Takeda Chemical Industries, Inc.

Takeda Pharmaceutical Company Limited

Ryuichi Tozawa

Yasuo Sugiyama

Hidefumi Yukimasa

Masakuni Kori

Kazuaki Kitano

Yoshio Taniyama

Takashi Sohda

Hitoshi Ikeda

Tsuneo Oda

Muneo Takatani

Eiji Sunahara

Tomoko Satomi

Mitsugu Nakata

Yoshitaka Yasuhara

Kazumasa Hamamura

The present invention relates to non-human animal embryonic stem cells in which a lecithin:cholesterol acyltransferase-like lysophospholipase endogenous gene is inactivated; non-human animals deficient in expression of LLPL gene; methods of screening for prophylactics and/or therapeutic drug using the cells or the animals; and prophylactics and/or therapeutic drug obtainable by the screening. The non-human animal ES cells of the invention in which their LLPL gene is inactivated are very useful in creating non-human animals deficient in expression of LLPL gene. The LLPL expression deficient non-human animals of the invention can be disease models for such diseases caused by insufficiency of the biological activities of LLPL since the animals lack various biological activities inducible by LLPL. Therefore, the animals of the invention are useful in screening for prophylactics and/or therapeutic drug for various diseases resulting from LLPL deficiency, as well as in elucidating the causes of LLPL-related diseases and examining therapeutic methods for such diseases. The screening methods of the invention are capable of efficiently screening for prophylactics and/or therapeutic drug for various diseases resulting from LLPL deficiency.

Animal with gene hypoexpression

The present invention provides novel esterase proteins, Specifically, the present invention provides proteins having the same or substantially the same amino acid sequence as the amino acid sequence represented by SEQ ID NO: 1 or SEQ ID NO: 7, or salts thereof; their partial peptides or salts thereof: DNAs encoding the proteins; recombinant vectors containing the DNAs; transformants, a method of manufacturing the proteins; pharmaceuticals comprising the proteins or DNAs; antibodies to the proteins; a method of screening compounds or salts thereof having an activity of promoting the esterase activity of the proteins; the compounds obtained by the screening; and pharmaceuticals comprising the said compounds; etc.

Isolated human protein having esterase activity and DNA encoding the same

Benzoxazepine compounds, their production and use

Benzoxazepine compounds, their production and use as lipid lowering

Condensed compounds, their production and use

N-containing, condensed heterocyclic compounds and salts thereof are disclosed which are useful for inhibiting squalene synthetase and fungal growth, and which are useful for treating or preventing hyperlipidemia. Also disclosed is a method for producing these compounds.

N-containing condensed heterocyclic compounds, their production, and

4,1-benzoxazepin derivatives and their use

Disclosed is a squalene synthetase inhibitor which comprises the compound represented by the formula ##STR1## wherein R.sub.1 is hydrogen or an optionally substituted hydrocarbon group; R.sub.2 is hydrogen, an optionally substituted alkyl group, an optionally substituted phenyl group or an optionally substituted aromatic heterocyclic ring group; X' is a substituent comprising an optionally esterified carboxyl group, an optionally substituted carbamoyl group, an optionally substituted hydroxyl group, an optionally substituted amino group or an optionally substituted heterocyclic radical having a protonizable hydrogen; Ring A is an optionally substituted benzene ring or an optionally substituted aromatic heterocyclic ring; Ring J' is a 7- to 8-membered heterocyclic ring containing at most three ring constituting hetero atoms; D is C or N; the Ring J' optionally having, besides R.sub.1, R.sub.2 and X', a further substituent; provided that the condensed ring composed of Ring A and ring J' is not a 2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepine ring, or a pharmaceutically acceptable salt thereof, and which is useful for the prophylaxis or therapy of hypercholesteremia or coronary sclerosis of mammals.

Condensed cyclic compounds and their use

Disclosed is a squalene synthetase inhibitor which comprises the compound represented by the formula (I) ##STR1## wherein R.sub.1 stands for H or an optionally substituted hydrocarbon group; R.sub.2 and R.sub.3 independently stand for H, an optionally substituted alkyl group, an optionally substituted phenyl group or an optionally substituted aromatic heterocyclic group; Z stands for a carbon chain containing a double bond or --Z'--C(OH)-- (Z' stands for a bond or a straight-chain or branched alkylene chain); the symbol ......... stands for a double bond or a single bond; Y stands for an optionally esterified carboxyl group, an optionally substituted carbamoyl group, an optionally substituted hydroxyl group, an optionally substituted amino group or an optionally substituted heterocyclic radical having a protonizable hydrogen; X stands for O or S; G stands for O or S; and the ring A is optionally substituted, or a pharmaceutically acceptable salt thereof, and which is useful for the prophylaxis or therapy of hypercholesteremia or coronary sclerosis of mammals.

Benzoxazepine-2-one compounds and their use

There is provided a squalene inhibitory composition containing a 1,1-bisphosphonic acid compound, a lower alkyl ester thereof, or a salt thereof, which is useful for treating hypercholesterolemia. There are also provided novel compounds having squalene synthetase inhibitory activity and a pharmaceutical composition for treating hypercholesterolemia containing a 1,1-bisphosphonic compound, a lower alkyl ester thereof or a salt thereof.

Method of inhibiting squalene synthetase

Growing community of inventors

Osaka, Japan

Ryuichi Tozawa