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公开(公告)号：US20200338094A1
公开(公告)日：2020-10-29
申请号：US16893012
申请日：2020-06-04
IPC分类号： A61K31/635 , A61K31/496 , A61K31/675 , A61K9/00 , A61K9/12 , A61K8/00
摘要： A library of heterocyclic compounds has been screened to identify particular compounds that have high inhibitory capacity for the Bcl family of regulatory proteins. Compounds identified as Bcl antagonists have been further screened to select pharmaceutical agents with both high potency and high specificity for eliminating senescent cells in comparison with replicative or quiescent cells of the same tissue type. Particular structures are identified in this disclosure that eliminate senescent cells with an EC50 in the nanomole range and a specificity around or above 100-fold. In accordance with this invention, heterocyclic compounds provided in this disclosure can be formulated for the treatment of a range of age-related conditions caused or mediated by senescent cells. Such conditions are exemplified by ophthalmic conditions, pulmonary conditions, and osteoarthritis.
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42.发明申请公开(公告)号：US20190175623A1
公开(公告)日：2019-06-13
申请号：US16181163
申请日：2018-11-05
IPC分类号： A61K31/635 , A61K9/00 , A61K8/00 , A61K31/496 , A61K31/675 , A61K9/12
摘要： A library of heterocyclic compounds has been screened to identify particular compounds that have high inhibitory capacity for the Bcl family of regulatory proteins. Compounds identified as Bcl antagonists have been further screened to select pharmaceutical agents with both high potency and high specificity for eliminating senescent cells in comparison with replicative or quiescent cells of the same tissue type. Particular structures are identified in this disclosure that eliminate senescent cells with an EC50 in the nanomolar range and a specificity around or above 100-fold. In accordance with this invention, heterocyclic compounds provided in this disclosure can be formulated for the treatment of a range of age-related conditions caused or mediated by senescent cells. Such conditions are exemplified by ophthalmic conditions, pulmonary conditions, and osteoarthritis.
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43.发明申请公开(公告)号：US20180110787A1
公开(公告)日：2018-04-26
申请号：US15808417
申请日：2017-11-09
IPC分类号： A61K31/635 , A61K9/12 , A61K9/00
CPC分类号： A61K31/635 , A61K8/00 , A61K9/0019 , A61K9/0048 , A61K9/0073 , A61K9/12 , A61K31/496 , A61K31/675
摘要： A library of heterocyclic compounds has been screened to identify particular compounds that have high inhibitory capacity for the Bcl family of regulatory proteins. Compounds identified as Bcl antagonists have been further screened to select pharmaceutical agents with both high potency and high specificity for eliminating senescent cells in comparison with replicative or quiescent cells of the same tissue type. Particular structures are identified in this disclosure that eliminate senescent cells with an EC50 in the nanomole range and a specificity around or above 100-fold. In accordance with this invention, heterocyclic compounds provided in this disclosure can be formulated for the treatment of a range of age-related conditions caused or mediated by senescent cells. Such conditions are exemplified by ophthalmic conditions, pulmonary conditions, and osteoarthritis.
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公开(公告)号：US20170326136A1
公开(公告)日：2017-11-16
申请号：US15481129
申请日：2017-04-06
申请人： Unity Biotechnology, Inc. , Buck Institute for Research on Aging , The Johns Hopkins University
发明人： Nathaniel David , Albert Davalos , Remi-Martin Laberge , Judith Campisi , Marco Demaria , Alain Vasserot , Chaekyu Kim , Okhee Jeon , Jennifer Elisseeff
IPC分类号： A61K31/496 , A61K47/36
CPC分类号： A61K31/496 , A61K9/0048 , A61K9/0073 , A61K31/404 , A61K31/4178 , A61K31/428 , A61K31/4375 , A61K31/495 , A61K31/5377 , A61K31/728 , A61K45/06 , A61K47/36 , C12N5/0081 , C12N2501/999 , C12N2503/02
摘要： This disclosure provides a technology for managing the sensation of pain in a subject in need thereof. Treatment methods according to this invention include administering to the subject a formulation that contains an effective amount of (4-[(4S,5R)-4,5-bis(4-chlorophenyl)-4,5-dihydro-2-[4-methoxy-2-(1-methylethoxy)phenyl]-1H-imidazol-1-yl]carbonyl]-2-piperazinone).
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45.发明申请公开(公告)号：US20170266211A1
公开(公告)日：2017-09-21
申请号：US15611589
申请日：2017-06-01
IPC分类号： A61K31/675
CPC分类号： A61K31/675
摘要： Disclosed herein are compounds that are effective for treatment of various disease states. Dosing includes both single administration and regimens of cycling dosages.
