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USE OF PITUITARY ADENYLATE CYCLASE-ACTIVATING POLYPEPTIDE (PACAP) AND PACAP ANALOGS AS ADJUNCTIVE TREATMENTS WITH INHIBITORS OF CALCINEURIN OR INHIBITORS OF THE MAMMALIAN TARGET OF RAPAMYCIN (mTOR) COMPLEXES

Номер патента: US20120309683A1. Автор: Batuman Vecihi, Coy David H., Li Min, Maderdrut Jerome L.. Владелец: The Administrators of the Tulane Educational Fund. Дата публикации: 06-12-2012.
This invention relates to methods and compositions for the treatment, management, reduction, or prevention of injuries to one or more major organs of the body, e.g., the brain, heart, lung, kidneys, liver, and gastrointestinal tract, of a mammal (e.g., a human) caused by one or more calcineurin or mammalian target of rapamycin (mTOR) complex inhibitors. The methods include administering an effective amount of one or more pituitary adenylate cyclase-activating polypeptide (PACAP)-like compounds to the mammal. Combination therapy with one or more PACAP-like compounds, either alone or in combination with one or more other prophylactic/therapeutic agents, plus one or more inhibitors of either calcineurin or the mTOR complexes can be used to treat organ transplantation, autoimmune diseases, graft-versus-host disease, Behçet's disease, hematological cancers, noninfectious uveitis, sarcoidosis, tuberous sclerosis complex, acute neurological diseases, age-related neurodegenerative diseases, Huntington's disease and other CAG codon repeat expansion diseases, keratoconjunctivitis sicca, and restenosis. 1. A method for treating , managing , or reducing an injury to one or more major organs of the body of a mammal resulting from administration of one or more of a calcineurin inhibitor , a mammalian target of rapamycin (mTOR) inhibitor , or a tyrosine kinase inhibitor to said mammal , said method comprising administering to said mammal an effective amount of at least one pituitary adenylate cyclase-activating polypeptide (PACAP)-like compound.2. The method of claim 1 , wherein said PACAP-like compound comprises a polypeptide sequence having at least 90% sequence identity to a sequence selected from SEQ ID NOs: 1 to 72.3. The method of or claim 1 , wherein said PACAP-like compound comprises a polypeptide sequence having at least 95% sequence identity to a sequence selected from SEQ ID NOs: 1 to 72.4. The method of any one of to claim 1 , wherein said PACAP-like compound comprises ...

ANALOGS OF PITUITARY ADENYLATE CYCLASE-ACTIVATING POLYPEPTIDE (PACAP) AND METHODS FOR THEIR USE

Номер патента: US20130065816A1. Автор: Coy David H., Li Min, Maderdrut Jerome L.. Владелец: The Administrators of the Tulane Educational Fund. Дата публикации: 14-03-2013.
This invention relates to novel analogs of pituitary adenylate cyclase-activating polypeptide (PACAP), which are agonists for the PACAP/vasoactive intestinal peptide (VIP) receptors: PAC1, VPAC1 and VPAC2 receptors. These PACAP analogs can be used as prophylactic/therapeutic agents for a wide range of medical disorders, including (but not limited to) cancer and autoimmune disease. These PACAP analogs can be coupled to suitable radionuclides and used in the localization, diagnosis and treatment of disseminated cancers and metastatic tumors, or coupled to small molecule therapeutics and used as vectors for targeted drug delivery. This invention also provides pharmaceutical compositions of one or more PACAP-like compounds of the invention either alone or in combination with one or more other prophylactic/therapeutic agents. 3. A polypeptide having at least 90% sequence identity to a sequence selected from SEQ ID NOs: 4-13.46.-. (canceled)7. The polypeptide of claim 1 , wherein said polypeptide is conjugated to one or more radionuclides or small molecules.8. The polypeptide of claim 7 , wherein said radionuclide is C claim 7 , N claim 7 , O claim 7 , F claim 7 , Fe claim 7 , Co claim 7 , Cu claim 7 , Cu claim 7 , Cu claim 7 , Cu claim 7 , Ga claim 7 , Ga claim 7 , Zn claim 7 , Zn claim 7 , As claim 7 , As claim 7 , As claim 7 , Br claim 7 , Br claim 7 , Rb claim 7 , Y claim 7 , Zr claim 7 , In claim 7 , In claim 7 , I claim 7 , I claim 7 , I claim 7 , I claim 7 , I claim 7 , Xe claim 7 , Lu claim 7 , Gd claim 7 , Gd claim 7 , Gd claim 7 , Gd claim 7 , Gd claim 7 , Tc claim 7 , Tc claim 7 , or Tc.9. (canceled)10. The polypeptide of claim 7 , wherein said small molecule is a therapeutic or anticancer agent selected from cisplatin claim 7 , carboplatin claim 7 , oxaliplatin claim 7 , bleomycin claim 7 , mitomycin C claim 7 , calicheamicins claim 7 , maytansinoids claim 7 , geldanamycin claim 7 , doxorubicin claim 7 , idarubicin claim 7 , daunorubicin claim 7 , epirubicin ...

