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 PDFInfo
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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
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- 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
- G01N33/5011—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 for testing antineoplastic activity
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- 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
- G01N33/502—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 for testing non-proliferative effects
- G01N33/5023—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 for testing non-proliferative effects on expression patterns
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- 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
- G01N33/502—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 for testing non-proliferative effects
- G01N33/5026—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 for testing non-proliferative effects on cell morphology
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- 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
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/573—Immunoassay; Biospecific binding assay; Materials therefor for enzymes or isoenzymes
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/90—Enzymes; Proenzymes
- G01N2333/91—Transferases (2.)
- G01N2333/912—Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)
- G01N2333/91205—Phosphotransferases in general
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2500/00—Screening for compounds of potential therapeutic value
- G01N2500/02—Screening 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)
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2500/00—Screening for compounds of potential therapeutic value
- G01N2500/10—Screening for compounds of potential therapeutic value involving cells
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- Engineering & Computer Science (AREA)
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Investigating Or Analysing Biological Materials (AREA)
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.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP11306686 | 2011-12-16 | ||
PCT/EP2012/075839 WO2013087937A1 (en) | 2011-12-16 | 2012-12-17 | Treatment of cancer by inhibition of the myd88/erk map kinase interaction |
Publications (1)
Publication Number | Publication Date |
---|---|
DK2791674T3 true DK2791674T3 (da) | 2016-10-03 |
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DK12808362.3T DK2791674T3 (da) | 2011-12-16 | 2012-12-17 | Fremgangsmåde til screening af forbindelser til behandling af cancer ved inhibering af myd88/erk-map-kinase-interaktion |
Country Status (16)
Country | Link |
---|---|
US (1) | US9683986B2 (da) |
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) |
DK (1) | DK2791674T3 (da) |
ES (1) | ES2595408T3 (da) |
HU (1) | HUE031160T2 (da) |
IL (1) | IL232842A (da) |
PL (1) | PL2791674T3 (da) |
PT (1) | PT2791674T (da) |
SI (1) | SI2791674T1 (da) |
WO (1) | WO2013087937A1 (da) |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
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 |
-
2012
- 2012-12-17 WO PCT/EP2012/075839 patent/WO2013087937A1/en active Application Filing
- 2012-12-17 PL PL12808362T patent/PL2791674T3/pl unknown
- 2012-12-17 KR KR1020147019311A patent/KR20140119698A/ko not_active Application Discontinuation
- 2012-12-17 HU HUE12808362A patent/HUE031160T2/en unknown
- 2012-12-17 ES ES12808362.3T patent/ES2595408T3/es active Active
- 2012-12-17 CA CA2858466A patent/CA2858466C/en active Active
- 2012-12-17 SI SI201230717A patent/SI2791674T1/sl unknown
- 2012-12-17 AU AU2012351486A patent/AU2012351486B2/en active Active
- 2012-12-17 US US14/364,582 patent/US9683986B2/en active Active
- 2012-12-17 CN CN201280069559.9A patent/CN104185789B/zh active Active
- 2012-12-17 EP EP12808362.3A patent/EP2791674B1/en active Active
- 2012-12-17 PT PT128083623T patent/PT2791674T/pt unknown
- 2012-12-17 DK DK12808362.3T patent/DK2791674T3/da active
- 2012-12-17 JP JP2014546573A patent/JP6049751B2/ja active Active
-
2014
- 2014-05-28 IL IL232842A patent/IL232842A/en active IP Right Grant
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2016
- 2016-10-03 CY CY20161100976T patent/CY1118071T1/el unknown
Also Published As
Publication number | Publication date |
---|---|
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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