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117 条记录 (耗时 0.042 秒)

    SSTR1-selective analogs
    21.
    发明授权
    SSTR1-selective analogs 失效
    SSTR1选择性类似物

    公开(公告)号：US07019109B2

    公开(公告)日：2006-03-28

    申请号：US10099240

    申请日：2002-03-15

    申请人： Jean E. F. Rivier ,  Jean Claude Reubi

    发明人： Jean E. F. Rivier ,  Jean Claude Reubi

    IPC分类号： C07K7/665 ,  C07K7/64

    CPC分类号： C07K14/6555 ,  A61K51/083 ,  A61K51/088

    摘要： Analogs of SRIF which are selective for SSTR1 in contrast to the other cloned SRIF receptors. These analogs are useful in determining the tissue and cellular expression of the receptor SSTR1 and its biological role in the endocrine, exocrine and nervous system, as well as in regulating tumor growth. SRIF analog peptides, such as des-AA1,2,5[D-Trp8, NαMeIAmp9, Tyr11]-SRIF and counterparts incorporating Cbm at the N-terminus and/or NαSer13, inhibit the binding of a universal SRIF radioligand to the cloned human receptor SSTR1, but they do not bind with significant affinity to human SSTR2, SSTR3, SSTR4 or SSTR5. By incorporating an iodinated tyrosine in position-2 or in position-11 in these SSTR1-selective SRIF analogs, a labeled compound useful in drug-screening methods is provided. The N-terminus accommodates bulky moieties without loss of selectivity, and a carbamoyl moiety or a conjugating agent that will accept a radioactive nuclide or will link to a cytotoxin may be present at the N-terminus.

    摘要翻译： 与其他克隆的SRIF受体相反，SRIF的选择性为SSTR1的类似物。 这些类似物可用于确定受体SSTR1的组织和细胞表达及其在内分泌，外分泌和神经系统中的生物学作用以及调节肿瘤生长。 SRIF类似物肽，例如des-AA 12,5，D-Trp 8，Nα，Me 3， SUP>，Tyr 11] - SRIF和在N末端和/或NαSer 13结合Cbm的对应物抑制结合 与克隆的人受体SSTR1通用的SRIF放射配体，但它们不以与人SSTR2，SSTR3，SSTR4或SSTR5的显着亲和力结合。 通过在这些SSTR1选择性SRIF类似物中掺入位置2或位置-11的碘化酪氨酸，提供了可用于药物筛选方法的标记化合物。 N-末端可容纳大量的部分而不损失选择性，并且可以在N-末端存在将接受放射性核素或将连接至细胞毒素的氨基甲酰基部分或共轭试剂。

    Melanin-concentrating hormones
    22.
    发明授权
    Melanin-concentrating hormones 失效
    黑色素浓缩激素

    公开(公告)号：US5049655A

    公开(公告)日：1991-09-17

    申请号：US326984

    申请日：1989-03-22

    申请人： Joan Vaughan ,  Wolfgang H. Fischer ,  Jean E. F. Rivier ,  Jean-Louis M. Nahon ,  Francoise G. Presse ,  Wylie W. Vale, Jr.

    发明人： Joan Vaughan ,  Wolfgang H. Fischer ,  Jean E. F. Rivier ,  Jean-Louis M. Nahon ,  Francoise G. Presse ,  Wylie W. Vale, Jr.

    IPC分类号： C12N15/09 ,  A61K38/00 ,  A61K38/04 ,  A61P35/00 ,  C07K7/06 ,  C07K7/08 ,  C07K7/64 ,  C07K14/00 ,  C07K14/575 ,  C12N15/12 ,  C12N15/16

