JP2017514806A5 - - Google Patents

Download PDF

Info

Publication number
JP2017514806A5
JP2017514806A5 JP2016562773A JP2016562773A JP2017514806A5 JP 2017514806 A5 JP2017514806 A5 JP 2017514806A5 JP 2016562773 A JP2016562773 A JP 2016562773A JP 2016562773 A JP2016562773 A JP 2016562773A JP 2017514806 A5 JP2017514806 A5 JP 2017514806A5
Authority
JP
Japan
Prior art keywords
cancer
pharmaceutical composition
kinase
group
inhibitor
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
JP2016562773A
Other languages
English (en)
Japanese (ja)
Other versions
JP2017514806A (ja
Filing date
Publication date
Application filed filed Critical
Priority claimed from PCT/US2015/025843 external-priority patent/WO2015160868A1/en
Publication of JP2017514806A publication Critical patent/JP2017514806A/ja
Publication of JP2017514806A5 publication Critical patent/JP2017514806A5/ja
Pending legal-status Critical Current

Links

JP2016562773A 2014-04-16 2015-04-15 Torキナーゼ阻害剤組み合わせ療法を使用して癌を治療する方法 Pending JP2017514806A (ja)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201461980124P 2014-04-16 2014-04-16
US61/980,124 2014-04-16
PCT/US2015/025843 WO2015160868A1 (en) 2014-04-16 2015-04-15 Methods for treating cancer using tor kinase inhibitor combination therapy

Related Child Applications (1)

Application Number Title Priority Date Filing Date
JP2019001134A Division JP6838085B2 (ja) 2014-04-16 2019-01-08 Torキナーゼ阻害剤組み合わせ療法を使用して癌を治療する方法

Publications (2)

Publication Number Publication Date
JP2017514806A JP2017514806A (ja) 2017-06-08
JP2017514806A5 true JP2017514806A5 (enExample) 2018-05-17

Family

ID=54321048

Family Applications (3)

Application Number Title Priority Date Filing Date
JP2016562773A Pending JP2017514806A (ja) 2014-04-16 2015-04-15 Torキナーゼ阻害剤組み合わせ療法を使用して癌を治療する方法
JP2019001134A Active JP6838085B2 (ja) 2014-04-16 2019-01-08 Torキナーゼ阻害剤組み合わせ療法を使用して癌を治療する方法
JP2020201107A Pending JP2021059548A (ja) 2014-04-16 2020-12-03 Torキナーゼ阻害剤組み合わせ療法を使用して癌を治療する方法

Family Applications After (2)

Application Number Title Priority Date Filing Date
JP2019001134A Active JP6838085B2 (ja) 2014-04-16 2019-01-08 Torキナーゼ阻害剤組み合わせ療法を使用して癌を治療する方法
JP2020201107A Pending JP2021059548A (ja) 2014-04-16 2020-12-03 Torキナーゼ阻害剤組み合わせ療法を使用して癌を治療する方法

Country Status (5)

Country Link
US (2) US9737535B2 (enExample)
EP (1) EP3131552B1 (enExample)
JP (3) JP2017514806A (enExample)
ES (1) ES2823756T3 (enExample)
WO (1) WO2015160868A1 (enExample)

