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HEMOKININ-1 RECEPTOR AND HEMOKININ-1-DERIVED PEPTIDE UPDATE

外国特許コード F120006981
整理番号 S2010-1150-C0
掲載日 2012年10月29日
出願国 世界知的所有権機関(WIPO)
国際出願番号 2011JP069178
国際公開番号 WO 2012026526
国際出願日 平成23年8月25日(2011.8.25)
国際公開日 平成24年3月1日(2012.3.1)
優先権データ
  • 特願2010-191039 (2010.8.27) JP
  • 201161471338 (2011.4.4) US
発明の名称 (英語) HEMOKININ-1 RECEPTOR AND HEMOKININ-1-DERIVED PEPTIDE UPDATE
発明の概要(英語) The present invention provides a peptide that is an antagonist for SP and suppresses pain, inflammation, and itching. Furthermore, the present invention provides a method for searching for analgesic, anti-inflammatory, and anti-itch medication that use a receptor specific to HK-1, said receptor being G protein-coupled receptor (GPR) 83.
従来技術、競合技術の概要(英語) BACKGROUND ART
SP is 11 amino acids peptide, whose amino acid sequence Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2 (SEQ ID NO:1) [in the formula, C-terminus of the carboxyl group of the methionine is amidated. Denoted as above] is.
On the other hand, the HK-1 five amino acids of the 11 peptide, the amino acid sequence being Arg-Ser-Arg-Thr-Arg-Gln-Phe-Tyr-Gly-Leu-Met-NH2 (SEQ ID NO:2) of the present invention.
Belonging to the tachykinin both the SP and HK-1. Here, the tachykinin, C-terminus FXGLM-NH2 (here, X is a hydrophobic amino acid) peptides with a.
SP as well as vertebrate, and is also found in invertebrates, inflammation, pain, itching, involved in muscle contraction or the like, has various functions of the body. Therefore, to find antagonists of the new SP, SP is involved in many of the symptoms (for example, pain, inflammation and itching and the like) for inhibiting believed to contribute to the development of a medicament.
By the previous study up to this point, the SP N-terminal fragment (SP(1-7) ) Arg-Pro-Lys-Pro-Gln-Gln-Phe-NH2 (SEQ ID NO:3) and the C-terminal fragment (SP(7-11) ) Phe-Phe-Gly-Leu-Met-NH2 (SEQ ID NO:4) and divided into 2, and these fragments have different functions have been reported (Non-Patent Document 1). Specifically, the rats are administered to the mouse SP pain-related behavior (e.g., scratching) to induce, by administering an N-terminal fragment of the SP of the pain-related behavior can be suppressed. On the other hand, the C-terminal fragment of the SP that administration of a pain-related behavior is triggered.
In addition, the SP N-terminal fragment (SP(1-7) ) Arg-Pro-Lys-Pro-Gln-Gln-Phe-NH2 (SEQ ID NO:3) and the SP N-terminal fragment of (SP(1-8) ) Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-NH2 (SEQ ID NO:5) due to the SP is possible to suppress the pain-related behavior has been reported (Non-Patent Document 2 and 3).
Incidentally, human and rodent HK-1 of the TAC4 gene suggested that the presence thereof from a peptide, HK-1 specific receptors, HK-1 SP to the same group of the receptor for the peptide (neurokinin -1 receptor (NK1R) ) are different from each other is not known whether or not.
HK-1 in the same manner as the SP NK1R has a high affinity for a (non-patent document 4, 5, and 6), as well as intrathecal and SP of the HK-1 by administering to rats induced scratching, the action taken depends on the concentration of peptide administration induced (Non-Patent Document 7), the, the action of the known L-703,606 andagonisuto be inhibited by NK1R (non-patent documents 7 and 8) based on the, HK-1 NK1R receptors suggests that may view of the water.
However, (1) the intrathecal administration of SP induced thermal hyperalgesia are known (Non-Patent Document 9 and 10), HK-1 administration can no reaction at all (non-patent documents 7 and 11) tachykinin hemokinin of a peptide, (2) such as from the distal region of the C D and C hemokinin hemokinin 12 constituted by one common amino acid sequence (EK C/D) before the administration of C/D hemokinin, SP can be induced to prevent the scratching, HK-1 is possible to suppress the scratching induced (non-patent document 8) cannot, as (3) well as receptor desensitization of intracellular signaling systems involved in a variety of protein kinase inhibitors for receptor desensitization due to the processing in the evaluation index and the prevention of the action, and SP-induced receptor HK-1 different protein kinases involved in desensitization may be suggested based on the image (non-patent document 12), NK1R is different from the specific receptor for the HK-1 (HK-1-preferred receptor) is present, the function of these receptors are similar to each other is estimated not the same (non-patent document 7, 8, and 13).
  • 出願人(英語)
  • ※2012年7月以前掲載分については米国以外のすべての指定国
  • UNIVERSITY OF MIYAZAKI
  • 発明者(英語)
  • NISHIMORI Toshikazu
  • NAKAYAMA Rumi
国際特許分類(IPC)
指定国 National States: AE AG AL AM AO AT AU AZ BA BB BG BH BR BW BY BZ CA CH CL CN CO CR CU CZ DE DK DM DO DZ EC EE EG ES FI GB GD GE GH GM GT HN HR HU ID IL IN IS JP KE KG KM KN KP KR KZ LA LC LK LR LS LT LU LY MA MD ME MG MK MN MW MX MY MZ NA NG NI NO NZ OM PE PG PH PL PT QA RO RS RU SC SD SE SG SK SL SM ST SV SY TH TJ TM TN TR TT TZ UA UG US UZ VC VN ZA ZM ZW
ARIPO: BW GH GM KE LR LS MW MZ NA SD SL SZ TZ UG ZM ZW
EAPO: AM AZ BY KG KZ MD RU TJ TM
EPO: AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR
OAPI: BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

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