    CPC分类号： C07K7/08 ,  C07K7/64 ,  A61K38/00 ,  Y10S530/827 ,  Y10S530/854

    摘要： Mammalian melanin-concentrating hormone (MCH) is isolated from rat tissue, purified and characterized. These MCH peptides are useful for treating skin disorders, for suppressing the proliferation of skin tumor cells, such as melanomas in mammals, and for modulating the secretion of ACTH. Generally, peptides are provided which have the following formula: ##STR1## or which are naturally occurring homologs of the peptide with said formula. The peptides which are the naturally occurring MCH homologs of mammalian species other than rat can also be obtained using the materials disclosed, as demonstrated specifically with human MCH, which is found to have the same structure as rat MCH. Also disclosed are the amino acid sequences of, and the nucleotide sequences of the cDNAs which encode, the putative precursors of rat MCH and human MCH. These precursors may also include one or more biologically active peptides N-terminally of the mature MCH's. Among these peptides, which are thought to be formed from the MCH precursors, are the peptide with the sequence H-Glu-Ile-Gly-Asp-Glu-Glu-Asn-Ser-Ala-Lys-Phe-Pro-Ile-NH.sub.2, which is cross-reactive with antibodies against alpha-MSH and CRF, and the peptide with the sequence H-Gly-X.sub.NGE -Phe-Pro-Ala-Glu-Asn-Gly-Val-Gln-Asn-Thr-Glu-Ser-Thr-Gln-Glu-OH, wherein X.sub.NGE is Pro-Ala-Val or Ser-Val-Ala, which is cross-reactive with antibodies against GRF.

    摘要翻译： 从大鼠组织中分离哺乳动物黑色素浓缩激素（MCH），进行纯化和表征。 这些MCH肽可用于治疗皮肤病症，抑制皮肤肿瘤细胞增殖，如哺乳动物的黑素瘤，以及调节ACTH的分泌。 通常，提供具有下式的肽：＆lt; IMAGE＆gt;或具有所述式的肽的天然存在同系物。 作为除大鼠之外的哺乳动物物种的天然存在的MCH同源物的肽也可以使用公开的材料获得，如用人MCH特异性证实的，其被发现具有与大鼠MCH相同的结构。 还公开了编码大鼠MCH和人MCH的推定前体的cDNA的氨基酸序列和cDNA的核苷酸序列。 这些前体还可以包括成熟MCH的N-末端的一种或多种生物活性肽。 在这些被认为由MCH前体形成的肽中，具有序列H-Glu-Ile-Gly-Asp-Glu-Glu-Asn-Ser-Ala-Lys-Phe-Pro-Ile-NH 2的肽 ，其与抗α-MSH和CRF的抗体具有交叉反应性，并且具有序列H-Gly-XNGE-Phe-Pro-Ala-Glu-Asn-Gly-Val-Gln-Asn-Thr-Glu-Ser -Thr-Gln-Glu -OH，其中XNGE是Pro-Ala-Val或Ser-Val-Ala，其与抗GRF的抗体交叉反应。

    Human inhibin
    23.
    发明授权
    Human inhibin 失效
    人抑制素

    公开(公告)号：US4737578A

    公开(公告)日：1988-04-12

    申请号：US848924

    申请日：1986-04-07

    申请人： Ronald M. Evans ,  Michael G. Rosenfeld ,  Gail Cerelli ,  Kelly E. Mayo ,  Joachim Spiess ,  Jean E. F. Rivier ,  Wylie W. Vale, Jr.

    发明人： Ronald M. Evans ,  Michael G. Rosenfeld ,  Gail Cerelli ,  Kelly E. Mayo ,  Joachim Spiess ,  Jean E. F. Rivier ,  Wylie W. Vale, Jr.

    IPC分类号： A61K38/00 ,  C07K14/575 ,  C07K7/10 ,  C07K13/00

    CPC分类号： C07K14/575 ,  A61K38/00 ,  Y10S930/26

    摘要： Proteins with inhibin activity having a weight of about 32,000 daltons. The molecule is composed of two chains having molecular weights of about 18,000 and about 14,000 daltons, respectively, which are bound together by disulfide bonding. The 18K chain is obtained from the human inhibin gene and has the formula: H-Ser-Thr-Pro-Leu-Met-Ser-Trp-Pro-Trp-Ser-Pro-Ser-Ala-Leu-Arg-Leu-Leu-Gln-Arg-Pro-Pro-Glu-Glu-Pro-Ala-Ala-His-Ala-Asn-Cys-His-Arg-Val-Ala-Leu-Asn-Ile-Ser-Phe-Gln-Glu-Leu-Gly-Trp-Glu-Arg-Trp-Ile-Val-Tyr-Pro-Pro-Ser-Phe-R.sub.65 -Phe-His-Tyr-Cys-His-Gly-Gly-Cys-Gly-Leu-His-Ile-Pro-Pro-Asn-Leu-Ser-Leu-Pro-Val-Pro-Gly-Ala-Pro-Pro-Thr-Pro-Ala-Gln-Pro-Tyr-Ser-Leu-Leu-Pro-Gly-Ala-Gln-Pro-Cys-Cys-Ala-Ala-Leu-Pro-Gly-Thr-Met-Arg-Pro-Leu-His-Val-Arg-Thr-Thr-Ser-Asp-Gly-Gly-Tyr-Ser-P e-Lys-Tyr-Glu-Thr-Val-Pro-Asn-Leu-Leu-Thr-Gln-His-Cys-Ala-Cys-Ile-OH, wherein R.sub.65 is Ile or Arg. The 18K chain is connected by disulfide bonding to the 14K chain.

