University of Texas System

Other

Takeda Chemical Industries, Inc.

University of Tsukuba

Nsk Corporation

Smithkline Beecham Corporation

Director-general of Agency of Industrial Science and Technology

Takeda Chemical Ind., Ltd.

501 Takeda Chemical Industries, Ltd.

Masashi Yanagisawa

Tomoh Masaki

Akihiro Inoue

Derk J Bergsma

Hiroshi Nagase

Yoko Irukayama

Tsuyoshi Saitoh

Miklos Gellai

Shelagh Wilson

David P Brooks

Tomoyasu Imai

Hiroaki Asano

Yoshio Yazaki

Masato Kitajima

Hiroki Kurihara

Naoshi Yamamoto

Susumu Nakano

Noriki Kutsumura

Hayashi Kodama

Yasuyuki Nagumo

Sadao Kimura

Youji Mitsui

Katsutoshi Goto

Sadao Sakakibara

The present invention aims to provide a novel low-molecular-weight compound showing an orexin receptor agonist activity and expected to be useful as a prophylactic or therapeutic agent for narcolepsy and the like. The present invention provides a compound represented by the formula (I): wherein each symbol is as described in the description, or a pharmaceutically acceptable acid addition salt thereof, which has an orexin receptor agonist activity, and an orexin receptor agonist containing the compound or a pharmaceutically acceptable acid addition salt thereof.

Sulfonamide derivative or pharmaceutically acceptable acid-addition salt

Provided is a formed rotary dresser that has regions in which diamond abrasive grains are scattered and arranged on an outer circumferential surface thereof brought into contact with a grindstone, and slit regions in which the diamond abrasive grains are not arranged on the outer circumferential surface thereof. The plurality of slit regions are provided to be inclined with respect to a rotational axis. A plurality of octahedral diamond abrasive grains are arranged along downstream edges of the slit regions in a rotating direction such that any face of an octahedron is parallel with the outer circumferential surface.

Former rotary dresser and dressing method

The purpose of the present invention is to provide a compound useful as a prophylactic or therapeutic agent for various diseases and symptoms related to orexin receptors, and a medical usage of the same. The present invention provides a morphinan derivative represented by the general formula (I) below or a pharmaceutically acceptable acid addition salt thereof, the morphinan derivative having excellent selectivity for and antagonism against orexin receptors and excellent therapeutic and prophylactic effects on drug dependence, and an orexin receptor antagonist and a therapeutic or prophylactic agent for drug dependence each containing it as an active ingredient. 

Morphinan derivative and medical usage thereof

The present invention aims to provide a novel low-molecular-weight compound exhibiting an orexin receptor agonist activity and expected to be useful as a prophylactic or therapeutic agent for narcolepsy and the like. The present invention provides a compound represented by the formula (I): wherein each symbol is as defined in the description, or a pharmaceutically acceptable acid addition salt thereof, which has an orexin receptor agonist activity, and an orexin receptor agonist containing the compound or a pharmaceutically acceptable acid addition salt thereof.

Sulfonamide derivative and pharmaceutically acceptable acid addition salt thereof

Methods and compositions for agonizing a type-2 orexin receptor (OX2R) in a cell determined to be in need thereof, including the general method of (a) administering to a subject a cyclic guanidinyl OX2R agonist and (b) detecting a resultant enhanced wakefulness or increased resistance to diet-induced accumulation of body fat, or abbreviated recovery from general anesthesia or jet lag.

Small-molecule agonists for type-2 orexin receptor

Polypeptides of HFGAN72 receptor ligands and polynucleotides encoding the polypeptides are provided. Methods of using these polypeptides to diagnose diseases relating to the under- or over-expression of HFGAN72 receptor ligands are also provided. In addition, methods of identifying agonists or antagonists of the interaction of HFGAN72 receptor ligands with the HFGAN72 receptor are provided. Methods of treatment by administering the identified agonists or antagonists to patients in need thereof are further disclosed.

Screening methods using ligands of the neutropeptide receptor HFGAN72

Polynucleotides encoding ligands of the neuropeptide receptor HFGAN72

An abrasive tool includes an electroformed layer having superabrasive grains electroplated on an outer surface of the electroformed layer, and a plurality of dimples arranged on the outer surface of the electroformed layer using a mold with projections made of gel adhesive. The concentration of the abrasive gains is regulated by changing the number of the dimples (i.e., changing a dimple-area-rate). The gel adhesive preferably has a viscosity of 500,000 cP or smaller. The dimple-area-rate is preferably from 7 to 70%.

