CA3088253A1 - Bcl-2 proteins degraders for cancer treatment - Google Patents

Bcl-2 proteins degraders for cancer treatment Download PDF

Info

Publication number
CA3088253A1
CA3088253A1 CA3088253A CA3088253A CA3088253A1 CA 3088253 A1 CA3088253 A1 CA 3088253A1 CA 3088253 A CA3088253 A CA 3088253A CA 3088253 A CA3088253 A CA 3088253A CA 3088253 A1 CA3088253 A1 CA 3088253A1
Authority
CA
Canada
Prior art keywords
compound
amino
sulfonyl
methyl
phenyl
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CA3088253A
Other languages
English (en)
French (fr)
Inventor
Guangrong Zheng
Daohong Zhou
Xuan Zhang
Sajid Khan
Yonghan HE
Peiyi Zhang
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
BioVentures LLC
Original Assignee
BioVentures LLC
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by BioVentures LLC filed Critical BioVentures LLC
Publication of CA3088253A1 publication Critical patent/CA3088253A1/en
Pending legal-status Critical Current

Links

Classifications

    • 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
    • A61K31/63—Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide
    • A61K31/635—Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide having a heterocyclic ring, e.g. sulfadiazine
    • G—PHYSICS
    • G06—COMPUTING OR CALCULATING; COUNTING
    • G06J—HYBRID COMPUTING ARRANGEMENTS
    • G06J1/00—Hybrid computing arrangements
    • 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 or sparfloxacin
    • 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
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/04—Antineoplastic agents specific for metastasis
    • 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
    • C07D401/02—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 two hetero rings
    • C07D401/04—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 two hetero rings directly linked by a ring-member-to-ring-member bond
    • 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
    • C07D417/02—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 two hetero rings
    • C07D417/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
    • 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
    • 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
    • G—PHYSICS
    • G06—COMPUTING OR CALCULATING; COUNTING
    • G06N—COMPUTING ARRANGEMENTS BASED ON SPECIFIC COMPUTATIONAL MODELS
    • G06N10/00—Quantum computing, i.e. information processing based on quantum-mechanical phenomena
    • G—PHYSICS
    • G06—COMPUTING OR CALCULATING; COUNTING
    • G06N—COMPUTING ARRANGEMENTS BASED ON SPECIFIC COMPUTATIONAL MODELS
    • G06N3/00—Computing arrangements based on biological models
    • G06N3/02—Neural networks
    • G06N3/06—Physical realisation, i.e. hardware implementation of neural networks, neurons or parts of neurons
    • G06N3/063—Physical realisation, i.e. hardware implementation of neural networks, neurons or parts of neurons using electronic means
    • G—PHYSICS
    • G06—COMPUTING OR CALCULATING; COUNTING
    • G06N—COMPUTING ARRANGEMENTS BASED ON SPECIFIC COMPUTATIONAL MODELS
    • G06N5/00—Computing arrangements using knowledge-based models
    • G06N5/01—Dynamic search techniques; Heuristics; Dynamic trees; Branch-and-bound
    • G—PHYSICS
    • G06—COMPUTING OR CALCULATING; COUNTING
    • G06N—COMPUTING ARRANGEMENTS BASED ON SPECIFIC COMPUTATIONAL MODELS
    • G06N5/00—Computing arrangements using knowledge-based models
    • G06N5/04—Inference or reasoning models
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N5/0613—Apparatus adapted for a specific treatment
    • A61N5/062—Photodynamic therapy, i.e. excitation of an agent
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/10—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
    • G—PHYSICS
    • G06—COMPUTING OR CALCULATING; COUNTING
    • G06N—COMPUTING ARRANGEMENTS BASED ON SPECIFIC COMPUTATIONAL MODELS
    • G06N3/00—Computing arrangements based on biological models
    • G06N3/02—Neural networks
    • G06N3/04—Architecture, e.g. interconnection topology
    • G06N3/044—Recurrent networks, e.g. Hopfield networks
    • G—PHYSICS
    • G06—COMPUTING OR CALCULATING; COUNTING
    • G06N—COMPUTING ARRANGEMENTS BASED ON SPECIFIC COMPUTATIONAL MODELS
    • G06N3/00—Computing arrangements based on biological models
    • G06N3/02—Neural networks
    • G06N3/04—Architecture, e.g. interconnection topology
    • G06N3/047—Probabilistic or stochastic networks

