摘要:
The cynomolgus monkey Dickkopf-4 (cDkk-4) protein, isolated nucleic acid molecules which encode the cDkk-4 protein, and recombinant vectors and hosts comprising DNA encoding the cDkk-4 protein are disclosed. Also disclosed are methods for identifying analytes which interfere with the interaction between the cDkk-4 protein and a homologous or heterologous Dkk receptor and analytes which interfere with the interaction and stimulate bone formation. Analytes identified using the methods are useful for treating osteoporosis and other bone loss disorders.
摘要:
The present invention provides rhesus monkey dickkopf-1 (rhDkk-1) and nucleotide sequences encoding it. Also provided herein are recombinant vectors, and recombinant hosts comprising rhDkk-1-encoding nucleotide sequences. Isolated rhDkk-1 can be used to screen and identify novel osteoanabolic compounds that stimulate bone formation for the treatment of osteoporosis or other disorders characterized by insufficient bone mass.
摘要:
Compounds of structural formula (I) as herein defined are disclosed as useful in a method for modulating the androgen receptor in a tissue selective manner in a patient in need of such modulation, as well as in a method of agonizing the androgen receptor in a patient, and in particular the method wherein the androgen receptor is antagonized in the prostate of a male patient or in the uterus of a female patient and agonized in bone and/or muscle tissue. These compounds are useful in the treatment of conditions caused by androgen deficiency or which can be ameliorated by androgen administration, including: osteoporosis, periodontal disease, bone fracture, bone damage following bone reconstructive surgery, sarcopenia, frailty, aging skin, male hypogonadism, post-menopausal symptoms in women, atherosclerosis, hypercholesterolemia, hyperlipidemia, aplastic anemia and other hematopoietic disorders, pancreatic cancer, renal cancer, arthritis and joint repair, alone or in combination with other active agents. In addition, these compounds are useful as pharmaceutical composition ingredients alone and in combination with other active agents.
摘要:
The cynomolgus monkey Dickkopf-4 (cDkk-4) protein, isolated nucleic acid molecules which encode the cDkk-4 protein, and recombinant vectors and hosts comprising DNA encoding the cDkk-4 protein are disclosed. Also disclosed are methods for identifying analytes which interfere with the interaction between the cDkk-4 protein and a homologous or heterologous Dkk receptor and analytes which interfere with the interaction and stimulate bone formation. Analytes identified using the methods are useful for treating osteoporosis and other bone loss disorders.
摘要:
The inhibition of natural bone formation experienced in the prophylaxis and/or treatment of bone resorption disease with a bisphosphonic acid or a pharmaceutically acceptable salt thereof is overcome by the concommitant administration of an agent that binds to the androgen receptor.
摘要:
Disclosed herein are methods and compositions for identifying morphogen analogs. The preferred methods and compositions relate to the discovery that morphogen upregulation of the mouse type X collagen promoter activity is mediated by a MEF-2 like sequence and requires an adjacent AP-1 sequence. Certain methods rest on the use of test cells comprising DNA defining a morphogen-responsive transcription activating element operatively associated with a reporter gene. Other methods rest on the use of DNAs for measuring morphogen-inducible DNA-binding. In certain preferred embodiments, the methods and DNAs involve an osteogenic protein 1 (OP-1) responsive transcription activating element. Substances that mediate interaction with and/or activate the OP-1 responsive transcription activating element are considered herein likely to be useful for reproducing in vivo effects of morphogens such as OP-1.
摘要:
The present invention provides rhesus monkey dickkopf-1 (rhDkk-1) and nucleotide sequences encoding it. Also provided herein are recombinant vectors, and recombinant hosts comprising rhDkk-1-encoding nucleotide sequences. Isolated rhDkk-1 can be used to screen and identify novel osteoanabolic compounds that stimulate bone formation for the treatment of osteoporosis or other disorders characterized by insufficient bone mass.
摘要:
Disclosed herein are methods and compositions for identifying morphogen analogs. The preferred methods and compositions relate to the discovery that morphogen upregulation of the mouse type X collagen promoter activity is mediated by a MEF-2 like sequence and requires an adjacent AP-1 sequence. Certain methods rest on the use of test cells comprising DNA defining a morphogen-responsive transcription activating element operatively associated with a reporter gene. Other methods rest on the use of DNAs for measuring morphogen-inducible DNA-binding. In certain preferred embodiments, the methods and DNAs involve an osteogenic protein 1 (OP-1) responsive transcription activating element. Substances that mediate interaction with and/or activate the OP-1 responsive transcription activating element are considered herein likely to be useful for reproducing in vivo effects of morphogens such as OP-1.
摘要:
The present invention relates to methods for inhibiting bone resorption in a mammal comprising administering to a mammal in need thereof a therapeutically effective amount of an EP4 receptor subtype antagonist.
摘要:
Disclosed herein are methods and compositions for identifying morphogen analogs. The preferred methods and compositions relate to the discovery that morphogen upregulation of the mouse type X collagen promoter activity is mediated by a MEF-2 like sequence and requires an adjacent AP-1 sequence. Certain methods rest on the use of test cells comprising DNA defining a morphogen-responsive transcription activating element operatively associated with a reporter gene. Other methods rest on the use of DNAs for measuring morphogen-inducible DNA-binding. In certain preferred embodiments, the methods and DNAs involve an osteogenic protein 1 (OP-1) responsive transcription activating element. Substances that mediate interaction with and/or activate the OP-1 responsive transcription activating element are considered herein likely to be useful for reproducing in vivo effects of morphogens such as OP-1.