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2016516815A (ja) * 2013-04-17 2016-06-09 シグナル ファーマシューティカルズ,エルエルシー 1−エチル−7−(2−メチル−6−(1H−1,2,4−トリアゾール−3−イル)ピリジン−3−イル)−3,4−ジヒドロピラジノ[2,3−b]ピラジン−2(1H)−オンに関する医薬製剤、プロセス、固形形態、及び使用方法
EP3033079B1 (en) 2013-08-12 2018-10-31 Pharmacyclics LLC Methods for the treatment of her2 amplified cancer
AU2015328121B2 (en) 2014-10-09 2019-11-21 Oncternal Therapeutics, Inc. Indolinone compounds and uses thereof
EP3436434B1 (en) 2016-03-31 2020-07-08 Oncternal Therapeutics, Inc. Indoline analogs and uses thereof
CN114569606B (zh) 2016-07-29 2024-04-19 英克特诺治疗公司 吲哚啉酮化合物的用途
MX394860B (es) * 2016-09-27 2025-03-24 Vertex Pharma Metodo para tratar cancer usando una combinacion de agentes que dañan adn e inhibidores de proteina cinasa dependiente de adn (adn-pk).
WO2018218633A1 (en) 2017-06-02 2018-12-06 Beijing Percans Oncology Co. Ltd. Combination therapies for treating cancers
AU2018289539B2 (en) * 2017-06-22 2024-07-04 Celgene Corporation Treatment of hepatocellular carcinoma characterized by hepatitis B virus infection
WO2019169389A1 (en) * 2018-03-02 2019-09-06 Epicentrx, Inc. Methods and compositions for treating cancer and sensitizing tumor cells to kinase inhibitors
WO2019195959A1 (en) 2018-04-08 2019-10-17 Cothera Biosciences, Inc. Combination therapy for cancers with braf mutation
WO2020036852A1 (en) 2018-08-13 2020-02-20 Beijing Percans Oncology Co. Ltd. Biomarkers for cancer therapy
CN114644643A (zh) * 2020-12-21 2022-06-21 南京大学 一类孪药及其合成方法和应用
CN113662942B (zh) * 2021-08-19 2023-02-07 中国人民解放军陆军军医大学第一附属医院 药物组合物及其在smo突变性髓母细胞瘤中的应用

