JO3413B1 - مشتقات نافثيريدين في صورة مضادات ألفا v بيتا 6 إنتيجرين لعلاج الأمراض الليفية e.g - Google Patents

مشتقات نافثيريدين في صورة مضادات ألفا v بيتا 6 إنتيجرين لعلاج الأمراض الليفية e.g

Info

Publication number
JO3413B1
JO3413B1 JOP/2015/0234A JOP20150234A JO3413B1 JO 3413 B1 JO3413 B1 JO 3413B1 JO P20150234 A JOP20150234 A JO P20150234A JO 3413 B1 JO3413 B1 JO 3413B1
Authority
JO
Jordan
Prior art keywords
span
dir
rtl
naphthyridine
derrivatives
Prior art date
Application number
JOP/2015/0234A
Other languages
Arabic (ar)
English (en)
Inventor
Paul Hancock Ashley
Martin Pritchard John
Andrew Anderson Niall
Howard James Campbell-Crawford Matthew
Mary Redmond Joanna
Original Assignee
Glaxosmithkline Ip Dev Ltd
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
Application filed by Glaxosmithkline Ip Dev Ltd filed Critical Glaxosmithkline Ip Dev Ltd
Application granted granted Critical
Publication of JO3413B1 publication Critical patent/JO3413B1/ar

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D471/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04Ortho-condensed systems
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic 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
    • A61K31/4353Heterocyclic 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 ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4375Heterocyclic 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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0053Mouth and digestive tract, i.e. intraoral and peroral administration
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00Drugs for disorders of the urinary system
    • A61P13/12Drugs for disorders of the urinary system of the kidneys
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19Carboxylic acids, e.g. valproic acid

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nutrition Science (AREA)
  • Physiology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Urology & Nephrology (AREA)
  • Pulmonology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
JOP/2015/0234A 2014-09-26 2015-09-22 مشتقات نافثيريدين في صورة مضادات ألفا v بيتا 6 إنتيجرين لعلاج الأمراض الليفية e.g JO3413B1 (ar)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
GBGB1417002.1A GB201417002D0 (en) 2014-09-26 2014-09-26 Novel compound

Publications (1)

Publication Number Publication Date
JO3413B1 true JO3413B1 (ar) 2019-10-20

Family

ID=51901158

Family Applications (1)

Application Number Title Priority Date Filing Date
JOP/2015/0234A JO3413B1 (ar) 2014-09-26 2015-09-22 مشتقات نافثيريدين في صورة مضادات ألفا v بيتا 6 إنتيجرين لعلاج الأمراض الليفية e.g

Country Status (37)

