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RU2001136014A - RECEPTOR-3 (R3) AGONISTS OF THE PEPTIDE ACTIVATOR OF THE PITUITARY ADENYLATICLICASE (RASAR) AND METHODS OF THEIR PHARMACOLOGICAL APPLICATION - Google Patents

RECEPTOR-3 (R3) AGONISTS OF THE PEPTIDE ACTIVATOR OF THE PITUITARY ADENYLATICLICASE (RASAR) AND METHODS OF THEIR PHARMACOLOGICAL APPLICATION

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Publication number
RU2001136014A
RU2001136014A RU2001136014/14A RU2001136014A RU2001136014A RU 2001136014 A RU2001136014 A RU 2001136014A RU 2001136014/14 A RU2001136014/14 A RU 2001136014/14A RU 2001136014 A RU2001136014 A RU 2001136014A RU 2001136014 A RU2001136014 A RU 2001136014A
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RU
Russia
Prior art keywords
seq
polypeptide
presented
pacap
mammal
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RU2001136014/14A
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Russian (ru)
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RU2269354C2 (en
Inventor
Кларк ПАН
Манами ЦУЦУМИ
Армен Б. ШАНАФЕЛТ
Original Assignee
Байер Корпорейшн
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Publication of RU2001136014A publication Critical patent/RU2001136014A/en
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Claims (31)

