87 results about "Antiestrogen" patented technology

Certain benzopyran antiestrogens are disclosed for treating estrogen sensitive diseases such as breast cancer. Prodrug forms provide ease of manufacturing, good shelf life, and bioavailability, and preferred stereoisomers are shown to be more effective than racemic mixtures.

The present invention relates to compounds of Formula (I),

methods for preparing these compounds, compositions, intermediates and derivatives thereof and for treating a condition including but not limited to ankylosing spondylitis, artherosclerosis, arthritis (such as rheumatoid arthritis, infectious arthritis, childhood arthritis, psoriatic arthritis, reactive arthritis), bone-related diseases (including those related to bone formation), breast cancer (including those unresponsive to anti-estrogen therapy), cardiovascular disorders, cartilage-related disease (such as cartilage injury/loss, cartilage degeneration, and those related to cartilage formation), chondrodysplasia, chondrosarcoma, chronic back injury, chronic bronchitis, chronic inflammatory airway disease, chronic obstructive pulmonary disease, diabetes, disorders of energy homeostasis, gout, pseudogout, lipid disorders, metabolic syndrome, multiple myeloma, obesity, osteoarthritis, osteogenesis imperfecta, osteolytic bone metastasis, osteomalacia, osteoporosis, Paget's disease, periodontal disease, polymyalgia rheumatica, Reiter's syndrome, repetitive stress injury, hyperglycemia, elevated blood glucose level, and insulin resistance.

Disclosed are methods and compositions comprising native, site-specifically mutagenized, and synthetic peptides comprising portions of the human estrogen receptor, or estrogen receptor co-activator, and nucleic acid compositions encoding these polypeptide compositions. Also disclosed are methods for synthesizing phosphotyrosyl and malonyltyrosyl peptide derivatives and their use as antiestrogen compositions in the treatment of breast cancers, the preparation of pharmaceutical compositions, diagnostic kits, and the development of related assays for use in antitumor therapies.

Methods and kits for diagnosing tumorigenicity and for determining whether a cancer patient is resistant to the pharmacological effects of antiestrogen therapy. Increased levels of the PCDGF (GP88) growth factor are indicative of tumorigenicity and resistance to the pharmacological effects of antiestrogen therapy. The methods and kits of the invention are useful for assessing the tumorigencity of a biological sample from a patient and determining whether the patient is a candidate for antiestrogen, including tamoxifen, therapy.

The present invention relates to the administration of compositions comprising an antiestrogen, preferably trans-clomiphene, for treating metabolic syndrome in a subject. The invention is also directed to methods for reducing fasting glucose levels in a subject by administering a composition comprising an antiestrogen, preferably trans-clomiphene.

Methods and compositions are provided for the identification of expression signatures in ER+ breast cancer cases, where the signatures correlate with responsiveness, or lack thereof, to treatment with tamoxifen or another antiestrogen agent against breast cancer The signature profiles are identified based upon sampling of reference breast tissue samples from independent cases of breast cancer and provide a reliable set of molecular criteria for predicting the efficacy of treating a subject with breast cancer with tamoxifen or another antiestrogen agent against breast cancer. Additional methods and compositions are provided for predicting responsiveness to tamoxifen or another antiestrogen agent against breast cancer in cases of breast cancer by use of three biomarkers. Two biomarkers display increased expression correlated with tamoxifen response while the third biomarker displays decreased expression correlated with tamoxifen response.

Methods and compositions are provided for the identification of expression signatures in ER+ breast cancer cases, where the signatures correlate with responsiveness, or lack thereof, to treatment with tamoxifen or another antiestrogen agent against breast cancer The signature profiles are identified based upon sampling of reference breast tissue samples from independent cases of breast cancer and provide a reliable set of molecular criteria for predicting the efficacy of treating a subject with breast cancer with tamoxifen or another antiestrogen agent against breast cancer. Additional methods and compositions are provided for predicting responsiveness to tamoxifen or another antiestrogen agent against breast cancer in cases of breast cancer by use of multiple biomarkers. Two biomarkers display increased expression correlated with tamoxifen response while two other biomarkers display decreased expression correlated with tamoxifen response.

The disclosure provides methods of treating bipolar disorder by administering an antiestrogen to reduce the severity and frequency of mood episodes. The disclosure further provides methods of treating depression with an antiestrogen in a descending dose protocol.

The present invention comprises the design, synthesis and development of a new class of chemotherapeutic agents for prophylactic and therapeutic treatments in a mammal, particularly a human, believed to be at risk of suffering from a hormone-responsive disorde. In an embodiment of the invention, such treatments include therapeutic compositions comprising novel steroidal antiestrogen and antiandrogen compounds. In a preferred embodiment, such a novel compound of the present invention has an address and a message component, which are made into a single composite entity for more aggressive intervention and effective treatment of hormone-responsive disorders, thereby prolonging the disease-free interval for the patient and reducing a number of side effects.

