IL217915A0 - Treatment of astrocytes-tumor cells with inhibitors of endothelin receptors - Google Patents

Treatment of astrocytes-tumor cells with inhibitors of endothelin receptors

Info

Publication number
IL217915A0
IL217915A0 IL217915A IL21791512A IL217915A0 IL 217915 A0 IL217915 A0 IL 217915A0 IL 217915 A IL217915 A IL 217915A IL 21791512 A IL21791512 A IL 21791512A IL 217915 A0 IL217915 A0 IL 217915A0
Authority
IL
Israel
Prior art keywords
astrocytes
inhibitors
treatment
tumor cells
endothelin receptors
Prior art date
Application number
IL217915A
Other languages
English (en)
Original Assignee
Univ Texas
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=42938154&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=IL217915(A0) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Univ Texas filed Critical Univ Texas
Publication of IL217915A0 publication Critical patent/IL217915A0/en

Links

Classifications

    • 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
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
    • 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
    • A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
    • A01K67/027—New or modified breeds of vertebrates
    • 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
    • A61K31/4188—1,3-Diazoles condensed with other heterocyclic ring systems, e.g. biotin, sorbinil
    • 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
    • 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
    • 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
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/10—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
    • A61N5/1077—Beam delivery systems
    • A61N5/1084—Beam delivery systems for delivering multiple intersecting beams at the same time, e.g. gamma knives
    • 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
    • A61P35/00—Antineoplastic agents
    • A61P35/04—Antineoplastic agents specific for metastasis
    • 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
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • C12N5/0618—Cells of the nervous system
    • C12N5/0622—Glial cells, e.g. astrocytes, oligodendrocytes; Schwann cells
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • C12N5/0693—Tumour cells; Cancer cells
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2227/00—Animals characterised by species
    • A01K2227/10—Mammal
    • A01K2227/105—Murine
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2267/00—Animals characterised by purpose
    • A01K2267/03—Animal model, e.g. for test or diseases
    • A01K2267/0331—Animal model for proliferative diseases
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2502/00—Coculture with; Conditioned medium produced by
    • C12N2502/08—Coculture with; Conditioned medium produced by cells of the nervous system
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2502/00—Coculture with; Conditioned medium produced by
    • C12N2502/30—Coculture with; Conditioned medium produced by tumour cells

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Biomedical Technology (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biotechnology (AREA)
  • Organic Chemistry (AREA)
  • Zoology (AREA)
  • Genetics & Genomics (AREA)
  • Wood Science & Technology (AREA)
  • Cell Biology (AREA)
  • Immunology (AREA)
  • Microbiology (AREA)
  • Biochemistry (AREA)
  • Hematology (AREA)
  • General Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Urology & Nephrology (AREA)
  • Pathology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Environmental Sciences (AREA)
  • Oncology (AREA)
  • General Physics & Mathematics (AREA)
  • Neurology (AREA)
  • Physics & Mathematics (AREA)
  • Toxicology (AREA)
  • Food Science & Technology (AREA)
  • Neurosurgery (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Analytical Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
IL217915A 2009-08-10 2012-02-02 Treatment of astrocytes-tumor cells with inhibitors of endothelin receptors IL217915A0 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US23268709P 2009-08-10 2009-08-10
PCT/US2010/044832 WO2011019630A2 (en) 2009-08-10 2010-08-09 Treatment of astrocytes-tumor cells with inhibitors of endothelin receptors

Publications (1)

Publication Number Publication Date
IL217915A0 true IL217915A0 (en) 2012-03-29

Family

ID=42938154

Family Applications (1)

Application Number Title Priority Date Filing Date
IL217915A IL217915A0 (en) 2009-08-10 2012-02-02 Treatment of astrocytes-tumor cells with inhibitors of endothelin receptors

Country Status (27)