1. Полипептид, выбранный из группы, состоящей из SEQ ID NO 11-14, SEQ ID NO 18, SEQ ID NO 21-26, SEQ ID NO 32-36, SEQ ID NO 40-53, SEQ ID NO 57-61, SEQ ID NO 63-99, SEQ ID NO 102-119, SEQ ID NO 121-137, SEQ ID NO 139-177, SEQ ID NO 179, 180, SEQ ID NO 183-202, SEQ ID NO 322-341, и его функционально эквивалентных фрагментов производных и вариантов.1. The polypeptide selected from the group consisting of SEQ ID NO 11-14, SEQ ID NO 18, SEQ ID NO 21-26, SEQ ID NO 32-36, SEQ ID NO 40-53, SEQ ID NO 57-61, SEQ ID NO 63-99, SEQ ID NO 102-119, SEQ ID NO 121-137, SEQ ID NO 139-177, SEQ ID NO 179, 180, SEQ ID NO 183-202, SEQ ID NO 322-341, and its functionally equivalent fragments of derivatives and variants. 2. Полинуклеотид, кодирующий полипептидную последовательность по п.1, или его вырожденный вариант.2. Polynucleotide encoding the polypeptide sequence according to claim 1, or its degenerate version. 3. Вектор, включающий полинуклеотид по п.2.3. The vector comprising the polynucleotide according to claim 2. 4. Клетка-хозяин, включающая вектор по п.3.4. A host cell, comprising the vector according to claim 3. 5. Способ получения полипептида, включающий: (a) культивирование клетки-хозяина по п.4 в условиях, подходящих для экспрессии указанного полипептида, и (b) выделение полипептида из культуры клетки-хозяина.5. A method for producing a polypeptide, comprising: (a) culturing a host cell according to claim 4 under conditions suitable for expression of said polypeptide, and (b) isolating the polypeptide from the culture of the host cell. 6. Фармацевтическая композиция, включающая полипептид по п.1 в сочетании с фармацевтически приемлемым носителем.6. A pharmaceutical composition comprising a polypeptide according to claim 1 in combination with a pharmaceutically acceptable carrier. 7. Генотерапевтическая композиция, включающая полинуклеотид по п.2 в сочетании с терапевтически эффективным генотерапевтическим вектором.7. Gene therapy composition comprising a polynucleotide according to claim 2 in combination with a therapeutically effective gene therapy vector. 8. Полипептид по п.1, отличающийся тем, что указанный полипептид представлен в SEQ ID NO 18.8. The polypeptide according to claim 1, characterized in that the polypeptide is presented in SEQ ID NO 18. 9. Полипептид по п.1, отличающийся тем, что указанный полипептид представлен в SEQ ID NO 32.9. The polypeptide according to claim 1, characterized in that the polypeptide is presented in SEQ ID NO 32. 10. Полипептид по п.1, отличающийся •тем, что указанный полипептид представлен в SEQ ID NO 43.10. The polypeptide according to claim 1, characterized in that said polypeptide is presented in SEQ ID NO 43. 11. Полипептид по п.1, отличающийся тем, что указанный полипептид представлен в SEQ ID NO 45.11. The polypeptide according to claim 1, characterized in that the polypeptide is presented in SEQ ID NO 45. 12. Полипептид по п.1, отличающийся тем, что указанный полипептид представлен в SEQ ID NO 47.12. The polypeptide according to claim 1, characterized in that the polypeptide is presented in SEQ ID NO 47. 13. Полипептид по п.1, отличающийся тем, что указанный полипептид представлен в SEQ ID NO 50.13. The polypeptide according to claim 1, characterized in that the polypeptide is presented in SEQ ID NO 50. 14. Полипептид по п.1, отличающийся тем, что указанный полипептид представлен в SEQ ID NO 52.14. The polypeptide according to claim 1, characterized in that the polypeptide is presented in SEQ ID NO 52. 15. Полипептид по п.1, отличающийся тем, что указанный полипептид представлен в SEQ ID NO 71.15. The polypeptide according to claim 1, characterized in that the polypeptide is presented in SEQ ID NO 71. 16. Полипептид по п.1, отличающийся тем, что указанный полипептид представлен в SEQ ID NO 72.16. The polypeptide according to claim 1, characterized in that the polypeptide is presented in SEQ ID NO 72. 17. Полипептид по п.1, отличающийся тем, что указанный полипептид представлен в SEQ ID NO 83.17. The polypeptide according to claim 1, characterized in that the polypeptide is presented in SEQ ID NO 83. 18. Полипептид по п.1, отличающийся тем, что указанный полипептид представлен в SEQ ID NO 86.18. The polypeptide according to claim 1, characterized in that the polypeptide is presented in SEQ ID NO 86. 19. Полипептид по п.1, отличающийся тем, что указанный полипептид представлен в SEQ ID NO 87.19. The polypeptide according to claim 1, characterized in that the polypeptide is presented in SEQ ID NO 87. 20. Очищенное тело, которое специфически связывается с полипептидом по п.1.20. A purified body that specifically binds to the polypeptide of claim 1. 21. Способ лечения метаболического расстройства у млекопитающего, включающий введение млекопитающему терапевтически эффективного количества агониста PACAP-R3.21. A method of treating a metabolic disorder in a mammal, comprising administering to the mammal a therapeutically effective amount of a PACAP-R3 agonist. 