    摘要翻译： 具有约32,000道尔顿重量的具有抑制素活性的蛋白质。 该分子由分子量分别为约18,000和约14,000道尔顿的两条链组成，它们通过二硫键结合在一起。 18K链由人抑制素基因得到，具有下式：H-Ser-Thr-Pro-Leu-Met-Ser-Trp-Pro-Trp-Ser-Pro-Ser-Ala-Leu-Arg-Leu-Leu Gln-Arg-Pro-Pro-Glu-Glu-Pro-Ala-Ala-His-Ala-Asn-Cys-His-Arg-Val-Ala-Le-Asn-Ile-Ser-Phe-Gln-Glu- Leu-Gly-Trp-Glu-Arg-Trp-Ile-Val-Tyr-Pro-Pro-Ser-Phe-R65-Phe-His-Tyr-Cys-His-Gly-Gly-Cys-Gly-Leu-His- Ile-Pro-Pro-As n-Leu-Ser-Leu-Pro-Val-Pro-Gly-Ala-Pro-Pro-Thr-Pro-Ala-Gln-Pro-Tyr-Ser-Leu-Leu-Pro-Gly -Ala-Gln-Pro-Cys-Cys-Ala-Ala-Leu-Pro-Gly-Thr-Met-Arg-Pr-Leu-His-Val-Arg-Thr-Thr-Ser-Asp-Gly-Gly- Tyr-Ser-P e-Lys-Tyr-Glu-Thr-Val-Pro-Asn-Leu-Leu-Thr-Gln-His-Cys-Ala-Cys-Ile-OH，其中R65是Ile或Arg。 18K链通过二硫键与14K链连接。

    Peptides containing an aliphatic-aromatic ketone side chain
    24.
    发明授权
    Peptides containing an aliphatic-aromatic ketone side chain 失效
    含有脂肪族 - 芳香族酮侧链的肽

    公开(公告)号：US4677193A

    公开(公告)日：1987-06-30

    申请号：US704299

    申请日：1985-02-22

    申请人： Jean E. F. Rivier ,  Harry A. Anderson ,  Wylie W. Vale, Jr.

    发明人： Jean E. F. Rivier ,  Harry A. Anderson ,  Wylie W. Vale, Jr.

    IPC分类号： A61K38/04 ,  A61K38/00 ,  A61K38/22 ,  A61P5/00 ,  C07K1/113 ,  C07K7/06 ,  C07K7/23 ,  C07K14/00 ,  C07K14/575 ,  C07K7/20

    CPC分类号： C07K7/23 ,  A61K38/00 ,  Y10S930/13

    摘要： GnRH peptide analogs which regulate the secretion of gonadotropins by the pituitary gland and either promote or inhibit the release of steroids by the gonads. Administration of an effective amount of a GnRH antagonist prevents ovulation of female mammalian eggs and/or the release of gonadotropins. Administration of GnRH agonists can be used to regulate fertility in male and female mammals.These and other peptide hormones exhibit improved binding efficiency and biological potency as a result having a residue in a critical, generally central location in the chain which residue contains a mixed alkyl ketone side-chain terminating in an aromatic group. Methods for efficiently synthesizing these peptides from readily available compounds are disclosed.

    摘要翻译： GnRH肽类似物，其调节垂体分泌促性腺激素并促进或抑制性腺释放类固醇。 施用有效量的GnRH拮抗剂可防止雌性哺乳动物卵的排卵和/或释放促性腺激素。 GnRH激动剂的施用可用于调节雄性和雌性哺乳动物的生育力。 这些和其它肽激素表现出改善的结合效率和生物效力，因此在链中的关键的，通常中心的位置具有残基，残基含有终止于芳族基团的混合烷基酮侧链。 公开了从容易获得的化合物有效地合成这些肽的方法。