The invention relates to a method for rapidly evaluating composition effect of estrogen and antiestrogen. The method comprises the following steps of: obtaining zebrafish embryos; mixing the estrogen with different concentration of antiestrogens to form different ratios of exposure liquid; putting the zebrafish embryos into the exposure liquid to expose for 96 hours lastingly, and maintaining the water temperature at 26+/-1 DEG C, wherein the photoperiod is 16 hours in daytime and 8 hours at night; exchanging 80% of exposure liquid after 24 hours, and recording the hatching rate, the aberration rate and the hatching time of the zebrafish embryos; collecting juvenile fishes to store for use after exposure is finished; and evaluating the composition effect on morphological level of embryonic development and/or gene transcription level. The method for evaluating the composition effect of estrogen and antiestrogen by the zebrafish embryos is simple, rapid and objective, just needs 96 hours, and is a novel method for rapidly evaluating the composition effect of the estrogen and the antiestrogen.

The present invention relates to methods and uses for preventing or treating hormone-dependent diseases, in particular breast cancer, in a mammal, by a combination of an progesterone-receptor antagonist, in particular the progesterone-receptor antagonist 11β-(4-acetylphenyl)-17β-hydroxy-17α-(1,1,2,2,2-pentafluoroethyl)-estra-4,9-dien-3-one or a pharmaceutically acceptable derivative or analogue thereof, and a pure antiestrogen, in particular a compound of general formula I as defined in the specification, for instance 11β-Fluoro-17α-methyl-7α-{5-[methyl(8,8,9,9,9-pentafluorononyl)amino]pentyl}-estra-1,3,5(10)-triene-3,17β-diol. The invention further relates to pharmaceutical compositions comprising said combination.

Novel methods for reduction or elimination the incidence of hot flushes, vasomotor symptoms, and night sweats while decreasing the risk of acquiring breast, uterine or endometrial cancer and furthermore having beneficial effect by inhibiting the development of osteoporosis, hypercholesterolemia, hyperlipidemia, atherosclerosis, hypertension, insulin resistance, diabetes type 2, loss of muscle mass, adiposity, Alzheimer's disease, loss of cognition, loss of memory, or vaginal dryness in susceptible warm-blooded animals including humans involving administration of an amount of a sex steroid precursor, particularly dehydroepiandrosterone (DHEA) and an antiestrogen or a selective estrogen receptor modulator, particularly compounds having the general structure:

Pharmaceutical compositions for delivery of active ingredient(s) and kit(s) useful to the invention are also disclosed.

The invention discloses a hybrid pseudo-estrogen and anti-estrogen effect recognition and prediction method based on enhanced sampling molecular dynamics simulation. The method, based on nuclear receptor allosteric and co-regulator factor regulation and control mechanisms, and by adopting an enhanced sampling molecular dynamics simulation method, identifies local and global free energy lowest points and carries out dynamic trajectory clustering, extracts steady-state conformation of an estrogen receptor alpha under the action of a ligand compound, judges estrogen interference effect of a tested compound according to the relationship between the 12th spiral stable position of the receptor and a co-regulator factor recruitment/inhibition mechanism, and identifies and predicts pseudo effect and resistant effect and hybrid pseudo-estrogen and anti-estrogen disruptors. Compared with a traditional in-vitro experiment method, the method is lower in cost and higher in efficiency and prevents the problem of cell specificity of the hybrid pseudo-estrogen and anti-estrogen disruptors; and compared with an existing computer-aided screening method, the method can effectively identify steady-state conformation and realize prediction of hybrid pseudo-estrogen and anti-estrogen interference effects.

The present invention comprises the design, synthesis and development of a new class of chemotherapeutic agents for prophylactic and therapeutic treatments in a mammal, particularly a human, believed to be at risk of suffering from a hormone-responsive disorder. In an aspect of the invention, such treatments include therapeutic compositions comprising novel steroidal antiestrogen and antiandrogen compounds. In a preferred aspect, such a novel compound of the present invention has an address and a message component, which are made into a single composite entity for more aggressive intervention and effective treatment of hormone-responsive disorders, thereby prolonging the disease-free interval for the patient and reducing a number of side effects.

The present invention relates to a combination therapy for elevating testosterone levels in male mammals in which an antiestrogen or pharmaceutically acceptable salt thereof is co-administered to the mammal with an additional therapeutic agent selected from an androgen and an aromatase inhibitor. The invention is also directed to a combination therapy for treating males with hypogonadism and disorders related thereto, including reduction of muscle mass. limitation of body performance capacity, reduction of bone density, reduction of libido, reduction of potency, reduction of benign prostatic hyperplasia and infertility.