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Theoretical Computer Science (AREA)
  • Physics & Mathematics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Mathematical Physics (AREA)
  • Software Systems (AREA)
  • Evolutionary Computation (AREA)
  • Epidemiology (AREA)
  • Data Mining & Analysis (AREA)
  • General Engineering & Computer Science (AREA)
  • Computing Systems (AREA)
  • Artificial Intelligence (AREA)
  • Computational Linguistics (AREA)
  • Biophysics (AREA)
  • Biomedical Technology (AREA)
  • Computational Mathematics (AREA)
  • Pure & Applied Mathematics (AREA)
  • Molecular Biology (AREA)
  • Mathematical Optimization (AREA)
  • Mathematical Analysis (AREA)
  • Condensed Matter Physics & Semiconductors (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Computer Hardware Design (AREA)
  • Neurology (AREA)
  • Fuzzy Systems (AREA)
  • Automation & Control Theory (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Oncology (AREA)
CA3088253A 2018-01-22 2019-01-22 Bcl-2 proteins degraders for cancer treatment Pending CA3088253A1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201862620219P 2018-01-22 2018-01-22
US62/620,219 2018-01-22
PCT/US2019/014545 WO2019144117A1 (en) 2018-01-22 2019-01-22 Bcl-2 proteins degraders for cancer treatment

Publications (1)

Publication Number Publication Date
CA3088253A1 true CA3088253A1 (en) 2019-07-25

Family

ID=67301223

Family Applications (1)

Application Number Title Priority Date Filing Date
CA3088253A Pending CA3088253A1 (en) 2018-01-22 2019-01-22 Bcl-2 proteins degraders for cancer treatment

Country Status (7)

Country Link
US (1) US12118414B2 (enExample)
EP (1) EP3743069B1 (enExample)
JP (1) JP7385284B2 (enExample)
CN (1) CN112105360B (enExample)
CA (1) CA3088253A1 (enExample)
ES (1) ES3041854T3 (enExample)
WO (1) WO2019144117A1 (enExample)

