AR111449A1 - SYNERGIC COMBINATION OF OLIGONUCLEOTIDES OF NUCLEIC ACIDS AND CHEMOTHERAPY WITH TAXANOS - Google Patents
SYNERGIC COMBINATION OF OLIGONUCLEOTIDES OF NUCLEIC ACIDS AND CHEMOTHERAPY WITH TAXANOSInfo
- Publication number
- AR111449A1 AR111449A1 ARP180100850A ARP180100850A AR111449A1 AR 111449 A1 AR111449 A1 AR 111449A1 AR P180100850 A ARP180100850 A AR P180100850A AR P180100850 A ARP180100850 A AR P180100850A AR 111449 A1 AR111449 A1 AR 111449A1
- Authority
- AR
- Argentina
- Prior art keywords
- nucleic acid
- splice variant
- gene
- combination
- docetaxel
- Prior art date
Links
- 150000007523 nucleic acids Chemical class 0.000 title abstract 10
- 108020004707 nucleic acids Proteins 0.000 title abstract 7
- 102000039446 nucleic acids Human genes 0.000 title abstract 7
- 108091034117 Oligonucleotide Proteins 0.000 title 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 title 1
- 238000002512 chemotherapy Methods 0.000 title 1
- 230000002195 synergetic effect Effects 0.000 title 1
- 101100182885 Homo sapiens MADD gene Proteins 0.000 abstract 8
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 abstract 8
- 229960003668 docetaxel Drugs 0.000 abstract 6
- 102100028822 MAP kinase-activating death domain protein Human genes 0.000 abstract 4
- 229940123237 Taxane Drugs 0.000 abstract 4
- 239000002246 antineoplastic agent Substances 0.000 abstract 4
- 229940127089 cytotoxic agent Drugs 0.000 abstract 4
- 206010028980 Neoplasm Diseases 0.000 abstract 3
- 108091028043 Nucleic acid sequence Proteins 0.000 abstract 3
- 108020004459 Small interfering RNA Proteins 0.000 abstract 3
- 230000001105 regulatory effect Effects 0.000 abstract 3
- DKPFODGZWDEEBT-QFIAKTPHSA-N taxane Chemical class C([C@]1(C)CCC[C@@H](C)[C@H]1C1)C[C@H]2[C@H](C)CC[C@@H]1C2(C)C DKPFODGZWDEEBT-QFIAKTPHSA-N 0.000 abstract 3
- 108020000948 Antisense Oligonucleotides Proteins 0.000 abstract 2
- 239000000074 antisense oligonucleotide Substances 0.000 abstract 2
- 238000012230 antisense oligonucleotides Methods 0.000 abstract 2
- 229940046044 combinations of antineoplastic agent Drugs 0.000 abstract 2
- 230000003247 decreasing effect Effects 0.000 abstract 2
- 238000000034 method Methods 0.000 abstract 2
- 239000000203 mixture Substances 0.000 abstract 2
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 abstract 2
- 229930012538 Paclitaxel Natural products 0.000 abstract 1
- 229960001573 cabazitaxel Drugs 0.000 abstract 1
- BMQGVNUXMIRLCK-OAGWZNDDSA-N cabazitaxel Chemical compound O([C@H]1[C@@H]2[C@]3(OC(C)=O)CO[C@@H]3C[C@@H]([C@]2(C(=O)[C@H](OC)C2=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=3C=CC=CC=3)C[C@]1(O)C2(C)C)C)OC)C(=O)C1=CC=CC=C1 BMQGVNUXMIRLCK-OAGWZNDDSA-N 0.000 abstract 1
- 201000011510 cancer Diseases 0.000 abstract 1
- 238000002648 combination therapy Methods 0.000 abstract 1
- 230000000295 complement effect Effects 0.000 abstract 1
- 239000000839 emulsion Substances 0.000 abstract 1
- 238000009472 formulation Methods 0.000 abstract 1
- 150000002632 lipids Chemical class 0.000 abstract 1
- 108020004999 messenger RNA Proteins 0.000 abstract 1
- 239000004005 microsphere Substances 0.000 abstract 1
- 229960001592 paclitaxel Drugs 0.000 abstract 1
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/7105—Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
-
- 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
-
- 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
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/111—General methods applicable to biologically active non-coding nucleic acids
-
- 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
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
- C12N15/1135—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against oncogenes or tumor suppressor genes
-
- 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
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/14—Type of nucleic acid interfering nucleic acids [NA]
-
- 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
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/50—Physical structure
- C12N2310/53—Physical structure partially self-complementary or closed
- C12N2310/531—Stem-loop; Hairpin
-
- 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
- C12N2320/00—Applications; Uses
- C12N2320/30—Special therapeutic applications
- C12N2320/31—Combination therapy
-
- 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
- C12N2320/00—Applications; Uses
- C12N2320/30—Special therapeutic applications
- C12N2320/33—Alteration of splicing
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Biomedical Technology (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Epidemiology (AREA)
- Plant Pathology (AREA)
- Microbiology (AREA)
- Biophysics (AREA)
