Takeda Chemical Industries, Inc.

National Cancer Center

Takeda Pharmaceutical Company Limited

Kabushiki Kaisha Tailor Yoshimura

Koji Yoshimura

Yuichi Hikichi

Kazuo Nakahama

Koichi Igarashi

Hideyuki Tanaka

Yasushi Shintani

Masayuki Takizawa

Toshiro Yamashita

Atsushi Nishimura

Hiroshi Nara

Masaaki Terada

Yoshihiko Kaisho

Kaori Ishimaru

Kazunori Nishi

Kazuhiro Ogi

Shoichi Ohkubo

Reiko Sasada

Yasuaki Itoh

Masakazu Kikuchi

Kenichi Noguchi

Shinichi Mogi

Yuko Noguchi

The polypeptide of the present invention has an activity of binding specifically to the cis-element of Chondromodulin-I (ChM-I) gene promoter and promoting the transcription of the ChM-I gene. The polypeptide of the present invention is usable in screening for a compound that promotes or inhibits the activity of the polypeptide.

Transcription factor polypeptide that regulates Chondromodulin-I expression

The present invention relates to a novel protein belonging to an ADAM family, a partial peptide thereof or a salt thereof, a DNA encoding the protein, a recombinant vector comprising the DNA, a transformant, a method for producing the protein, a medicine comprising the protein or the DNA, an antibody against the protein, a method/kit for screening for a compound or a salt thereof which promotes or inhibits the protease activity or the extracellular metric degrading enzyme activity (preferably, the peptidoglycan degrading enzyme activity) of the protein, a compound obtained by the screening, and a medicine comprising the compound. The present protein and a DNA encoding it can be used, for example, as an agent for treating or preventing various diseases such as disc herniation, ischialgia, glomerular nephritis, diabetic nephropathy, hepatic fibrosis, pulmonary fibrosis or osteopetrosis. In addition, the present antibody can be used for quantitating the present protein in a test solution. Further, the present protein is useful as a reagent for screening for a compound which promotes or inhibits the protease activity of the present protein.

Protein and DNA thereof

The present invention provides a compound represented by Formula:wherein ring A and ring B may be same or different and each is an optionally substituted homocyclic or heterocyclic ring and the like, each Rmay be same or different and is a hydrogen atom, an optionally substituted hydrocarbon group, an acyl group, an optionally substituted heterocyclic group or SR, etc., Xis a bond, an optionally substituted divalent Caliphatic hydrocarbon group or &#x2014;NR&#x2014;, etc, Xis a bond, an optionally substituted divalent Caliphatic hydrocarbon group, &#x2014;NR&#x2014;, &#x2014;O&#x2014; or &#x2014;S(O)&#x2014; (wherein p is 0, 1 or 2), each Y may be same or different and is a hydrogen atom, an optionally substituted hydrocarbon group, a halogen atom, a carboxyl group, an acyl group, an optionally substituted hydroxy group, an optionally substituted amino group, SR, an oxo group, a thioxo group, an optionally substituted imino group, a nitro group, a cyano group, etc., each m may be same or different and is 0 or 1, n is an integer of 1 to 3, qis an integer of 1 to 2n+4, qis an integer of 0 to 2n+3, and the sum of qand qis 2n+4 or a salt thereof.

Thiol compounds, their production and use

A passage extending from the upper pocket to the lower outlet being formed. The lower end of the passage has a receptacle positioned immediately above the outlet. At a location upward of the receptacle, another outlet that opens to one side of the passage is formed. The outlet and the lower outlet are connected to each other via an outlet passage. When a cell phone is dropped in from the upper pocket, it glides down inside the passage and is received by the receptacle established at the lower end. When the wearer of the jacket inserts fingers through the lower outlet and pushes up the receptacle, he can easily push out the cell phone held inside through the outlet, which opens to one side of the passage. The cell phone can be taken out from the lower outlet which is connected to the outlet via an outlet passage.

Jacket

The present invention relates to novel secretory polypeptides and precursor proteins thereof, which show a high homology to MIA (melanoma inhibitor activity)/CD-RAP (bovine cartilage-derived retinoic acid-sensitive protein); are specifically expressed in the cartilage tissue; and have an effect on the cartilage differentiation. The polypeptides and the DNAs encoding the same can be used for the diagnosis, treatment, or prevention of bone and joint diseases or pathological angiogenesis. As well, the polypeptides are useful as a reagent for screening a compound that promotes or inhibits the activity of the polypeptides. The antibody to the polypeptides can be used for the detection, quantification, or neutralization of the polypeptide in a test sample fluid. Further by using the promoter of the present invention, a therapeutic protein can be expressed predominantly in the cartilage tissue for a gene therapy.

Polypeptide and DNA thereof

Polypeptide and production thereof

Compounds represented by general formula (1) or salts thereof which have a matrix metalloprotease inhibitory activity and are useful as drugs, wherein the rings A and B represent each an optionally substituted homocycle or heterocycle, etc.; R s are the same or different and each represents hydrogen, optionally substituted hydrocarbyl, acyl, etc.; X represents a bond, optionally substituted divalent aliphatic hydrocarbyl, etc.; X represents a bond, optionally substituted divalent aliphatic hydrocarbyl, &mdash;O&mdash;, etc.; Ys are the same or different represents hydrogen, optionally substituted hydrocarbyl, oxo, etc.; m is 0 or 1; n is an integer of 1 to 3; q is an integer of 1 to 2n&plus;4; and q is an integer of 0 to 2n&plus;3, provided that q &plus;q is 2n&plus;4.

The present invention provides a polypeptide represented by the following amino acid sequence:

Nucleic acids encoding HST 2 muteins

The present invention provides a polypeptide represented by the following amino acid sequence: ##STR1## wherein n is 0 or 1 and X represents Pro Ala Gly Thr Arg Ala Asn Asn Thr Leu Leu Asp Ser Arg Gly Trp Gly Thr Leu Leu Ser Arg Ser Arg Ala Gly or a fragment thereof (n=0: SEQ ID NO:1, n=1: SEQ ID NO:2), a recombinant DNA coding for the polypeptide, a vector containing the recombinant DNA, the preparation of a transformant carrying the vector, and the production of the polypeptide with the transformant. The use of this peptide in pharmaceutical compositions is also provided.

Hst-2 muteins, pharmaceutical compositions and kits comprising same, and

Disclosed are respiratory-deficient yeast except Saccharomyces cerevisiae AH22R.sup.-, said respiratory-deficient yeast being transformed with a DNA containing a gene encoding a protein foreign to yeast and a method for preparing a protein foreign to yeast described above, which comprises culturing the yeast, and producing and accumulating the protein in a culture. The respiratory-deficient yeast of the present invention can produce a higher amount of protein than its parent strain.

Method for increasing gene expression using protease deficient yeasts

A DNA sequence wherein a DNA segment coding for a signal peptide of the formula:

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Tsukuba, Japan

Koji Yoshimura