ANALOGS OF PITUITARY ADENYLATE CYCLASE-ACTIVATING POLYPEPTIDE (PACAP) AND METHODS FOR THEIR USE

Номер патента: US20150104388A1. Автор: Coy David H., Li Min, Maderdrut Jerome L.. Владелец: . Дата публикации: 16-04-2015.
This invention relates to novel analogs of pituitary adenylate cyclase-activating polypeptide (PACAP), which are agonists for the PACAP/vasoactive intestinal peptide (VIP) receptors: PAC1, VPAC1 and VPAC2 receptors. These PACAP analogs can be used as prophylactic/therapeutic agents for a wide range of medical disorders, including (but not limited to) cancer and autoimmune disease. These PACAP analogs can be coupled to suitable radionuclides and used in the localization, diagnosis and treatment of disseminated cancers and metastatic tumors, or coupled to small molecule therapeutics and used as vectors for targeted drug delivery. This invention also provides pharmaceutical compositions of one or more PACAP-like compounds of the invention either alone or in combination with one or more other prophylactic/therapeutic agents. 1. An isolated compound having formula (I) , or a pharmaceutically acceptable salt thereof:{'br': None, 'sup': 1', '1', '2', '3', '4', '5', '6', '7', '8', '9', '10', '11', '12', '13', '14', '15-', '16', '17', '18', '19', '20', '21', '22', '23', '24', '25', '26', '27', '28', '30', '31', '32', '33', '34', '35', '36', '37', '38', '2, 'R-A-A-A-A-A-A-A-A-A-A-A-A-A-A-AA-A-A-A-A-A-A-A-A-A-A-A-A-A-A-A-A-A-A-A-A-A-R,'}wherein:{'sup': '1', 'smallcaps': D', 'D', 'D', 'D, 'Ais His, -His, Tyr, -Tyr, Trp, -Trp, Pal, or -Pal;'}{'sup': '2', 'smallcaps': D', 'D', 'D', 'D', 'D, 'Ais Ser, -Ser, hSer, N-Me-Ser, Thr, -Thr, Ala, -Ala, Ile, -Ile, Pro, -Pro, Abu, Aib, Acb, Ach, Acpe, or Acpr;'}{'sup': '3', 'Ais Pip;'}{'sup': '4', 'smallcaps': 'D', 'Ais Gly, Ala, -Ala, β-Ala, Gaba, Abu, Aib, Acb, Ach, Acpe, or Acpr;'}{'sup': '5', 'Ais Ile, Leu, Nle, Val, Nva, Aib, Acb, Ach, Acpe, or Acpr;'}{'sup': '6', 'Ais Phe, Tyr, Trp, Cha, Bip, or Nal;'}{'sup': '7', 'Ais Thr, Ser, hSer, or Val;'}{'sup': '8', 'Ais Asp, Asn, or Glu;'}{'sup': '9', 'Ais Ser, hSer, Thr, Asn, Asp, Ala, Abu, Aib, Acb, Ach, Acpe, or Acpr;'}{'sup': '10', 'Ais Tyr, Phe, Cha, Nal, or Trp;'}{'sup': '11', 'Ais Ser, ...

ANALOGS OF PITUITARY ADENYLATE CYCLASE-ACTIVATING POLYPEPTIDE (PACAP) AND METHODS FOR THEIR USE

Номер патента: US20160122406A1. Автор: Coy David H., Maderdrut Jerome L.. Владелец: . Дата публикации: 05-05-2016.
This invention relates to analogs of pituitary adenylate cyclase-activating polypeptide (PACAP), which are agonists for the PACAP/vasoactive intestinal peptide (VIP) receptors: PAC, VPACand VPACreceptors. These PACAP analogs can be used as prophylactic/therapeutic agents for a wide range of medical disorders. These PACAP analogs coupled to suitable radionuclides can be used in the localization, diagnosis and treatment of disseminated cancers and metastatic tumors, and coupled to small molecule therapeutics can be used as vectors for targeted drug delivery. This invention also provides pharmaceutical compositions of one or more PACAP analogs of the invention either alone or in combination with one or more other prophylactic/therapeutic agent. 3. A PACAP analog having at least 90% sequence identity to a sequence selected from SEQ ID NOs: 4-78 , wherein said PACAP analog comprises an imidazole-4-acetic acid (Iaa) , an imidazole-4-acrylic acid (Iac) , an imidazole-4-carboxylic acid (Ica) , or 3-pyridylacetic acid (Paa) at position 1.4. The PACAP analog of claim 3 , wherein the amino acid residue at position 2 is selected from Ser claim 3 , D-Ser claim 3 , hSer claim 3 , N-Me-Ser claim 3 , Thr claim 3 , D-Thr claim 3 , D-Tyr claim 3 , Ala claim 3 , D-Ala claim 3 , Ile claim 3 , D-He claim 3 , Pro claim 3 , Hyp claim 3 , Abu claim 3 , Aib claim 3 , Acb claim 3 , Ach claim 3 , Acpe claim 3 , or Acpr.5. The PACAP analog of any one of and claim 3 , wherein the amino acid residue at position 16 is selected from Gln claim 3 , Glu claim 3 , Asn claim 3 , Asp claim 3 , Ala claim 3 , Aib claim 3 , Acb claim 3 , Ach claim 3 , Acpe claim 3 , and Acpr.6. The PACAP analog of any one of to claim 3 , wherein the amino acid residue at position 17 is selected from Met claim 3 , Nle claim 3 , Leu claim 3 , Ile claim 3 , Ala claim 3 , Abu claim 3 , Aib claim 3 , Acb claim 3 , Ach claim 3 , Acpe claim 3 , and Acpr.7. The PACAP analog of any one of to claim 3 , wherein the amino acid residue ...

