JP2019533987A5 - - Google Patents
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- JP2019533987A5 JP2019533987A5 JP2019511562A JP2019511562A JP2019533987A5 JP 2019533987 A5 JP2019533987 A5 JP 2019533987A5 JP 2019511562 A JP2019511562 A JP 2019511562A JP 2019511562 A JP2019511562 A JP 2019511562A JP 2019533987 A5 JP2019533987 A5 JP 2019533987A5
- Authority
- JP
- Japan
- Prior art keywords
- snv
- mtor
- inhibitors
- agent
- trametinib
- 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.)
- Granted
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- 238000000034 method Methods 0.000 claims description 72
- 239000003795 chemical substances by application Substances 0.000 claims description 34
- 102100023085 Serine/threonine-protein kinase mTOR Human genes 0.000 claims description 24
- 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 claims description 24
- 239000003112 inhibitor Substances 0.000 claims description 23
- 101000692672 Homo sapiens Phosphoinositide 3-kinase regulatory subunit 4 Proteins 0.000 claims description 22
- 101000692692 Homo sapiens Phosphoinositide 3-kinase regulatory subunit 6 Proteins 0.000 claims description 22
- 101000771237 Homo sapiens Serine/threonine-protein kinase A-Raf Proteins 0.000 claims description 22
- 102100026481 Phosphoinositide 3-kinase regulatory subunit 4 Human genes 0.000 claims description 22
- 102100026253 Phosphoinositide 3-kinase regulatory subunit 6 Human genes 0.000 claims description 22
- 102100029437 Serine/threonine-protein kinase A-Raf Human genes 0.000 claims description 22
- 108010055323 EphB4 Receptor Proteins 0.000 claims description 21
- 208000006737 Lymphatic Abnormalities Diseases 0.000 claims description 21
- 229960004066 trametinib Drugs 0.000 claims description 17
- 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 description 17
- 239000012824 ERK inhibitor Substances 0.000 claims description 13
- 239000002829 mitogen activated protein kinase inhibitor Substances 0.000 claims description 13
- 210000000416 exudates and transudate Anatomy 0.000 claims description 12
- 229940079593 drug Drugs 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 11
- 102000039446 nucleic acids Human genes 0.000 claims description 11
- 108020004707 nucleic acids Proteins 0.000 claims description 11
- 150000007523 nucleic acids Chemical class 0.000 claims description 11
- 206010025323 Lymphomas Diseases 0.000 claims description 10
- 239000002773 nucleotide Substances 0.000 claims description 10
- 125000003729 nucleotide group Chemical group 0.000 claims description 10
- 229940124302 mTOR inhibitor Drugs 0.000 claims description 9
- 239000003628 mammalian target of rapamycin inhibitor Substances 0.000 claims description 9
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 claims description 8
- 229960002930 sirolimus Drugs 0.000 claims description 8
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 claims description 8
- 239000012472 biological sample Substances 0.000 claims description 7
- 206010051228 Chylothorax Diseases 0.000 claims description 6
- 206010025219 Lymphangioma Diseases 0.000 claims description 6
- 238000004458 analytical method Methods 0.000 claims description 6
- 229950006418 dactolisib Drugs 0.000 claims description 5