Families Citing this family (32)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109152933B (zh) * 2016-04-21 2022-12-02 生物风险投资有限责任公司 诱导抗细胞凋亡bcl-2家族蛋白的降解的化合物及其用途
KR20190084063A (ko) 2016-10-28 2019-07-15 이칸 스쿨 오브 메디슨 엣 마운트 시나이 Ｅｚｈ２-매개성 암 치료용 조성물 및 방법
ES3041854T3 (en) 2018-01-22 2025-11-17 Bioventures Llc Bcl-2 proteins degraders for cancer treatment
JP7503851B2 (ja) * 2019-05-06 2024-06-21 アイカーン スクール オブ メディスン アット マウント シナイ Ｈｐｋ１の分解剤としてのヘテロ二官能性化合物
AU2020310147A1 (en) * 2019-07-10 2022-01-06 Recurium Ip Holdings, Llc Bcl-2 protein inhibitors
CN112707900B (zh) * 2019-10-24 2022-06-10 上海科技大学 蛋白降解剂及其在疾病治疗中的应用
US20230167105A1 (en) * 2020-04-28 2023-06-01 Recurium Ip Holdings, Llc Bcl-2 protein inhibitors
JP2023548981A (ja) * 2020-11-10 2023-11-21 ダイアレクティク・セラピューティクス・インコーポレイテッド 低分子製剤
CA3173819A1 (en) * 2020-12-23 2022-06-30 Dana-Farber Cancer Institute, Inc. Small molecule degraders of phosphatidylinositol-5-phosphate 4-kinase type 2 and uses thereof
JP2024505562A (ja) 2021-02-02 2024-02-06 レス ラボラトイレス セルビエル 選択的ｂｃｌ－ｘｌ ｐｒｏｔａｃ化合物及び使用の方法
CN113248415B (zh) * 2021-05-26 2022-08-09 苏州正永生物医药有限公司 一种abt-737关键中间体的制备方法以及abt-737的制备方法
JP2024526085A (ja) 2021-06-11 2024-07-17 シーク， インコーポレイテッド 超伝導量子回路のための磁束バイアスのシステム及び方法
JP2024534223A (ja) * 2021-09-01 2024-09-18 シーザン ハイスーク ファーマシューティカル カンパニー リミテッド Ｂｃｌ－２ファミリータンパク質を分解する化合物及びその医薬的な応用
US20250197387A1 (en) * 2021-09-17 2025-06-19 Kymera Therapeutics, Inc. Bcl-xl degraders and uses thereof
US20250136593A1 (en) * 2021-11-17 2025-05-01 Hitgen Inc. Degradation agent and use thereof
JP7825122B2 (ja) * 2022-01-04 2026-03-06 上海科技大学 Ｂｃｌ－２ファミリータンパク質リガンド化合物に基づいて開発したタンパク質分解剤及びそれらの応用
WO2023215449A1 (en) 2022-05-06 2023-11-09 Treeline Biosciences, Inc. Tetrahydroisoquinoline heterobifunctional bcl-xl degraders
EP4519259A1 (en) 2022-05-06 2025-03-12 Treeline Biosciences, Inc. Tetrahydroisoquinoline heterobifunctional bcl-xl degraders
EP4519260A1 (en) 2022-05-06 2025-03-12 Treeline Biosciences, Inc. Tetrahydroisoquinoline heterobifunctional bcl-xdegraders
US20260092057A1 (en) * 2022-05-12 2026-04-02 Kymera Therapeutics, Inc. Bcl-xl/bcl-2 degraders and uses thereof
CN117247374B (zh) * 2022-06-10 2026-03-17 四川科伦博泰生物医药股份有限公司 一种bcl-xl抑制剂及其制药用途
TW202402272A (zh) * 2022-07-12 2024-01-16 中國商正大天晴藥業集團股份有限公司 含有三氟甲基基團的化合物
TW202430522A (zh) * 2022-09-30 2024-08-01 大陸商江蘇恆瑞醫藥股份有限公司 一種用於ｂｃｌ－２蛋白靶向降解的嵌合體化合物、其製備方法及其在醫藥上的應用
CN120659777A (zh) * 2022-10-03 2025-09-16 佛罗里达大学研究基金公司 募集Cereblon的Bcl-xL/Bcl-2双重降解剂
WO2024078581A1 (en) * 2022-10-12 2024-04-18 Appicine Therapeutics (Hk) Limited Selective bcl-xl protac compounds and uses thereof
WO2024153185A1 (zh) * 2023-01-18 2024-07-25 苏州宜联生物医药有限公司 包含bcl-2家族蛋白降解剂的抗体药物偶联物及其制备方法和用途
JP2026507476A (ja) * 2023-02-17 2026-03-04 チア タイ ティエンチン ファーマシューティカル グループ カンパニー リミテッド トリフルオロメタンスルホニル基を含む化合物
WO2024179577A1 (zh) * 2023-03-01 2024-09-06 西藏海思科制药有限公司 一种Bcl-2家族蛋白降解剂的药物组合物
CN118724870B (zh) * 2023-03-28 2026-04-28 暨南大学 蛋白降解靶向嵌合体及其应用
TW202535872A (zh) 2023-11-07 2025-09-16 美商樹線生物科學公司 四氫異喹啉異雙功能ｂｃｌ－ｘｌ降解劑
TW202527930A (zh) 2023-11-07 2025-07-16 美商樹線生物科學公司 四氫異喹啉異雙功能ｂｃｌ－ｘｌ降解劑
WO2025101575A1 (en) 2023-11-07 2025-05-15 Treeline Biosciences, Inc. Tetrahydroisoquinoline heterobifunctional bcl-x l degraders

