AU2019209292B2 - Quinoxalinone compounds, compositions, methods, and kits for increasing genome editing efficiency - Google Patents

Quinoxalinone compounds, compositions, methods, and kits for increasing genome editing efficiency Download PDF

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AU2019209292B2
AU2019209292B2 AU2019209292A AU2019209292A AU2019209292B2 AU 2019209292 B2 AU2019209292 B2 AU 2019209292B2 AU 2019209292 A AU2019209292 A AU 2019209292A AU 2019209292 A AU2019209292 A AU 2019209292A AU 2019209292 B2 AU2019209292 B2 AU 2019209292B2
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compound
cell
dna
formula
fold
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AU2019209292A1 (en
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Kevin M. Cottrell
Diego Sebastian D'astolfo
Sudipta Mahajan
John Patrick Maxwell
Mark A. Morris
Marc Saul Weinberg
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Vertex Pharmaceuticals Inc
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Vertex Pharmaceuticals Inc
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    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07D241/40—Benzopyrazines
    • C07D241/44—Benzopyrazines with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring
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    • 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
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    • A61K31/00—Medicinal preparations containing organic active ingredients
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    • A61K31/5375—1,4-Oxazines, e.g. morpholine
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    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
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    • C12N15/90—Stable introduction of foreign DNA into chromosome
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  • Nitrogen Condensed Heterocyclic Rings (AREA)
AU2019209292A 2018-01-17 2019-01-16 Quinoxalinone compounds, compositions, methods, and kits for increasing genome editing efficiency Active AU2019209292B2 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201862618385P 2018-01-17 2018-01-17
US62/618,385 2018-01-17
PCT/US2019/013785 WO2019143677A1 (en) 2018-01-17 2019-01-16 Quinoxalinone compounds, compositions, methods, and kits for increasing genome editing efficiency

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AU2019209292A1 AU2019209292A1 (en) 2020-09-03
AU2019209292B2 true AU2019209292B2 (en) 2023-10-05

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EP (1) EP3740483B1 (enExample)
JP (1) JP7483612B2 (enExample)
KR (1) KR20200110687A (enExample)
CN (1) CN111770921B (enExample)
AU (1) AU2019209292B2 (enExample)
BR (1) BR112020013626A2 (enExample)
CA (1) CA3088791A1 (enExample)
EA (1) EA202091707A1 (enExample)
ES (1) ES2940786T3 (enExample)
IL (1) IL276081B2 (enExample)
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Families Citing this family (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20190127713A1 (en) 2016-04-13 2019-05-02 Duke University Crispr/cas9-based repressors for silencing gene targets in vivo and methods of use
US11427838B2 (en) 2016-06-29 2022-08-30 Vertex Pharmaceuticals Incorporated Materials and methods for treatment of myotonic dystrophy type 1 (DM1) and other related disorders
