Sankyo Company, Limited

Daiichi Sankyo Company, Limited

Futoshi Nara

Takahide Nishi

Takaichi Shimozato

Shojiro Miyazaki

Toshiyasu Takemoto

Tohru Takahashi

Ryuji Hashimoto

Shinji Yamaguchi

Christine Rothe

Andrea Allersdorfer

Marlon Hinner

Alexander Wiedenmann

Andreas Hohlbaum

Gabriele Matschiner

Rachida Siham Bel Aiba

Bradley Lunde

Tomohiro Nishizawa

Takahide Aburatani

Chikako Nagasaki

Tsuyoshi Nakamura

Yukiko Sekiguchi

Takashi Izumi

Kiyoaki Yonesu

Kazuishi Kubota

Yumiko Mizuno

The present disclosure relates to novel lipocalin muteins which bind to PCSK9. The disclosure also provides corresponding nucleic acid molecules encoding lipocalin muteins and methods for producing lipocalin muteins as well as their encoding nucleic acid molecules.

Nucleic acid molecules encoding muteins of human tear lipocalin which bind PCSK9

Human tear lipocalins which bind PCSK9 and methods of use thereof

A method for treating an immunology-related disease. The method involves administering to a mammal in need thereof a pharmaceutically effective amount of an amino acid compound, a pharmacologically acceptable salt thereof or a pharmacologically acceptable ester thereof. The compound has the following formula: wherein Rand Rare each hydrogen; Ris hydrogen; Ris C-Calkyl; n is 2; X is &#x2550;N-D, wherein D is hydrogen, C-Calkyl or phenyl; Y is ethylene, ethynylene, &#x2014;CO&#x2014;CHor phenylene; Z is ethylene or trimethylene; Ris unsubstituted C-Ccycloalkyl, unsubstituted C-Caryl, or C-Ccycloalkyl or C-Caryl substituted with 1 to 3 substituents selected from the group consisting of halogen, lower alkyl, halogeno lower alkyl and lower alkoxy; and Rand Rare each hydrogen.

Method for treating a immunology-related disease

The objects of the present invention are: elucidation of an enzyme that phosphorylates in vivo a compound such as (2R)-2-amino-2-methyl-4-[5-(5-phenylpentanoyl)thiophen-2-yl]butan-1-ol and provision of a method of phosphorylating the aforementioned compound; provision of a method of screening for a substance phosphorylated by the aforementioned enzyme; provision of a method of determining the ability of a subject to phosphorylate a test compound. Provision of a method of phosphorylating the aforementioned compound using a human fructosamine-3-kinase-related protein and/or fructosamine-3-kinase, and a method of determining the ability of a subject to phosphorylate a test compound.

Drug-phosphorylating enzyme

A compound having a formula II(a): wherein Rand Rare hydrogen lower alkyl, lower aliphatic acyl, or lower alkoxycarbonyl; Ris C-Calkyl; n is 2 or 3; X is a formula &#x2550;N-D, wherein D is hydrogen, C-Calkyl or phenyl; Y is ethylene, ethynylene, &#x2014;CO&#x2014;CH&#x2014;, &#x2014;CH(OH)&#x2014;CH&#x2014; or phenylene; Z is C-Calkylene; Ris C-Ccycloalkyl or C-Caryl; Rand Rare hydrogen, lower alkyl, halogeno lower alkyl, lower alkoxy or lower alkylthio; and Rand Rare hydrogen or lower alkyl.

Amino alcohol compounds or phosphonic acid derivatives thereof

A method for suppressing the number of peripheral blood lymphocytes involving administering to a human in need thereof a pharmaceutically effective amount of a compound which is (2R) -2-amino-2-methyl-4-{1-methyl-5-[4-(4-methylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol or a pharmacologically acceptable salt thereof, such as the hydrochloride salt.

Method for suppressing the number of peripheral blood lymphocytes using an amino alcohol compound

A compound having immunosuppressive activity with low toxicity or a pharmacological salt thereof. The compound has a general formula (I) shown below or a pharmacologically acceptable salt thereof, or a pharmacologically acceptable prodrug thereof 

Heterocyclic compound

A method for the prevention or treatment of an immunology-related disease, which is not rheumatoid arthritis or psoriasis, in a mammal in need thereof which involves administering to the mammal a pharmaceutically effective amount of a compound, a pharmacologically acceptable salt of the compound or a pharmacologically acceptable ester of the compound, wherein the compound is a compound having a formula (Ia): wherein Rand Rare each a hydrogen, Ris hydrogen; Ris C-Calkyl; n is 2; X is &#x2550;N&#x2014;D, wherein D is hydrogen C-Calkyl or phenyl; Y is ethylene, ethynylene, &#x2014;CO&#x2014;CHor phenylene; Z is ethylene or trimethylene; Ris an unsubstituted C-Ccycloalkyl, an unsubstituted C-Caryl, or a C-Ccycloalkyl or a C-Caryl substituted with 1 to 3 substituents selected from the group consisting of halogen, lower alkyl, halogeno lower alkyl and lower alkoxy; and Rand Rare each hydrogen.

Amino alcohol compounds and phosphonic acid compounds having excellent immunosuppressive activity, pharmacologically acceptable salts thereof and pharmacologically acceptable esters thereof, and pharmaceutical compositions comprising such compounds, the compounds having the following formula: wherein Rand Reach represent hydrogen, or a protecting group of the amino group; Rrepresents hydrogen, or a protecting group of the hydroxyl group; Rrepresents a lower alkyl group; n is 1 to 6; X represents oxygen or nitrogen, which is unsubstituted or substituted with a lower alkyl group; Y represents ethylene; Z represents a C&#x2013;Calkylene; Rrepresents an aryl group; and Rand Reach represents hydrogen; provided that when Rrepresents hydrogen, then Z represents a group other than a single bond or a straight chain C&#x2013;Calkylene group.

Amino alcohol compounds

Compounds of formula (I) which exhibit excellent immune suppression activity, pharmacologically acceptable salts thereof, esters thereof or other derivatives:wherein Rand Rare a hydrogen atom, an amino protecting group; Ris a hydrogen atom, a hydroxy protecting group; Ris a lower alkyl group; n is an integer from 1 to 6; X is an ethylene group; Y is a C-Calkylene group, a C-Calkylene group substituted with 1 to 3 substituents selected from substituent group a and b; Ris an aryl group; Rand Rare a hydrogen atom, a group selected from substituent group a; with the proviso when Ris a hydrogen atom, Y is not a single bond or a straight chain C-Calkylene group.

Amino alcohol derivatives

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Yachiyo, Japan

Futoshi Nara