RU2016140626A - Комбинация ингибитора EGFR и ингибитора MEK для применения в лечении рака, вызванного мутировавшим NRAS - Google Patents
Комбинация ингибитора EGFR и ингибитора MEK для применения в лечении рака, вызванного мутировавшим NRAS Download PDFInfo
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- RU2016140626A RU2016140626A RU2016140626A RU2016140626A RU2016140626A RU 2016140626 A RU2016140626 A RU 2016140626A RU 2016140626 A RU2016140626 A RU 2016140626A RU 2016140626 A RU2016140626 A RU 2016140626A RU 2016140626 A RU2016140626 A RU 2016140626A
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- Prior art keywords
- egfr inhibitor
- inhibitor
- nras
- use according
- paragraphs
- Prior art date
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- 229940121647 egfr inhibitor Drugs 0.000 title claims 13
- 102100039788 GTPase NRas Human genes 0.000 title claims 6
- 101000744505 Homo sapiens GTPase NRas Proteins 0.000 title claims 6
- 229940124647 MEK inhibitor Drugs 0.000 title claims 4
- 239000002829 mitogen activated protein kinase inhibitor Substances 0.000 title claims 4
- 206010028980 Neoplasm Diseases 0.000 title claims 3
- 201000011510 cancer Diseases 0.000 title claims 3
- 150000003839 salts Chemical class 0.000 claims 5
- 229960003278 osimertinib Drugs 0.000 claims 3
- DUYJMQONPNNFPI-UHFFFAOYSA-N osimertinib Chemical compound COC1=CC(N(C)CCN(C)C)=C(NC(=O)C=C)C=C1NC1=NC=CC(C=2C3=CC=CC=C3N(C)C=2)=N1 DUYJMQONPNNFPI-UHFFFAOYSA-N 0.000 claims 3
- 101150073096 NRAS gene Proteins 0.000 claims 2
- 230000035772 mutation Effects 0.000 claims 2
- HUFOZJXAKZVRNJ-UHFFFAOYSA-N n-[3-[[2-[4-(4-acetylpiperazin-1-yl)-2-methoxyanilino]-5-(trifluoromethyl)pyrimidin-4-yl]amino]phenyl]prop-2-enamide Chemical compound COC1=CC(N2CCN(CC2)C(C)=O)=CC=C1NC(N=1)=NC=C(C(F)(F)F)C=1NC1=CC=CC(NC(=O)C=C)=C1 HUFOZJXAKZVRNJ-UHFFFAOYSA-N 0.000 claims 2
- 229950009855 rociletinib Drugs 0.000 claims 2
- 102200006531 rs121913529 Human genes 0.000 claims 2
- 102200006540 rs121913530 Human genes 0.000 claims 2
- 102200006651 rs121917756 Human genes 0.000 claims 2
- 229950010746 selumetinib Drugs 0.000 claims 2
- CYOHGALHFOKKQC-UHFFFAOYSA-N selumetinib Chemical group OCCONC(=O)C=1C=C2N(C)C=NC2=C(F)C=1NC1=CC=C(Br)C=C1Cl CYOHGALHFOKKQC-UHFFFAOYSA-N 0.000 claims 2
- 102000001301 EGF receptor Human genes 0.000 claims 1
- 108060006698 EGF receptor Proteins 0.000 claims 1
- 239000005411 L01XE02 - Gefitinib Substances 0.000 claims 1
- 239000005551 L01XE03 - Erlotinib Substances 0.000 claims 1
- 206010029260 Neuroblastoma Diseases 0.000 claims 1
- 108091000080 Phosphotransferase Proteins 0.000 claims 1
- 102000001253 Protein Kinase Human genes 0.000 claims 1
- 229960001686 afatinib Drugs 0.000 claims 1
- ULXXDDBFHOBEHA-CWDCEQMOSA-N afatinib Chemical compound N1=CN=C2C=C(O[C@@H]3COCC3)C(NC(=O)/C=C/CN(C)C)=CC2=C1NC1=CC=C(F)C(Cl)=C1 ULXXDDBFHOBEHA-CWDCEQMOSA-N 0.000 claims 1
- ACWZRVQXLIRSDF-UHFFFAOYSA-N binimetinib Chemical compound OCCONC(=O)C=1C=C2N(C)C=NC2=C(F)C=1NC1=CC=C(Br)C=C1F ACWZRVQXLIRSDF-UHFFFAOYSA-N 0.000 claims 1
- 229960002271 cobimetinib Drugs 0.000 claims 1
- RESIMIUSNACMNW-BXRWSSRYSA-N cobimetinib fumarate Chemical compound OC(=O)\C=C\C(O)=O.C1C(O)([C@H]2NCCCC2)CN1C(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(I)C=C1F.C1C(O)([C@H]2NCCCC2)CN1C(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(I)C=C1F RESIMIUSNACMNW-BXRWSSRYSA-N 0.000 claims 1