Family Cites Families (86)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4394448A (en) 1978-02-24 1983-07-19 Szoka Jr Francis C Method of inserting DNA into living cells
US4529561A (en) 1978-03-24 1985-07-16 The Regents Of The University Of California Method for producing liposomes in selected size range
US4241046A (en) 1978-11-30 1980-12-23 Papahadjopoulos Demetrios P Method of encapsulating biologically active materials in lipid vesicles
US4925661A (en) 1984-04-19 1990-05-15 Leaf Huang Target-specific cytotoxic liposomes
US4957735A (en) 1984-06-12 1990-09-18 The University Of Tennessee Research Corporation Target-sensitive immunoliposomes- preparation and characterization
US4755388A (en) 1984-11-09 1988-07-05 The Regents Of The University Of California Liposome-encapsulated 5-fluoropyrimidines and methods for their use
DE3542773A1 (de) 1985-12-04 1987-06-11 Roehm Pharma Gmbh Hautwirksame pharmaka mit liposomen als wirkstofftraeger
US4828837A (en) 1987-03-30 1989-05-09 Liposome Technology, Inc. Non-crystalline minoxidil composition, its production and application
US5077211A (en) 1988-07-06 1991-12-31 Applied Genetics, Inc. Purification and administration of dna repair enzymes
US5223409A (en) 1988-09-02 1993-06-29 Protein Engineering Corp. Directed evolution of novel binding proteins
US5043164A (en) 1989-01-17 1991-08-27 The University Of Tennessee Research Corporation Blood-stable, cholesterol-free liposomes
US5064655A (en) 1989-02-24 1991-11-12 Liposome Technology, Inc. Liposome gel composition and method
US5744101A (en) 1989-06-07 1998-04-28 Affymax Technologies N.V. Photolabile nucleoside protecting groups
US5264618A (en) 1990-04-19 1993-11-23 Vical, Inc. Cationic lipids for intracellular delivery of biologically active molecules
US5270339A (en) 1991-04-05 1993-12-14 Kanagafuchi Kagaku Kogyo Kabushiki Kaisha Phenoxybenzene derivative
US5491069A (en) 1994-02-18 1996-02-13 The Regents Of The University Of California Biomarkers of cell senescence
US5888764A (en) 1995-01-20 1999-03-30 Uab Research Foundation Human fas gene promoter region
DE19713393C2 (de) 1997-04-01 2002-12-05 Apotech Res & Dev Ltd Flip-Gen und Flip-Protein
JPH11349568A (ja) 1998-06-08 1999-12-21 Maruho Co Ltd ラクタム誘導体及びその医薬用途
CA2338328A1 (en) * 1998-07-21 2000-02-03 Thomas Jefferson University Small molecule inhibitors of bcl-2 proteins
AUPR038200A0 (en) 2000-09-26 2000-10-19 Beta Peptide Foundation Pty Ltd, The Compositions and methods for delaying, preventing, rejuvenating or reversing senescence
WO2002097053A2 (en) 2001-05-30 2002-12-05 The Regents Of The University Of Michigan Small molecule antagonists of bcl2 family proteins
ES2276895T3 (es) 2002-05-07 2007-07-01 Institut Pasteur Cribado de peptidos qque inhiben la union de pp1c a las proteinas bcl-2, bcl-xi y bcl-w.
AU2003245436A1 (en) 2003-01-23 2004-08-23 The Trustees Of Columbia University In The City Of New York Old-35, a gene associated with senescence and terminal cell differentiation, and uses thereof
ES2382377T3 (es) 2003-05-30 2012-06-07 Gemin X Pharmaceuticals Canada Inc. Compuestos triheterocíclicos, composiciones, y métodos para tratar cáncer
US20050208151A1 (en) 2003-10-30 2005-09-22 Entelos, Inc. Treatment of rheumatoid arthritis with FLIP antagonists
US7973161B2 (en) 2003-11-13 2011-07-05 Abbott Laboratories Apoptosis promoters
JP2007525661A (ja) 2003-12-12 2007-09-06 セントルイス ユニバーシティー 大分子その他の分析物の検出用生物センサー
RU2361872C2 (ru) 2004-05-26 2009-07-20 Эйсай Ар Энд Ди Менеджмент Ко., Лтд. Циннамидное соединение
AU2005277223C1 (en) 2004-08-20 2009-05-21 The Regents Of The University Of Michigan Small molecule inhibitors of anti-apoptotic Bcl-2 family members and the uses thereof