Country Link
US (3) US9956209B2 (cg-RX-API-DMAC10.html)
EP (2) EP3428167A1 (cg-RX-API-DMAC10.html)
JP (1) JP6611799B2 (cg-RX-API-DMAC10.html)
KR (1) KR101998000B1 (cg-RX-API-DMAC10.html)
CN (1) CN107074848B (cg-RX-API-DMAC10.html)
AR (1) AR101994A1 (cg-RX-API-DMAC10.html)
AU (1) AU2015320858B2 (cg-RX-API-DMAC10.html)
BR (1) BR112017006251A2 (cg-RX-API-DMAC10.html)
CA (1) CA2962315A1 (cg-RX-API-DMAC10.html)
CL (1) CL2017000705A1 (cg-RX-API-DMAC10.html)
CO (1) CO2017002714A2 (cg-RX-API-DMAC10.html)
CR (1) CR20170112A (cg-RX-API-DMAC10.html)
CY (1) CY1121071T1 (cg-RX-API-DMAC10.html)
DK (1) DK3197892T3 (cg-RX-API-DMAC10.html)
DO (1) DOP2017000081A (cg-RX-API-DMAC10.html)
EA (1) EA031481B1 (cg-RX-API-DMAC10.html)
ES (1) ES2690748T3 (cg-RX-API-DMAC10.html)
GB (1) GB201417002D0 (cg-RX-API-DMAC10.html)
HR (1) HRP20181796T1 (cg-RX-API-DMAC10.html)
HU (1) HUE041827T2 (cg-RX-API-DMAC10.html)
IL (1) IL250592A0 (cg-RX-API-DMAC10.html)
JO (1) JO3413B1 (cg-RX-API-DMAC10.html)
LT (1) LT3197892T (cg-RX-API-DMAC10.html)
MA (1) MA40580B1 (cg-RX-API-DMAC10.html)
MX (1) MX2017003948A (cg-RX-API-DMAC10.html)
PE (1) PE20170502A1 (cg-RX-API-DMAC10.html)
PH (1) PH12017500361B1 (cg-RX-API-DMAC10.html)
PL (1) PL3197892T3 (cg-RX-API-DMAC10.html)
PT (1) PT3197892T (cg-RX-API-DMAC10.html)
RS (1) RS58000B1 (cg-RX-API-DMAC10.html)
SG (1) SG11201701183YA (cg-RX-API-DMAC10.html)
SI (1) SI3197892T1 (cg-RX-API-DMAC10.html)
SM (1) SMT201800513T1 (cg-RX-API-DMAC10.html)
TW (1) TW201629056A (cg-RX-API-DMAC10.html)
UA (1) UA119181C2 (cg-RX-API-DMAC10.html)
UY (1) UY36314A (cg-RX-API-DMAC10.html)
WO (1) WO2016046225A1 (cg-RX-API-DMAC10.html)

Families Citing this family (26)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB201305668D0 (en) 2013-03-28 2013-05-15 Glaxosmithkline Ip Dev Ltd Avs6 Integrin Antagonists
GB201417018D0 (en) 2014-09-26 2014-11-12 Glaxosmithkline Ip Dev Ltd Novel compounds
GB201417002D0 (en) * 2014-09-26 2014-11-12 Glaxosmithkline Ip Dev Ltd Novel compound
GB201417011D0 (en) 2014-09-26 2014-11-12 Glaxosmithkline Ip Dev Ltd Novel compounds
GB201417094D0 (en) 2014-09-26 2014-11-12 Glaxosmithkline Ip Dev Ltd Novel compounds
GB201604589D0 (en) * 2016-03-18 2016-05-04 Glaxosmithkline Ip Dev Ltd Chemical compound