Family Cites Families (96)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3507866A (en) 1967-08-08 1970-04-21 Merck & Co Inc 1h - imidazo(4,5-b)pyrazin - 2 - one and processes for their preparation
US3567725A (en) 1968-11-20 1971-03-02 Merck & Co Inc Process for preparation of 1h-imidazo-(4,5-b)pyrazin-2-ones
US4294836A (en) 1980-03-24 1981-10-13 Sterling Drug Inc. 1,3-Dihydro-6-(pyridinyl)-2H-imidazo[4,5-b]pyridin-2-ones and -imidazo[4,5-b]-pyridine-2-thiones and their cardiotonic use
US4317909A (en) 1980-03-24 1982-03-02 Sterling Drug Inc. Preparation of 1,3-dihydro-5-(pyridinyl)-2H-imidazo[4,5-b]pyridin-2-ones
US4294837A (en) 1980-03-28 1981-10-13 Sterling Drug Inc. 1,3-Dihydro-6-(pyridinyl)-2H-imidazo[4,5-b]pyridin-2-ones and -imidazo[4,5-b]pyridine-2-thiones and their cardiotonic use
US4309537A (en) 1980-03-28 1982-01-05 Sterling Drug Inc. Production of imidazo[4,5-b]pyridin-2-ones or thiones
GB8709448D0 (en) 1987-04-21 1987-05-28 Pfizer Ltd Heterobicyclic quinoline derivatives
JPS63275582A (ja) 1987-05-02 1988-11-14 Naade Kenkyusho:Kk 2−アミノイミダゾ〔4,5−b〕ピリジン誘導体の製造方法
DD262026A1 (de) 1987-07-10 1988-11-16 Akad Wissenschaften Ddr Verfahren zur herstellung von 4-substituierten 6-(pyrid-4-yl)-2,4-dihydro-1h-imidazo[4,5-b]pyrid-2-onen
FR2643903A1 (fr) 1989-03-03 1990-09-07 Union Pharma Scient Appl Nouveaux derives de benzimidazole, leurs procedes de preparation, intermediaires de synthese, compositions pharmaceutiques les contenant, utiles notamment pour le traitement des maladies cardiovasculaires, et des ulceres duodenaux
US4963561A (en) 1990-02-28 1990-10-16 Sterling Drug Inc. Imidazopyridines, their preparation and use
TW274550B (enExample) 1992-09-26 1996-04-21 Hoechst Ag
DE19601627A1 (de) 1996-01-18 1997-07-24 Bayer Ag Heteroatomhaltige Cyclopentanopyridyl-Oxazolidinone
US6031105A (en) 1996-04-09 2000-02-29 Pfizer Inc Substituted pyridines
WO1999016438A1 (en) 1997-09-26 1999-04-08 Asta Medica Aktiengesellschaft Azabenzimidazole-based compounds for modulating serine/threonine protein kinase function
ZA9810490B (en) 1997-12-03 1999-05-20 Dainippon Pharmaceutical Co 2-Aryl-8-oxodihydropurine derivative process for the preparation thereof pharmaceutical composition containing the same and intermediate therefor
JP2003146987A (ja) 1999-05-31 2003-05-21 Dainippon Pharmaceut Co Ltd 2−アリールプリン−9−アセトアミド誘導体
JP3814125B2 (ja) 1999-06-02 2006-08-23 大日本住友製薬株式会社 2−アリール−8−オキソジヒドロプリン誘導体からなる医薬
JP2002100363A (ja) 2000-09-25 2002-04-05 Mitsubishi Chemicals Corp リチウム二次電池用正極材料、リチウム二次電池用正極及びリチウム二次電池
JP2002167387A (ja) 2000-11-29 2002-06-11 Dainippon Pharmaceut Co Ltd 2−(7,8−ジヒドロ−8−オキソ−9h−プリン−9−イル)酢酸誘導体
EP1347982B1 (en) 2000-12-12 2005-11-16 Neurogen Corporation Spiro isobenzofuran-1,4'-piperidin]-3-ones and 3h-spiroisobenzofuran-1,4'-piperidines
WO2002076954A1 (en) 2001-03-23 2002-10-03 Smithkline Beecham Corporation Compounds useful as kinase inhibitors for the treatment of hyperproliferative diseases
NZ531928A (en) 2001-09-04 2005-10-28 Boehringer Ingelheim Pharma Novel dihydropteridinones, method for producing the same and the use thereof as medicaments
WO2003032989A1 (en) 2001-10-18 2003-04-24 Boehringer Ingelheim Pharmaceuticals, Inc. 1,4-disubstituted benzo-fused urea compounds as cytokine inhibitors
US7247621B2 (en) 2002-04-30 2007-07-24 Valeant Research & Development Antiviral phosphonate compounds and methods therefor
US20040063658A1 (en) 2002-05-06 2004-04-01 Roberts Christopher Don Nucleoside derivatives for treating hepatitis C virus infection
WO2004042002A2 (en) 2002-08-05 2004-05-21 University Of Massachusetts Compounds for modulating rna interference
AU2003270701B2 (en) 2002-10-31 2009-11-12 Amgen Inc. Antiinflammation agents
EP1590341B1 (en) 2003-01-17 2009-06-17 Warner-Lambert Company LLC 2-aminopyridine substituted heterocycles as inhibitors of cellular proliferation
CN101200457A (zh) 2003-02-26 2008-06-18 贝林格尔英格海姆法玛两合公司 二氢蝶啶酮、其制法及作为药物制剂的用途
GB2400101A (en) 2003-03-28 2004-10-06 Biofocus Discovery Ltd Compounds capable of binding to the active site of protein kinases
TW200503737A (en) 2003-04-23 2005-02-01 Wyeth Corp Water soluble wortmannin derivatives
