MX2021002559A - Polycyclic compounds and methods for the targeted degradation of rapidly accelerated fibrosarcoma polypeptides. - Google Patents
Polycyclic compounds and methods for the targeted degradation of rapidly accelerated fibrosarcoma polypeptides.Info
- Publication number
- MX2021002559A MX2021002559A MX2021002559A MX2021002559A MX2021002559A MX 2021002559 A MX2021002559 A MX 2021002559A MX 2021002559 A MX2021002559 A MX 2021002559A MX 2021002559 A MX2021002559 A MX 2021002559A MX 2021002559 A MX2021002559 A MX 2021002559A
- Authority
- MX
- Mexico
- Prior art keywords
- target protein
- raf
- present disclosure
- rapidly accelerated
- polypeptides
- Prior art date
Links
- 230000015556 catabolic process Effects 0.000 title abstract 3
- 238000006731 degradation reaction Methods 0.000 title abstract 3
- 201000008808 Fibrosarcoma Diseases 0.000 title abstract 2
- 238000000034 method Methods 0.000 title 1
- 125000003367 polycyclic group Chemical group 0.000 title 1
- 229920001184 polypeptide Polymers 0.000 title 1
- 102000004196 processed proteins & peptides Human genes 0.000 title 1
- 108090000765 processed proteins & peptides Proteins 0.000 title 1
- 102000004169 proteins and genes Human genes 0.000 abstract 7
- 108090000623 proteins and genes Proteins 0.000 abstract 7
- 150000001875 compounds Chemical class 0.000 abstract 3
- 102000006275 Ubiquitin-Protein Ligases Human genes 0.000 abstract 2
- 108010083111 Ubiquitin-Protein Ligases Proteins 0.000 abstract 2
- 230000001588 bifunctional effect Effects 0.000 abstract 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract 2
- 230000005764 inhibitory process Effects 0.000 abstract 2
- 101000941994 Homo sapiens Protein cereblon Proteins 0.000 abstract 1
- 102100032783 Protein cereblon Human genes 0.000 abstract 1
- 102000018471 Proto-Oncogene Proteins B-raf Human genes 0.000 abstract 1
- 108010091528 Proto-Oncogene Proteins B-raf Proteins 0.000 abstract 1
- 238000009825 accumulation Methods 0.000 abstract 1
- 230000002776 aggregation Effects 0.000 abstract 1
- 238000004220 aggregation Methods 0.000 abstract 1
- 230000006552 constitutive activation Effects 0.000 abstract 1
- 201000010099 disease Diseases 0.000 abstract 1
- 208000035475 disorder Diseases 0.000 abstract 1
- 230000000694 effects Effects 0.000 abstract 1
- 239000003112 inhibitor Substances 0.000 abstract 1
- 239000003446 ligand Substances 0.000 abstract 1
- 239000000203 mixture Substances 0.000 abstract 1
- 230000000144 pharmacologic effect Effects 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
- A61K47/55—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug, i.e. a dimer, oligomer or polymer of pharmacologically or therapeutically active compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
- C07K5/06034—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06078—Dipeptides with the first amino acid being neutral and aromatic or cycloaliphatic
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06139—Dipeptides with the first amino acid being heterocyclic
- C07K5/06165—Dipeptides with the first amino acid being heterocyclic and Pro-amino acid; Derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06191—Dipeptides containing heteroatoms different from O, S, or N
Abstract
The present disclosure relates to bifunctional compounds, ULMâ LâPTM, which find utility as modulators of Rapidly Accelerated Fibrosarcoma (RAF, such as c-RAF, A- RAF and/or B-RAF; the target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hippel-Lindau, cereblon, Inhibitors of Apotosis Proteins or mouse double-minute homolog 2 ligand which binds to the respective E3 ubiquitin ligase and on the other end a moiety which binds the target protein RAF, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein, or the constitutive activation of the target protein, are treated or prevented with compounds and compositions of the present disclosure.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201862728581P | 2018-09-07 | 2018-09-07 | |