US7533068B2 (en) 2004-12-23 2009-05-12 D-Wave Systems, Inc. Analog processor comprising quantum devices
PL1888550T3 (pl) 2005-05-12 2014-12-31 Abbvie Bahamas Ltd Promotory apoptozy
EP2135078B1 (en) 2007-03-09 2013-08-21 DiscoveRx Corporation Methods for identifying agents and their use for the prevention or stabilization of fibrosis
EA200901212A1 (ru) 2007-03-29 2010-04-30 Новартис Аг 3-имидазолилиндолы, предназначенные для лечения пролиферативных заболеваний
US20100310504A1 (en) 2007-09-26 2010-12-09 Lowe Scott W Methods for treating fibrosis by modulating cellular senescence
US8039668B2 (en) 2008-10-17 2011-10-18 Burnham Institute For Medical Research Naphthalene-based inhibitors of anti-apoptotic proteins
WO2009085216A2 (en) 2007-12-20 2009-07-09 Squicor Compositions and methods for detecting or elimninating senescent cells to diagnose or treat disease
US20090312373A1 (en) 2008-03-11 2009-12-17 The General Hospital Corporation Methods for the treatment of cancer using piperlongumine and piperlongumine analogs
US8168784B2 (en) 2008-06-20 2012-05-01 Abbott Laboratories Processes to make apoptosis promoters
US20100086941A1 (en) 2008-10-01 2010-04-08 Adami Guy R Methods for determining aged based accumulation of senescent cells using senescence specific DNA damage markers
NZ593536A (en) 2008-12-19 2013-07-26 Genentech Inc Quinoline derivatives and methods of use
WO2010080503A1 (en) 2008-12-19 2010-07-15 Genentech, Inc. Heterocyclic compounds and methods of use
WO2010138588A2 (en) 2009-05-26 2010-12-02 Abbott Laboratories Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
EP2289528A1 (en) 2009-07-21 2011-03-02 DSM IP Assets B.V. Novel nutraceutical compositions containing black pepper or its constituents improving mental performance
US8318737B2 (en) 2009-09-02 2012-11-27 Canthera Therapeutics Inc. Compounds and compositions for treating cancer
US8349832B2 (en) 2009-09-02 2013-01-08 Canthera Therapeutics Compounds and compositions for treating cancer
US20120157455A1 (en) 2009-09-02 2012-06-21 Canthera Therapeutics, Inc. Compounds And Compositions For Treating Cancer
EP2519260A2 (en) 2009-12-31 2012-11-07 Deutsches Krebsforschungszentrum Novel modulators of trail signalling
CN101774875A (zh) 2010-01-08 2010-07-14 北京欧凯纳斯科技有限公司 一种荜拔酰胺类化合物的合成方法
CN102125552A (zh) 2010-01-20 2011-07-20 李绍路 荜茇酰胺衍生物在制备治疗癌症的药物中的用途及其药物组合物
CN102146054A (zh) 2010-02-10 2011-08-10 新昌县来益科技开发有限公司 荜茇酰胺衍生物及其药物组合物和在制备抑制肿瘤生长的药物中的用途
WO2011130395A1 (en) 2010-04-13 2011-10-20 University Of Utah Research Foundation Inhibitors of flip to treat cancer
ES2603129T3 (es) 2010-11-23 2017-02-23 Abbvie Ireland Unlimited Company Métodos de tratamiento utilizando inhibidores selectivos de Bcl-2
EP2668180B1 (en) 2011-01-25 2018-08-01 The Regents of The University of Michigan Bcl-2/bcl-xl inhibitors for use in the treatment of cancer
US8940737B2 (en) 2011-10-14 2015-01-27 Abbvie Inc. Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
EP2602330A1 (en) 2011-12-07 2013-06-12 Palacky University, Olomouc Method of determination of cancer cell drug sensitivity towards Aurora kinase inhibitors and overcoming their resistance
KR102668696B1 (ko) 2012-01-12 2024-05-29 예일 유니버시티 E3 유비퀴틴 리가아제에 의한 표적 단백질 및 다른 폴리펩티드의 증진된 분해를 위한 화합물 및 방법
US9828344B2 (en) 2012-06-01 2017-11-28 LEIBNIZ-INSTITUT FÜR ALTERSFORSCHUNG FRITZ-LIPMANN-INSTITUT e.V. (FLI) Inhibitors of the notch signaling pathway and secretion for use in medicine
US9108923B2 (en) 2012-07-20 2015-08-18 Howard Hughes Medical Institute Compounds, compositions, and methods for cancer therapy
CN103601670B (zh) 2012-11-20 2016-06-15 中国人民解放军第二军医大学 荜拔酰胺类似物及其制备方法与应用