HUE029877T2 (en) 2003-05-30 2017-04-28 Gilead Pharmasset Llc Modified fluorinated nucleoside analogues
ATE461196T1 (de) 2003-06-26 2010-04-15 Merck Sharp & Dohme Benzodiazepin-cgrp-rezeptor-antagonisten
CN101123968A (zh) 2004-06-04 2008-02-13 艾科斯有限公司 肥大细胞病的治疗方法
DE102004029784A1 (de) 2004-06-21 2006-01-05 Boehringer Ingelheim Pharma Gmbh & Co. Kg Neue 2-Benzylaminodihydropteridinone, Verfahren zur deren Herstellung und deren Verwendung als Arzneimittel
WO2006001266A1 (ja) 2004-06-23 2006-01-05 Banyu Pharmaceutical Co., Ltd. 2-アリールプリン誘導体の製造方法
GB0420719D0 (en) 2004-09-17 2004-10-20 Addex Pharmaceuticals Sa Novel allosteric modulators
CN101065016A (zh) 2004-09-24 2007-10-31 詹森药业有限公司 蛋白激酶的抑制剂咪唑并[4,5-b]吡嗪酮
CN101048410B (zh) 2004-10-29 2010-06-23 泰博特克药品有限公司 抑制hiv的双环嘧啶衍生物
US7855205B2 (en) 2004-10-29 2010-12-21 Janssen Pharmaceutica Nv Pyrimidinyl substituted fused-pyrrolyl compounds useful in treating kinase disorders
SE0403006D0 (sv) 2004-12-09 2004-12-09 Biovitrum Ab New compounds
WO2006065703A1 (en) 2004-12-13 2006-06-22 Sunesis Pharmaceuticals, Inc. Pyrido pyrimidinones, dihydro pyrimido pyrimidinones and pteridinones useful as raf kinase inhibitors
ATE398613T1 (de) 2005-02-16 2008-07-15 Astrazeneca Ab Chemische verbindungen
WO2006091737A1 (en) 2005-02-24 2006-08-31 Kemia, Inc. Modulators of gsk-3 activity
MX2007012393A (es) 2005-04-05 2008-02-22 Pharmacopeia Inc Derivados de purina e imidazopiridina para la inmunosupresion.
NZ561648A (en) * 2005-04-15 2009-11-27 Schering Corp Methods and composition of IGF1R inhibitors for treating or preventing cancer
US20090281075A1 (en) 2006-02-17 2009-11-12 Pharmacopeia, Inc. Isomeric purinones and 1h-imidazopyridinones as pkc-theta inhibitors
WO2007106503A2 (en) 2006-03-13 2007-09-20 Osi Pharmaceuticals, Inc. Combined treatment with an egfr kinase inhibitor and an agent that sensitizes tumor cells to the effects of egfr kinase inhibitors
BRPI0709750A2 (pt) * 2006-04-05 2011-07-26 Novartis Ag combinaÇÕes de agentes terapÊuticos para tratamento de cÂncer
US20090311249A1 (en) 2006-06-02 2009-12-17 Luca Gianni Capecitabine Combination Therapy
EP2995619B1 (en) 2006-08-02 2019-09-25 Cytokinetics, Inc. Certain chemical entities comprising imidazopyrimidines, compositions and methods
EP2364702A3 (en) 2006-09-05 2012-01-25 Emory University Kinase inhibitors for preventing or treating pathogen infection and method of use thereof
WO2008030744A2 (en) 2006-09-05 2008-03-13 Board Of Regents, The University Of Texas System Inhibitors of c-met and uses thereof
CL2007002866A1 (es) 2006-10-04 2008-07-04 Pharmacopeia Inc Compuestos derivados de 6-sustituidos-2-(bencimidazolil) purina y purinona; composicion farmaceutica que comprende a dicho compuesto; y uso del compuesto en el tratamiento de enfermedades autoinmunes, enfermedad inflamatoria, enfermedad mediada por m
US7902187B2 (en) 2006-10-04 2011-03-08 Wyeth Llc 6-substituted 2-(benzimidazolyl)purine and purinone derivatives for immunosuppression
ZA200902384B (en) 2006-10-19 2010-07-28 Signal Pharm Llc Heteroaryl compounds, compositions thereof, and use thereof as protein kinase inhibitors
EP2090577B1 (en) 2006-10-19 2017-04-05 Signal Pharmaceuticals, LLC Heteroaryl compounds, compositions thereof, and their use as protein kinase inhibitors
PE20090368A1 (es) * 2007-06-19 2009-04-28 Boehringer Ingelheim Int Anticuerpos anti-igf
WO2009008992A2 (en) 2007-07-06 2009-01-15 Osi Pharmaceuticals Inc. Combination anti-cancer therapy comprising an inhibitor of both mtorc1 and mt0rc2
EP2219646A4 (en) 2007-12-21 2010-12-22 Univ Rochester PROCESS FOR EXTENDING THE LIFE OF EUKARYOTIC ORGANISMS
CA2715181A1 (en) 2008-02-21 2009-08-27 Astrazeneca Ab Combination therapy 238
CA2990929C (en) * 2008-03-18 2022-04-12 Genentech, Inc. Combinations of an anti-her2 antibody-drug conjugate and chemotherapeutic agents, and methods of use
CA2726691C (en) * 2008-07-25 2016-11-08 Infocom Corporation Use of oncogene nrf2 for cancer prognosis
US8110578B2 (en) 2008-10-27 2012-02-07 Signal Pharmaceuticals, Llc Pyrazino[2,3-b]pyrazine mTOR kinase inhibitors for oncology indications and diseases associated with the mTOR/PI3K/Akt pathway
