DK2791674T3 - Fremgangsmåde til screening af forbindelser til behandling af cancer ved inhibering af myd88/erk-map-kinase-interaktion - Google Patents

Fremgangsmåde til screening af forbindelser til behandling af cancer ved inhibering af myd88/erk-map-kinase-interaktion Download PDF

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DK2791674T3
DK2791674T3 DK12808362.3T DK12808362T DK2791674T3 DK 2791674 T3 DK2791674 T3 DK 2791674T3 DK 12808362 T DK12808362 T DK 12808362T DK 2791674 T3 DK2791674 T3 DK 2791674T3
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myd88
cancer
dna damage
selecting
treatment
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DK12808362.3T
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Alain Kfoury
Isabelle Coste-Invernizzi
Serge Lebecque
Toufic Renno
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Univ Claude Bernard Lyon
Les Hospices Civils De Lyon
Inst Nat De La Santé Et De La Rech Medicale
Centre Nat De La Rech Scient (Cnrs)
Centre Léon Bérard
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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008Chemical 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
    • G01N33/5011Chemical 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 for testing antineoplastic activity
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
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    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
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    • G01N33/502Chemical 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 for testing non-proliferative effects
    • G01N33/5023Chemical 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 for testing non-proliferative effects on expression patterns
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008Chemical 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
    • G01N33/502Chemical 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 for testing non-proliferative effects
    • G01N33/5026Chemical 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 for testing non-proliferative effects on cell morphology
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
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    • GPHYSICS
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    • G01N2333/91Transferases (2.)
    • G01N2333/912Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)
    • G01N2333/91205Phosphotransferases in general
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2500/00Screening for compounds of potential therapeutic value
    • G01N2500/02Screening involving studying the effect of compounds C on the interaction between interacting molecules A and B (e.g. A = enzyme and B = substrate for A, or A = receptor and B = ligand for the receptor)
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2500/00Screening for compounds of potential therapeutic value
    • G01N2500/10Screening for compounds of potential therapeutic value involving cells

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Claims (15)