Country Link
US (2) US8999934B2 (enExample)
EP (1) EP2464218B1 (enExample)
JP (1) JP2013501791A (enExample)
KR (1) KR20120088665A (enExample)
CN (1) CN102510719B (enExample)
AU (1) AU2010282744B2 (enExample)
BR (1) BR112012003103A2 (enExample)
CA (1) CA2770397A1 (enExample)
CL (1) CL2012000333A1 (enExample)
DK (1) DK2464218T3 (enExample)
EA (1) EA023864B1 (enExample)
ES (1) ES2543280T3 (enExample)
HR (1) HRP20150890T1 (enExample)
HU (1) HUE026005T2 (enExample)
IL (1) IL217915A0 (enExample)
IN (1) IN2012DN01261A (enExample)
MA (1) MA33571B1 (enExample)
MX (1) MX2012001562A (enExample)
NZ (1) NZ598078A (enExample)
PL (1) PL2464218T3 (enExample)
PT (1) PT2464218E (enExample)
SG (1) SG178828A1 (enExample)
SI (1) SI2464218T1 (enExample)
TN (1) TN2012000054A1 (enExample)
TW (1) TWI483938B (enExample)
WO (1) WO2011019630A2 (enExample)
ZA (1) ZA201200980B (enExample)

Families Citing this family (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TW201309298A (zh) * 2011-02-04 2013-03-01 Actelion Pharmaceuticals Ltd 治療惡性神經膠質瘤之醫藥組合物
CA2840170A1 (en) * 2011-06-21 2012-12-27 The Johns Hopkins University Focused radiation for augmenting immune-based therapies against neoplasms
HK1249052A1 (zh) 2015-03-06 2018-10-26 BeyondSpring Pharmaceuticals Inc. 治疗与ras突变相关的癌症的方法
WO2016144636A1 (en) * 2015-03-06 2016-09-15 Beyondspring Pharmaceuticals, Inc. Method of treating a brain tumor
EP3334726B1 (en) 2015-07-13 2022-03-16 Beyondspring Pharmaceuticals, Inc. Plinabulin compositions
CN116726183A (zh) 2015-08-03 2023-09-12 Enb治疗公司 用于治疗与etbr激活相关的癌症的组合物和方法
JP6996728B2 (ja) * 2016-01-07 2022-01-17 学校法人自治医科大学 グルコーストランスポーター１発現用アデノ随伴ウイルスベクター
US10912748B2 (en) 2016-02-08 2021-02-09 Beyondspring Pharmaceuticals, Inc. Compositions containing tucaresol or its analogs
WO2017209272A1 (ja) * 2016-06-03 2017-12-07 国立大学法人東京大学 がん転移阻害剤
CN109475524A (zh) 2016-06-06 2019-03-15 万春药业公司 用于减少中性粒细胞减少症的组合物和方法
WO2018129381A1 (en) 2017-01-06 2018-07-12 Beyondspring Pharmaceuticals, Inc. Tubulin binding compounds and therapeutic use thereof
KR20190109479A (ko) 2017-02-01 2019-09-25 비욘드스프링 파마수티컬스, 인코포레이티드. 호중구감소증의 감소 방법
SG11201908472VA (en) 2017-02-15 2019-10-30 Univ California Compositions and methods for activating nk cells
WO2019140324A1 (en) 2018-01-12 2019-07-18 Enb Therapeutics, Inc. Deuterated compounds, compositions, and methods for treating cancers associated with etbr activation
WO2019147615A1 (en) 2018-01-24 2019-08-01 Beyondspring Pharmaceuticals, Inc. Composition and method for reducing thrombocytopenia via the administration of plinabulin
CN109232546B (zh) 2018-09-25 2020-09-04 中国人民解放军总医院 一种嘧啶磺酰胺类衍生物的医药用途
PL3974421T3 (pl) 2019-05-22 2024-11-04 Wuxi Biocity Biopharmaceutics Co., Ltd. Krystaliczna postać związku sulfonamidu pirymidyny i sposób jego otrzymywania
CN112062857B (zh) * 2019-06-10 2024-08-09 鸿运华宁（杭州）生物医药有限公司 Eta抗体与bnp的融合蛋白质，及其药物组合物和应用
AU2020355109B2 (en) * 2019-09-25 2025-06-12 The Board Of Trustees Of The Leland Stanford Junior University Thalamic input to orbitofrontal cortex drives brain-wide, frequency-dependent inhibition mediated by GABA and zona incerta
EP4319751A4 (en) 2021-04-09 2025-02-26 Beyondspring Pharmaceuticals, Inc. THERAPEUTIC COMPOSITIONS AND METHODS FOR THE TREATING OF TUMORS