EP3037421A3 (en) 2008-11-25 2016-11-30 University Of Rochester Mlk inhibitors and methods of use
EP2396007A1 (en) 2009-02-10 2011-12-21 Celgene International Sarl Methods for treating non-small cell lung cancer using 5-azacytidine
ES2557316T3 (es) * 2009-09-08 2016-01-25 F. Hoffmann-La Roche Ag Compuestos de piridín-3-il-carboxamida 4-sustituidos y métodos de utilización
CA2778615C (en) 2009-10-26 2019-04-23 Signal Pharmaceuticals, Llc Methods of synthesis and purification of heteroaryl compounds
WO2011057222A1 (en) * 2009-11-06 2011-05-12 Infinity Pharmaceuticals, Inc. Oral formulations of a hedgehog pathway inhibitor
AU2010321773A1 (en) * 2009-11-20 2012-06-14 Infinity Pharmaceuticals, Inc. Methods and compositions for treating hedgehog-associated cancers
EP2531194B1 (en) 2010-02-03 2018-04-18 Signal Pharmaceuticals, LLC Identification of lkb1 mutation as a predictive biomarker for sensitivity to tor kinase inhibitors
US20120028972A1 (en) 2010-07-30 2012-02-02 Lilly Wong Biomarker assays for detecting or measuring inhibition of tor kinase activity
CA2828483A1 (en) 2011-02-23 2012-11-01 Intellikine, Llc Combination of kinase inhibitors and uses thereof
CA2837840C (en) * 2011-06-10 2020-08-04 Mersana Therapeutics, Inc. Protein-polymer-drug conjugates
CN105039520A (zh) 2011-08-03 2015-11-11 西格诺药品有限公司 作为lkb1状态的预测性生物标志物的基因表达谱的鉴定
ES2894958T3 (es) 2011-10-19 2022-02-16 Signal Pharm Llc Tratamiento del cáncer con inhibidores de la quinasa TOR
US10400284B2 (en) * 2011-11-25 2019-09-03 Integragen Method for predicting responsiveness to a treatment with an EGFR inhibitor
UA114496C2 (uk) 2011-12-02 2017-06-26 Сігнал Фармасьютікалз, Елелсі ФАРМАЦЕВТИЧНІ КОМПОЗИЦІЇ 7-(6-(2-ГІДРОКСИПРОПАН-2-ІЛ)ПІРИДИН-3-ІЛ)-1-((ТРАНС)-4-МЕТОКСИЦИКЛОГЕКСИЛ)-3,4-ДИГІДРОПІРАЗИНО[2,3-b]ПІРАЗИН-2(1H)-ОНУ, ЇХ ТВЕРДІ ФОРМИ І СПОСОБИ ЇХ ЗАСТОСУВАННЯ
CN104271159B (zh) 2012-02-24 2017-11-28 西格诺药品有限公司 利用tor激酶抑制剂联合治疗来治疗非小细胞肺癌的方法
TWI583385B (zh) 2012-03-15 2017-05-21 標誌製藥公司 使用tor之激酶抑制劑之癌症治療
SG11201405724RA (en) 2012-03-15 2014-10-30 Signal Pharm Llc Treatment of cancer with tor kinase inhibitors
KR20200034818A (ko) 2012-03-15 2020-03-31 시그날 파마소티칼 엘엘씨 Tor 키나제 억제제를 사용한 암의 치료
EA028062B1 (ru) 2012-03-15 2017-10-31 СИГНАЛ ФАРМАСЬЮТИКАЛЗ, ЭлЭлСи Лечение рака ингибиторами tor киназы
AU2013202768B2 (en) 2012-10-18 2015-11-05 Signal Pharmaceuticals, Llc Treatment of cancer with TOR kinase inhibitors
AU2013203714B2 (en) 2012-10-18 2015-12-03 Signal Pharmaceuticals, Llc Inhibition of phosphorylation of PRAS40, GSK3-beta or P70S6K1 as a marker for TOR kinase inhibitory activity
BR112015026021A2 (pt) * 2013-04-17 2017-07-25 Signal Pharm Llc terapia de combinação compreendendo um inibidor de tor quinase e n-(3-(5-flúor-2-(4-(2-met-oxietoxi)fenilamino)pirimidin-4-ilamino)fenil)acrilamida para o tratamento de câncer
BR112015026006B1 (pt) 2013-04-17 2022-10-18 Signal Pharmaceuticals, Llc Uso de um composto em combinação com um fármaco imunomodulador imid® para tratamento ou prevenção de um câncer, composição farmacêutica e kit compreendendo os referidos compostos
WO2014172431A1 (en) 2013-04-17 2014-10-23 Signal Pharmaceuticals, Llc Combination therapy comprising a dihydropyrazino-pyrazine compound and an androgen receptor antagonist for treating prostate cancer
HK1221150A1 (zh) 2013-04-17 2017-05-26 西格诺药品有限公司 用二氢吡嗪并-吡嗪类对癌症的治疗
WO2014172436A1 (en) 2013-04-17 2014-10-23 Signal Pharmaceuticals, Llc Combination therapy comprising a tor kinase inhibitor and a 5-substituted quinazolinone compound for treating cancer
WO2014172424A1 (en) 2013-04-17 2014-10-23 Signal Pharmaceuticals, Llc Treatment of cancer with dihydropyrazino-pyrazines
BR112015026238A8 (pt) 2013-04-17 2019-12-24 Signal Pharm Llc composto dihidropirazino-pirazina, composição farmacêutica que o compreende, uso do composto, métodos para inibir ou medir a fosforilação e para inibir a atividade da proteína quinase, bem como kit
TWI631949B (zh) 2013-04-17 2018-08-11 標誌製藥公司 使用tor激酶抑制劑組合療法以治療癌症之方法
US20150099754A1 (en) 2013-10-04 2015-04-09 Signal Pharmaceuticals, Llc Treatment of cancer characterized by gene mutations
US9415049B2 (en) * 2013-12-20 2016-08-16 Celgene Avilomics Research, Inc. Heteroaryl compounds and uses thereof

