CN102558165B - 用作iap抑制剂的smac肽模拟物 - Google Patents
用作iap抑制剂的smac肽模拟物 Download PDFInfo
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- CN102558165B CN102558165B CN201110446951.8A CN201110446951A CN102558165B CN 102558165 B CN102558165 B CN 102558165B CN 201110446951 A CN201110446951 A CN 201110446951A CN 102558165 B CN102558165 B CN 102558165B
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- YEYHFKBVNARCNE-UHFFFAOYSA-N pyrido[2,3-b]pyrazine Chemical compound N1=CC=NC2=CC=CN=C21 YEYHFKBVNARCNE-UHFFFAOYSA-N 0.000 description 1
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- JXAZAUKOWVKTLO-UHFFFAOYSA-L sodium pyrosulfate Chemical compound [Na+].[Na+].[O-]S(=O)(=O)OS([O-])(=O)=O JXAZAUKOWVKTLO-UHFFFAOYSA-L 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
- 238000000935 solvent evaporation Methods 0.000 description 1
- NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical class C([C@H]1C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1)[C@@H](C)O)NC(=O)CNC(=O)[C@H](C)N)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 NHXLMOGPVYXJNR-ATOGVRKGSA-N 0.000 description 1
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- UEUXEKPTXMALOB-UHFFFAOYSA-J tetrasodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O UEUXEKPTXMALOB-UHFFFAOYSA-J 0.000 description 1
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Classifications
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- 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
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- 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
- C07D417/04—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 directly linked by a ring-member-to-ring-member bond
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- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/427—Thiazoles not condensed and containing further heterocyclic rings
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- 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
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- 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
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- C07K5/06191—Dipeptides containing heteroatoms different from O, S, or N
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyridine Compounds (AREA)
- Pyrrole Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
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| US83500006P | 2006-08-02 | 2006-08-02 | |
| US60/835,000 | 2006-08-02 |
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| CN2007800329568A Division CN101511860B (zh) | 2006-08-02 | 2007-07-31 | 用作iap抑制剂的smac肽模拟物 |
Publications (2)
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| CN102558165A CN102558165A (zh) | 2012-07-11 |
| CN102558165B true CN102558165B (zh) | 2014-08-13 |
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| CN201110446951.8A Active CN102558165B (zh) | 2006-08-02 | 2007-07-31 | 用作iap抑制剂的smac肽模拟物 |
| CN2007800329568A Active CN101511860B (zh) | 2006-08-02 | 2007-07-31 | 用作iap抑制剂的smac肽模拟物 |
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| CN2007800329568A Active CN101511860B (zh) | 2006-08-02 | 2007-07-31 | 用作iap抑制剂的smac肽模拟物 |
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Families Citing this family (88)
| Publication number | Priority date | Publication date | Assignee | Title |