- JOGKUKXHTYWRGZ-UHFFFAOYSA-N dactolisib Chemical compound O=C1N(C)C2=CN=C3C=CC(C=4C=C5C=CC=CC5=NC=4)=CC3=C2N1C1=CC=C(C(C)(C)C#N)C=C1 JOGKUKXHTYWRGZ-UHFFFAOYSA-N 0.000 claims description 5
- 108700028369 Alleles Proteins 0.000 claims description 4
- 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 description 4
- 229960002271 cobimetinib Drugs 0.000 claims description 4
- 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 description 4
- 238000009396 hybridization Methods 0.000 claims description 4
- 102000040430 polynucleotide Human genes 0.000 claims description 4
- 108091033319 polynucleotide Proteins 0.000 claims description 4
- 239000002157 polynucleotide Substances 0.000 claims description 4
- 230000002159 abnormal effect Effects 0.000 claims description 3
- 238000001514 detection method Methods 0.000 claims description 3
- RDSACQWTXKSHJT-NSHDSACASA-N n-[3,4-difluoro-2-(2-fluoro-4-iodoanilino)-6-methoxyphenyl]-1-[(2s)-2,3-dihydroxypropyl]cyclopropane-1-sulfonamide Chemical compound C1CC1(C[C@H](O)CO)S(=O)(=O)NC=1C(OC)=CC(F)=C(F)C=1NC1=CC=C(I)C=C1F RDSACQWTXKSHJT-NSHDSACASA-N 0.000 claims description 3
- JLOXTZFYJNCPIS-FYWRMAATSA-N (z)-3-amino-3-(4-aminophenyl)sulfanyl-2-[2-(trifluoromethyl)phenyl]prop-2-enenitrile Chemical compound C=1C=CC=C(C(F)(F)F)C=1C(\C#N)=C(/N)SC1=CC=C(N)C=C1 JLOXTZFYJNCPIS-FYWRMAATSA-N 0.000 claims description 2
- GFMMXOIFOQCCGU-UHFFFAOYSA-N 2-(2-chloro-4-iodoanilino)-N-(cyclopropylmethoxy)-3,4-difluorobenzamide Chemical compound C=1C=C(I)C=C(Cl)C=1NC1=C(F)C(F)=CC=C1C(=O)NOCC1CC1 GFMMXOIFOQCCGU-UHFFFAOYSA-N 0.000 claims description 2
- RWEVIPRMPFNTLO-UHFFFAOYSA-N 2-(2-fluoro-4-iodoanilino)-N-(2-hydroxyethoxy)-1,5-dimethyl-6-oxo-3-pyridinecarboxamide Chemical compound CN1C(=O)C(C)=CC(C(=O)NOCCO)=C1NC1=CC=C(I)C=C1F RWEVIPRMPFNTLO-UHFFFAOYSA-N 0.000 claims description 2
- RCLQNICOARASSR-SECBINFHSA-N 3-[(2r)-2,3-dihydroxypropyl]-6-fluoro-5-(2-fluoro-4-iodoanilino)-8-methylpyrido[2,3-d]pyrimidine-4,7-dione Chemical compound FC=1C(=O)N(C)C=2N=CN(C[C@@H](O)CO)C(=O)C=2C=1NC1=CC=C(I)C=C1F RCLQNICOARASSR-SECBINFHSA-N 0.000 claims description 2
- HKVAMNSJSFKALM-GKUWKFKPSA-N Everolimus Chemical compound C1C[C@@H](OCCO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 HKVAMNSJSFKALM-GKUWKFKPSA-N 0.000 claims description 2
- 229950003054 binimetinib Drugs 0.000 claims description 2
- 230000015572 biosynthetic process Effects 0.000 claims description 2
- BSMCAPRUBJMWDF-KRWDZBQOSA-N cobimetinib Chemical compound C1C(O)([C@H]2NCCCC2)CN1C(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(I)C=C1F BSMCAPRUBJMWDF-KRWDZBQOSA-N 0.000 claims description 2
- 229960005167 everolimus Drugs 0.000 claims description 2
- 210000001365 lymphatic vessel Anatomy 0.000 claims description 2
- 238000005259 measurement Methods 0.000 claims description 2
- 238000007894 restriction fragment length polymorphism technique Methods 0.000 claims description 2
- CYOHGALHFOKKQC-UHFFFAOYSA-N selumetinib Chemical compound OCCONC(=O)C=1C=C2N(C)C=NC2=C(F)C=1NC1=CC=C(Br)C=C1Cl CYOHGALHFOKKQC-UHFFFAOYSA-N 0.000 claims description 2
- 238000012163 sequencing technique Methods 0.000 claims description 2
- 102000030797 EphB4 Receptor Human genes 0.000 claims 7
- -1 PD0325901 Chemical compound 0.000 claims 1
- 239000000523 sample Substances 0.000 claims 1