PCT/US2019/050114 WO2020051564A1 (en) | 2018-09-07 | 2019-09-07 | Polycyclic compounds and methods for the targeted degradation of rapidly accelerated fibrosarcoma polypeptides |
Publications (1)
Publication Number | Publication Date |
---|---|
MX2021002559A true MX2021002559A (en) | 2021-07-21 |
Family
ID=68051923
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
MX2021002559A MX2021002559A (en) | 2018-09-07 | 2019-09-07 | Polycyclic compounds and methods for the targeted degradation of rapidly accelerated fibrosarcoma polypeptides. |
Country Status (9)
Country | Link |
---|---|
EP (1) | EP3846907A1 (en) |
JP (2) | JP2022500368A (en) |
KR (2) | KR102642203B1 (en) |
CN (1) | CN113164775A (en) |
AU (2) | AU2019335516B2 (en) |
CA (1) | CA3109981A1 (en) |
IL (1) | IL281188A (en) |
MX (1) | MX2021002559A (en) |
WO (1) | WO2020051564A1 (en) |
Families Citing this family (17)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2019099868A2 (en) | 2017-11-16 | 2019-05-23 | C4 Therapeutics, Inc. | Degraders and degrons for targeted protein degradation |
JP2021519337A (en) | 2018-03-26 | 2021-08-10 | シー4 セラピューティクス, インコーポレイテッド | Cereblon binder for the degradation of Ikaras |
WO2019204354A1 (en) | 2018-04-16 | 2019-10-24 | C4 Therapeutics, Inc. | Spirocyclic compounds |
CA3162266A1 (en) * | 2019-12-17 | 2021-06-24 | Nikolai Kley | Bifunctional agents for protein recruitment and/or degradation |
CN115298173A (en) * | 2020-03-31 | 2022-11-04 | 田边三菱制药株式会社 | Hydroxypyrrolidine derivatives and medical use thereof |
CN115996719A (en) | 2020-06-19 | 2023-04-21 | C4医药公司 | BRAF degradation agent |
WO2021255213A1 (en) * | 2020-06-19 | 2021-12-23 | F. Hoffmann-La Roche Ag | Heterobifunctional compounds as degraders of braf |
JP2023539663A (en) * | 2020-08-28 | 2023-09-15 | アルビナス・オペレーションズ・インコーポレイテッド | Rapidly Progressive Fibrosarcoma Proteolytic Compounds and Related Methods of Use |
JP2024504932A (en) | 2021-01-13 | 2024-02-02 | モンテ ローザ セラピューティクス, インコーポレイテッド | isoindolinone compound |
WO2022266206A1 (en) * | 2021-06-16 | 2022-12-22 | Erasca, Inc. | Kras inhibitor conjugates |
WO2022270994A1 (en) | 2021-06-25 | 2022-12-29 | 한국화학연구원 | Novel bifunctional heterocyclic compound having btk degradation function via ubiquitin proteasome pathway, and use thereof |
WO2023023941A1 (en) * | 2021-08-24 | 2023-03-02 | Biofront Ltd (Cayman) | Hpk1 degraders, compositions comprising the hpki degrader, and methods of using the same |
CA3235512A1 (en) * | 2021-10-22 | 2023-04-27 | Xiaobao Yang | Crbn e3 ligase ligand compound, protein degrader developed based thereon and their applications |
TW202330548A (en) * | 2021-11-30 | 2023-08-01 | 英屬開曼群島商百濟神州有限公司 | Compounds for the degradation of egfr kinase |
CN115894450B (en) * | 2021-11-30 | 2023-09-12 | 山东如至生物医药科技有限公司 | Novel polycyclic compound and composition and application thereof |
WO2024054591A1 (en) | 2022-09-07 | 2024-03-14 | Arvinas Operations, Inc. | Rapidly accelerated fibrosarcoma (raf) degrading compounds and associated methods of use |
CN115806503A (en) * | 2022-12-02 | 2023-03-17 | 中国海洋大学 | Selective histone deacetylase inhibitor as well as preparation method and application thereof |
Family Cites Families (19)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU2005206929B2 (en) | 2004-01-16 | 2008-01-24 | The Regents Of The University Of Michigan | Conformationally constrained Smac mimetics and the uses thereof |