    CRF analogs
    26.
    发明授权
    CRF analogs 失效
    CRF类似物

    公开(公告)号：US4594329A

    公开(公告)日：1986-06-10

    申请号：US610110

    申请日：1984-05-14

    申请人： Wylie W. Vale, Jr. ,  Jean E. F. Rivier

    发明人： Wylie W. Vale, Jr. ,  Jean E. F. Rivier

    IPC分类号： A61K38/00 ,  C07K14/575 ,  C07K7/00 ,  A61K37/02

    CPC分类号： C07K14/57509 ,  A61K38/00 ,  Y10S436/817

    摘要： Analogs of rCRF and oCRF are disclosed that can be administered to achieve a substantial elevation of ACTH, .beta.-endorphin, .beta.-lipotropin, other products of the pro-opiomelanocortin gene and corticosterone levels and/or a lowering of blood pressure over an extended period of time. One analog which has been found to be particularly potent is: H-Ser-Gln-Glu-Pro-Pro-Ile-Ser-Leu-Asp-Leu-Thr-Phe-His-Leu-Leu-Arg-Glu-Met-Leu-Glu-Met-Ala-Lys-Ala-Glu-Gln-Glu-Ala-Glu-Gln-Ala-Ala-Leu-Asn-Arg-Leu-Leu-Leu-Glu-Glu-Ala-NH.sub.2. In the analogs, one or more of the first five N-terminal residues may be deleted or may be substituted by a peptide up to 10 amino acids long and/or by an acylating agent containing up to 7 carbon atoms. A number of other substitutions may also be made throughout the chain. These analogs or pharmaceutically or veterinarily acceptable salts thereof, dispersed in a pharmaceutically or veterinarily acceptable liquid or solid carrier, can be administered to mammals, including humans. These analogs may also be used as stimulants to elevate mood and improve memory and learning, as well as diagnostically.

    摘要翻译： 公开了rCRF和oCRF的类似物，其可被施用以实现ACTH，β-内啡肽，β-促肌动蛋白，前 - 肌动蛋白皮质素基因的其他产物和皮​​质酮水平的显着升高和/或延长期间的血压降低 的时间。 已经发现特别有效的一种类似物是：H-Ser-Gln-Glu-Pro-Pro-Ile-Ser-Leu-Asp-Leu-Thr-Phe-His-Leu-Leu-Arg-Glu- Leu-Glu-Met-Ala-Lys-Ala-Glu-Gln-Glu-Ala-Glu-Gln-Ala-Ala-Leu-Asn -Arg-Leu-Leu-Leu-Glu-Glu-Ala-NH2。 在类似物中，前五个N-末端残基中的一个或多个可以被缺失或可被长达10个氨基酸的肽和/或被含有至多7个碳原子的酰化剂所取代。 还可以在整个链中进行许多其它取代。 分散在药学上或兽医学上可接受的液体或固体载体中的这些类似物或其药学或兽医学上可接受的盐可以施用于哺乳动物，包括人。 这些类似物也可以用作兴奋剂以提高心情，改善记忆和学习以及诊断。

    GRF Analogs
    28.
    发明授权
    GRF Analogs 失效
    GRF类似物

    公开(公告)号：US4529595A

    公开(公告)日：1985-07-16

    申请号：US457862

    申请日：1983-01-13

    申请人： Jean E. F. Rivier ,  Wylie W. Vale, Jr.

    发明人： Jean E. F. Rivier ,  Wylie W. Vale, Jr.

    IPC分类号： C07K14/61 ,  A23K1/16 ,  A61K38/00 ,  A61K38/25 ,  C07K14/60 ,  C07C103/52 ,  A61K37/02

    CPC分类号： C07K14/60 ,  A23K20/147 ,  A61K38/00 ,  Y10S930/12

    摘要： Human pancreatic GRF analogs which are extremely potent in stimulating the release of pituitary GH in mammals and which have the formula: H-R-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-R.sub.15 -Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-R.sub.27 -Ser-Arg-Gln-Gln-Gly-Glu-Ser-Asn-Gln-Glu-Arg-Gly-Ala-Y wherein R is selected from the D- and L-isomers of Tyr, Phe and His, R.sub.15 is Gly or D-Ala, R.sub.27 is selected from the group consisting of the D- and L-isomers of Ala, Nle, Ile, Leu, Met and Val, and Y signifies the carboxyl moiety of the amino acid residue at the C-terminal and is the radical --COOR.sub.1,--CR.sub.1 O,--CONHNHR.sub.1,--CON(R.sub.1)(R.sub.2) or --CH.sub.2 OR.sub.1, with R.sub.1 and R.sub.2 being lower alkyl or hydrogen, provided that when R is Tyr, R.sub.27 is other than Met. Phe may be substituted for Tyr in the 10-position, and D-Ala may be substituted for Gly in the 28-position. These peptides or biologically active fragments thereof, which will generally extend from the N-terminal to the vicinity of a residue between positions 27 and 32, as well as nontoxic salts of any of the foregoing, may be administered therapeutically to animals, including humans, and may be used diagnostically.

