The Experts below are selected from a list of 19221 Experts worldwide ranked by ideXlab platform
David J Hosfield - One of the best experts on this subject based on the ideXlab platform.
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discovery of cc 90011 a potent and selective Reversible Inhibitor of lysine specific demethylase 1 lsd1
Journal of Medicinal Chemistry, 2020Co-Authors: Toufike Kanouni, Christophe Severin, Robert Cho, Natalie Y Y Yuen, Lihong Shi, Chon Lai, Joselyn R Del Rosario, Ryan Stansfield, Lee N Lawton, David J HosfieldAbstract:Histone demethylase LSDl (KDMlA) belongs to the flavin adenine dinucleotide (FAD) dependent family of monoamine oxidases and is vital in regulation of mammalian biology. Dysregulation and overexpre...
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discovery of cc 90011 a potent and selective Reversible Inhibitor of lysine specific demethylase 1 lsd1
Journal of Medicinal Chemistry, 2020Co-Authors: Toufike Kanouni, Christophe Severin, Robert Cho, Natalie Y Y Yuen, Lihong Shi, Chon Lai, Joselyn R Del Rosario, Ryan Stansfield, Lee N Lawton, David J HosfieldAbstract:Histone demethylase LSDl (KDMlA) belongs to the flavin adenine dinucleotide (FAD) dependent family of monoamine oxidases and is vital in regulation of mammalian biology. Dysregulation and overexpression of LSD1 are hallmarks of a number of human diseases, particularly cancers that are characterized as morphologically poorly differentiated. As such, Inhibitors of LSD1 have potential to be beneficial as a cancer therapy. The most clinically advanced Inhibitors of LSDl are covalent Inhibitors derived from tranylcypromine (TCP). Herein, we report the discovery of a novel series of Reversible and selective LSDl Inhibitors. Exploration of structure-activity relationships (SARs) and optimization of ADME properties resulted in the identification of clinical candidate CC-90011. CC-90011 exhibits potent on-target induction of cellular differentiation in acute myeloid leukemia (AML) and small cell lung cancer (SCLC) cell lines, and antitumor efficacy in patient-derived xenograft (PDX) SCLC models. CC-90011 is currently in phase 2 trials in patients with first line, extensive stage SCLC (ClinicalTrials.gov identifier: NCT03850067).
Karen Sutherland - One of the best experts on this subject based on the ideXlab platform.
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palbociclib commercial manufacturing process development part iii deprotection followed by crystallization for api particle property control
Organic Process Research & Development, 2016Co-Authors: Brian Patrick Chekal, Jason Ewers, Steven M Guinness, Kyle R Leeman, Ronald J Post, Anil Rane, Karen Sutherland, Ke Wang, Mark Webster, Gregory J WithbroeAbstract:A three-step commercial manufacturing route has been developed for palbociclib, a highly selective, Reversible Inhibitor of CDK 4/6. The third step of the palbociclib process is composed of an acid-catalyzed deprotection reaction telescoped through extractive workup and distillation operations into a controlled crystallization process. The selection of n-butanol and anisole as the cosolvents for this step allowed for the development of a robust process for each unit operation and for tight control of the API particle size.
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palbociclib commercial manufacturing process development part ii regioselective heck coupling with polymorph control for processability
Organic Process Research & Development, 2016Co-Authors: Mark T Maloney, Kyle R Leeman, Ke Wang, Brian P Jones, Mark Olivier, Javier Magano, Nathan D Ide, Andrew S Palm, David R Bill, Karen SutherlandAbstract:A three-step commercial manufacturing route has been developed for palbociclib, a highly selective, Reversible Inhibitor of CDK 4/6. The second step, which utilizes a Heck coupling to install the enol ether side chain, is described. A highly regioselective catalyst was identified for this transformation along with reaction conditions that ensure robustness upon scale-up. Effective removal of palladium was accomplished via filtration of insoluble metal and an extractive chelation step. Finally, efficient isolation of coupled product 3 was achieved through careful polymorph control via seeding and an optimized cooling protocol that avoids nucleation of a kinetically favored, slow-filtering polymorph.
Simon P. Elliott - One of the best experts on this subject based on the ideXlab platform.
