 20 from Preclinical Characterization of BET Family Bromodomain Inhibitor ABBV-075 Suggests Combination Therapeutic Strategies

Author

Yu Shen, Warren M. Kati, Keith F. McDaniel, Saul H. Rosenberg, Steven W. Elmore, Guowei Fang, Fred Kohlhapp, Xin Lu, Tamar Uziel, Lisa Hasvold, Dachun Liu, John K. Pratt, Steve Fidanze, Le Wang, George S. Sheppard, Cherrie K. Donawho, Denise Wilcox, Xiaoli Huang, Scott E. Warder, Emily J. Faivre, Lloyd T. Lam, Leiming Li, Daniel H. Albert, Xiaoyu Lin, and Mai H. Bui

Abstract

ABBV-075 inhibits hypoxia induced transcription of proangiogenesis factors

Published
2023
Full Text
View/download PDF

11. Supplemental figure 19 from Preclinical Characterization of BET Family Bromodomain Inhibitor ABBV-075 Suggests Combination Therapeutic Strategies

Author

Yu Shen, Warren M. Kati, Keith F. McDaniel, Saul H. Rosenberg, Steven W. Elmore, Guowei Fang, Fred Kohlhapp, Xin Lu, Tamar Uziel, Lisa Hasvold, Dachun Liu, John K. Pratt, Steve Fidanze, Le Wang, George S. Sheppard, Cherrie K. Donawho, Denise Wilcox, Xiaoli Huang, Scott E. Warder, Emily J. Faivre, Lloyd T. Lam, Leiming Li, Daniel H. Albert, Xiaoyu Lin, and Mai H. Bui

Abstract

Tumor environmental factors such as hypoxia or the presence of prosurvival cytokine such as IL-6 does not significantly change cellular sensitivity to ABBV-075

Published
2023
Full Text
View/download PDF

12. Supplemental figure 21 from Preclinical Characterization of BET Family Bromodomain Inhibitor ABBV-075 Suggests Combination Therapeutic Strategies

Author

Yu Shen, Warren M. Kati, Keith F. McDaniel, Saul H. Rosenberg, Steven W. Elmore, Guowei Fang, Fred Kohlhapp, Xin Lu, Tamar Uziel, Lisa Hasvold, Dachun Liu, John K. Pratt, Steve Fidanze, Le Wang, George S. Sheppard, Cherrie K. Donawho, Denise Wilcox, Xiaoli Huang, Scott E. Warder, Emily J. Faivre, Lloyd T. Lam, Leiming Li, Daniel H. Albert, Xiaoyu Lin, and Mai H. Bui

Abstract

ABBV-075 induces differentiation markers in HL-60 cells

Published
2023
Full Text
View/download PDF

13. Supplemental figure 12 from Preclinical Characterization of BET Family Bromodomain Inhibitor ABBV-075 Suggests Combination Therapeutic Strategies

Author

Yu Shen, Warren M. Kati, Keith F. McDaniel, Saul H. Rosenberg, Steven W. Elmore, Guowei Fang, Fred Kohlhapp, Xin Lu, Tamar Uziel, Lisa Hasvold, Dachun Liu, John K. Pratt, Steve Fidanze, Le Wang, George S. Sheppard, Cherrie K. Donawho, Denise Wilcox, Xiaoli Huang, Scott E. Warder, Emily J. Faivre, Lloyd T. Lam, Leiming Li, Daniel H. Albert, Xiaoyu Lin, and Mai H. Bui

Abstract

PP2A activator PTZ does not enhance ABBV-075 induced apoptosis in solid tumor cell lines

Published
2023
Full Text
View/download PDF

14. Supplemental figure legends from Preclinical Characterization of BET Family Bromodomain Inhibitor ABBV-075 Suggests Combination Therapeutic Strategies

Author

Yu Shen, Warren M. Kati, Keith F. McDaniel, Saul H. Rosenberg, Steven W. Elmore, Guowei Fang, Fred Kohlhapp, Xin Lu, Tamar Uziel, Lisa Hasvold, Dachun Liu, John K. Pratt, Steve Fidanze, Le Wang, George S. Sheppard, Cherrie K. Donawho, Denise Wilcox, Xiaoli Huang, Scott E. Warder, Emily J. Faivre, Lloyd T. Lam, Leiming Li, Daniel H. Albert, Xiaoyu Lin, and Mai H. Bui

Abstract

supplemental figure legends

Published
2023
Full Text
View/download PDF

15. Supplemental figure 1 from Preclinical Characterization of BET Family Bromodomain Inhibitor ABBV-075 Suggests Combination Therapeutic Strategies

Author

Yu Shen, Warren M. Kati, Keith F. McDaniel, Saul H. Rosenberg, Steven W. Elmore, Guowei Fang, Fred Kohlhapp, Xin Lu, Tamar Uziel, Lisa Hasvold, Dachun Liu, John K. Pratt, Steve Fidanze, Le Wang, George S. Sheppard, Cherrie K. Donawho, Denise Wilcox, Xiaoli Huang, Scott E. Warder, Emily J. Faivre, Lloyd T. Lam, Leiming Li, Daniel H. Albert, Xiaoyu Lin, and Mai H. Bui