    摘要翻译： 人胰腺GRF类似物在刺激哺乳动物垂体GH的释放方面非常有效，具有以下分子式：HR-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu -R15-Gln-Leu-Se-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-R27-Ser-Arg-Gln-Gln-Gly-Glu-Ser-Asn-Gln-Glu-Arg- Gly-Ala-Y其中R选自Tyr，Phe和His的D-和L-异构体，R15是Gly或D-Ala，R27选自Ala， Nle，Ile，Leu，Met和Val，Y表示C-末端的氨基酸残基的羧基部分，是-COOR1，-CR1O，-CONHNHR1，-CON（R1）（R2）或-CH2OR1 其中R1和R2是低级烷基或氢，条件是当R为Tyr时，R27不是Met。 Phe可以取代10位的Tyr，D-Ala可以取代28位的Gly。 这些肽或其生物活性片段通常从N末端延伸至位置27和32之间的残基，以及前述任何一种的无毒盐，可以治疗性地给予动物，包括人， 并且可以在诊断上使用。

    CCK Agonists II
    29.
    发明授权
    CCK Agonists II 失效
    CCK激动剂二

    公开(公告)号：US4490364A

    公开(公告)日：1984-12-25

    申请号：US522846

    申请日：1983-08-12

    申请人： Jean E. F. Rivier ,  Botond Penke

    发明人： Jean E. F. Rivier ,  Botond Penke

    IPC分类号： A61K38/00 ,  C07K14/595 ,  A61K37/00 ,  C07C103/52

    CPC分类号： C07K14/5955 ,  A61K38/00

    摘要： Analogs of CCK(1-8) having dissociated activity with respect to stimulating the contraction of the gall bladder and arresting the secretion of gastric acid. Various analogs also exhibit improved anticonvulsive potency. The peptides are characterized by the following formula:X--R.sub.0 --R.sub.1 --Tyr(Y)--R.sub.3 --R.sub.4 --Trp--R.sub.6 --R.sub.7 --R.sub.8 --NHQwherein X is H, Suc, Ac, Oxa, Mal, Glt, Prp, Prl or Acr; R.sub.0 is Gln, pGlu, Cys, Tyr, Tyr(OCH.sub.3), des--NH.sub.2 --Tyr or desR.sub.0 ; R.sub.1 is Asp, Tyr(OH or SE), Ser(OH or SE), Hyp(OH or SE), Thr(OH or SE), Cys, Tyr(OCH.sub.3) or desR.sub.1 ; Y is OH or SE; R.sub.3 is Met, Nva or Nle; R.sub.4 is Gly, D--Cys or D--Ala; R.sub.6 is Met, Nva or Nle; R.sub.7 is Asp, Ser(SE), Thr(SE) or Hyp(SE); R.sub.8 is Phe or Tyr(OCH.sub.3); and Q is lower alkyl, fluoro lower alkyl or hydrogen; provided that when R.sub.3 and R.sub.6 are Met and R.sub.7 is Asp then R.sub.4 is D--Ala. A pharmaceutically acceptable salt thereof may also be employed.

    摘要翻译： CCK（1-8）的类似物具有相对于刺激胆囊收缩和阻止胃酸分泌的离解活性。 各种类似物也表现出改善的抗惊厥药效。 肽通过下式表征：X-R0-R1-Tyr（Y）-R3-R4-Trp-R6-R7-R8-NHQ其中X是H，Suc，Ac，Oxa，Mal，Glt，Prp， Prl或Acr; R0是Gln，pGlu，Cys，Tyr，Tyr（OCH3），des-NH2-Tyr或desR0; R1是Asp，Tyr（OH或SE），Ser（OH或SE），Hyp（OH或SE），Thr（OH或SE），Cys，Tyr（OCH3）或desR1; Y是OH或SE; R3是Met，Nva或Nle; R4是Gly，D-Cys或D-Ala; R6是Met，Nva或Nle; R7是Asp，Ser（SE），Thr（SE）或Hyp（SE）; R8是Phe或Tyr（OCH3）; Q为低级烷基，氟低级烷基或氢; 条件是当R 3和R 6为Met且R 7为Asp时，R 4为D-Ala。 也可以使用其药学上可接受的盐。