Abrasive tool and the method of producing the same

MY1 polypeptides and polynucleotides and methods for producing such polypeptides by recombinant techniques are disclosed. Also disclosed are methods for utilizing MY1 polypeptides and polynucleotides in the design of protocols for the treatment of infections such as bacterial, fungal, protozoan and viral infections, particularly infections caused by HIV-1 or HIV-2; pain; cancers; anorexia nervosa; bulimia; cachexia; obesity; diabetes; asthma; Parkinson's disease; acute heart failure; hypotension; hypertension; urinary retention; osteoporosis; angina pectoris; myocardial infarction; ulcers; asthma; allergies; benign prostatic hypertrophy; and psychotic and neurological disorders, including anxiety, schizophrenia, manic depression, delirium, dementia, severe mental retardation and dyskinesias, such as Huntington's disease or Gilles dela Tourett's syndrome, among others, and diagnostic assays for such conditions.

Polynucleotides encoding MY1 receptor

Ligands of the neuropeptide receptor HFGAN72

A cloned DNA molecule is disclosed. The DNA molecule encodes a human endothelin-3 protein having the amino acid sequence: Glu-Gly-Ala-Pro-Glu-His-His-Arg-Ser-Arg-Arg-Cys-Thr-Cys-Phe-Thr-Tyr-Lys-As p-Lys-Glu-Cys-Val-Tyr-Tyr-Cys-His-Leu-Asp-Ile-Ile-Trp-Ile-Asn-Thr-Pro-Glu or any portion of said amino acid sequence containing Cys-Thr-Cys-Phe-Thr-Tyr-Lys-Asp-Lys-Glu-Cys-Val-Tyr-Tyr-Cys-His-Leu-Asp-Il e-Ile-Trp. Also disclosed is a method of producing mature endothelin-3 protein. In the method, the host cell is cultured, allowing mature endothelin-3 to accumulate in the culture medium, and the mature endothelin-3 protein is separated from the culture medium.

DNA encoding human endothelin-3, and use thereof

Disclosed is a nucleic acid segment encoding endothelin converting enzyme-2 (ECE-2), that produces mature ET-1 from big ET-1 both in vitro and in transfected cells. Also disclosed is a polypeptide composition comprising partially purified ECE-2 and methods of using ECE-2 to screen candidate substances as inhibitors of ECE-2. Methods of producing recombinant ECE-2 are also disclosed.

Recombinant endothelin converting enzyme-2 and its use in ECE inhibitor

Endothelin-1 (ET-1), a 21-residue vasoactive peptide, is produced in vascular endothelial cells from the 38-residue inactive intermediate, big endothelin-1 via a specific cleavage at Trp21-Val22. The protease that catalyzes the conversion, endothelin converting enzyme (ECE), constitutes a potential regulatory site for the production of the active peptide. Disclosed herein is the identification of ECE-1, a novel membrane-bound neutral Zn.sup.2+ metalloprotease that is expressed abundantly in endothelial cells in vivo, and structurally related to neutral endopeptidase 24.11 and Kell blood group protein. When transfected into cultured cells that normally secrete only big ET-1, the ECE-1 cDNA conferred the ability to secrete mature ET-1. In transfected cells, ECE-1 processes endogenously synthesized big ET-1 as well as exogenously supplied big ET-1, which interacts with ECE-1 on the cell surface. The remarkable specificity of ECE-1 provides a target for selective pharmacological intervention to alter ET-1 production in certain clinical disorders.

Methods of screening of effectors of endothelin converting enzyme-1

Disclosed are (1) a DNA sequence containing a DNA segment coding for endothelin-2 or human endothelin-3, (2) a precursor protein and a mature peptide of endothelin-2 or human endothelin-3, (3) a transformant carrying a DNA sequence containing a DNA segment coding for endothelin-2 or human endothelin-3 and (4) a method for preparing mature endothelin-2 or endothelin-3 which comprises culturing the transformant described in (3), producing and accumulating a protein in a culture medium, and collecting the same. Cells transfected or transformed with the DNA allow large amounts of endothelin-2 or endothelin-3 to be produced, which causes the advantageous production of endothelin-2 or endothelin-3. Endothelin-2 and endothelin-3 can be utilized as hypotension therapeutic agents or local vasoconstrictors to animals including humans.

Growing community of inventors

Tsukuba, Japan

Masashi Yanagisawa