89 results about "Antiestrogen" patented technology

The present invention relates to quantitative molecular indicators that can guide clinical decisions in breast cancer, such as estrogen receptor (ESR1)-positive, lymph node-negative breast cancer. In particular, the invention concerns certain genes, the varied expression of which indicates the likelihood of recurrence of surgically resected breast cancer in patients who are not treated with a therapeutic agent in the adjuvant setting. In addition, the invention concerns the use of quantitative measurement of the expression of certain genes, including the ESR1 gene, that measure as a continuous variable, to determine (a) the likelihood of a beneficial response to the anti-estrogen therapeutic agent, such as tamoxifen; and (b) the potential magnitude of beneficial response to chemotherapy.

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.

Compounds for the treatment of estrogen-receptor related maladies are provided. Compounds with anti-androgenic properties also are provided. In particular, the invention provides compounds that are tetrahydroquinoline phenylamide derivatives and are useful for the treatment of breast and prostate cancer, and osteoporosis.

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.

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.

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 present invention provides methods for increasing sensitivity of cancer cells to an antiestrogen agent, such as a selective estrogen receptor modulator (SERM). The methods include administering to the subject a polynucleotide in an amount effective to increase the antiestrogen agent sensitivity of the cancer cells. The cancer cells may be estrogen receptor positive, such as ER-α66 positive or ER-α36 positive, prior to the administering. Also provided are methods for decreasing the amount of estrogen receptor present in a cancer cell, methods for determining whether antiestrogen agent sensitivity of cancer cells in a subject can be increased, methods for diagnosing whether a subject has, or is at risk for developing, cancer, and methods for identifying an agent that increases the amount of let-7 miRNA in a cell.

Disclosed are methods and compositions for inhibiting the growth of a tumor (e.g., a malignant tumor) in a subject. In particular, combination therapies for treating a tumor in a subject by co-administering an agent selected from i) an effective amount of an anti-estrogen agent; ii) an effective amount of a receptor tyrosine kinase inhibitor; iii) an effective amount of a MEK / PI3 kinase / AKT inhibitor; iv) an effective amount of MM-151; v) an effective amount of an mTOR inhibitor; and / or vi) an effective amount of trastuzumab or TMD1, and / or combinations thereof; and an effective amount of a bispecific anti-ErbB2 / anti-ErbB3 antibody. Also disclosed is a bispecific anti-ErbB2 / anti-ErbB3 antibody for use in the therapy of a tumor in combination with an agent selected from i) an effective amount of an anti-estrogen agent; ii) an effective amount of a receptor tyrosine kinase inhibitor; iii) an effective amount of a MEK / PI3 kinase / AKT inhibitor; iv) an effective amount of MM-151; v) an effective amount of an mTOR inhibitor; and / or vi) an effective amount of trastuzumab or TMD1, and / or combinations thereof.

Acquired and de novo endocrine resistance are major clinical problems in the management of breast cancer patients. Though the antiestrogen tamoxifen prolongs disease-free and overall survival in the adjuvant setting, and induces remissions in over half of the patients with estrogen receptor positive metastatic disease, all patients eventually acquire tamoxifen resistance. Furthermore, many of the resistant tumors actually appear to be stimulated by tamoxifen just as they are by estrogens. The present invention provides methods of predicting endocrine resistance comprising detecting the biological activity and / or expression of p38 MAPK and / or AIB1. The invention further provides methods of reducing, reversing, or preventing endocrine resistance comprising contacting a breast or prostate tumor with a p38 MAPK pathway inhibitor.

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.

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

The invention relates to a letrozole I-type crystal and a preparation method thereof, in particular to an anhydrous letrozole crystal. The structure and characteristics of the anhydrous letrozole crystal are represented by X-radial powder diffraction, differential scanning calorimetry, infrared spectrum and the like. Characteristic diffraction peaks, which are positioned at the degrees 2theta of 13.08+ / -0.2, 14.06+ / -0.2, 17.04+ / -0.2, 21.44+ / -0.2 and 29.24+ / -0.2, are positioned in the X-radial powder diffraction pattern of the crystal powder. The anhydrous letrozole crystal is simple in preparation process, the yield and purity of the crystal are high, and the anhydrous letrozole crystal has good stability and is suitable for production of medicinal preparations. The invention also provides a method for preparing the anhydrous letrozole crystal by using an anhydrous and pure organic solvent as a crystallization solvent and application of the crystal in the medicinal preparations which are used for treating advanced breast cancer of a patient after menopause by antiestrogen.

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.

Novel methods for prevention, reduction or elimination of the incidence of male androgen deficiency symptoms or diseases including male hypogonadism-associated symptoms and diseases associated with low serum testosterone and / or low DHEA or low total androgens in susceptible warm-blooded animals including humans involving administration of an amount of a sex steroid precursor, particularly dehydroepiandrosterone (DHEA) and a selective estrogen receptor modulator (SERM) (particularly acolbifene), an antiestrogen or a prodrug of the two. The symptoms or diseases are loss of libido, erectile dysfunction, tiredness, loss of energy, depression, bone loss, muscle loss, muscle weakness, fat accumulation, memory loss, cognition loss, Alzheimer's disease, dementia, loss of body hair, fertility problems, insomnia, gynecomastia, anemia, hot flushes, sweats, decreased sense of well-being, obesity, osteoporosis, hypercholesterolemia, hyperlipidemia, atherosclerosis, hypertension, insulin resistance, cardiovascular disease and type 2 diabetes. 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 an estrogen receptor regulator of a formula (I) or a pharmaceutically acceptable salt thereof. The compounds can combine with the estrogen receptor alpha to produce the anti-breast cancer function and produce regulation function in uterus and other parts at the same time. The compounds have strong function of combining with the estrogen receptor alpha in vitro, and can effectively antagonize the combination of estrogen and the estrogen receptor alpha, thus treating breast cancer caused by excessive estrogen, while playing the role of regulating in the uterus and other parts.

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.

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 antiprogestin, in particular the antiprogestin 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.

The invention relates to compounds that are analogs of a cyclic peptide, cyclo[EKTOVNOGN] (SEQ ID NO: 13), AFPep, that has anti-estrotrophic activity. The analogs of the invention include peptides and peptidomimetics that inhibit estrogen receptor-dependent cell proliferation. The compounds of the invention are useful for treating cell proliferative disorders or physiological conditions characterized by undesirable or unwanted estrogen induced cell proliferation, including breast cancer.