Sumitomo Pharmaceuticals Company Limited

Dainippon Sumitomo Pharma Co., Ltd.

Japan Science and Technology Agency

Kaoru Kikuchi

Toru Kimura

Kazuo Kumagai

Akiyoshi Kishino

Nobuo Hosotani

Hiroshi Noguchi

Chikao Nakayama

Hajime Fujisawa

Yasunori Murakami

Akira Ito

Yoko Ishige

Makoto Inoue

The present invention provides screening methods for agonists or antagonists of Sema6C using Plexin-A1, and tools for the screening and the like. It evaluates a case of making a recombinant protein having an extracellular domain of Semaphorin 6C contact a protein having an extracellular domain of Plexin-A1 by comparing it with a case of contacting a recombinant protein and a target substance having an extracellular domain of Semaphorin 6C, or the target substance with a protein having an extracellular domain of Plexin-A1. The evaluation will be carried out by the connectivity of a protein having an extracellular domain of Semaphorin 6C, a growth cone collapse activity of Plexin-A1 expressing cell, or a contractile activity of Plexin-A1 expressing cell.

Screening method for agonists or antagonists of semaphorin 6C by determining the effect of a test compound on the interaction between semaphorin 6C and plexin-A1

To provide a semaphorin inhibitor; a peripheral or central nerve regeneration promoter which contains said semaphorin inhibitor as an active ingredient; and a preventive or remedy for a neuropathic disease and a neurodegenerative disease containing said nerve regeneration promoter, or the like. A low-molecular weight compound, which acts at a concentration of 10 &#x3bc;g/ml or below to inhibit the growth cone collapse activity of semaphorin such as semaphorin 3A, semaphorin 6C or the like and/or the nerve outgrowth inhibitory activity of semaphorin in a collagen gel and which does not substantially affect cell proliferation, is obtained from the culture of strain SPF-3059 belonging to the genusThe low-molecular weight compound with the semaphorin inhibitory activity thus obtained exhibits the in vivo nerve-regeneration promoting action.

Nerve regeneration promoters containing semaphorin inhibitor as the active ingredient

Novel semaphorin Z; a gene thereof; a partial peptide of the semaphorin Z; an antibody; a DNA or an RNA complementary to the semaphorin Z gene; a method for screening a semaphorin Z inhibitor by using the semaphorin Z; the semaphorin Z inhibitor obtained by the screening; and a CNS neuron regeneration promoter comprising the inhibitor.

Semaphorin Z and gene encoding the same

To provide a semaphorin inhibitor; a peripheral or central nerve regeneration promoter which contains said semaphorin inhibitor as an active ingredient; and a preventive or remedy for a neuropathic disease and a neurodegenerative disease containing said nerve regeneration promoter, or the like. A low-molecular weight compound, which acts at a concentration of 10 &#x3bc;g/ml or below to inhibit the growth cone collapse activity of semaphorin such as semaphorin 3A, semaphorin 6C or the like and/or the nerve outgrowth inhibitory activity of semaphorin in a collagen gel and which does not substantially affect cell proliferation, is obtained from the culture of strain SPF-3059 belonging to the genus. The low-molecular weight compound with the semaphorin inhibitory activity thus obtained exhibits the in vivo nerve-regeneration promoting action.

The present invention provides Semaphorin W inhibiting neurite outgrowth, and a gene therefor, as well as other Semaphorins hybridizing to said Semaphorin W gene, modified proteins or partial peptides of said Semaphorin W, antibodies against said Semaphorin W, antisense nucleotides against said Semaphorin W gene, and the use of such substances as pharmaceutical or diagnostic agents or laboratory reagents. The present invention further provides a method of screening for Semaphorin W antagonists employing said Semaphorin W, Semaphorin W antagonists obtained by said screening method, pharmaceutical agents comprising such antagonists, and transgenic animals involving said Semaphorin W.

Semaphorin gene: Semaphorin W

Semaphorin Y inhibiting neurite outgrowth, and a nucleotide sequence therefor, as well as other Semaphorin sequences hybridizing to the Semaphorin Y sequence, modified proteins or partial peptides of Semaphorin Y, antibodies against Semaphorin Y, antisense nucleotides against Semaphorin Y gene, and the use of such substances as pharmaceutical or diagnostic agents or laboratory reagents are disclosed. Further, a method of screening for Semaphorin Y antagonists employing Semaphorin Y, Semaphorin Y antagonists obtained by the screening method, pharmaceutical agents comprising such antagonists, and transgenic animals involving Semaphorin Y are also disclosed.

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Takarazuka, Japan

Kaoru Kikuchi