GB201604680D0 (en) * 2016-03-21 2016-05-04 Glaxosmithkline Ip Dev Ltd Chemical Compounds
GB201604681D0 (en) 2016-03-21 2016-05-04 Glaxosmithkline Ip Dev Ltd Chemical Compounds
MA46745A (fr) 2016-11-08 2021-03-31 Bristol Myers Squibb Co Dérivés d'indazole en tant qu'antagonistes de l'intégrine alpha v
BR112019009293A2 (pt) 2016-11-08 2019-07-30 Bristol-Myers Squibb Company pirrol amidas como inibidores de integrina alfa v
MX377359B (es) 2016-11-08 2025-03-10 Bristol Myers Squibb Co Compuestos mono y espirocíclicos que continen ciclobutano y azetidina como inhibidores de la integrina alfa v.
NZ754207A (en) 2016-11-08 2025-09-26 Bristol Myers Squibb Co 3-substituted propionic acids as alpha v integrin inhibitors
EP3538527B1 (en) 2016-11-08 2021-10-13 Bristol-Myers Squibb Company Azole amides and amines as alpha v integrin inhibitors
USRE50554E1 (en) 2016-12-23 2025-08-26 Pliant Therapeutics, Inc. Amino acid compounds and methods of use
KR102891803B1 (ko) 2017-02-28 2025-11-28 모픽 테라퓨틱, 인코포레이티드 αvβ6 인테그린 억제제
EP3760202A1 (en) 2017-02-28 2021-01-06 Morphic Therapeutic, Inc. Inhibitors of (alpha-v)(beta-6) integrin
WO2018167295A1 (en) * 2017-03-17 2018-09-20 Technische Universität München LIGANDS FOR INTEGRIN αvβ8, SYNTHESIS AND USES THEREOF
BR112020008893A2 (pt) 2017-11-07 2020-10-13 Bristol-Myers Squibb Company derivados de pirrolopirazina como inibidores de alfa v integrina
CN108208177A (zh) * 2017-11-28 2018-06-29 上海交通大学医学院附属新华医院 含丁酸类化合物的组合物及其应用
EP3843727A4 (en) * 2018-08-29 2022-08-17 Morphic Therapeutic, Inc. INHIBITORS OF (ALPHA-V)(BETA-6) INTEGRIN
UY38352A (es) 2018-08-29 2020-03-31 Morphic Therapeutic Inc Inhibidores de integrina alfavbeta6
JP7540998B2 (ja) 2018-08-29 2024-08-27 モーフィック セラピューティック,インコーポレイテッド αvβ6インテグリンの阻害
ES3027421T3 (en) * 2018-08-29 2025-06-13 Morphic Therapeutic Inc Inhibitors of (alpha-v)(beta-6) integrin
US12351634B2 (en) * 2018-10-09 2025-07-08 INSERM (Institut National de la Santé et de la Recherche Médicale) Use of cilengitide for ameliorating cardiac fibrosis occurring in response to myocardial infarction
JP2022511029A (ja) * 2018-12-04 2022-01-28 スミトモ ダイニッポン ファーマ オンコロジー, インコーポレイテッド がんの処置のための薬剤としての使用のためのcdk9インヒビターおよびその多形
GB202010626D0 (en) 2020-07-10 2020-08-26 Univ Nottingham Compound