- 102100031983 Ephrin type-B receptor 4 Human genes 0.000 description 14
- 230000005764 inhibitory process Effects 0.000 description 5
- 230000001926 lymphatic effect Effects 0.000 description 5
- 230000004202 respiratory function Effects 0.000 description 5
- 230000004083 survival effect Effects 0.000 description 5
- 230000011664 signaling Effects 0.000 description 3
- 102000010400 1-phosphatidylinositol-3-kinase activity proteins Human genes 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 108091007960 PI3Ks Proteins 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 230000005754 cellular signaling Effects 0.000 description 2
- 102000054765 polymorphisms of proteins Human genes 0.000 description 2
- 230000009261 transgenic effect Effects 0.000 description 2
- 241000252212 Danio rerio Species 0.000 description 1
- 102100023266 Dual specificity mitogen-activated protein kinase kinase 2 Human genes 0.000 description 1
- 101710146529 Dual specificity mitogen-activated protein kinase kinase 2 Proteins 0.000 description 1
- 102000006992 Interferon-alpha Human genes 0.000 description 1
- 108010047761 Interferon-alpha Proteins 0.000 description 1
- 229940124647 MEK inhibitor Drugs 0.000 description 1
- 102100024193 Mitogen-activated protein kinase 1 Human genes 0.000 description 1
- 208000012868 Overgrowth Diseases 0.000 description 1
- 239000012828 PI3K inhibitor Substances 0.000 description 1
- 208000002151 Pleural effusion Diseases 0.000 description 1
- 102000018679 Tacrolimus Binding Proteins Human genes 0.000 description 1
- 108010027179 Tacrolimus Binding Proteins Proteins 0.000 description 1
- 230000000735 allogeneic effect Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229940043441 phosphoinositide 3-kinase inhibitor Drugs 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 238000011521 systemic chemotherapy Methods 0.000 description 1
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2022206535A JP2023052057A (ja) | 2016-08-31 | 2022-12-23 | リンパ系疾患の診断及び治療のための組成物及び方法 |
| JP2024169918A JP2025016454A (ja) | 2016-08-31 | 2024-09-30 | リンパ系疾患の診断及び治療のための組成物及び方法 |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662382147P | 2016-08-31 | 2016-08-31 | |
| US62/382,147 | 2016-08-31 | ||
| PCT/US2017/049453 WO2018045078A2 (en) | 2016-08-31 | 2017-08-30 | Compositions and methods for the diagnosis and treatment of lymphatic system disorders |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2022206535A Division JP2023052057A (ja) | 2016-08-31 | 2022-12-23 | リンパ系疾患の診断及び治療のための組成物及び方法 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2019533987A JP2019533987A (ja) | 2019-11-28 |
| JP2019533987A5 true JP2019533987A5 (https=) | 2020-10-08 |
| JP7202287B2 JP7202287B2 (ja) | 2023-01-11 |
Family
ID=61309356
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2019511562A Active JP7202287B2 (ja) | 2016-08-31 | 2017-08-30 | リンパ系疾患の診断及び治療のための組成物及び方法 |
| JP2022206535A Withdrawn JP2023052057A (ja) | 2016-08-31 | 2022-12-23 | リンパ系疾患の診断及び治療のための組成物及び方法 |
| JP2024169918A Pending JP2025016454A (ja) | 2016-08-31 | 2024-09-30 | リンパ系疾患の診断及び治療のための組成物及び方法 |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2022206535A Withdrawn JP2023052057A (ja) | 2016-08-31 | 2022-12-23 | リンパ系疾患の診断及び治療のための組成物及び方法 |
| JP2024169918A Pending JP2025016454A (ja) | 2016-08-31 | 2024-09-30 | リンパ系疾患の診断及び治療のための組成物及び方法 |