1. Fremgangsmåde til udvælgelse af in wfro-forbindelser, der kan potensere virkningen af et DNA-skade-inducerende kemoterapimiddel til behandling af cancer, omfattende følgende trin: a) at tilvejebringe mindst en kandidatforbindelse; b) at bringe mindst en kandidatforbindelse i kontakt med et ERK MAPK-protein og et MyD88-protein under betingelser, der er egnede til at lade ERK MAPK og MyD88 interagere i fravær af kandidatmolekylet; c) at bestemme interaktionen mellem ERK MAPK og MyD88 målt i nærvær og i fravær af mindst en kandidatforbindelse; og d) at udvælge en kandidatforbindelse, der inhiberer interaktionen mellem ERK MAPK og MyD88.
2. Fremgangsmåde til udvælgelse af in v/Yro-forbindelser, der kan potensere virkningen af et DNA-skade-inducerende kemoterapimiddel til behandling af cancer ifølge krav 1, hvor et eller begge af ERK MAPK og MyD88 er knyttet til en detekterbar markering.
3. Fremgangsmåde til udvælgelse af in v/fro-forbindelser, der kan potensere virkningen af et DNA-skade-inducerende kemoterapimiddel til behandling af cancer ifølge et hvilket som helst af kravene 1-2, hvor interaktionen mellem ERK MAPK og MyD88 bestemmes under anvendelse af et to-hybrid-system, affinitetskromatografi, co-immunpræcipitation, subcellulær fraktionering og isolering af store molekylkomplekser, immunblotting, immunmærkning, et proximity ligation-assay, et immunpræcipitation-assay, et biacore-assay eller et GST pull-down-assay.
4. Fremgangsmåde til udvælgelse af in v/Yro-forbindelser, der kan potensere virkningen af et DNA-skade-inducerende kemoterapimiddel til behandling af cancer ifølge et hvilket som helst af kravene 1-3, hvor det DNA-skade-inducerende kemoterapimiddel er udvalgt i gruppen bestående af oxaliplatin, cisplatin, carboplatin, doxorubicin, etoposid, bleomycin og blandinger deraf.
5. Fremgangsmåde til udvælgelse af in v/Yro-forbindelser, der kan potensere virkningen af et DNA-skade-inducerende kemoterapimiddel til behandling af cancer ifølge et hvilket som helst af kravene 1-4, hvor canceren er udvalgt i gruppen bestående af kolorektal cancer, tarmkræft, melanom, lungekræft og cervixcancer.
6. Fremgangsmåde til udvælgelse af in v/Yro-forbindelser, der kan potensere virkningen af et DNA-skade-inducerende kemoterapimiddel til behandling af cancer, omfattende følgende trin: a) at tilvejebringe mindst en kandidatforbindelse; b) at tilvejebringe transformerede celler, der stabilt eksprimerer MyD88 under styring af en inducerbar promoter, og som eksprimerer et reportergen under styring af en promoter fra MAPK-vejen udvalgt blandt SRE-promoteren, ELK-promoteren og MyC-promoteren; c) at inducere overekspression af MYD88 i de transformerede celler i nærvær af mindst en kandidatforbindelse; d) at måle ekspressionen af reportergenet og udvælge mindst en kandidatforbindelse, der inhiberer ekspressionen af reportergenet; e) at tilvejebringe immortaliserede fibroblaster transformeret ved transfektion med MyD88 og Myc-onkogener; f) Monitorering af fokusdannelse i nærvær af mindst en kandidatforbindelse udvalgt i trin d) og i nærvær af mindst et DNA-skade-inducerende kemoterapimiddel og at udvælge en kandidatforbindelse, der potenserer den inhibe-rende virkning af det DNA-skade-inducerende kemoterapimiddel på fokusdannelse.
7. Fremgangsmåde til udvælgelse af in wYro-forbindelser, der kan potensere virkningen af et DNA-skade-inducerende kemoterapimiddel til behandling af cancer ifølge krav 6, hvor, i trin b), promoteren fra MAPK-vejen er SRE-promoteren.
8. Fremgangsmåde til udvælgelse af in v/Yro-forbindelser, der kan potensere virkningen af et DNA-skade-inducerende kemoterapimiddel til behandling af cancer ifølge et hvilket som helst af kravene 6-7, hvor fremgangsmåden yderligere omfatter følgende trin: - at tilvejebringe transformerede celler, der stabilt eksprimerer MyD88 under styring af en inducerbar promoter og eksprimerer et reportergen under sty ring af en promoter fra inflammationsvejen udvalgt blandt Nf-kB-promoteren og ISRE-promoteren; - at inducere overekspression af MYD88 i de transformerede celler i nærvær af mindst en kandidatforbindelse; - at måle ekspressionen af reportergenet og udvælge en kandidatforbindelse, som ikke inhiberer ekspressionen af reportergenet.
9. Fremgangsmåde til udvælgelse af in wYro-forbindelser, der kan potensere virkningen af et DNA-skade-inducerende kemoterapimiddel til behandling af cancer ifølge krav 8, hvor promoteren fra inflammationsvejen er Nf-kB.
10. Fremgangsmåde til udvælgelse af in v/Yro-forbindelser, der kan potensere virkningen af et DNA-skade-inducerende kemoterapimiddel til behandling af cancer ifølge et hvilket som helst af kravene 6-9, hvor, i trin b), cellerne er udvalgt blandt HCT116-cellelinjen, A375-cellelinjen og en HeLa-cellelinje.
11. Fremgangsmåde til udvælgelse af in vitro-forbindelser, der kan potensere virkningen af et DNA-skade-inducerende kemoterapimiddel til behandling af cancer ifølge et hvilket som helst af kravene 6-10, hvor den inducerbare promoter er en antibiotikum-inducerbar promoter.
12. Fremgangsmåde til udvælgelse af in wfro-forbindelser, der kan potensere virkningen af et DNA-skade-inducerende kemoterapimiddel til behandling af cancer ifølge et hvilket som helst af kravene 6-11, hvor de immortaliserede fibroblaster er NIFI3T3-immortaliserede fibroblaster.
13. Fremgangsmåde til udvælgelse af in v/Yro-forbindelser, der kan potensere virkningen af et DNA-skade-inducerende kemoterapimiddel til behandling af cancer ifølge et hvilket som helst af kravene 6-12, hvor canceren er udvalgt i gruppen bestående af kolorektal cancer, tarmkræft, melanom, lungekræft og cervixcancer.
14. Fremgangsmåde til udvælgelse af in v/Yro-forbindelser, der kan potensere virkningen af et DNA-skade-inducerende kemoterapimiddel til behandling af cancer ifølge et hvilket som helst af kravene 6-13, hvor det DNA-skade-inducerende kemoterapimiddel er udvalgt blandt oxaliplatin, cisplatin, carbo- platin, doxorubicin, etoposid, bleomycin og blandinger deraf.
15. Fremgangsmåde til udvælgelse af in vitro-forbindelser, der kan potensere virkningen af et DNA-skade-inducerende kemoterapimiddel til behandling af cancer ifølge et hvilket som helst af kravene 6-14, hvor kandidatforbindelsen fra trin a) udvælges i henhold til en fremgangsmåde ifølge et hvilket som helst af kravene 1-5.
DK12808362.3T 2011-12-16 2012-12-17 Fremgangsmåde til screening af forbindelser til behandling af cancer ved inhibering af myd88/erk-map-kinase-interaktion DK2791674T3 (da)