Family Cites Families (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU736026B2 (en) 1997-12-17 2001-07-26 Merck & Co., Inc. Integrin receptor antagonists
ATE294163T1 (de) 1997-12-17 2005-05-15 Merck & Co Inc Integrin-rezeptor-antagonisten
DE60035779T2 (de) 1999-06-02 2008-04-30 Merck & Co., Inc. Alpha v integrin-rezeptor antagonisten
EP1194151A4 (en) 1999-06-23 2003-01-15 Merck & Co Inc ANTAGONISTS OF THE INTEGRIN RECEPTORS
AU7743400A (en) * 1999-10-04 2001-05-10 Merck & Co., Inc. Integrin receptor antagonists
YU32502A (sh) 1999-11-08 2004-12-31 Merck & Co.Inc. Postupak i intermedijeri za proizvodnju imidazolidinonskih antagonista alfa v integrina
US6921767B2 (en) 2000-06-15 2005-07-26 Pharmacia Corporation Cycloalkyl alkanoic acids as integrin receptor antagonists derivatives
US7119098B2 (en) 2000-06-15 2006-10-10 Pharmacia Corporation Heteroarylakanoic acids as intergrin receptor antagonists
ATE353219T1 (de) 2000-07-26 2007-02-15 Merck & Co Inc Alpha v integrin-rezeptor-antagonisten
WO2002022616A2 (en) 2000-09-14 2002-03-21 Merck & Co., Inc. Alpha v integrin receptor antagonists
JP2004517853A (ja) 2001-01-03 2004-06-17 メルク エンド カムパニー インコーポレーテッド 歯周病の治療方法及び治療用組成物
DE10112771A1 (de) 2001-03-16 2002-09-26 Merck Patent Gmbh Inhibitoren des Integrins alpha¶v¶beta¶6¶
AR037517A1 (es) 2001-11-05 2004-11-17 Novartis Ag Derivados de naftiridinas, un proceso para su preparacion, composicion farmaceutica y el uso de los mismos para la preparacion de un medicamento para el tratamiento de una enfermedad inflamatoria
BRPI0308585B8 (pt) 2002-03-13 2021-05-25 Biogen Idec Inc anticorpo isolado ou fragmento de ligação a antígeno do mesmo que se liga à alfavbeta6, composição, método de detecção in vitro de alfavbeta6 e construção de dna
US20040224986A1 (en) * 2002-08-16 2004-11-11 Bart De Corte Piperidinyl targeting compounds that selectively bind integrins
US20050043344A1 (en) 2002-12-20 2005-02-24 Pharmacia Corporation Heteroarylalkanoic acids as integrin receptor antagonists derivatives
US6932865B2 (en) 2003-04-11 2005-08-23 Lockheed Martin Corporation System and method of making single-crystal structures through free-form fabrication techniques
JP5732701B2 (ja) 2007-03-23 2015-06-10 アムジエン・インコーポレーテツド 3−置換キノリンまたはキノキサリン誘導体およびホスファチジルイノシトール3−キナーゼ(pi3k)阻害剤としてのそれらの使用
US8563566B2 (en) 2007-08-01 2013-10-22 Valeant Pharmaceuticals International Naphthyridine derivatives as potassium channel modulators
EP2211615A4 (en) 2007-10-22 2010-10-13 Glaxosmithkline Llc PYRIDOSULFONAMIDE DERIVATIVES AS PI3 KINASE INHIBITORS
WO2011111880A1 (ko) 2010-03-08 2011-09-15 주식회사 메디젠텍 세포핵에서 세포질로의 gsk3의 이동을 억제하는 화합물을 함유하는 세포핵에서 세포질로의 gsk3 이동에 의해 발생되는 질환의 치료 또는 예방용 약학적 조성물
GB201305668D0 (en) * 2013-03-28 2013-05-15 Glaxosmithkline Ip Dev Ltd Avs6 Integrin Antagonists
WO2015048819A1 (en) 2013-09-30 2015-04-02 The Regents Of The University Of California Anti-alphavbeta1 integrin compounds and methods
GB201417011D0 (en) 2014-09-26 2014-11-12 Glaxosmithkline Ip Dev Ltd Novel compounds
GB201417094D0 (en) 2014-09-26 2014-11-12 Glaxosmithkline Ip Dev Ltd Novel compounds
GB201417018D0 (en) 2014-09-26 2014-11-12 Glaxosmithkline Ip Dev Ltd Novel compounds
GB201417002D0 (en) * 2014-09-26 2014-11-12 Glaxosmithkline Ip Dev Ltd Novel compound
ES2892954T3 (es) 2015-02-19 2022-02-07 Ocuterra Therapeutics Inc Derivados fluorados del ácido 3-(2-oxo-3-(3-(5,6,7,8-tetrahidro-1,8-naftiridin-2-il)propil)imidazolidin-1-il)propanoico y usos de los mismos
CA2981371A1 (en) 2015-03-10 2016-09-15 The Regents Of The University Of California Anti-alphavbeta1 integrin inhibitors and methods of use
GB201604589D0 (en) 2016-03-18 2016-05-04 Glaxosmithkline Ip Dev Ltd Chemical compound
GB201604680D0 (en) 2016-03-21 2016-05-04 Glaxosmithkline Ip Dev Ltd Chemical Compounds