MA51619A (fr) * 2018-01-17 2021-04-14 Vertex Pharma Inhibiteurs de la protéine kinase dépendante de l'adn
BR112020013626A2 (pt) 2018-01-17 2020-12-01 Vertex Pharmaceuticals Incorporated compostos de quinoxalinona, composições, métodos e kits para aumentar a eficiência de edição de genoma
JP7466448B2 (ja) 2018-01-17 2024-04-12 バーテックス ファーマシューティカルズ インコーポレイテッド Ｄｎａ－ｐｋ阻害剤
EP3740580A4 (en) 2018-01-19 2021-10-20 Duke University GENOME ENGINEERING WITH CRISPR-CAS SYSTEMS IN EUKARYONTS
WO2020084034A1 (en) 2018-10-26 2020-04-30 F. Hoffmann-La Roche Ag Multispecific antibody screening method using recombinase mediated cassette exchange
EP4022057A1 (en) * 2019-08-27 2022-07-06 Vertex Pharmaceuticals Incorporated Compositions and methods for treatment of disorders associated with repetitive dna
WO2022136306A1 (en) * 2020-12-21 2022-06-30 Aarhus Universitet Dopaminergic neuron progenitor cells or cell derivatives thereof obtained from lineage restricted pluripotent stem cells
CN112750498B (zh) * 2020-12-30 2022-06-24 同济大学 靶向逆转录引物结合位点从而抑制hiv病毒复制的方法
TW202302848A (zh) 2021-02-26 2023-01-16 美商維泰克斯製藥公司 以crispr/sacas9治療第1型肌強直性營養不良之組合物及方法
EP4298221A1 (en) 2021-02-26 2024-01-03 Vertex Pharmaceuticals Incorporated Compositions and methods for treatment of myotonic dystrophy type 1 with crispr/slucas9
CA3213120A1 (en) * 2021-03-10 2022-09-15 adMare Therapeutics Society 7-morpholino-1,6-naphthyridin-5-yl derivatives and pharmaceutical compositions thereof useful as dna-pk inhibitor
WO2023018637A1 (en) 2021-08-09 2023-02-16 Vertex Pharmaceuticals Incorporated Gene editing of regulatory elements
CN114685494B (zh) * 2022-03-16 2024-04-16 中国人民解放军军事科学院军事医学研究院 SpCas9抑制剂的合成制备方法及其应用
US20250326754A1 (en) * 2022-05-11 2025-10-23 adMare Therapeutics Society DNA-PK Inhibitor Compounds and Uses Thereof
WO2024229292A2 (en) * 2023-05-02 2024-11-07 Duke University Compositions and methods for engineering mature ipsc-derived and esc-derived hepatocytes
WO2025049254A1 (en) * 2023-08-25 2025-03-06 Juno Therapeutics, Inc. Pyrazolopyridine based inhibitors of dna-dependent protein kinase and compositions and application in gene editing

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014159690A1 (en) * 2013-03-12 2014-10-02 Vertex Pharmaceuticals Incorporated Dna-pk inhibitors

Family Cites Families (111)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US789538A (en) 1904-11-11 1905-05-09 Colin E Ham Dumb-bell.
US3773919A (en) 1969-10-23 1973-11-20 Du Pont Polylactide-drug mixtures
US4217344A (en) 1976-06-23 1980-08-12 L'oreal Compositions containing aqueous dispersions of lipid spheres
US4235871A (en) 1978-02-24 1980-11-25 Papahadjopoulos Demetrios P Method of encapsulating biologically active materials in lipid vesicles
US4186183A (en) 1978-03-29 1980-01-29 The United States Of America As Represented By The Secretary Of The Army Liposome carriers in chemotherapy of leishmaniasis
US4261975A (en) 1979-09-19 1981-04-14 Merck & Co., Inc. Viral liposome particle
US4485054A (en) 1982-10-04 1984-11-27 Lipoderm Pharmaceuticals Limited Method of encapsulating biologically active materials in multilamellar lipid vesicles (MLV)
US4501728A (en) 1983-01-06 1985-02-26 Technology Unlimited, Inc. Masking of liposomes from RES recognition
US4946787A (en) 1985-01-07 1990-08-07 Syntex (U.S.A.) Inc. N-(ω,(ω-1)-dialkyloxy)- and N-(ω,(ω-1)-dialkenyloxy)-alk-1-yl-N,N,N-tetrasubstituted ammonium lipids and uses therefor