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46.发明申请公开(公告)号：US20200338097A1
公开(公告)日：2020-10-29
申请号：US16899401
申请日：2020-06-11
IPC分类号： A61K31/675
摘要： Disclosed herein are compounds that are effective for treatment of various disease states. Dosing includes both single administration and regimens of cycling dosages.
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47.发明申请公开(公告)号：US20190269675A1
公开(公告)日：2019-09-05
申请号：US16403389
申请日：2019-05-03
申请人： Buck Institute for Research and Aging , Unity Biotechnology, Inc. , Mayo Foundation for Medical Education and Research
发明人： Shankar J. Chinta , Judith Campisi , Julie K. Andersen , Remi-Martin Laberge , Nathaniel David , James L. Kirkland , Tamar Tchkonia , Yi Zhu
IPC分类号： A61K31/496 , A61K9/00 , A61P9/10 , A61K47/36 , A61P11/00 , A61P27/02 , C12N5/00 , A61K31/728 , A61K31/4178 , A61K45/06 , A61K31/4375 , A61K31/404 , A61K31/5377 , A61K31/495 , A61K31/428
摘要： This invention establishes a new paradigm for treatment of Parkinson's disease (PD) by eliminating senescent cells that reside in or around the site of the disease pathophysiology. Exposure of test subjects to the herbicide paraquat (PQ) increases the risk for developing Parkinson's disease. The data in this disclosure show that PQ induces a senescence arrest and SASP in astrocytes, in culture and in vivo in mice, and senescent cell markers were present in astrocytes in midbrain tissue from PD patients. In a transgenic mouse model, senescent cell ablation protected against PQ-induced PD-like neuropathology. Removal of senescent cells from affected sites using small molecule agents that specifically target senescent cells can help prevent or ameliorate signs and symptoms of the disease.
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48.发明申请公开(公告)号：US20180139939A1
公开(公告)日：2018-05-24
申请号：US15870172
申请日：2018-01-12
IPC分类号： A01K67/027 , A61K49/00 , C12N15/85
CPC分类号： A01K67/0275 , A01K2217/052 , A01K2227/105 , A01K2267/0393 , A61K49/0008 , C12N15/8509 , C12N2015/859 , C12N2830/008
摘要： This disclosure provides non-human animal models for age-related disorders and age-sensitive traits, particularly those caused by senescence-inducing stimuli, wherein the models comprise transgenes selectively expressed by senescent cells. The disclosure further provides methods for identifying therapeutic agents effective for treating or preventing age-related disorders and age-sensitive traits using the animal models, therapeutic agents identified using such methods, pharmaceutical compositions comprising the identified therapeutic agents, and methods of treating or preventing age-related disorders and age-sensitive traits.
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公开(公告)号：US09884065B2
公开(公告)日：2018-02-06
申请号：US15077630
申请日：2016-03-22
IPC分类号： A61P35/04 , A61K31/56 , A61K31/573 , G01N33/50 , A61K31/352 , A61K45/06
CPC分类号： A61K31/573 , A01K67/0275 , A01K2217/052 , A01K2217/30 , A01K2227/105 , A01K2267/0331 , A01K2267/0393 , A61K31/352 , A61K31/4545 , A61K31/522 , A61K38/085 , A61K38/28 , A61K39/21 , A61K45/06 , A61N5/10 , A61N2005/1089 , G01N33/5011 , G01N33/502 , G01N33/5023 , G01N33/5044 , G01N2500/10
摘要： Methods are provided herein for enhancing the effectiveness of medical therapies by administering agents that suppress a biological damage response that is inducible by the medical therapy administered to a subject. In certain embodiments, a method is provided for administering an anti-senescent cell agent that suppresses a biological response comprising cellular senescence that is induced by the medical therapy.
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公开(公告)号：US10655144B2
公开(公告)日：2020-05-19
申请号：US15870172
申请日：2018-01-12
IPC分类号： C12N15/85 , A01K67/027 , A61K49/00
摘要： This disclosure provides non-human animal models for age-related disorders and age-sensitive traits, particularly those caused by senescence-inducing stimuli, wherein the models comprise transgenes selectively expressed by senescent cells. The disclosure further provides methods for identifying therapeutic agents effective for treating or preventing age-related disorders and age-sensitive traits using the animal models, therapeutic agents identified using such methods, pharmaceutical compositions comprising the identified therapeutic agents, and methods of treating or preventing age-related disorders and age-sensitive traits.
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