WO2014089124A1 (en) 2012-12-03 2014-06-12 Cenexys, Inc. Immunogenic compositions for inducing an immune response for elimination of senescent cells
GB201311910D0 (en) 2013-07-03 2013-08-14 Glaxosmithkline Ip Dev Ltd Novel Compounds
EP3689886A1 (en) 2013-01-16 2020-08-05 The Regents of The University of Michigan Bcl-2/bcl-xl inhibitors and their use in the treatment of cancer
RU2015149680A (ru) 2013-04-21 2017-05-24 Йеда Ресеарч Энд Девелопмент Ко. Лтд. Агенты для подавления активности и/или снижения количества bcl-xl и/или bcl-w
IL286427B2 (en) 2014-01-28 2024-08-01 Mayo Found Medical Education & Res Inhibitors bcl-2 anti-apoptotic protein family members for treatment of non cancer pulmonary disease or an opthalmic disease
US10002107B2 (en) 2014-03-12 2018-06-19 D-Wave Systems Inc. Systems and methods for removing unwanted interactions in quantum devices
RU2738833C9 (ru) 2014-04-14 2022-02-28 Арвинас, Оперэйшнз, Инк. Имидные модуляторы протеолиза и способы их применения
EP3139942B1 (en) 2014-05-05 2019-12-18 Bioventures, Llc COMPOSITIONS AND METHODS FOR INHIBITING ANTIAPOPTOTIC Bcl-2 PROTEINS AS ANTI-AGING AGENTS
WO2016014625A1 (en) 2014-07-22 2016-01-28 Board Of Trustees Of The University Of Arkansas Compositions and methods for selectively depleting senescent cells
US10071164B2 (en) 2014-08-11 2018-09-11 Yale University Estrogen-related receptor alpha based protac compounds and associated methods of use
US10552755B2 (en) 2014-08-22 2020-02-04 D-Wave Systems Inc. Systems and methods for improving the performance of a quantum processor to reduce intrinsic/control errors
US9694084B2 (en) 2014-12-23 2017-07-04 Dana-Farber Cancer Institute, Inc. Methods to induce targeted protein degradation through bifunctional molecules
WO2016118859A1 (en) 2015-01-22 2016-07-28 Board Of Trustees Of The University Of Arkansas Compositions and methods for selectively depleting senescent cells comprising flip
WO2016118855A1 (en) 2015-01-22 2016-07-28 Board Of Trustees Of The University Of Arkansas Compositions and methods for selectively depleting senescent cells comprising death receptors
US20180000816A1 (en) 2015-02-06 2018-01-04 Unity Biotechnology, Inc. Use of a Heterocyclic Bcl-xL Inhibitor and Related Analogs for Removing Senescent Cells in the Treatment of Eye Diseases and Other Age-Related Conditions
WO2016182608A2 (en) 2015-02-10 2016-11-17 D-Wave Systems Inc. Systems, devices, articles, and methods for quantum processor architecture
CA2979895A1 (en) * 2015-03-18 2016-09-22 Immunobiochem Corporation Conjugates for the treatment of cancer targeted at intracellular tumor-associated antigens
EP3270917A4 (en) 2015-03-18 2018-08-08 Arvinas, Inc. Compounds and methods for the enhanced degradation of targeted proteins
CN105085620B (zh) 2015-06-25 2018-05-08 中山大学附属第一医院 一种靶向泛素化降解Smad3的化合物
AU2016295984B2 (en) 2015-07-21 2021-05-27 Fundació Investigació Hospital General Universitari De València Per A La Investigació Biomèdica I Ciències De La Salut Combination comprising pterostilbene for the treatment of cancer
US10772962B2 (en) 2015-08-19 2020-09-15 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of bromodomain-containing proteins
WO2017101851A1 (en) 2015-12-18 2017-06-22 Unity Biotechnology, Inc. Acylsulfonamide derivatives for treating senescence-associated diseases and disorders
US20190054097A1 (en) 2016-04-21 2019-02-21 Bioventures, Llc Compositions targeting senescent cells and the uses thereof
CN109152933B (zh) 2016-04-21 2022-12-02 生物风险投资有限责任公司 诱导抗细胞凋亡bcl-2家族蛋白的降解的化合物及其用途
US10296352B2 (en) 2016-06-15 2019-05-21 University Of Southern California Nested quantum annealing correction
ES3041854T3 (en) 2018-01-22 2025-11-17 Bioventures Llc Bcl-2 proteins degraders for cancer treatment