- 229960001433 erlotinib Drugs 0.000 claims 1
- AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 claims 1
- 229960002584 gefitinib Drugs 0.000 claims 1
- XGALLCVXEZPNRQ-UHFFFAOYSA-N gefitinib Chemical group C=12C=C(OCCCN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 XGALLCVXEZPNRQ-UHFFFAOYSA-N 0.000 claims 1
- 239000003226 mitogen Substances 0.000 claims 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims 1
- 102000020233 phosphotransferase Human genes 0.000 claims 1
- 108060006633 protein kinase Proteins 0.000 claims 1
- 102000016914 ras Proteins Human genes 0.000 claims 1
- 230000001105 regulatory effect Effects 0.000 claims 1
- 102200006537 rs121913529 Human genes 0.000 claims 1
- 102200006539 rs121913529 Human genes 0.000 claims 1
- 102200006538 rs121913530 Human genes 0.000 claims 1
- 102200006541 rs121913530 Human genes 0.000 claims 1
- LIRYPHYGHXZJBZ-UHFFFAOYSA-N trametinib Chemical compound CC(=O)NC1=CC=CC(N2C(N(C3CC3)C(=O)C3=C(NC=4C(=CC(I)=CC=4)F)N(C)C(=O)C(C)=C32)=O)=C1 LIRYPHYGHXZJBZ-UHFFFAOYSA-N 0.000 claims 1
- 229960004066 trametinib Drugs 0.000 claims 1
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims 1
- 230000003612 virological effect Effects 0.000 claims 1
Classifications
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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
- 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
- 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
- A61K31/4164—1,3-Diazoles
- A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
-
- 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
- A61K31/4458—Non condensed piperidines, e.g. piperocaine only substituted in position 2, e.g. methylphenidate
-
- 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
- A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
-
- 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
- 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
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- A61K48/005—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered
- A61K48/0058—Nucleic acids adapted for tissue specific expression, e.g. having tissue specific promoters as part of a contruct
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biochemistry (AREA)
- Pulmonology (AREA)
- Biomedical Technology (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Claims (8)
1. Ингибитор EGFR (рецептор эпидермального фактора роста) для применения в лечении рака, вызванного мутировавшим NRAS (вирусный онкоген RAS нейробластомы), где ингибитор EGFR вводят в комбинации с ингибитором MEK (MAP (митогенактивируемая) протеинкиназа/регулируемая внеклеточными сигналами киназа-киназа), и мутация NRAS выбрана из E63K, G12V, G12R, G12A, G12D, G12S и G12C или роста копийности гена NRAS.
2. Ингибитор EGFR для применения по п. 1, где ингибитор EGFR выбран из гефитиниба, эрлотиниба, афатиниба, AZD9291 и CO1686 или их фармацевтически приемлемой соли.
3. Ингибитор EGFR для применения по пп. 1 или 2, где ингибитор EGFR выбран из AZD9291 и CO1686 или их фармацевтически приемлемой соли.
4. Ингибитор EGFR для применения по любому из пп. 1-3, где ингибитор MEK выбран из селуметиниба, траметиниба, MEK-162 и кобиметиниба или их фармацевтически приемлемой соли.
5. Ингибитор EGFR для применения по любому из пп. 1-4, где рак, вызванный мутировавшим NRAS, представляет собой вызванный мутировавшим NRAS немелкоклеточный рак легких.