US4897355A (en) 1985-01-07 1990-01-30 Syntex (U.S.A.) Inc. N[ω,(ω-1)-dialkyloxy]- and N-[ω,(ω-1)-dialkenyloxy]-alk-1-yl-N,N,N-tetrasubstituted ammonium lipids and uses therefor
US5049386A (en) 1985-01-07 1991-09-17 Syntex (U.S.A.) Inc. N-ω,(ω-1)-dialkyloxy)- and N-(ω,(ω-1)-dialkenyloxy)Alk-1-YL-N,N,N-tetrasubstituted ammonium lipids and uses therefor
US4797368A (en) 1985-03-15 1989-01-10 The United States Of America As Represented By The Department Of Health And Human Services Adeno-associated virus as eukaryotic expression vector
US4774085A (en) 1985-07-09 1988-09-27 501 Board of Regents, Univ. of Texas Pharmaceutical administration systems containing a mixture of immunomodulators
US4837028A (en) 1986-12-24 1989-06-06 Liposome Technology, Inc. Liposomes with enhanced circulation time
US5264618A (en) 1990-04-19 1993-11-23 Vical, Inc. Cationic lipids for intracellular delivery of biologically active molecules
WO1991017424A1 (en) 1990-05-03 1991-11-14 Vical, Inc. Intracellular delivery of biologically active substances by means of self-assembling lipid complexes
US5173414A (en) 1990-10-30 1992-12-22 Applied Immune Sciences, Inc. Production of recombinant adeno-associated virus vectors
US5436150A (en) 1992-04-03 1995-07-25 The Johns Hopkins University Functional domains in flavobacterium okeanokoities (foki) restriction endonuclease
US5487994A (en) 1992-04-03 1996-01-30 The Johns Hopkins University Insertion and deletion mutants of FokI restriction endonuclease
US5356802A (en) 1992-04-03 1994-10-18 The Johns Hopkins University Functional domains in flavobacterium okeanokoites (FokI) restriction endonuclease
US5587308A (en) 1992-06-02 1996-12-24 The United States Of America As Represented By The Department Of Health & Human Services Modified adeno-associated virus vector capable of expression from a novel promoter
DE69534629D1 (de) 1994-01-18 2005-12-29 Scripps Research Inst Derivate von zinkfingerproteinen und methoden
US6140466A (en) 1994-01-18 2000-10-31 The Scripps Research Institute Zinc finger protein derivatives and methods therefor
US6242568B1 (en) 1994-01-18 2001-06-05 The Scripps Research Institute Zinc finger protein derivatives and methods therefor
JP4285766B2 (ja) 1994-03-23 2009-06-24 オハイオ ユニバーシティ 緻密にした核酸および細胞へのデリバリ
GB9824544D0 (en) 1998-11-09 1999-01-06 Medical Res Council Screening system
USRE39229E1 (en) 1994-08-20 2006-08-08 Gendaq Limited Binding proteins for recognition of DNA
US5789538A (en) 1995-02-03 1998-08-04 Massachusetts Institute Of Technology Zinc finger proteins with high affinity new DNA binding specificities
US5925523A (en) 1996-08-23 1999-07-20 President & Fellows Of Harvard College Intraction trap assay, reagents and uses thereof
GB2338237B (en) 1997-02-18 2001-02-28 Actinova Ltd In vitro peptide or protein expression library
GB9703369D0 (en) 1997-02-18 1997-04-09 Lindqvist Bjorn H Process
GB9710809D0 (en) 1997-05-23 1997-07-23 Medical Res Council Nucleic acid binding proteins
GB9710807D0 (en) 1997-05-23 1997-07-23 Medical Res Council Nucleic acid binding proteins
US6410248B1 (en) 1998-01-30 2002-06-25 Massachusetts Institute Of Technology General strategy for selecting high-affinity zinc finger proteins for diverse DNA target sites
ES2341926T3 (es) 1998-03-02 2010-06-29 Massachusetts Institute Of Technology Poliproteinas con dedos de cinc que tienen enlazadores mejorados.