Also Published As

Publication number Publication date
BR112017006251A2 (pt) 2017-12-12
US10342783B2 (en) 2019-07-09
WO2016046225A1 (en) 2016-03-31
IL250592A0 (en) 2017-04-30
AU2015320858A1 (en) 2017-03-09
HUE041827T2 (hu) 2019-05-28
UY36314A (es) 2016-04-29
PH12017500361A1 (en) 2017-07-17
EP3428167A1 (en) 2019-01-16
KR101998000B1 (ko) 2019-07-08
MX2017003948A (es) 2017-06-26
US20180271845A1 (en) 2018-09-27
LT3197892T (lt) 2018-12-10
SI3197892T1 (sl) 2018-12-31
CA2962315A1 (en) 2016-03-31
JP6611799B2 (ja) 2019-11-27
CY1121071T1 (el) 2019-12-11
US20190275016A1 (en) 2019-09-12
KR20170055489A (ko) 2017-05-19
RS58000B1 (sr) 2019-01-31
SG11201701183YA (en) 2017-04-27
PT3197892T (pt) 2018-12-12
AR101994A1 (es) 2017-01-25
CO2017002714A2 (es) 2017-06-30
DOP2017000081A (es) 2017-04-30
US20170290817A1 (en) 2017-10-12
ES2690748T3 (es) 2018-11-22
CN107074848B (zh) 2019-11-01
MA40580A (fr) 2017-08-02
TW201629056A (zh) 2016-08-16
SMT201800513T1 (it) 2018-11-09
MA40580B1 (fr) 2018-09-28
EA201790715A1 (ru) 2017-07-31
PL3197892T3 (pl) 2019-05-31
EA031481B1 (ru) 2019-01-31
EP3197892A1 (en) 2017-08-02
GB201417002D0 (en) 2014-11-12
JP2017528507A (ja) 2017-09-28
US9956209B2 (en) 2018-05-01
CL2017000705A1 (es) 2017-11-03
CR20170112A (es) 2017-05-26
PH12017500361B1 (en) 2017-07-17
AU2015320858B2 (en) 2018-10-18
EP3197892B1 (en) 2018-09-05
CN107074848A (zh) 2017-08-18
HRP20181796T1 (hr) 2018-12-28
PE20170502A1 (es) 2017-04-27
DK3197892T3 (en) 2018-11-26
UA119181C2 (uk) 2019-05-10

Similar Documents

Publication Publication Date Title
JO3413B1 (ar) مشتقات نافثيريدين في صورة مضادات ألفا v بيتا 6 إنتيجرين لعلاج الأمراض الليفية e.g
EA201790407A1 (ru) Зонды для визуализации белка хантингтина
JO3489B1 (ar) مركبات تراي أزولوبيريميدين واستخداماتها
EA201501142A1 (ru) Гетероциклические соединения в качестве средств для борьбы с вредителями
EA201692301A1 (ru) Производные бороновой кислоты и их терапевтическое применение
EP3302275A4 (en) WELDING DISPLAY OF PHYSIOLOGICAL CONDITIONS
EA201692219A1 (ru) Способы получения противовирусных соединений
MX2017010276A (es) Composiciones para el cuidado bucal y metodos de uso.
EA201791002A1 (ru) Новые соединения, модулирующие fxr (nr1h4)
MY207356A (en) Nrf2 regulators
EA201791873A1 (ru) Полиморф ингибиторов syk
BR112016025356A2 (pt) 4-fenilpiperidinas substituido, sua preparação e utilização
JOP20170100B1 (ar) توليف مركبات إندازول
EA201791058A1 (ru) Морфолин- и 1,4-оксазепан-амиды в качестве агонистов соматостатинового рецептора подтипа 4 (sstr4)
EA201691674A1 (ru) 1,2-замещенные циклопентаны в качестве антагонистов рецептора орексина
EA201790519A1 (ru) Терапевтические соединения в качестве ингибиторов рецептора орексина-1
EA201691982A1 (ru) 5,6-дизамещенные пиридин-2-карбоксамиды в качестве агонистов каннабиноидных рецепторов
EA201600434A1 (ru) Применение производных бензимидазолпролина
EA201790400A1 (ru) Зонды для визуализации белка хантингтина
EP4599830A3 (en) Isoxazoline compounds for use in treating demodicosis
EA201692270A1 (ru) Производные нафтиридиндиона
MX390799B (es) Sintesis de complejo de zinc-lisina a partir de cloruro de zinc.
DOP2019000021A (es) Derivado de triazolopirazinona útil como un inhibidor de pde1 humana
CY1120744T1 (el) Παραγωγα οξικου οξεος αζαϊνδολης και η χρηση αυτων ως ρυθμιστων υποδοχεων προσταγλανδινης d2
PH12015502717B1 (en) Anti-fibrogenic compounds, methods and uses thereof