Abstract: The present invention provides a transgenic mouse retaining a DNA that encodes an exogenous GPR40 in an expressible state, wherein (1) the insulin secretion capacity has been increased, and/or (2) the glucose tolerance has been improved, compared with the corresponding non-transgenic mouse, or a portion of the living body thereof, a screening method for a prophylactic/therapeutic drug for diabetes mellitus and metabolic syndrome using the transgenic mouse, and the like.

Abstract: The present invention provides a non-human mammal deficient in the expression of the SLC-1 gene, having the characteristics of (1) a lower blood insulin level in glucose tolerance test, (2) increased insulin sensitivity, (3) higher resistance to obesity even on high fat diet, (4) a smaller white fat cell size, and (5) accentuated lipolysis, compared with the corresponding wild-type animal, or a portion of the body thereof. Also provided is an obesity and/or type II diabetes model non-human mammal that is deficient in the expression of the SLC-1 gene, having the characteristics of (1) elevated expression of adiponectin, (2) delayed onset of hyperglycemia, (3) a lower blood glycohemoglobin level, and (4) accentuated energy consumption, compared with the corresponding obesity and/or type II diabetes model non-human mammal wherein the expression of the gene is normal, or a portion of the body thereof.

Abstract: The present invention provides a non-human mammal, or a part of its living body, which stably retains a DNA encoding a heterologous PPAR? in an expressible state, and has one or more different genetic modifications resulting in a pathological condition identical or similar to a disease associated with the regulation of PPAR? activity or a foreign DNA under the control of a promoter having PPRE, as well as a method of screening for agonists/antagonists for the heterologous PPAR? using the animal.

Abstract: This invention relates to an optically active benzothiepin derivative represented by the formula: wherein R represents a lower alkyl group; R1 and R2 independently represent a lower alkyl group, or may bind together to form a ring, which exhibits excellent osteogenesis-promoting action and is useful as a prophylactic or therapeutic drug for bone diseases.

Abstract: A compound represented by the formula: wherein X represents a sulfur atom or an oxygen atom; Y represents an optionally oxidized sulfur atom or an oxygen atom; Z represents a bond or a divalent hydrocarbon group; R1 represents an optionally substituted hydrocarbon group; R2 represents an optionally amidated or esterified carboxyl group; ring A represents an optionally substituted aromatic 5-membered heterocyclic ring; or a salt thereof. A compound of the above formula possesses cell differentiation inducing factor action-enhancing activity and anti-matrix metalloprotease activity and that is useful in the prevention and treatment of bone diseases such as osteoporosis, bone fractures, osteoarthritis and rheumatoid arthritis, arteriosclerosis, cancer metastasis, and diseases based on nerve degeneration.

Abstract: A compound represented by the formula: wherein X represents a sulfur atom or an oxygen atom; Y represents an optionally oxidized sulfur atom or an oxygen atom; Z represents a bond or a divalent hydrocarbon group; R1 represents an optionally substituted hydrocarbon group; R2 represents an optionally amidated or esterified carboxyl group; ring A represents an optionally substituted aromatic 5-membered heterocyclic ring; or a salt thereof. A compound of the above formula possesses cell differentiation inducing factor action-enhancing activity and anti-matrix metalloprotease activity and that is useful in the prevention and treatment of bone diseases such as osteoporosis, bone fractures, osteoarthritis and rheumatoid arthritis, arteriosclerosis, cancer metastasis, and diseases based on nerve degeneration.

Abstract: A compound represented by the formula: 1

Abstract: This invention relates to an optically active benzothiepin derivative represented by the formula: wherein R represents a lower alkyl group; R1 and R2 independently represent a lower alkyl group, or may bind together to form a ring, which exhibits excellent osteogenesis-promoting action and is useful as a prophylactic or therapeutic drug for bone diseases.

Abstract: A compound represented by the formula: wherein X represents a sulfur atom or an oxygen atom; Y represents an optionally oxidized sulfur atom or an oxygen atom; Z represents a bond or a divalent hydrocarbon group; R1 represents an optionally substituted hydrocarbon group; R2 represents an optionally amidated or esterified carboxyl group; ring A represents an optionally substituted aromatic 5-membered heterocyclic ring; or a salt thereof. A compound of the above formula possesses cell differentiation inducing factor action-enhancing activity and anti-matrix metalloprotease activity and that is useful in the prevention and treatment of bone diseases such as osteoporosis, bone fractures, osteoarthritis and rheumatoid arthritis, arteriosclerosis, cancer metastasis, and diseases based on nerve degeneration.

Abstract: A compound represented by the formula: ##STR1## wherein X represents a sulfur atom or an oxygen atom; Y represents an optionally oxidized sulfur atom or an oxygen atom; Z represents a bond or a divalent hydrocarbon group; R.sup.1 represents an optionally substituted hydrocarbon group; R.sup.2 represents an optionally amidated or esterified carboxyl group; ring A represents an optionally substituted aromatic 5-membered heterocyclic ring; or a salt thereof. A compound of the above formula possesses cell differentiation inducing factor action-enhancing activity and anti-matrix metalloprotease activity and that is useful in the prevention and treatment of bone diseases such as osteoporosis, bone fractures, osteoarthritis and rheumatoid arthritis, arteriosclerosis, cancer metastasis, and diseases based on nerve degeneration.