Country Status (8)
| Country | Link |
|---|---|
| US (2) | US11401553B2 (https=) |
| EP (2) | EP4023769A1 (https=) |
| JP (3) | JP7202287B2 (https=) |
| AU (2) | AU2017319507B2 (https=) |
| CA (1) | CA3034786A1 (https=) |
| DK (1) | DK3506899T3 (https=) |
| ES (1) | ES2906333T3 (https=) |
| WO (1) | WO2018045078A2 (https=) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2019336798B2 (en) * | 2018-09-07 | 2025-07-17 | The Children's Hospital Of Philadelphia | Compositions and methods for the diagnosis and treatment of lymphatic system disorders |
| US12070468B2 (en) * | 2020-05-14 | 2024-08-27 | The Trustees Of Columbia University In The City Of New York | Compositions and methods for the treatment and prevention of vascular malformations |
| WO2021231814A1 (en) * | 2020-05-14 | 2021-11-18 | The Trustees Of Columbia University In The City Of New York | Compositions and methods for the treatment and prevention of vascular malformations |
| WO2023229605A1 (en) * | 2022-05-27 | 2023-11-30 | Avalo Therapeutics, Inc. | Methods and treatment for complex lymphatic malformations |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9212416D0 (en) | 1992-06-11 | 1992-07-22 | Medical Res Council | Reversible binding substances |
| US6057098A (en) | 1997-04-04 | 2000-05-02 | Biosite Diagnostics, Inc. | Polyvalent display libraries |
| US20080131887A1 (en) * | 2006-11-30 | 2008-06-05 | Stephan Dietrich A | Genetic Analysis Systems and Methods |
| US9018912B2 (en) | 2011-05-17 | 2015-04-28 | Inphi Corporation | System and method for managing parallel-connected battery cells |
| US10835513B2 (en) | 2013-06-28 | 2020-11-17 | The Regents Of The University Of California | Methods and treatments for the learning and memory deficits associated with Noonan syndrome |
| US10307370B2 (en) | 2013-10-08 | 2019-06-04 | AI Therapeutics, Inc. | Rapamycin for the treatment of lymphangioleiomyomatosis |
| JP6678583B2 (ja) | 2013-12-20 | 2020-04-22 | バイオメッド バレー ディスカバリーズ，インコーポレイティド | ２型ｍｅｋ阻害剤およびｅｒｋ阻害剤の組み合わせを用いるがん処置 |
| JP6429306B2 (ja) * | 2014-03-26 | 2018-11-28 | 国立大学法人東北大学 | Ｃｆｃ症候群モデルマウスの作製とその治療法の確立 |
| WO2018126192A1 (en) | 2016-12-30 | 2018-07-05 | Children's Medical Center Corporation | Map2k1 (mek1) as a therapeutic target for arteriovenous malformations and associated disorders |
-
2017
- 2017-08-30 DK DK17847498.7T patent/DK3506899T3/da active
- 2017-08-30 EP EP21214113.9A patent/EP4023769A1/en active Pending
- 2017-08-30 CA CA3034786A patent/CA3034786A1/en active Pending
- 2017-08-30 WO PCT/US2017/049453 patent/WO2018045078A2/en not_active Ceased
- 2017-08-30 US US16/327,060 patent/US11401553B2/en active Active
- 2017-08-30 AU AU2017319507A patent/AU2017319507B2/en active Active
- 2017-08-30 JP JP2019511562A patent/JP7202287B2/ja active Active
- 2017-08-30 ES ES17847498T patent/ES2906333T3/es active Active
- 2017-08-30 EP EP17847498.7A patent/EP3506899B1/en active Active
-
2022
- 2022-07-28 US US17/815,647 patent/US12509729B2/en active Active
- 2022-12-23 JP JP2022206535A patent/JP2023052057A/ja not_active Withdrawn
-
2024
- 2024-02-21 AU AU2024201122A patent/AU2024201122A1/en active Pending
- 2024-09-30 JP JP2024169918A patent/JP2025016454A/ja active Pending
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