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| RS52545B (sr) | 2004-04-07 | 2013-04-30 | Novartis Ag | Inhibitori protein apoptoze (iap) |
| AU2005274937B2 (en) | 2004-07-15 | 2011-08-18 | Medivir Ab | IAP binding compounds |
| MX2007007195A (es) | 2004-12-20 | 2007-10-08 | Genentech Inc | Inhibidores de pirrolidina de iap. |
| ES2456671T3 (es) | 2005-02-25 | 2014-04-23 | Tetralogic Pharmaceuticals Corporation | Inhibidores diméricos de IAP |
| US7772177B2 (en) | 2005-05-18 | 2010-08-10 | Aegera Therapeutics, Inc. | BIR domain binding compounds |
| WO2007048224A1 (en) | 2005-10-25 | 2007-05-03 | Aegera Therapeutics Inc. | Iap bir domain binding compounds |
| TWI504597B (zh) | 2006-03-16 | 2015-10-21 | Pharmascience Inc | 結合於細胞凋亡抑制蛋白（ｉａｐ）之桿狀病毒ｉａｐ重複序列（ｂｉｒ）區域之化合物 |
| AU2007250443B2 (en) | 2006-05-16 | 2013-06-13 | Pharmascience Inc. | IAP BIR domain binding compounds |
| KR20090041391A (ko) | 2006-07-24 | 2009-04-28 | 테트랄로직 파마슈티칼스 | 이량체성 ｉａｐ 길항제 |
| CL2007002166A1 (es) | 2006-07-24 | 2008-01-25 | Tetralogic Pharm Corp | Compuestos derivados de heterociclos de nitrogeno, antagonistas de los inhibidores de las proteinas de la apoptosis; sus composiciones farmaceuticas; y uso de dichos compuestos para el tratamiento del cancer. |
| US20100056495A1 (en) * | 2006-07-24 | 2010-03-04 | Tetralogic Pharmaceuticals Corporation | Dimeric iap inhibitors |
| KR20090082221A (ko) * | 2006-10-19 | 2009-07-29 | 노파르티스 아게 | 유기 화합물 |
| CN101541325A (zh) * | 2006-11-28 | 2009-09-23 | 诺瓦提斯公司 | Iap抑制剂用于治疗急性髓性白血病的用途 |
| KR20090087094A (ko) * | 2006-11-28 | 2009-08-14 | 노파르티스 아게 | Ｉａｐ 억제제 및 ｆｌｔ3 억제제의 조합물 |
| US8063218B2 (en) * | 2006-12-19 | 2011-11-22 | Genentech, Inc. | Imidazopyridine inhibitors of IAP |
| PE20130150A1 (es) | 2007-04-30 | 2013-02-27 | Genentech Inc | Inhibidores de las iap |
| US9750729B2 (en) | 2008-05-16 | 2017-09-05 | Dana-Farber Cancer Institute, Inc. | Immunomodulation by IAP inhibitors |
| CN102171209A (zh) | 2008-08-02 | 2011-08-31 | 健泰科生物技术公司 | Iap抑制剂 |
| US8841067B2 (en) | 2009-01-09 | 2014-09-23 | Dana-Farber Cancer Institute, Inc. | NOL3 is a predictor of patient outcome |
| US8283372B2 (en) | 2009-07-02 | 2012-10-09 | Tetralogic Pharmaceuticals Corp. | 2-(1H-indol-3-ylmethyl)-pyrrolidine dimer as a SMAC mimetic |
| UY32826A (es) | 2009-08-04 | 2011-02-28 | Takeda Pharmaceutical | Compuestos heterocíclicos |
| US20120129895A1 (en) * | 2009-08-11 | 2012-05-24 | Colleen Conway | Methods of treatment |
| PE20121132A1 (es) * | 2009-08-12 | 2012-09-04 | Novartis Ag | Formulaciones orales solidas y formas cristalinas de un inhibidor de la proteina de apoptosis |
| WO2011098904A1 (en) | 2010-02-12 | 2011-08-18 | Aegera Therapeutics, Inc. | Iap bir domain binding compounds |
| UY33236A (es) | 2010-02-25 | 2011-09-30 | Novartis Ag | Inhibidores dimericos de las iap |
| US8835458B2 (en) | 2010-08-31 | 2014-09-16 | Hanmi Science Co., Ltd | Quinoline or quinazoline derivatives with apoptosis inducing activity on cells |
| WO2012052758A1 (en) | 2010-10-22 | 2012-04-26 | Astrazeneca Ab | Response biomarkers for iap antagonists in human cancers |
| UY33794A (es) | 2010-12-13 | 2012-07-31 | Novartis Ag | Inhibidores diméricos de las iap |
| US9181266B2 (en) | 2011-07-13 | 2015-11-10 | Novartis Ag | 2-piperidin-1-yl-acetamide compounds for use as tankyrase inhibitors |
| CN103814032A (zh) | 2011-07-13 | 2014-05-21 | 诺华股份有限公司 | 用作端锚聚合酶抑制剂的4-氧代-3,5,7,8-四氢-4H-吡喃并[4,3-d]嘧啶基化合物 |