Abstract: Disclosed is a parathyroid hormone (PTH) (1-34) derivative in which at least the amino acid residue at the 10-position is substituted by an acidic amino acid residue. The derivatives of the present invention showing potent cAMP-producing activity and bone formation activity, and thus are useful as therapeutic agents for bone diseases, etc.

Abstract: This invention provides a pharmaceutical composition comprising a non-peptide osteogenic promoting substance and a biodegradable polymer, which can be safely used as a prophylactic/therapeutic agent for various bone diseases (e.g., bone fractures).

Abstract: The present invention provides a pharmaceutical composition for inhibiting bone resorption or for preventing or treating osteoporosis which comprises a quinoline or quinazoine derivative as an active ingredient.

Abstract: This invention relates to a compound represented by the formula: ##STR1## wherein B represents a hydrogen atom or a lower alkyl group; ring A represents a benzene ring which may have one or more substituents; ....... represents a single or double bond; Q.sub.1 represents the group represented by the formula, ##STR2## ,or a hydrocarbon residue substituted with the group represented by the formula, ##STR3## wherein X represents a bond or a spacer having a chain length of 1 to 4 atoms as the linear moiety which may have one or more side chains; R.sup.1 and R.sup.2, whether identical or not, independently represent a hydrogen atom or a lower alkyl, or may bind together to form a ring; Q.sub.2 represents a hydrogen atom, a hydrocarbon residue which may be substituted or a heterocyclic ring residue which may be substituted; or a salt thereof.

Abstract: A transmucosal therapeutic composition comprising a physiologically active peptide or protein and a cytidine nucleotide derivative was produced. The above composition results in a satisfactory transmucosal absorption of physiologically active peptides or proteins which are otherwise hardly absorbed from the mucosa. Since it allows self-administration to the mucosa, such as the nasal, vaginal or digestive tract mucosa, in lieu of injection which causes pain, the invention is of great utility as a pharmaceutical dosage form for physiologically active peptides or proteins which must be administered over a protracted time.

Abstract: The present invention provides a pharmaceutical composition for inhibiting bone resorption or for preventing or treating osteoporosis which comprises a quinoline or quinazoine derivative as an active ingredient.

Abstract: The present invention relates to a compound of the general formula (I): ##STR1## wherein ring A is a benzene ring that may be substituted; Y is a divalent group as a constituent member of ring B forming a 5- to 8-membered ring; Q.sub.1 is a group of the formula --X--P(O)(OR.sup.1)(OR.sup.2) wherein X is a bond or a divalent group; R.sup.1 and R.sup.2, identical or different, are hydrogen or a lower alkyl, or may be combined together to form a ring; Q.sub.2 is hydrogen, a hydrocarbon group that may be substituted or a heterocyclic group that may be substituted; and the group of the formula --CON(Q.sub.1)(Q.sub.2) is connected to the a- or b-position carbon atom, or a salt thereof, which is useful as prophylactic and therapeutic agents of various metabolic bone diseases such as osteoporosis.

Abstract: This invention relates to a compound represented by the formula: ##STR1## wherein B represents a hydrogen atom or a lower alkyl group; ring A represents a benzene ring which may have one or more substituents; .multidot..multidot..multidot..multidot..multidot. represents a single or double bond; Q.sub.1 represents the group represented by the formula, ##STR2## or a hydrocarbon residue substituted with the group represented by the formula, ##STR3## wherein X represents a bond or a spacer having a chain length of 1 to 4 atoms as the linear moiety which may have one or more side chains; R.sup.1 and R.sup.2, whether identical or not, independently represent a hydrogen atom or a lower alkyl, or may bind together to form a ring; Q.sub.2 represents a hydrogen atom, a hydrocarbon residue which may be substituted or a heterocyclic ring residue which may be substituted; or a salt thereof.

Abstract: A bisphosphonic acid derivative of the general formula (I): ##STR1## wherein A is an optionally substituted cyclic group; R.sup.1 is hydrogen atom or a lower alkanoyl group; R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are the same or different and are hydrogen atom or a lower alkyl group; m is 0, 1 or 2; and n is an integer from 2 to 10, or a salt thereof is disclosed. A process for its production and a bone resorption inhibitor containing the compound of the general formula (I) or a salt thereof are also disclosed.

Abstract: A transmucosal therapeutic composition comprising a physiologically active peptide or protein and a cytidine nucleotide derivative is described. The above composition results in a satisfactory transmucosal absorption of physiologically active peptides or proteins which are otherwise hardly absorbed from the mucosa. Since it allows self-administration to the mucosa, such as the nasal, vaginal or digestive tract mucosa, in lieu of injection which causes pain, the invention is of great utility as a pharmaceutical dosage form for physiologically active peptides or proteins which must be administered over a protracted time.