Also Published As

Publication number Publication date
EP3743069C0 (en) 2025-08-06
EP3743069A1 (en) 2020-12-02
CN112105360A (zh) 2020-12-18
EP3743069A4 (en) 2021-06-09
JP7385284B2 (ja) 2023-11-22
JP2021511342A (ja) 2021-05-06
EP3743069B1 (en) 2025-08-06
US20210085675A1 (en) 2021-03-25
US12118414B2 (en) 2024-10-15
CN112105360B (zh) 2024-01-30
WO2019144117A1 (en) 2019-07-25
ES3041854T3 (en) 2025-11-17

Similar Documents

Publication Publication Date Title
CA3088253A1 (en) Bcl-2 proteins degraders for cancer treatment
US11319316B2 (en) Compounds that induce degradation of anti-apoptotic Bcl-2 family proteins and the uses thereof
US20220169628A1 (en) Therapeutic agents and methods of treatment
US12441722B2 (en) Therapeutic agents and methods of treatment
US9133139B2 (en) Fluoroalkyl-1,4-benzodiazepinone compounds
US20190054097A1 (en) Compositions targeting senescent cells and the uses thereof
JP6630364B2 (ja) 水溶性プロドラッグ
JP7794910B2 (ja) Ｅａａｔ２活性化因子およびその使用方法
HK40038404B (en) Bcl-2 proteins degraders for cancer treatment
HK40038404A (en) Bcl-2 proteins degraders for cancer treatment
JP2019532967A (ja) フェノチアジン誘導体及びその使用方法
CA3018991C (en) Compounds that induce degradation of anti-apoptotic bcl-2 family proteins and the uses thereof
HK40060209A (en) Therapeutic agents and methods of treatment
HK40074265A (en) Therapeutic agents and methods of treatment
DE112013007543T5 (de) Neu substituierte 2-Aminoquinazolin-4(3H)-one Derivate als Malaria Aspartat protease Inhibitoren