6. Ингибитор EGFR для применения по любому из пп. 1-5, где мутация NRAS выбрана из E63K, G12V и G12R или роста копийности гена NRAS.
7. Ингибитор EGFR для применения по любому из пп. 1-6, где ингибитор EGFR представляет собой AZD9291 или его фармацевтически приемлемую соль.
8. Ингибитор EGFR для применения по любому из пп. 1-7, где ингибитор MEK представляет собой селуметиниб или его фармацевтически приемлемую соль.
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201461975088P | 2014-04-04 | 2014-04-04 | |
| US61/975,088 | 2014-04-04 | ||
| US201462013573P | 2014-06-18 | 2014-06-18 | |
| US62/013,573 | 2014-06-18 | ||
| PCT/GB2015/051042 WO2015150826A1 (en) | 2014-04-04 | 2015-04-02 | Combination of egfr inhibitor and mek inhibitor for use in the treatment of nras mutated cancer |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| RU2016140626A true RU2016140626A (ru) | 2018-05-07 |
| RU2016140626A3 RU2016140626A3 (ru) | 2018-10-23 |
| RU2683276C2 RU2683276C2 (ru) | 2019-03-27 |
Family
ID=52824498
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2016140626A RU2683276C2 (ru) | 2014-04-04 | 2015-04-02 | Комбинация ингибитора EGFR и ингибитора MEK для применения в лечении рака, вызванного мутировавшим NRAS |
Country Status (15)
| Country | Link |
|---|---|
| US (2) | US20200237758A1 (ru) |
| EP (1) | EP3125885B1 (ru) |
| JP (1) | JP6549147B2 (ru) |
| KR (1) | KR102406334B1 (ru) |
| CN (1) | CN106456774A (ru) |
| AU (1) | AU2015242407B2 (ru) |
| CA (1) | CA2943402C (ru) |
| DK (1) | DK3125885T3 (ru) |
| ES (1) | ES2890556T3 (ru) |
| HU (1) | HUE055747T2 (ru) |
| MA (1) | MA39841A (ru) |
| MX (1) | MX369111B (ru) |
| PL (1) | PL3125885T3 (ru) |
| RU (1) | RU2683276C2 (ru) |
| WO (1) | WO2015150826A1 (ru) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2780168C1 (ru) * | 2019-02-18 | 2022-09-20 | Корея Инститьют Оф Сайенс Энд Текнолоджи | Новое производное пиридо [3,4-d] пиримидин-8-она, обладающее ингибирующей протеинкиназы активностью, и фармацевтическая композиция для предупреждения, облегчения или лечения рака, содержащее указанное выше |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AR110038A1 (es) | 2016-05-26 | 2019-02-20 | Kalyra Pharmaceuticals Inc | Compuestos inhibidores de egfr; composición farmacéutica que lo comprende; métodos para mejorar o tratar un cáncer; método para inhibir la replicación de un crecimiento maligno o un tumor; métodos para inhibir la actividad del egfr; y usos de los compuestos |
| WO2018218633A1 (en) | 2017-06-02 | 2018-12-06 | Beijing Percans Oncology Co. Ltd. | Combination therapies for treating cancers |
| WO2019195959A1 (en) | 2018-04-08 | 2019-10-17 | Cothera Biosciences, Inc. | Combination therapy for cancers with braf mutation |
| AU2019253706A1 (en) * | 2018-04-09 | 2020-11-26 | G1 Therapeutics, Inc. | Treatment of cancers having driving oncogenic mutations |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003086467A1 (en) * | 2002-04-08 | 2003-10-23 | Smithkline Beecham Corporation | Cancer treatment method comprising administering an erb-family inhibitor and a raf and/or ras inhibitor |