Abstract

BRD4 binding to Myc regulatory region

Published
2023
Full Text
View/download PDF

16. Supplemental figure 6 from Preclinical Characterization of BET Family Bromodomain Inhibitor ABBV-075 Suggests Combination Therapeutic Strategies

Author

Yu Shen, Warren M. Kati, Keith F. McDaniel, Saul H. Rosenberg, Steven W. Elmore, Guowei Fang, Fred Kohlhapp, Xin Lu, Tamar Uziel, Lisa Hasvold, Dachun Liu, John K. Pratt, Steve Fidanze, Le Wang, George S. Sheppard, Cherrie K. Donawho, Denise Wilcox, Xiaoli Huang, Scott E. Warder, Emily J. Faivre, Lloyd T. Lam, Leiming Li, Daniel H. Albert, Xiaoyu Lin, and Mai H. Bui

Abstract

Expression of exogenous Bcl-XL rescues ABBV-075 induced apoptosis but not cell cycle arrest

Published
2023
Full Text
View/download PDF

17. Supplemental figure 4 & 5 from Preclinical Characterization of BET Family Bromodomain Inhibitor ABBV-075 Suggests Combination Therapeutic Strategies

Author

Yu Shen, Warren M. Kati, Keith F. McDaniel, Saul H. Rosenberg, Steven W. Elmore, Guowei Fang, Fred Kohlhapp, Xin Lu, Tamar Uziel, Lisa Hasvold, Dachun Liu, John K. Pratt, Steve Fidanze, Le Wang, George S. Sheppard, Cherrie K. Donawho, Denise Wilcox, Xiaoli Huang, Scott E. Warder, Emily J. Faivre, Lloyd T. Lam, Leiming Li, Daniel H. Albert, Xiaoyu Lin, and Mai H. Bui

Abstract

Down regulation of Bcl-XL by MS417 and ABBV-075

Published
2023
Full Text
View/download PDF

18. Supplemental figure 9 from Preclinical Characterization of BET Family Bromodomain Inhibitor ABBV-075 Suggests Combination Therapeutic Strategies

Author

Yu Shen, Warren M. Kati, Keith F. McDaniel, Saul H. Rosenberg, Steven W. Elmore, Guowei Fang, Fred Kohlhapp, Xin Lu, Tamar Uziel, Lisa Hasvold, Dachun Liu, John K. Pratt, Steve Fidanze, Le Wang, George S. Sheppard, Cherrie K. Donawho, Denise Wilcox, Xiaoli Huang, Scott E. Warder, Emily J. Faivre, Lloyd T. Lam, Leiming Li, Daniel H. Albert, Xiaoyu Lin, and Mai H. Bui

Abstract

ABBV-075 inhibits genes that are important for cell cycle

Published
2023
Full Text
View/download PDF

19. Preclinical Characterization of BET Family Bromodomain Inhibitor ABBV-075 Suggests Combination Therapeutic Strategies

Author

Xiaoli Huang, Lisa A. Hasvold, Guowei Fang, Yu Shen, Denise Wilcox, Cherrie K. Donawho, George S. Sheppard, Le Wang, Fred Kohlhapp, Dachun Liu, Tamar Uziel, Leiming Li, Lloyd T. Lam, Daniel H. Albert, Scott E. Warder, Steven W. Elmore, Saul H. Rosenberg, Xiaoyu Lin, Xin Lu, Mai H. Bui, Keith F. McDaniel, Warren M. Kati, Emily J. Faivre, John K. Pratt, and Steve D. Fidanze

Subjects
0301 basic medicine, Cancer Research, Pyridones, Azacitidine, Apoptosis, Pharmacology, Biology, Transfection, 03 medical and health sciences, chemistry.chemical_compound, Cell Line, Tumor, medicine, Humans, Multiple myeloma, Sulfonamides, Bortezomib, Venetoclax, Cancer, Myeloid leukemia, Androgen Antagonists, Drug Synergism, medicine.disease, Lymphoma, Bromodomain, 030104 developmental biology, Oncology, chemistry, Cancer research, medicine.drug
Abstract

ABBV-075 is a potent and selective BET family bromodomain inhibitor that recently entered phase I clinical trials. Comprehensive preclinical characterization of ABBV-075 demonstrated broad activity across cell lines and tumor models, representing a variety of hematologic malignancies and solid tumor indications. In most cancer cell lines derived from solid tumors, ABBV-075 triggers prominent G1 cell-cycle arrest without extensive apoptosis. In this study, we show that ABBV-075 efficiently triggers apoptosis in acute myeloid leukemia (AML), non-Hodgkin lymphoma, and multiple myeloma cells. Apoptosis induced by ABBV-075 was mediated in part by modulation of the intrinsic apoptotic pathway, exhibiting synergy with the BCL-2 inhibitor venetoclax in preclinical models of AML. In germinal center diffuse large B-cell lymphoma, BCL-2 levels or venetoclax sensitivity predicted the apoptotic response to ABBV-075 treatment. In vivo combination studies uncovered surprising benefits of low doses of ABBV-075 coupled with bortezomib and azacitidine treatment, despite the lack of in vitro synergy between ABBV-075 and these agents. The in vitro/in vivo activities of ABBV-075 described here may serve as a useful reference to guide the development of ABBV-075 and other BET family inhibitors for cancer therapy. Cancer Res; 77(11); 2976–89. ©2017 AACR.

Published
2017
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results