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1693372A1 (en) 2000-12-18 2006-08-23 Actelion Pharmaceuticals Ltd. Novel Sulfamides and their use as endothelin receptor antagonists
GB0223854D0 (en) * 2002-10-12 2002-11-20 Astrazeneca Ab Therapeutic treatment
US20050043233A1 (en) * 2003-04-29 2005-02-24 Boehringer Ingelheim International Gmbh Combinations for the treatment of diseases involving cell proliferation, migration or apoptosis of myeloma cells or angiogenesis
US20060058311A1 (en) * 2004-08-14 2006-03-16 Boehringer Ingelheim International Gmbh Combinations for the treatment of diseases involving cell proliferation
ES2393117T3 (es) 2005-09-12 2012-12-18 Actelion Pharmaceuticals Ltd. Composición farmacéutica estable que comprende una pirimidina-sulfamida
MX2010008994A (es) 2008-02-20 2010-09-07 Actelion Pharmaceuticals Ltd Combinacion que comprende paclitaxel para el tratamiento del cancer de ovario.
TW201309298A (zh) 2011-02-04 2013-03-01 Actelion Pharmaceuticals Ltd 治療惡性神經膠質瘤之醫藥組合物

Also Published As

Publication number Publication date
MX2012001562A (es) 2013-01-29
EP2464218A2 (en) 2012-06-20
TWI483938B (zh) 2015-05-11
WO2011019630A2 (en) 2011-02-17
SG178828A1 (en) 2012-04-27
ZA201200980B (en) 2012-10-31
CL2012000333A1 (es) 2013-01-25
TN2012000054A1 (en) 2013-09-19
JP2013501791A (ja) 2013-01-17
WO2011019630A3 (en) 2011-06-03
EP2464218B1 (en) 2015-05-27
US20120144510A1 (en) 2012-06-07
ES2543280T3 (es) 2015-08-17
CN102510719B (zh) 2015-07-22
AU2010282744A1 (en) 2012-03-22
EA023864B1 (ru) 2016-07-29
KR20120088665A (ko) 2012-08-08
CA2770397A1 (en) 2011-02-17
US20150352113A1 (en) 2015-12-10
PL2464218T3 (pl) 2015-12-31
TW201109315A (en) 2011-03-16
SI2464218T1 (sl) 2015-10-30
IN2012DN01261A (enExample) 2015-05-15
HK1171336A1 (en) 2013-03-28
NZ598078A (en) 2013-07-26
PT2464218E (pt) 2015-09-16
EA201270264A1 (ru) 2013-02-28
HRP20150890T1 (hr) 2015-09-25
CN102510719A (zh) 2012-06-20
AU2010282744B2 (en) 2014-08-28
MA33571B1 (fr) 2012-09-01
BR112012003103A2 (pt) 2016-04-19
US8999934B2 (en) 2015-04-07
DK2464218T3 (en) 2015-07-20
HUE026005T2 (en) 2016-04-28

Similar Documents

Publication Publication Date Title
ZA201700326B (en) Inhibitors of beta-secretase
SG10201802522SA (en) Treatment of pluripotent cells
ZA201109340B (en) Pyrimidinones as pi3k inhibitors
ZA201005236B (en) Electrode and electrode coating
GB0911566D0 (en) T cell receptors
EP2438246A4 (en) CONSTRUCTION ASPECTS
BR112012003103A2 (pt) tratamento de células de astrócitos tumorais com inibidor de receptores de endotelina
GB0915515D0 (en) Treatment of vasculoproliferative conditions
IL218018A0 (en) Novel n-substituted-pyrrolidines as inhibitors of mdm2-p-53 interactions
ZA201206456B (en) Uses of dgati inhibitors
PL2393919T3 (pl) Nowa ciągła ludzka linia komórkowa
PT2506840T (pt) Utilizações de inibidores de fatores induzíveis de hipoxia
EP2496230A4 (en) INHIBITORS OF IRE-1 ALPHA
EP2455088A4 (en) INHIBITOR OF LIFT OF TRIGLYCERIDE RATE IN BLOOD
IL217756A0 (en) Inhibitors of jnk
EP2398484A4 (en) Inhibition of multiple cell activation signals
FI20095792L (fi) Ihmissolujen käyttö
TWM372743U (en) Improved structure of Kendama
TWM365675U (en) Improved structure of teapoy
GB0908609D0 (en) New use of isoQC inhibitors
IL200674A0 (en) Solar arrangement and method of use
TWM372203U (en) Structure of goggles
TWM374127U (en) Structure of three-string Huqin
GB201012495D0 (en) Targeted differntiation of stem cells
GB0902661D0 (en) Inhibitors