US6140081A (en) 1998-10-16 2000-10-31 The Scripps Research Institute Zinc finger binding domains for GNN
US6534261B1 (en) 1999-01-12 2003-03-18 Sangamo Biosciences, Inc. Regulation of endogenous gene expression in cells using zinc finger proteins
US6599692B1 (en) 1999-09-14 2003-07-29 Sangamo Bioscience, Inc. Functional genomics using zinc finger proteins
US6453242B1 (en) 1999-01-12 2002-09-17 Sangamo Biosciences, Inc. Selection of sites for targeting by zinc finger proteins and methods of designing zinc finger proteins to bind to preselected sites
US7070934B2 (en) 1999-01-12 2006-07-04 Sangamo Biosciences, Inc. Ligand-controlled regulation of endogenous gene expression
US7030215B2 (en) 1999-03-24 2006-04-18 Sangamo Biosciences, Inc. Position dependent recognition of GNN nucleotide triplets by zinc fingers
US6794136B1 (en) 2000-11-20 2004-09-21 Sangamo Biosciences, Inc. Iterative optimization in the design of binding proteins
AU776576B2 (en) 1999-12-06 2004-09-16 Sangamo Biosciences, Inc. Methods of using randomized libraries of zinc finger proteins for the identification of gene function
US6689558B2 (en) 2000-02-08 2004-02-10 Sangamo Biosciences, Inc. Cells for drug discovery
US20020061512A1 (en) 2000-02-18 2002-05-23 Kim Jin-Soo Zinc finger domains and methods of identifying same
AU2001263155A1 (en) 2000-05-16 2001-11-26 Massachusetts Institute Of Technology Methods and compositions for interaction trap assays
JP2002060786A (ja) 2000-08-23 2002-02-26 Kao Corp 硬質表面用殺菌防汚剤
WO2002020500A2 (en) 2000-09-01 2002-03-14 Icos Corporation Materials and methods to potentiate cancer treatment
US7067317B2 (en) 2000-12-07 2006-06-27 Sangamo Biosciences, Inc. Regulation of angiogenesis with zinc finger proteins
CA2441931A1 (en) 2001-03-23 2002-10-03 Douglas A. Levinson Method and system for high-throughput screening
GB0108491D0 (en) 2001-04-04 2001-05-23 Gendaq Ltd Engineering zinc fingers
US6589591B1 (en) 2001-07-10 2003-07-08 Baylor College Of Medicine Method for treating medical devices using glycerol and an antimicrobial agent
JP2005500061A (ja) 2001-08-20 2005-01-06 ザ スクリップス リサーチ インスティテュート Ｃｎｎについての亜鉛フィンガー結合ドメイン
US7262054B2 (en) 2002-01-22 2007-08-28 Sangamo Biosciences, Inc. Zinc finger proteins for DNA binding and gene regulation in plants
WO2003087341A2 (en) 2002-01-23 2003-10-23 The University Of Utah Research Foundation Targeted chromosomal mutagenesis using zinc finger nucleases
US7074596B2 (en) 2002-03-25 2006-07-11 Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College Synthesis and use of anti-reverse mRNA cap analogues
US7361635B2 (en) 2002-08-29 2008-04-22 Sangamo Biosciences, Inc. Simultaneous modulation of multiple genes
WO2004085418A2 (en) 2003-03-24 2004-10-07 Luitpold Pharmaceuticals, Inc. Xanthones, thioxanthones and acridinones as dna-pk inhibitors
US8409861B2 (en) 2003-08-08 2013-04-02 Sangamo Biosciences, Inc. Targeted deletion of cellular DNA sequences
US20070134796A1 (en) 2005-07-26 2007-06-14 Sangamo Biosciences, Inc. Targeted integration and expression of exogenous nucleic acid sequences
US7888121B2 (en) 2003-08-08 2011-02-15 Sangamo Biosciences, Inc. Methods and compositions for targeted cleavage and recombination
US7972854B2 (en) 2004-02-05 2011-07-05 Sangamo Biosciences, Inc. Methods and compositions for targeted cleavage and recombination
AU2005232665B2 (en) 2004-04-08 2010-05-13 Sangamo Therapeutics, Inc. Methods and compositions for treating neuropathic and neurodegenerative conditions
US7253273B2 (en) 2004-04-08 2007-08-07 Sangamo Biosciences, Inc. Treatment of neuropathic pain with zinc finger proteins
EP2027262B1 (en) 2006-05-25 2010-03-31 Sangamo Biosciences Inc. Variant foki cleavage half-domains
CN104072561B (zh) 2007-06-19 2017-12-22 路易斯安那州州立大学及农业机械学院管理委员会 信使rna帽的抗‑反向硫代磷酸类似物的合成和用途
EP2315829B1 (en) 2008-08-08 2015-02-11 Mayo Foundation For Medical Education And Research Induced pluripotent stem cells
ES2751916T3 (es) 2010-02-08 2020-04-02 Sangamo Therapeutics Inc Semidominios de escisión genomanipulados
DE102011118830A1 (de) 2011-11-18 2013-05-23 Merck Patent Gmbh Morpholinylbenzotriazine
WO2013130824A1 (en) 2012-02-29 2013-09-06 Sangamo Biosciences, Inc. Methods and compositions for treating huntington's disease
MX371331B (es) 2012-04-24 2020-01-27 Vertex Pharma Inhibidores de la proteina cinasa dependiente de acido desoxirribonucleico(adn-pk).