| CA2850330A1 (en) | 2011-09-30 | 2013-04-04 | Tetralogic Pharmaceuticals Corporation | Smac mimetic (birinapant) for use in the treatment of proliferative diseases (cancer) |
| US8859541B2 (en) * | 2012-02-27 | 2014-10-14 | Boehringer Ingelheim International Gmbh | 6-alkynylpyridines |
| EP2852584B1 (en) * | 2012-05-22 | 2018-02-28 | F. Hoffmann-La Roche AG | Substituted dipyridylamines and uses thereof |
| KR20140011773A (ko) * | 2012-07-19 | 2014-01-29 | 한미약품 주식회사 | 이중 저해 활성을 갖는 헤테로고리 유도체 |
| CA2907912A1 (en) | 2013-05-01 | 2014-11-06 | F. Hoffmann-La Roche Ag | C-linked heterocycloalkyl substituted pyrimidines and their uses |
| CN105451726B (zh) | 2013-06-25 | 2021-03-16 | 沃尔特和伊利莎豪医学研究所 | 治疗细胞内感染的方法 |
| US10570204B2 (en) | 2013-09-26 | 2020-02-25 | The Medical College Of Wisconsin, Inc. | Methods for treating hematologic cancers |
| SG10201900002QA (en) | 2014-01-24 | 2019-02-27 | Dana Farber Cancer Institue Inc | Antibody molecules to pd-1 and uses thereof |
| EP3099717B1 (en) | 2014-01-31 | 2019-03-27 | Novartis AG | Antibody molecules to tim-3 and uses thereof |
| US20150259420A1 (en) | 2014-03-14 | 2015-09-17 | Novartis Ag | Antibody molecules to lag-3 and uses thereof |
| ES2771926T3 (es) | 2014-09-13 | 2020-07-07 | Novartis Ag | Terapias de combinación |
| AU2015327868A1 (en) | 2014-10-03 | 2017-04-20 | Novartis Ag | Combination therapies |
| MA41044A (fr) | 2014-10-08 | 2017-08-15 | Novartis Ag | Compositions et procédés d'utilisation pour une réponse immunitaire accrue et traitement contre le cancer |
| TWI716362B (zh) | 2014-10-14 | 2021-01-21 | 瑞士商諾華公司 | 針對ｐｄ－ｌ１之抗體分子及其用途 |
| WO2016079527A1 (en) | 2014-11-19 | 2016-05-26 | Tetralogic Birinapant Uk Ltd | Combination therapy |
| WO2016097773A1 (en) | 2014-12-19 | 2016-06-23 | Children's Cancer Institute | Therapeutic iap antagonists for treating proliferative disorders |
| HK1248603A1 (zh) | 2015-03-10 | 2018-10-19 | Aduro Biotech, Inc. | 用於活化"干扰素基因的刺激剂"依懒性信号传导的组合物和方法 |
| GB201506871D0 (en) | 2015-04-22 | 2015-06-03 | Glaxosmithkline Ip Dev Ltd | Novel compounds |
| EP3878465A1 (en) | 2015-07-29 | 2021-09-15 | Novartis AG | Combination therapies comprising antibody molecules to tim-3 |
| DK3317301T3 (da) | 2015-07-29 | 2021-06-28 | Immutep Sas | Kombinationsterapier omfattende antistofmolekyler mod lag-3 |
| US20180222982A1 (en) | 2015-07-29 | 2018-08-09 | Novartis Ag | Combination therapies comprising antibody molecules to pd-1 |
| EP3370768B9 (en) | 2015-11-03 | 2022-03-16 | Janssen Biotech, Inc. | Antibodies specifically binding pd-1 and their uses |
| WO2017106656A1 (en) | 2015-12-17 | 2017-06-22 | Novartis Ag | Antibody molecules to pd-1 and uses thereof |
| CA3020792A1 (en) | 2016-04-20 | 2017-10-26 | Glaxosmithkline Intellectual Property Development Limited | Conjugates comprising ripk2 inhibitors |
| GB201610147D0 (en) | 2016-06-10 | 2016-07-27 | Glaxosmithkline Ip Dev Ltd | Novel compounds |
| WO2018009466A1 (en) | 2016-07-05 | 2018-01-11 | Aduro Biotech, Inc. | Locked nucleic acid cyclic dinucleotide compounds and uses thereof |
| CN106496213B (zh) * | 2016-09-30 | 2019-08-20 | 东南大学 | Lcl161前药及其制备方法和应用 |
| JP6899993B2 (ja) * | 2016-10-04 | 2021-07-07 | 国立医薬品食品衛生研究所長 | 複素環化合物 |
| AU2018241944A1 (en) | 2017-03-31 | 2019-08-15 | Boehringer Ingelheim International Gmbh | Anticancer combination therapy |
| UY37695A (es) | 2017-04-28 | 2018-11-30 | Novartis Ag | Compuesto dinucleótido cíclico bis 2’-5’-rr-(3’f-a)(3’f-a) y usos del mismo |
| WO2018237173A1 (en) | 2017-06-22 | 2018-12-27 | Novartis Ag | Antibody molecules to cd73 and uses thereof |