22. Способ по п.21, отличающийся тем, что агонист PACAP-R3 характеризуется по крайней мере 10-кратной избирательностью в отношении PACAP-R3 по сравнению с PACAP-R2 или PACAP-R31.22. The method according to item 21, wherein the PACAP-R3 agonist is characterized by at least 10-fold selectivity for PACAP-R3 compared to PACAP-R2 or PACAP-R31. 23. Способ по п.21, отличающийся тем, что агонист PACAP-R3 характеризуется по крайней мере 100-кратной избирательностью в отношении PACAP-R3 по сравнению с PACAP-R2 или PACAP-R1.23. The method according to item 21, wherein the PACAP-R3 agonist is characterized by at least 100-fold selectivity for PACAP-R3 compared to PACAP-R2 or PACAP-R1. 24. Способ по п.21, отличающийся тем, что агонист PACAP-R3 выбирают из группы, состоящей из SEQ ID NO 11-14, SEQ ID NO 18, SEQ ID NO 21-26, SEQ ID NO 32-36, SEQ ID NO 40-53, SEQ ID NO 57-61, SEQ ID NO 63-99, SEQ ID NO 102-119, SEQ ID NO 121-137, SEQ ID NO 139-177, SEQ ID NO 179, 180, SEQ ID NO 183-202, SEQ ID NO 322-341, и его функционально эквивалентных фрагментов, производных и вариантов.24. The method according to item 21, wherein the PACAP-R3 agonist is selected from the group consisting of SEQ ID NO 11-14, SEQ ID NO 18, SEQ ID NO 21-26, SEQ ID NO 32-36, SEQ ID NO 40-53, SEQ ID NO 57-61, SEQ ID NO 63-99, SEQ ID NO 102-119, SEQ ID NO 121-137, SEQ ID NO 139-177, SEQ ID NO 179, 180, SEQ ID NO 183-202, SEQ ID NO 322-341, and its functionally equivalent fragments, derivatives and variants. 25. Способ по п.24, отличающийся тем, что агонист R3 выбирают из группы, состоящей из SEQ ID NO 18, SEQ ID NO 32, SEQ ID NO 43, SEQ ID NO 45, SEQ ID NO 47, SEQ ID NO 50, SEQ ID NO 52, SEQ ID NO 71, SEQ ID NO 72, SEQ ID NO 83, SEQ ID NO 86 и SEQ ID NO 87.25. The method according to paragraph 24, wherein the R3 agonist is selected from the group consisting of SEQ ID NO 18, SEQ ID NO 32, SEQ ID NO 43, SEQ ID NO 45, SEQ ID NO 47, SEQ ID NO 50, SEQ ID NO 52, SEQ ID NO 71, SEQ ID NO 72, SEQ ID NO 83, SEQ ID NO 86 and SEQ ID NO 87. 26. Способ по п.21, отличающийся тем, что указанным метаболическим расстройством является диабет 2-го типа.26. The method according to item 21, wherein the specified metabolic disorder is type 2 diabetes. 27. Способ по п.21, отличающийся тем, что указанное терапевтически эффективное количество находится в диапазоне от примерно 0,1 мкг/кг до примерно 1 мг/кг.27. The method according to item 21, wherein the specified therapeutically effective amount is in the range from about 0.1 μg / kg to about 1 mg / kg 28. Способ по п.21, отличающийся тем, что упомянутым метаболическим расстройством является преддиабетическое состояние нарушенной переносимости глюкозы.28. The method according to item 21, wherein said metabolic disorder is a prediabetic state of impaired glucose tolerance. 29. Вариант вазоактивного кишечного пептида, имеющий одну из структур, показанных на фиг.1, и его функциональные эквиваленты.29. A variant of a vasoactive intestinal peptide having one of the structures shown in FIG. 1 and its functional equivalents. 30. Способ стимуляции секреции инсулина в глюкозо-зависимом режиме у нуждающегося в этом млекопитающего, включающий введение указанному млекопитающему полипептида, выбранного из группы, состоящей из полипептидов фиг.1.30. A method of stimulating glucose-dependent insulin secretion in a mammal in need thereof, comprising administering to said mammal a polypeptide selected from the group consisting of the polypeptides of FIG. 1. 31. Способ лечения респираторного заболевания у млекопитающего, включающий введение млекопитающему терапевтически эффективного количества пептида, выбранного из группы, состоящей из SEQ ID NO 11-14, SEQ ID NO 18, SEQ ID NO 21-26, SEQ ID NO 32-36, SEQ ID NO 40-53, SEQ ID NO 57-61, SEQ ID NO 63-99, SEQ ID NO 102-119, SEQ ID NO 121-137, SEQ ID NO 139-177, SEQ ID NO 179, 180, SEQ ID NO 183-202, SEQ ID NO 322-341, и его функционально эквивалентных фрагментов производных и вариантов.31. A method of treating a respiratory disease in a mammal, comprising administering to the mammal a therapeutically effective amount of a peptide selected from the group consisting of SEQ ID NOS 11-14, SEQ ID NOS 18, SEQ ID NOS 21-26, SEQ ID NOS 32-36, SEQ ID NO 40-53, SEQ ID NO 57-61, SEQ ID NO 63-99, SEQ ID NO 102-119, SEQ ID NO 121-137, SEQ ID NO 139-177, SEQ ID NO 179, 180, SEQ ID NO 183-202, SEQ ID NO 322-341, and its functionally equivalent fragments of derivatives and variants.
RU2001136014/15A 1999-09-28 2000-09-27 Agonists of hypophysis adenylate cyclase peptide-activator receptor-3(r3)(pacap) and methods for their pharmacological using RU2269354C2 (en)

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US40783299A 1999-09-28 1999-09-28
US09/407,832 1999-09-28
US59528000A 2000-06-15 2000-06-15
US09/595,280 2000-06-15

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