AU2013266968B2 (en) 2012-05-25 2017-06-29 Emmanuelle CHARPENTIER Methods and compositions for RNA-directed target DNA modification and for RNA-directed modulation of transcription
AU2013293270B2 (en) 2012-07-25 2018-08-16 Massachusetts Institute Of Technology Inducible DNA binding proteins and genome perturbation tools and applications thereof
US9181535B2 (en) 2012-09-24 2015-11-10 The Chinese University Of Hong Kong Transcription activator-like effector nucleases (TALENs)
US20140310830A1 (en) 2012-12-12 2014-10-16 Feng Zhang CRISPR-Cas Nickase Systems, Methods And Compositions For Sequence Manipulation in Eukaryotes
IL239344B2 (en) 2012-12-12 2024-06-01 Broad Inst Inc Systems engineering, methods and optimal guiding components for sequence manipulation
CN113355357B (zh) 2012-12-12 2024-12-03 布罗德研究所有限公司 对用于序列操纵的改进的系统、方法和酶组合物进行的工程化和优化
EP2840140B2 (en) 2012-12-12 2023-02-22 The Broad Institute, Inc. Crispr-Cas based method for mutation of prokaryotic cells
US20140186843A1 (en) 2012-12-12 2014-07-03 Massachusetts Institute Of Technology Methods, systems, and apparatus for identifying target sequences for cas enzymes or crispr-cas systems for target sequences and conveying results thereof
WO2014093709A1 (en) 2012-12-12 2014-06-19 The Broad Institute, Inc. Methods, models, systems, and apparatus for identifying target sequences for cas enzymes or crispr-cas systems for target sequences and conveying results thereof
EP2931899A1 (en) 2012-12-12 2015-10-21 The Broad Institute, Inc. Functional genomics using crispr-cas systems, compositions, methods, knock out libraries and applications thereof
EP3031921B1 (en) 2012-12-12 2025-03-12 The Broad Institute, Inc. Delivery, engineering and optimization of systems, methods and compositions for sequence manipulation and therapeutic applications
WO2014093655A2 (en) 2012-12-12 2014-06-19 The Broad Institute, Inc. Engineering and optimization of systems, methods and compositions for sequence manipulation with functional domains
US8697359B1 (en) 2012-12-12 2014-04-15 The Broad Institute, Inc. CRISPR-Cas systems and methods for altering expression of gene products
US10227610B2 (en) 2013-02-25 2019-03-12 Sangamo Therapeutics, Inc. Methods and compositions for enhancing nuclease-mediated gene disruption
US11332719B2 (en) 2013-03-15 2022-05-17 The Broad Institute, Inc. Recombinant virus and preparations thereof
US20160040155A1 (en) 2013-04-16 2016-02-11 University Of Washington Through Its Center For Commercialization Activating an alternative pathway for homology-directed repair to stimulate targeted gene correction and genome engineering
DE102013008118A1 (de) 2013-05-11 2014-11-13 Merck Patent Gmbh Arylchinazoline
WO2014204724A1 (en) 2013-06-17 2014-12-24 The Broad Institute Inc. Delivery, engineering and optimization of tandem guide systems, methods and compositions for sequence manipulation
RU2716420C2 (ru) 2013-06-17 2020-03-11 Те Брод Инститьют Инк. Доставка и применение систем crispr-cas, векторов и композиций для целенаправленного воздействия и терапии в печени
MX374532B (es) 2013-06-17 2025-03-06 Broad Inst Inc Suministro, uso y aplicaciones terapéuticas de los sistemas y composiciones crispr-cas, para actuar sobre trastornos y enfermedades utilizando componentes víricos.