| CN118307674A (zh) | 2017-06-22 | 2024-07-09 | 诺华股份有限公司 | 针对cd73的抗体分子及其用途 |
| TW201922291A (zh) | 2017-11-16 | 2019-06-16 | 瑞士商諾華公司 | 組合療法 |
| US12398209B2 (en) | 2018-01-22 | 2025-08-26 | Janssen Biotech, Inc. | Methods of treating cancers with antagonistic anti-PD-1 antibodies |
| CN108484640B (zh) * | 2018-05-22 | 2020-09-15 | 南京华威医药科技集团有限公司 | 一种抗肿瘤的细胞凋亡蛋白抑制剂 |
| AR126019A1 (es) | 2018-05-30 | 2023-09-06 | Novartis Ag | Anticuerpos frente a entpd2, terapias de combinación y métodos de uso de los anticuerpos y las terapias de combinación |
| US20210214459A1 (en) | 2018-05-31 | 2021-07-15 | Novartis Ag | Antibody molecules to cd73 and uses thereof |
| TWI848953B (zh) | 2018-06-09 | 2024-07-21 | 德商百靈佳殷格翰國際股份有限公司 | 針對癌症治療之多特異性結合蛋白 |
| WO2020027225A1 (ja) | 2018-07-31 | 2020-02-06 | ファイメクス株式会社 | 複素環化合物 |
| EP3866801A4 (en) | 2018-10-16 | 2022-11-09 | Dana-Farber Cancer Institute, Inc. | DEGRADER OF WILD-TYPE AND MUTANT FORMS OF LRRK2 |
| WO2020148447A1 (en) | 2019-01-17 | 2020-07-23 | Debiopharm International S.A. | Combination product for the treatment of cancer |
| TWI894135B (zh) | 2019-01-25 | 2025-08-21 | 德商百靈佳殷格翰國際股份有限公司 | 編碼ccl21之重組棒狀病毒 |
| EP3947368B1 (en) | 2019-04-04 | 2025-09-03 | Dana-Farber Cancer Institute, Inc. | Bifunctional compounds comprising a cdk2/5 ligand, a linker and a e3 ubiquitin ligase binding degron for the treatment of cancer |
| KR20220024106A (ko) | 2019-05-20 | 2022-03-03 | 노파르티스 아게 | Mcl-1 억제제 항체-약물 접합체 및 사용 방법 |
| WO2021020585A1 (ja) | 2019-07-31 | 2021-02-04 | ファイメクス株式会社 | 複素環化合物 |
| US20220348651A1 (en) | 2019-09-18 | 2022-11-03 | Novartis Ag | Entpd2 antibodies, combination therapies, and methods of using the antibodies and combination therapies |
| MX2022003628A (es) | 2019-09-25 | 2022-07-21 | Debiopharm Int Sa | Regímenes de dosificación para el tratamiento de pacientes con carcinoma de células escamosas avanzado localmente. |
| JP2023510426A (ja) | 2020-01-20 | 2023-03-13 | アストラゼネカ・アクチエボラーグ | 癌を治療するための上皮細胞増殖因子受容体チロシンキナーゼ阻害剤 |
| BR112022023753A2 (pt) | 2020-06-03 | 2022-12-20 | Boehringer Ingelheim Int | Rhabdovírus recombinante que codifica para uma proteína de fusão fc de domínio extracelular cd80 |
| CA3200858A1 (en) | 2020-11-24 | 2022-06-02 | Novartis Ag | Anti-cd48 antibodies, antibody drug conjugates, and uses thereof |
| US20240042051A1 (en) | 2020-11-24 | 2024-02-08 | Francesca Rocchetti | Mcl-1 inhibitor antibody-drug conjugates and methods of use |
| CN117794929A (zh) | 2021-02-02 | 2024-03-29 | 法国施维雅药厂 | 选择性bcl-xl protac化合物及使用方法 |
| US20250339547A1 (en) | 2022-05-20 | 2025-11-06 | Novartis Ag | Met bcl-xl inhibitor antibody-drug conjugates and methods of use thereof |
| IL317102A (en) | 2022-05-20 | 2025-01-01 | Novartis Ag | EPHA2 BCL-XL inhibitor antibody-drug conjugates and methods of using them |
| AU2024234194A1 (en) | 2023-03-10 | 2025-08-07 | Novartis Ag | Panras inhibitor antibody-drug conjugates and methods of use thereof |
| WO2024240858A1 (en) | 2023-05-23 | 2024-11-28 | Valerio Therapeutics | Protac molecules directed against dna damage repair system and uses thereof |
| PY24103486A (es) | 2023-11-22 | 2025-06-06 | Servier Lab | Conjugados de anticuerpo anti-cd74-fármaco y métodos de uso de los mismos |
| WO2025215536A1 (en) | 2024-04-10 | 2025-10-16 | Novartis Ag | Macrocyclic panras inhibitors for the treatment of cancer |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005097791A1 (en) * | 2004-04-07 | 2005-10-20 | Novartis Ag | Inhibitors of iap |