CA2558615C (en) | 2004-03-23 | 2013-10-29 | Genentech, Inc. | Azabicyclo-octane inhibitors of iap |
DK2253614T3 (en) | 2004-04-07 | 2013-01-07 | Novartis Ag | IAP inhibitors |
CN101035802A (en) | 2004-07-02 | 2007-09-12 | 健泰科生物技术公司 | Inhibitors of IAP |
EP1836201B2 (en) | 2004-12-20 | 2013-09-04 | Genentech, Inc. | Pyrrolidine inhibitors of iap |
WO2007101347A1 (en) | 2006-03-07 | 2007-09-13 | Aegera Therapeutics Inc. | Bir domain binding compounds |
WO2008014236A1 (en) | 2006-07-24 | 2008-01-31 | Tetralogic Pharmaceuticals Corporation | Dimeric iap inhibitors |
NZ580468A (en) | 2007-04-13 | 2012-02-24 | Univ Michigan | Diazo bicyclic smac mimetics and the uses thereof |
US9500653B2 (en) | 2010-12-07 | 2016-11-22 | Yale University | Small-molecule hydrophobic tagging of fusion proteins and induced degradation of same |
WO2013071039A1 (en) | 2011-11-09 | 2013-05-16 | Ensemble Therapeutics | Macrocyclic compounds for inhibition of inhibitors of apoptosis |
CN117736134A (en) | 2012-01-12 | 2024-03-22 | 耶鲁大学 | Compounds and methods for enhancing degradation of target proteins and other polypeptides by E3 ubiquitin ligases |
US9603889B2 (en) | 2012-10-02 | 2017-03-28 | Bristol-Myers Squibb Company | IAP antagonists |
WO2015006524A1 (en) | 2013-07-12 | 2015-01-15 | Bristol-Myers Squibb Company | Iap antagonists |
KR20210132233A (en) * | 2014-04-14 | 2021-11-03 | 아비나스 오퍼레이션스, 인코포레이티드 | Imide-based modulators of proteolysis and associated methods of use |
US20160058872A1 (en) | 2014-04-14 | 2016-03-03 | Arvinas, Inc. | Imide-based modulators of proteolysis and associated methods of use |
GB201504314D0 (en) * | 2015-03-13 | 2015-04-29 | Univ Dundee | Small molecules |
BR112017019751A2 (en) * | 2015-03-18 | 2018-05-29 | Arvinas Inc | bifunctional compound, pharmaceutical composition, and methods for treating or preventing a disease or disorder, and for degrading a target protein in a cell |
EP3544957A4 (en) * | 2016-11-22 | 2020-09-02 | Dana-Farber Cancer Institute, Inc. | Degradation of protein kinases by conjugation of protein kinase inhibitors with e3 ligase ligand and methods of use |
MX2019007649A (en) * | 2016-12-23 | 2019-09-10 | Arvinas Operations Inc | Compounds and methods for the targeted degradation of rapidly accelerated fibrosarcoma polypeptides. |
-
2019
- 2019-09-07 KR KR1020217009937A patent/KR102642203B1/en active IP Right Grant
- 2019-09-07 CA CA3109981A patent/CA3109981A1/en active Pending
- 2019-09-07 WO PCT/US2019/050114 patent/WO2020051564A1/en unknown
- 2019-09-07 CN CN201980073600.1A patent/CN113164775A/en active Pending
- 2019-09-07 AU AU2019335516A patent/AU2019335516B2/en active Active
- 2019-09-07 EP EP19773614.3A patent/EP3846907A1/en active Pending
- 2019-09-07 MX MX2021002559A patent/MX2021002559A/en unknown
- 2019-09-07 JP JP2021512854A patent/JP2022500368A/en active Pending
- 2019-09-07 KR KR1020247005115A patent/KR20240028539A/en active Application Filing
-
2021
- 2021-03-02 IL IL281188A patent/IL281188A/en unknown
-
2022
- 2022-09-08 AU AU2022228150A patent/AU2022228150A1/en active Pending
-
2023
- 2023-08-03 JP JP2023127233A patent/JP2023159166A/en active Pending
Also Published As
Publication number | Publication date |
---|---|
EP3846907A1 (en) | 2021-07-14 |
KR102642203B1 (en) | 2024-03-04 |
CN113164775A (en) | 2021-07-23 |
AU2019335516A1 (en) | 2021-03-11 |
CA3109981A1 (en) | 2020-03-12 |
IL281188A (en) | 2021-04-29 |
KR20240028539A (en) | 2024-03-05 |
AU2022228150A1 (en) | 2022-09-29 |
WO2020051564A1 (en) | 2020-03-12 |
JP2022500368A (en) | 2022-01-04 |
JP2023159166A (en) | 2023-10-31 |
AU2019335516B2 (en) | 2022-06-16 |
KR20210073519A (en) | 2021-06-18 |
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