CN105492611A (zh) 2013-06-17 2016-04-13 布罗德研究所有限公司 用于序列操纵的优化的crispr-cas双切口酶系统、方法以及组合物
CN105683379A (zh) 2013-06-17 2016-06-15 布罗德研究所有限公司 用于对有丝分裂后细胞的疾病和障碍进行靶向和建模的系统、方法和组合物的递送、工程化和优化
EP3725885A1 (en) 2013-06-17 2020-10-21 The Broad Institute, Inc. Functional genomics using crispr-cas systems, compositions methods, screens and applications thereof
WO2014204723A1 (en) 2013-06-17 2014-12-24 The Broad Institute Inc. Oncogenic models based on delivery and use of the crispr-cas systems, vectors and compositions
KR101448678B1 (ko) 2013-08-12 2014-10-08 김형기 단추 재봉실의 뿌리감기 장치
US20150095137A1 (en) 2013-09-27 2015-04-02 Stout Partners LP System and apparatus for effective coordination and scheduling of accesses to rate limited online sites to obtain data for use in assessing social metrics based on domain tailored evaluation of social media exposure
WO2015048577A2 (en) 2013-09-27 2015-04-02 Editas Medicine, Inc. Crispr-related methods and compositions
JP6408569B2 (ja) 2013-10-17 2018-10-17 バーテックス ファーマシューティカルズ インコーポレイテッドＶｅｒｔｅｘ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｉｎｃｏｒｐｏｒａｔｅｄ Ｄｎａ−ｐｋ阻害剤としての（ｓ）−ｎ−メチル−８−（１−（（２’−メチル−［４，５’−ビピリミジン］−６−イル）アミノ）プロパン−２−イル）キノリン−４−カルボキサミドおよびその重水素化誘導体の共結晶
HRP20180804T1 (hr) 2013-10-17 2018-08-10 Vertex Pharmaceuticals Incorporated Inhibitori dnk-pk
AU2014353006B2 (en) 2013-11-20 2019-04-04 Signalchem Life Sciences Corp. Quinazoline derivatives as TAM family kinase inhibitors
WO2015168079A1 (en) 2014-04-29 2015-11-05 Infinity Pharmaceuticals, Inc. Pyrimidine or pyridine derivatives useful as pi3k inhibitors
WO2016028682A1 (en) 2014-08-17 2016-02-25 The Broad Institute Inc. Genome editing using cas9 nickases
KR102531016B1 (ko) 2014-11-21 2023-05-10 리제너론 파마슈티칼스 인코포레이티드 쌍 형성된 가이드 rna를 사용하는 표적화된 유전자 변형을 위한 방법 및 조성물
EP3433362B1 (en) 2016-03-23 2021-05-05 Dana-Farber Cancer Institute, Inc. Methods for enhancing the efficiency of gene editing
MA45670A (fr) 2016-07-13 2019-05-22 Vertex Pharma Procédés, compositions et kits pour augmenter l'efficacité d'édition du génome
EP3388517A1 (en) 2017-04-10 2018-10-17 Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. Compounds for increasing genome editing efficiency
KR102537447B1 (ko) 2017-04-10 2023-05-30 막스-플랑크-게젤샤프트 츄어 푀르더룽 데어 비쎈샤프텐 에.파우. 유전체 편집 효율 증가를 위한 화합물
MA51619A (fr) 2018-01-17 2021-04-14 Vertex Pharma Inhibiteurs de la protéine kinase dépendante de l'adn
JP7466448B2 (ja) 2018-01-17 2024-04-12 バーテックス ファーマシューティカルズ インコーポレイテッド Ｄｎａ－ｐｋ阻害剤
BR112020013626A2 (pt) 2018-01-17 2020-12-01 Vertex Pharmaceuticals Incorporated compostos de quinoxalinona, composições, métodos e kits para aumentar a eficiência de edição de genoma

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014159690A1 (en) * 2013-03-12 2014-10-02 Vertex Pharmaceuticals Incorporated Dna-pk inhibitors

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