Family Cites Families (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2714880A1 (de) * | 1977-04-02 | 1978-10-26 | Hoechst Ag | Cephemderivate und verfahren zu ihrer herstellung |
| JPS59141547A (ja) * | 1983-02-01 | 1984-08-14 | Eisai Co Ltd | 鎮痛作用を有する新規ペプタイドおよび製法 |
| FR2575753B1 (fr) * | 1985-01-07 | 1987-02-20 | Adir | Nouveaux derives peptidiques a structure polycyclique azotee, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| DK167813B1 (da) * | 1989-12-07 | 1993-12-20 | Carlbiotech Ltd As | Pentapeptidderivat, farmaceutisk acceptable salte heraf, fremgangsmaade til fremstilling deraf og farmaceutisk praeparat indeholdende et saadant derivat |
| US5559209A (en) * | 1993-02-18 | 1996-09-24 | The General Hospital Corporation | Regulator regions of G proteins |
| US6472172B1 (en) * | 1998-07-31 | 2002-10-29 | Schering Aktiengesellschaft | DNA encoding a novel human inhibitor-of-apoptosis protein |
| TR200200767T1 (tr) | 2000-05-23 | 2002-09-23 | Vertex Pharmaceuticals Incorporated | Kaspaz engelleyiciler ve kullanımları |
| US6608026B1 (en) * | 2000-08-23 | 2003-08-19 | Board Of Regents, The University Of Texas System | Apoptotic compounds |
| US20020160975A1 (en) * | 2001-02-08 | 2002-10-31 | Thomas Jefferson University | Conserved XIAP-interaction motif in caspase-9 and Smac/DIABLO for mediating apoptosis |
| US20030157522A1 (en) * | 2001-11-09 | 2003-08-21 | Alain Boudreault | Methods and reagents for peptide-BIR interaction screens |
| WO2004005248A1 (en) | 2002-07-02 | 2004-01-15 | Novartis Ag | Peptide inhibitors of smac protein binding to inhibitor of apoptosis proteins (iap) |
| ATE415413T1 (de) * | 2002-07-15 | 2008-12-15 | Univ Princeton | Iap-bindende verbindungen |
| US20040171554A1 (en) * | 2003-02-07 | 2004-09-02 | Genentech, Inc. | Compositions and methods for enhancing apoptosis |
| WO2005049853A2 (en) * | 2003-11-13 | 2005-06-02 | Genentech, Inc. | Compositions and methods for screening pro-apoptotic compounds |
| CA2553871A1 (en) * | 2004-01-16 | 2005-08-04 | The Regents Of The University Of Michigan | Smac peptidomimetics and the uses thereof |
| SE527038C2 (sv) * | 2004-02-26 | 2005-12-13 | Ingenjoers N Per Oskar Persson | Kassett och apparat för vätskefrysning |
| CN1926118A (zh) * | 2004-03-01 | 2007-03-07 | 德克萨斯大学董事会 | 二聚的小分子细胞凋亡增强剂 |
| BRPI0511350A (pt) | 2004-07-02 | 2007-12-04 | Genentech Inc | composto, métodos de indução da apoptose em uma célula, de sensibilização de uma célula à um sinal apoptótico, de inibição da ligação de uma proteìna iap e de tratamento de uma doença e cáncer e usos de um composto |
| MX2007007195A (es) * | 2004-12-20 | 2007-10-08 | Genentech Inc | Inhibidores de pirrolidina de iap. |
| US20060218632A1 (en) * | 2005-03-28 | 2006-09-28 | Cisco Technology, Inc.; | Method and system for installing premise equipment |
| US8044209B2 (en) * | 2006-10-12 | 2011-10-25 | Novartis Ag | Pyrrolydine derivatives as IAP inhibitors |
| ATE542798T1 (de) * | 2006-12-07 | 2012-02-15 | Novartis Ag | Organische verbindungen |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
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Non-Patent Citations (1)
| Title |
|---|
| A Small Molecule Smac Mimic Potentiates TRAIL- and TNFa-Mediated Cell Death;Lin Li, et al.;《science》;20040930;P1471-1474 * |
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