57 results about "Oestrogen receptor" patented technology

Triazine derivatives of formula (I), which exhibit pharmacological activity at estrogen receptors alpha (ER alpha) and beta (ER beta) are described herein. The described invention also includes compositions and medicaments containing the triazine derivatives as well as processes for the preparation and use of such compounds, compositions and medicaments.

The invention discloses an oxo-bridged bicyclo-heptylene sulfonamides compound containing different alkyl chain lengths, as well as a preparation method and application thereof, and belongs to the technical field of medicines. 3-(4-hydroxycyclohexyl phenyl)-4-(4-alkoxy phenyl)-furan and a phenylethylene sulfonamide derivative are adopted as raw materials, no catalyst is needed, the raw materials are reacted at 90 DEG C for 8 hours, and the oxo-bridged bicyclo-heptylene sulfonamides compound containing the different alkyl chain lengths is obtained through one-step preparation. The action mode of the oxo-bridged bicyclo-heptylene sulfonamides compound is different from the action mode of existing anti-breast cancer drug tamoxifen, and the compound not only can be used for effectively inhibiting the growth of a breast cancer cell MCF-7, but also has favorable estrogen receptor alpha down-regulation activity equivalent to fulvestrant, and shows an application prospect of the compound in breast cancer therapy.

The present invention relates to novel N-substituted azetidine derivatives < of the formula (I); wherein SERMF is a Selective Estrogen Receptor Modilator fragment; X is no atom, O, S, CH2, carbonyl, N—R5; R1 is H, (C1-8)alkyl, (C3-8)cycloalkyl, (C3-6)heterocycloalkyl, (C2-6)alkenyl, (C2-6)alkynyl, (C1-4)alkylcarbonyl, (C1-4)alkoxy(C2-4)alkyl, (C3-6)cycloalkyl(C1-3)-alkyl, (C3-6)heterocycloalkyl(C1-3)alkyl, each independently optionally substituted with one or more halogen, nitrile, hydroxyl or (C1-2)alkyl; R5 is H, (C1-3)alkyl, optionally substituted with one or more fluorine; R17, R18 and R19 are independently of each other H, fluorine, nitrile or (C1-3)-alkyl, optionally substituted with one or more fluorine; or a prodrug, isotopically-labelled derivative or pharmaceutically acceptable salt thereof, > to pharmaceutical compositions comprising these compounds and to their use in therapy, in particular to their use for the prevention or treatment of ovulatory dysfunction, uterine cancer, endometrium cancer, ovarian cancer, endometriosis, osteoporosis, prostate cancer, benign prostatic hypertrophy, and breast cancer, in particular ER-positive breast cancer, more in particular ER-positive, hormone treatment-resistant breast cancer. Said N-substituted azetidine derivatives have estrogen receptor alpha (ERa) antagonistic and—in certain embodiments—selective estrogen receptor downregulating (SERD) activity in ER-positive breast cancer cells.

The present invention is directed to compositions regarding a specific mutation in estrogen receptor alpha and their use as diagnostic markers in breast tissue, such as premalignant lesions, for the development of breast cancer. More specifically, cells of breast cancer whose nucleic acid comprises the estrogen receptor alpha mutation identify the breast cancer to be an invasive breast cancer.

The invention discloses a method for screening an estrogen receptor Alpha (ER Alpha) single-chain antibody with a phage antibody library. The method comprises the following steps: using an ER Alpha protein as an immunogen for immunizing a New Zealand white rabbit and extracting total RNA of spleen; amplifying VH and VL fragments by RT-PCR, and splicing an scFv gene; constructing a PCANTAB5E-ScFv recombinant plasmid, electrotransforming E. coli TG1 competent cells with the recombinant plasmid to construct a phage single-chain antibody library; using ER Alph-positive breast cancer tissue sections and ER Alpha protein as solid phase antigens for performing affinity enrichment screening on the antibody library; and identifying positive clones with a method of combining a Phage-ElLSA method with breast cancer cell smear immunochemistry. The invention establishes a method for specifically screening ER from the phage antibody library by using the ER Alpha -positive breast cancer tissue sections, and identifying the positive clones with the method of combining the Phage-ElLSA method with the breast cancer cell smear immunochemistry, and provides a new idea for a phage antibody library screening method.

The invention described herein provides a method for the treatment of an oestrogen receptor positive breast cancer in a subject in need thereof comprising administering to said subject a therapeutically effective amount of an MPS1 inhibitor, wherein:

• (i) said subject has previously been treated with an endocrine therapy; and/or
• (ii) said breast cancer is resistant to endocrine therapy.

The invention discloses a primer used for performing pyrophosphoric acid detection on PvuII and XbaI polymorphism of an intron 1 of an estrogen receptor gene alpha. The primer comprises a specific primer and a primer, wherein the specific primer is used for amplifying the PvuII and XbaI nucleic acid fragment of the estrogen receptor gene alpha from a sample nucleic acid, and the primer is used for performing pyrophosphoric acid sequencing on the obtained nucleic acid fragment. By adopting the pyrophosphoric acid sequencing technology, through the specific amplification primer and the pyrophosphoric acid sequencing primer disclosed by the invention, the PvuII and XbaI polymorphism of the intron 1 of the estrogen receptor gene alpha, which is related with hormone-dependent diseases, can be detected. The primer used for performing the pyrophosphoric acid detection on the PvuII and XbaI polymorphism of the intron 1 of the estrogen receptor gene alpha is high in specificity and accuracy, and can be clinically used as an auxiliary index and screening of early prevention and early diagnosis on agnogenic hypomenorrhea and other certain hormone-dependent related diseases.