Similar Documents

Publication Publication Date Title
JP2017514806A5 (enExample)
JP2019070012A5 (enExample)
AU2014248568B2 (en) Compounds for treatment of cancer
JP2022058398A (ja) Braf-v600関連疾患の治療に使用するためのplx-8394またはplx-7904
KR20210087440A (ko) 삼중 음성 유방암의 치료를 위한 병용 요법
Yamada et al. Emergence of TNIK inhibitors in cancer therapeutics
JP2014097929A5 (enExample)
JP2015520753A5 (enExample)
EA201591738A1 (ru) Пиридиновые производные в качестве ингибиторов реаранжированной в процессе трансфекции (ret) киназы
ES2688809T3 (es) Combinaciones de compuestos inhibidores de AKT y MEK para tratar el cáncer
JP2016533366A5 (enExample)
HRP20191593T1 (hr) 1-((3s,4r)-4-(3-fluorfenil)-1-(2-metoksietil)pirolidin-3-il)-3-(4-metil-3-(2-metilpirimidin-5-il)-1-fenil-1h-pirazol-5-il)urea kao inhibitor trka kinaze
EA201790546A1 (ru) Производные пиридона в качестве ингибиторов киназы, реаранжированной во время трансфекции (ret)
RU2016110874A (ru) Комбинация ингибитора alk и ингибитора cdk для лечения клеточных пролиферативных заболеваний
JP2015512398A5 (enExample)
ES2917526T3 (es) Compuestos de aminonaptoquinona y composición farmacéutica para bloquear el sistema ubiquitinación-proteasoma en enfermedades
JP2013528215A5 (enExample)
CN106573000B (zh) 作为抗癌药物的芳基胺取代的喹喔啉
EP3125901B1 (en) Derivatives of cephalosporin for treating cancer
WO2024209717A1 (ja) 腫瘍治療用医薬組成物
JP2017514805A5 (enExample)
RU2016135413A (ru) Фармацевтические комбинации, включающие ингибитор pi3k, для лечения рака
Zhang et al. Synthesis and Biological Activity of Multi-targeting Platinum (Ⅱ) Anticancer Complexes
RU2020140303A (ru) Композиция и способ для лечения рака, связанного с мутацией egfr
Sackett et al. 20 Inhibitors Targeting