| BRPI0921888A2 (pt) * | 2008-11-11 | 2015-12-29 | Lilly Co Eli | terapia de combinação de inibidor de egfr inibidor da p70 s6 quinase |
| RS60190B1 (sr) * | 2011-07-27 | 2020-06-30 | Astrazeneca Ab | 2-(2,4,5-supstituisani-anilino) pirimidinski derivati kao egfr modulatori korisni za lečenje raka |
| KR102080535B1 (ko) * | 2011-11-23 | 2020-02-24 | 메디뮨 엘엘씨 | Her3에 특이적인 결합 분자 및 이의 용도 |
| US20150071918A1 (en) * | 2012-05-09 | 2015-03-12 | H. Lee Moffitt Cancer Center And Research Institute, Inc. | Peptides for the treatment of cancer |
| EP2884971A4 (en) * | 2012-08-16 | 2016-01-06 | Ohio State Innovation Foundation | STAT3 INHIBITORS AND THEIR ANTICANCER USE |
| US20140066465A1 (en) * | 2012-09-04 | 2014-03-06 | The Cleveland Clinic Foundation | CANCER TREATMENT USING TYROSINE KINASE AND NF-kB INHIBITORS |
-
2015
- 2015-04-02 WO PCT/GB2015/051042 patent/WO2015150826A1/en active Application Filing
- 2015-04-02 EP EP15715805.6A patent/EP3125885B1/en active Active
- 2015-04-02 CA CA2943402A patent/CA2943402C/en active Active
- 2015-04-02 CN CN201580022665.5A patent/CN106456774A/zh active Pending
- 2015-04-02 AU AU2015242407A patent/AU2015242407B2/en active Active
- 2015-04-02 MA MA039841A patent/MA39841A/fr unknown
- 2015-04-02 RU RU2016140626A patent/RU2683276C2/ru active
- 2015-04-02 PL PL15715805T patent/PL3125885T3/pl unknown
- 2015-04-02 JP JP2016560813A patent/JP6549147B2/ja active Active
- 2015-04-02 DK DK15715805.6T patent/DK3125885T3/da active
- 2015-04-02 MX MX2016013048A patent/MX369111B/es active IP Right Grant
- 2015-04-02 ES ES15715805T patent/ES2890556T3/es active Active
- 2015-04-02 KR KR1020167030569A patent/KR102406334B1/ko active IP Right Grant
- 2015-04-02 HU HUE15715805A patent/HUE055747T2/hu unknown
- 2015-04-02 US US15/301,448 patent/US20200237758A1/en not_active Abandoned
-
2020
- 2020-12-16 US US17/123,777 patent/US20210177844A1/en not_active Abandoned
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2780168C1 (ru) * | 2019-02-18 | 2022-09-20 | Корея Инститьют Оф Сайенс Энд Текнолоджи | Новое производное пиридо [3,4-d] пиримидин-8-она, обладающее ингибирующей протеинкиназы активностью, и фармацевтическая композиция для предупреждения, облегчения или лечения рака, содержащее указанное выше |
Also Published As
| Publication number | Publication date |
|---|---|
| EP3125885A1 (en) | 2017-02-08 |
| WO2015150826A1 (en) | 2015-10-08 |
| DK3125885T3 (da) | 2021-09-27 |
| US20210177844A1 (en) | 2021-06-17 |
| KR20160135362A (ko) | 2016-11-25 |
| ES2890556T3 (es) | 2022-01-20 |
| CN106456774A (zh) | 2017-02-22 |
| RU2683276C2 (ru) | 2019-03-27 |
| AU2015242407A1 (en) | 2016-10-13 |
| CA2943402A1 (en) | 2015-10-08 |
| HUE055747T2 (hu) | 2021-12-28 |
| MA39841A (fr) | 2017-02-08 |
| AU2015242407B2 (en) | 2017-11-09 |
| EP3125885B1 (en) | 2021-06-30 |
| JP2017511341A (ja) | 2017-04-20 |
| MX2016013048A (es) | 2017-04-27 |
| US20200237758A1 (en) | 2020-07-30 |
| CA2943402C (en) | 2022-12-13 |
| MX369111B (es) | 2019-10-29 |
| PL3125885T3 (pl) | 2021-12-06 |
| JP6549147B2 (ja) | 2019-07-24 |
| RU2016140626A3 (ru) | 2018-10-23 |
| KR102406334B1 (ko) | 2022-06-07 |
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