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PCT/EP2012/075839 WO2013087937A1 (en) 2011-12-16 2012-12-17 Treatment of cancer by inhibition of the myd88/erk map kinase interaction

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EP (1) EP2791674B1 (da)
JP (1) JP6049751B2 (da)
KR (1) KR20140119698A (da)
CN (1) CN104185789B (da)
AU (1) AU2012351486B2 (da)
CA (1) CA2858466C (da)
CY (1) CY1118071T1 (da)
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ES (1) ES2595408T3 (da)
HU (1) HUE031160T2 (da)
IL (1) IL232842A (da)
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AU2005274985A1 (en) * 2004-07-19 2006-02-23 Schering Corporation MyD88 as a therapeutic target for cancer
WO2006113530A2 (en) 2005-04-15 2006-10-26 University Of Maryland, Baltimore Selective inhibition of tlr4 signaling
EP1892301A4 (en) * 2005-06-07 2008-09-17 Banyu Pharma Co Ltd METHOD FOR EVALUATING A CONNECTION BY RSK1

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SI2791674T1 (sl) 2016-12-30
EP2791674B1 (en) 2016-07-06
CA2858466C (en) 2021-10-19
AU2012351486A1 (en) 2014-07-31
EP2791674A1 (en) 2014-10-22
CY1118071T1 (el) 2017-06-28
PT2791674T (pt) 2016-10-07
KR20140119698A (ko) 2014-10-10
US20140329261A1 (en) 2014-11-06
HUE031160T2 (en) 2017-06-28
JP6049751B2 (ja) 2016-12-21
JP2015501939A (ja) 2015-01-19
PL2791674T3 (pl) 2017-01-31
US9683986B2 (en) 2017-06-20
IL232842A (en) 2017-08-31
WO2013087937A1 (en) 2013-06-20
AU2012351486B2 (en) 2018-01-04
IL232842A0 (en) 2014-07-31
ES2595408T3 (es) 2016-12-29
CN104185789B (zh) 2016-08-24
CA2858466A1 (en) 2013-06-20
CN104185789A (zh) 2014-12-03

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