The invention relates to the production of hepatocyte cell lines useful in toxicology screens or therapy. A mammalian hepatocyte comprises, as a single polypeptide, a fusion protein comprising a c-myc protein and an oestrogen receptor, or functional fragments thereof.

The invention relates to an application of 2`,2`-dimethyl-2`H, 4H-3, 6`-bis- benzopyran-4-ketone , in particular to an application of the compound 2`,2`-dimethyl-2`H, 4H-3, 6`-bis- benzopyran-4-ketone in preparing drugs for treating related diseases such as estrogen receptor ER-Alpha subtype and ER-Beta subtype, belonging to the medicine field. In the condition of low concentration, the compound does not change the expressions of ER-Alpha66, ER-Alpha46 and ER-Alpha36; while in the condition of high concentration, the compound can inhibit the expressions of the three at the same time. Meanwhile, the compound can kill breast cancer cell MCF7 that expresses the ER-Alpha66, the ER-Alpha46 and the ER-Alpha36. Therefore, the compound can be also used as the regulator of the estrogen receptor ER-Alpha36 to treat diseases caused by abnormal expression of the estrogen receptor ER-Alpha36, such as tumor, osteoporosis, asthma, heart disease or senile dementia , etc.

The invention discloses a breast cancer organoid culture solution as well as a preparation method and a culture method thereof. The culture solution is prepared from the following components: a basic culture medium, 1 to 5mM of L-alanyl-L-glutamine, 90 to 110U/mL of a blue chain double antibody, 0.5 to 1 percent (vol/vol) of an N2 additive, 1 to 2 percent (vol/vol) of a B27 additive, 0.06 to 0.1 mM of non-essential amino acid, 0.1 to 0.5 mu M of SB 203580, 3 to 8mM of nicotinamide, a growth factor and a system stabilizing factor. According to the culture solution disclosed by the invention, not only can very high cell and tissue activity be maintained in a culture process of breast cancer tissue cells, but also the breast cancer tissue cells can be cultured by simulating a disordered hormone environment in the body of a patient; the expression levels of the estrogen receptor PR and the progestational hormone receptor ER during preservation of the in-vitro cultured breast cancer organoid sample can better express the inherent pathological characteristics of the estrogen receptor PR and the progestational hormone receptor ER.

The invention discloses application of ligustilide to prevention and treatment of breast cancer. A research represents that the ligustilide has a certain inhibition effect on negative and positive breast cancer cells of an estrogen receptor alpha (ERalpha). Furthermore, existing breast-cancer-resisting drugs including tamoxifen and the like in the market mainly have effects on the positive breast cancer cells of the estrogen receptor alpha, but have very slight effects on the negative breast cancer cells of the estrogen receptor alpha; the research provided by the invention represents that the ligustilide can be used for increasing ERalpha protein expression of the breast cancer cells, and furthermore, the ligustilide and the tamoxifen are cooperated to realize the effect of preventing and treating the breast cancer.

The present invention relates to methods for estimation of efficacy of therapeutic treatment of cancer patients, in particular breast cancer patients. The estimation is based on determining of the status of aberration of the estrogen receptor alpha gene (ESR1) in situ, and, optionally, the status of aberration of a gene related to ESR1. In particular, the invention relates to determining the presence or absence and, if present, the type of aberration, e.g. amplification, duplication, polyploidization, deletion or translocation of the ESR1 gene in the tumor cells of the patient. The invention further relates to a kit-in-parts comprising probes for the determining the status of aberration of ESR1 and ESR1-related genes in situ.

The invention discloses a RT-PCR primer and method for amplifying estrogen receptor alpha genes in female chinemys reevesii. The RT-PCR primer comprises a primer pairs as shown in SEQ ID No:1 and SEQID No:2. The method comprises the following steps: 1) extracting total RNA of a to-be-amplified sample; 2) reversely transcribing the extracted total RNA into cDNA; 3) amplifying the cDNA by using theRT-PCR primer; PT-PCR primer is the PT-PCR primer. According to the invention, a set of RT-PCR primers are designed, the total RNA of the to-be-amplified sample is extracted, and then reverse transcription is conducted to obtain the cDNA. The cDNA is amplified by using the RT-PCR primer. Under the premise of cost reducing, a great number of estrogen receptor alpha genes in female chinemys reevesii fallopian tubes are amplified rapidly and accurately, and large-scale and more intuitive studies of the estrogen receptor alpha genes in the female chinemys reevesii are effectively achieved.

The invention makes a 16α-substituted steroidal compound available having formula 1, wherein the dotted ring is a fully saturated, a fully aromatic or a saturated ring with a Δ5-10 double bond; R¹ is (C₁-C₃)alkyl or (C₂-C₃)alkenyl, and each of these groups can be substituted with one or more halogens; R² is (C₁-C₄;)alkyl, (C₂-C₄)alkenyl or methylene, and each of these groups can be substituted with one or more halogens; R³ is methyl or ethyl; or a prodrug thereof, which compound can be used for an estrogen receptor α selective treatment