Legal Events

Date Code Title Description
EEER Examination request

Effective date: 20231031

D15 Examination report completed

Free format text: ST27 STATUS EVENT CODE: A-2-2-D10-D15-D126 (AS PROVIDED BY THE NATIONAL OFFICE); EVENT TEXT: EXAMINER'S REPORT

Effective date: 20241105

MFA Maintenance fee for application paid

Free format text: FEE DESCRIPTION TEXT: MF (APPLICATION, 6TH ANNIV.) - STANDARD

Year of fee payment: 6

U00 Fee paid

Free format text: ST27 STATUS EVENT CODE: A-2-2-U10-U00-U101 (AS PROVIDED BY THE NATIONAL OFFICE); EVENT TEXT: MAINTENANCE REQUEST RECEIVED

Effective date: 20250107

U11 Full renewal or maintenance fee paid

Free format text: ST27 STATUS EVENT CODE: A-2-2-U10-U11-U102 (AS PROVIDED BY THE NATIONAL OFFICE); EVENT TEXT: MAINTENANCE FEE PAYMENT DETERMINED COMPLIANT

Effective date: 20250107

Free format text: ST27 STATUS EVENT CODE: A-2-2-U10-U11-U102 (AS PROVIDED BY THE NATIONAL OFFICE); EVENT TEXT: MAINTENANCE FEE PAYMENT PAID IN FULL

Effective date: 20250107

P11 Amendment of application requested

Free format text: ST27 STATUS EVENT CODE: A-2-2-P10-P11-P100 (AS PROVIDED BY THE NATIONAL OFFICE); EVENT TEXT: AMENDMENT RECEIVED - RESPONSE TO EXAMINER'S REQUISITION

Effective date: 20250305

W00 Other event occurred

Free format text: ST27 STATUS EVENT CODE: A-2-2-W10-W00-W111 (AS PROVIDED BY THE NATIONAL OFFICE); EVENT TEXT: CORRESPONDENT DETERMINED COMPLIANT

Effective date: 20250307

P11 Amendment of application requested

Free format text: ST27 STATUS EVENT CODE: A-2-2-P10-P11-P102 (AS PROVIDED BY THE NATIONAL OFFICE); EVENT TEXT: AMENDMENT DETERMINED COMPLIANT

Effective date: 20250711

P13 Application amended

Free format text: ST27 STATUS EVENT CODE: A-2-2-P10-P13-X000 (AS PROVIDED BY THE NATIONAL OFFICE); EVENT TEXT: APPLICATION AMENDED

Effective date: 20250711

MFA Maintenance fee for application paid

Free format text: FEE DESCRIPTION TEXT: MF (APPLICATION, 7TH ANNIV.) - STANDARD

Year of fee payment: 7

U00 Fee paid

Free format text: ST27 STATUS EVENT CODE: A-2-2-U10-U00-U101 (AS PROVIDED BY THE NATIONAL OFFICE); EVENT TEXT: MAINTENANCE REQUEST RECEIVED

Effective date: 20251229

U11 Full renewal or maintenance fee paid

Free format text: ST27 STATUS EVENT CODE: A-2-2-U10-U11-U102 (AS PROVIDED BY THE NATIONAL OFFICE); EVENT TEXT: MAINTENANCE FEE PAYMENT PAID IN FULL

Effective date: 20251229