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Fatal poisoning with a new phenylethylamine: 4-methylthioamphetamine (4-MTA
2016Co-Authors: Simon P. ElliottAbstract:There has been much publicity in the United Kingdom regarding a new phenylethylamine-based compound called 4-methylthioamphetamine (4-MTA), also known as para-methylthioamphetamine (p-MTA), MTA or "Flatliner". Chemically, 4-MTA is an amphetamine derivative and is a non-neurotoxic potent serotonin-releasing agent and Reversible Inhibitor of rat monoamine oxidase-A. Analysis of postmortem blood and urine specimens in a case implicating 3,4-methylenedioxymethamphetamine revealed the pr sence of 4-MTA at a concentration of 4.6 mg/L in femoral blood and 87.2 mg/L in the urine. The concentration of 4-MTA in perimortem blood was measured at 4.2 mg/L. This is the first reported case of death involving 4-MTA in the United Kingdom and the first case known to involve 4-MTA only
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Fatal Poisoning With a New Phenylethylamine: 4-Methylthioamphetamine (4-MTA)
Journal of Analytical Toxicology, 2000Co-Authors: Simon P. ElliottAbstract:: There has been much publicity in the United Kingdom regarding a new phenylethylamine-based compound called 4-methylthioamphetamine (4-MTA), also known as para-methylthioamphetamine (p-MTA), MTA or "Flatliner". Chemically, 4-MTA is an amphetamine derivative and is a non-neurotoxic potent serotonin-releasing agent and Reversible Inhibitor of rat monoamine oxidase-A. Analysis of postmortem blood and urine specimens in a case implicating 3,4-methylenedioxymethamphetamine revealed the presence of 4-MTA at a concentration of 4.6 mg/L in femoral blood and 87.2 mg/l in the urine. The concentration of 4-MTA in perimortem blood was measured at 4.2 mg/L. This is the first reported case of death involving 4-MTA in the United Kingdom and the first case known to involve 4-MTA only.
Toufike Kanouni - One of the best experts on this subject based on the ideXlab platform.
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discovery of cc 90011 a potent and selective Reversible Inhibitor of lysine specific demethylase 1 lsd1
Journal of Medicinal Chemistry, 2020Co-Authors: Toufike Kanouni, Christophe Severin, Robert Cho, Natalie Y Y Yuen, Lihong Shi, Chon Lai, Joselyn R Del Rosario, Ryan Stansfield, Lee N Lawton, David J HosfieldAbstract:Histone demethylase LSDl (KDMlA) belongs to the flavin adenine dinucleotide (FAD) dependent family of monoamine oxidases and is vital in regulation of mammalian biology. Dysregulation and overexpre...
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discovery of cc 90011 a potent and selective Reversible Inhibitor of lysine specific demethylase 1 lsd1
Journal of Medicinal Chemistry, 2020Co-Authors: Toufike Kanouni, Christophe Severin, Robert Cho, Natalie Y Y Yuen, Lihong Shi, Chon Lai, Joselyn R Del Rosario, Ryan Stansfield, Lee N Lawton, David J HosfieldAbstract:Histone demethylase LSDl (KDMlA) belongs to the flavin adenine dinucleotide (FAD) dependent family of monoamine oxidases and is vital in regulation of mammalian biology. Dysregulation and overexpression of LSD1 are hallmarks of a number of human diseases, particularly cancers that are characterized as morphologically poorly differentiated. As such, Inhibitors of LSD1 have potential to be beneficial as a cancer therapy. The most clinically advanced Inhibitors of LSDl are covalent Inhibitors derived from tranylcypromine (TCP). Herein, we report the discovery of a novel series of Reversible and selective LSDl Inhibitors. Exploration of structure-activity relationships (SARs) and optimization of ADME properties resulted in the identification of clinical candidate CC-90011. CC-90011 exhibits potent on-target induction of cellular differentiation in acute myeloid leukemia (AML) and small cell lung cancer (SCLC) cell lines, and antitumor efficacy in patient-derived xenograft (PDX) SCLC models. CC-90011 is currently in phase 2 trials in patients with first line, extensive stage SCLC (ClinicalTrials.gov identifier: NCT03850067).
Gregory J Withbroe - One of the best experts on this subject based on the ideXlab platform.
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palbociclib commercial manufacturing process development part iii deprotection followed by crystallization for api particle property control
Organic Process Research & Development, 2016Co-Authors: Brian Patrick Chekal, Jason Ewers, Steven M Guinness, Kyle R Leeman, Ronald J Post, Anil Rane, Karen Sutherland, Ke Wang, Mark Webster, Gregory J WithbroeAbstract:A three-step commercial manufacturing route has been developed for palbociclib, a highly selective, Reversible Inhibitor of CDK 4/6. The third step of the palbociclib process is composed of an acid-catalyzed deprotection reaction telescoped through extractive workup and distillation operations into a controlled crystallization process. The selection of n-butanol and anisole as the cosolvents for this step allowed for the development of a robust process for each unit operation and for tight control of the API particle size.