- Physics & Mathematics (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Composiciones y métodos para tratar cánceres, que comprenden administrar una combinación de agentes antineoplásicos, donde la combinación comprende agentes quimioterapéuticos derivados de taxanos y una o más moléculas de ácidos nucleicos capaces de regular negativamente la expresión de al menos una variante de empalme del gen IG20, donde no todas las variantes de empalme del gen IG20 son reguladas negativamente. En una forma de realización, la variante de empalme del gen IG20 es una variante de empalme MADD y las moléculas de ácidos nucleicos son siARN, ARNhc y oligonucleótidos antisentido que comprenden una secuencia de ácido nucleico complementaria de la secuencia de ácido nucleico del exón 13L de la variante de empalme MADD o un transcripto de ARNm del exón 13L de la variante de empalme MADD. Métodos para tratar cánceres donde se aplica una terapia combinada con moléculas de ácidos nucleicos capaces de regular negativamente la expresión de al menos una variante de empalme del gen IG20 y agentes quimioterapéuticos derivados de taxanos. Reivindicación 1: Una combinación de agentes antineoplásicos útiles para tratar cáncer caracterizado porque comprende una cantidad eficaz de una o más moléculas de ácido nucleico con capacidad de disminuir la expresión de por lo menos una variante de corte y empalme del gen IG20, en donde no se disminuye la expresión de todas las variantes de corte y empalme del gen IG20, y uno o mas quimioterapéuticos derivados de taxano. Reivindicación 3: La combinación de la reivindicación 2, caracterizada porque la por lo menos una variante de corte y empalme del gen IG20 es una variante de corte y empalme MADD que exhibe el exón 13L. Reivindicación 4: La combinación de la reivindicación 2, caracterizada porque la una o más moléculas de ácido nucleico con capacidad de disminuir la expresión de la por lo menos una variante de corte y empalme del gen IG20 se seleccionan de ARNpi, ARNhp y oligonucleótidos antisentido. Reivindicación 7: La combinación de la reivindicación 6, caracterizada porque el ARNpi y ARNhp está codificado por una molécula de ácido nucleico que incluye la estructura: Xₛₑₙₜⁱᵈₒ - bucle horquilla - Xₐₙₜⁱₛₑₙₜⁱᵈₒ, en donde X incluye o consiste esencialmente en una secuencia de ácido nucleico CGGCGAATCTATGACAATC (SEQ ID Nº 1). Reivindicación 14: La combinación de la reivindicación 1, caracterizada porque el uno o más quimioterapéuticos derivados de taxano se seleccionan de paclitaxel, docetaxel, cabazitaxel, análogo de Taxol SID 350, emulsión de docetaxel ANX-514, formulación de docetaxel CKD-810, microesferas lipídicas de docetaxel, nanofármacos cargados con docetaxel CRLX301, docetaxel-PNP y docetaxel liposomal.Compositions and methods for treating cancers, comprising administering a combination of antineoplastic agents, wherein the combination comprises chemotherapeutic agents derived from taxanes and one or more nucleic acid molecules capable of negatively regulating the expression of at least one splice variant of the IG20 gene, where not all splice variants of the IG20 gene are negatively regulated. In one embodiment, the splice variant of the IG20 gene is a MADD splice variant and the nucleic acid molecules are siRNA, hRNA and antisense oligonucleotides comprising a nucleic acid sequence complementary to the exon 13L nucleic acid sequence of the MADD splice variant or an exon 13L mRNA transcript of the MADD splice variant. Methods to treat cancers where a combination therapy with nucleic acid molecules capable of negatively regulating the expression of at least one splice variant of the IG20 gene and taxane-derived chemotherapeutic agents is applied. Claim 1: A combination of antineoplastic agents useful for treating cancer characterized in that it comprises an effective amount of one or more nucleic acid molecules capable of decreasing the expression of at least one splice variant of the IG20 gene, wherein it is not It reduces the expression of all splice variants of the IG20 gene, and one or more taxane-derived chemotherapeutic agents. Claim 3: The combination of claim 2, characterized in that the at least one splice variant of the IG20 gene is a MADD splice variant that exhibits exon 13L. Claim 4: The combination of claim 2, characterized in that the one or more nucleic acid molecules capable of decreasing the expression of the at least one splice variant of the IG20 gene are selected from siRNA, hRNA and antisense oligonucleotides. Claim 7: The combination of claim 6, characterized in that the siRNA and hRNA is encoded by a nucleic acid molecule that includes the structure: Xₛₑₙₜⁱᵈₒ - hairpin loop - Xₐₙₜⁱₛₑₙₜⁱᵈₒ, wherein X includes or consists essentially of a CGGCGAATCTATGACAATC nucleic acid sequence (SEQ ID No. 1). Claim 14: The combination of claim 1, characterized in that the one or more taxane-derived chemotherapeutic agents are selected from paclitaxel, docetaxel, cabazitaxel, Taxol analog SID 350, docetaxel emulsion ANX-514, docetaxel formulation CKD-810, microspheres Lipids of docetaxel, nanopharmaceuticals loaded with docetaxel CRLX301, docetaxel-PNP and docetaxel liposomal.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762481868P | 2017-04-05 | 2017-04-05 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AR111449A1 true AR111449A1 (en) | 2019-07-17 |
Family
ID=63712825
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ARP180100850A AR111449A1 (en) | 2017-04-05 | 2018-04-05 | SYNERGIC COMBINATION OF OLIGONUCLEOTIDES OF NUCLEIC ACIDS AND CHEMOTHERAPY WITH TAXANOS |
Country Status (3)
| Country | Link |
|---|---|
| AR (1) | AR111449A1 (en) |
| TW (1) | TW201902488A (en) |
| WO (1) | WO2018187519A1 (en) |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007084954A2 (en) * | 2006-01-19 | 2007-07-26 | The Board Of Trustees Of The University Of Illinois | Selective inhibition of ig20 splice variants to treat cancers |
-
2018
- 2018-04-03 TW TW107111856A patent/TW201902488A/en unknown
- 2018-04-05 WO PCT/US2018/026161 patent/WO2018187519A1/en not_active Ceased
- 2018-04-05 AR ARP180100850A patent/AR111449A1/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| TW201902488A (en) | 2019-01-16 |
| WO2018187519A1 (en) | 2018-10-11 |
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