Use of pituitary adenylate cyclase-activating polypeptide (pacap) and pacap analogs for treating contrast-induced nephropathy

Номер патента: US20140314838A1. Автор: David H. Coy, Jerome L. Maderdrut, Min Li, Vecihi Batuman. Владелец: Tulane University. Дата публикации: 23-10-2014.
Featured are methods and compositions for treating, managing, preventing, or reducing injury to the kidney of a mammal (e.g., a human) caused by one or more iodinated radiocontrast media. The methods include administering an effective amount of one or more pituitary adenylate cyclase-activating polypeptide (PACAP)-like compounds, which includes native human PACAP38, native human PACAP27, native human vasoactive intestinal peptide (VIP), their agonists, analogs, fragments, and derivatives, with activities toward one or more of the PACAP/VIP receptors, including all of their various isoforms. Also provided are pharmaceutical compositions of one or more PACAP-like compounds, either alone or in combination with one or more other prophylactic/therapeutic agents useful for treating, managing, or preventing injury to the kidney of a mammal (e.g., a human) undergoing treatment with one or more iodinated radiocontrast media. Also featured is an in vivo mouse model for testing the efficacy of cytoprotective agents against contrast-induced nephropathy.

Analogs of pituitary adenylate cyclase-activating polypeptide (PACAP) and methods for their use

Номер патента: US8916517B2. Автор: David H. Coy, Jerome L. Maderdrut, Min Li. Владелец: Administrators of the Tulane Educational Fund . Дата публикации: 23-12-2014.
This invention relates to novel analogs of pituitary adenylate cyclase-activating polypeptide (PACAP), which are agonists for the PACAP/vasoactive intestinal peptide (VIP) receptors: PAC1, VPAC1 and VPAC2 receptors. These PACAP analogs can be used as prophylactic/therapeutic agents for a wide range of medical disorders, including (but not limited to) cancer and autoimmune disease. These PACAP analogs can be coupled to suitable radionuclides and used in the localization, diagnosis and treatment of disseminated cancers and metastatic tumors, or coupled to small molecule therapeutics and used as vectors for targeted drug delivery. This invention also provides pharmaceutical compositions of one or more PACAP-like compounds of the invention either alone or in combination with one or more other prophylactic/therapeutic agents.

Use of pituitary adenylate cyclase-activating polypeptide (pacap) and pacap analogs as adjunctive treatments with anticancer agents

Номер патента: CA2738549A1. Автор: David H. Coy, Jerome L. Maderdrut, Min Li, Vecihi Batuman. Владелец: Tulane University. Дата публикации: 01-04-2010.
La présente invention concerne des procédés et des compositions pour le traitement, le contrôle ou la prévention de lésions d'un ou plusieurs des organes du corps, tels que le cerveau, le coer, le poumon, les reins, le foie, et le tractus gastro-intestinal, d'humains ou d'autres mammifères causées par un ou plusieurs agents anticancéreux. Les procédés de cette invention consistent en l'administration d'une quantité efficace d'un ou plusieurs composés de type polypeptide activateur d'adénylate cyclase hypophysaire (PACAP), qui comprennent PACAP38 humain natif, PACAP27 humain natif, le peptide intestinal vasoactif (VIP) humain natif, leurs agonistes, analogues, fragments, et dérivés, ayant des activités sur un ou plusieurs des récepteurs de PACAP/VIP, comprenant toutes leurs différentes isoformes. Cette invention concerne en outre des compositions pharmaceutiques d'un ou plusieurs composés de type PACAP de l'invention, seuls ou en combinaison avec un ou plusieurs autres agents prophylactiques/thérapeutiques utiles pour le traitement, le contrôle ou la prévention de lésions des organes du corps d'humains ou d'autres mammifères soumis à une chimiothérapie anticancéreuse. Une thérapie d'association avec un ou plusieurs composés de type PACAP plus un ou plusieurs agents anticancéreux peut être utilisée dans le traitement de cancers hématologiques. The present invention relates to methods and compositions for the treatment, control, or prevention of damage to one or more of the body's organs, such as the brain, heart, lung, kidney, liver, and tract. gastrointestinal, humans or other mammals caused by one or more anticancer agents. The methods of this invention comprise the administration of an effective amount of one or more pituitary adenylate cyclase activator polypeptide (PACAP) compounds, which include native human PACAP38, native human PACAP27, vasoactive intestinal peptide (VIP ) native human, their agonists, ...
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