48 results about "Palbociclib" patented technology

The present application discloses combinations for treating estrogen receptor-positive and HER2-positive breast cancer patients. The combinations comprise pertuzumab and trastuzumab (e.g. a fixed dose combination of pertuzumab and trastuzumab, PH FDC) plus giredestrant. In one embodiment, the combination further includes a CDK4 / 6 inhibitor, such as abemaciclib or palbociclib.

The invention provides a PET tracer precursor compound of a targeted CDK4 / 6 receptor and a preparation method and application of the PET tracer precursor compound, and further discloses a < 68 > Ga-labeled PET tracer. The PET tracer precursor compound is simple in preparation method, short in preparation time, high in radiochemical yield and suitable for industrial production. And the probe has the advantages of good in-vivo and in-vitro stability, high specificity, high intake and the like, and can be used for accurately and stably detecting and positioning tumor or inflammation parts. Besides, the PET tracer is a Ga-68-labeled targeted CDK4 / 6 radioactive probe synthesized on the basis of a compound Palbociclib, qualitative diagnosis of CDK4 / 6 in tumors can be achieved, then noninvasive accurate quantification of CDK4 / 6 in tumors is achieved, a reliable basis is provided in the stages of clinical staging, treatment decision making, curative effect monitoring and the like, and finally accurate diagnosis and treatment are achieved.

Provided are a combination therapy comprising inavolisib, palbociclib and fulvestrant and methods of treating PIC3CA-mutant, hormone receptor positive (HR+) and HER2 negative (HER2-) locally advanced or metastatic breast cancer comprising administering a therapeutically effective amount of inavolisib, palbociclib and fulvestrant. The combination therapy produces a statistically significant and clinically meaningful improvement to the patient as compared to administering palbociclib and fulvestrant alone to a comparable patient.

The invention discloses a fluorescent / photoacoustic dual-mode diagnosis and treatment probe for detection and photodynamic removal of senescent cells, a preparation method and application, the probe takes a sulfur-substituted hemicyanine dye as a parent structure, a novel bromo-glycoside ligand is covalently coupled, and a blue-green solid is obtained after gradient purification. The probe system shows a remarkable optical response characteristic on beta-galactosidase (beta-Gal) and ideal singlet oxygen (1O2) generation efficiency; an optical signal and a photodynamic therapy effect of the probe can be specifically activated by beta-galactosidase (beta-Gal) overexpressed in cancerous cells and senescent cells under a light excitation condition; the result is successfully verified in a palbociclib-induced senescence melanoma model. According to the probe disclosed by the invention, collaborative regulation and control of dual-mode visual monitoring and precise photodynamic therapy of beta-Gal enzyme activity are realized for the first time, a novel tool is provided for researching a molecular mechanism of cell aging and developing a diagnosis and treatment strategy of aging-related diseases, and the probe has a remarkable application value in the fields of anti-tumor treatment and degenerative diseases.

The disclosure describes selective and potent CDK 4 / 6 inhibitors that show advantageous inhibition of cancer growth, even at low concentrations. A class of the CDK 4 / 6 inhibitors relates to substituted pyridopyrimidines compounds having a fatty acid moiety, and are namely derivatives of Palbociclib of general formula [2A], wherein R1 is hydrogen, aryl, alkyl, alkoxy, cycloalkyl, or heterocyclyl; R2 is hydrogen, halogen, alkyl, acyl, cycloalkyl, alkoxy, alkoxy alkyl, haloalkyl, hydroxy alkyl, alkenyl, alkynyl, nitrile, or nitro; R3 is hydrogen, halogen, alkyl, haloalkyl, hydroxy alkyl, or cycloalkyl; and n is an integer from 9 to 20. These compounds may be used as pharmaceutical compounds for anti-cancer therapies, and are useful for the treatment, prevention and / or amelioration of cancer.

The description discloses selective and potent CDK 4 / 6 inhibitors that exhibit advantageous inhibition of cancer growth, even at low concentrations. One class of CDK 4 / 6 inhibitors refers to substituted pyrrolopyrimidine compounds having a fatty acid moiety and specifically derived from Palbociclib of the general formula [2A], where R1 is hydrogen, aryl, alkyl, alkoxy, cycloalkyl, or heterocyclyl; R2 is hydrogen, halogen, alkyl, acyl, cycloalkyl, alkoxy, alkoxyalkyl, haloalkyl, hydroxyalkyl, alkenyl, alkynyl, nitrile, or nitro; R3 is hydrogen, halogen, alkyl, haloalkyl, hydroxyalkyl, or cycloalkyl; yn is an integer from 9 to 20. These compounds can be used as pharmaceutical compounds for anticancer therapies and are useful for the treatment, prevention and / or improvement of cancer.

The present specification relates to a therapeutic combination of kapatinib, a CDK4 / 6 inhibitor (such as palbociclib, ribociclib, or abelsib) and fulvestrant for use in the treatment of breast cancer, and methods of treating a breast cancer patient with a combination of kapatinib, a CDK4 / 6 inhibitor (such as palbociclib, ribociclib, or abelsib) and fulvestrant.

To provide methods for treating cancer.SOLUTION: Provided is a drug for inhibiting tumor growth or causing tumor regression in a subject with estrogen receptor alpha-positive breast cancer brain metastasis, the subject having one or more estrogen receptor alpha mutations selected from the group consisting of Y537S, Y537C, Y537N, D538G, and S463P. The drug comprises, as an active ingredient, a therapeutically effective amount of RAD1901 having a given structure, or a salt or solvate thereof, which is used in combination with palbociclib.SELECTED DRAWING: None

The invention discloses a preparation method of an anti-breast cancer drug palbociclib key intermediate, and belongs to the field of medical technology synthesis. The preparation method comprises the following steps: reacting a compound VIII with N, O-dimethyl hydroxylamine in the presence of an organic solvent, alkali and a condensing agent to prepare a compound VII, and then carrying out nucleophilic substitution reaction, methylation reaction, Wittig-Horner reaction, bromination and oxidation reaction to prepare an intermediate compound I. The whole reaction route is shortened, the use of flammable and explosive organic metal reagents is avoided, the operability is strong, the method is green and environment-friendly, the total yield and purity of the product are improved, and the method is suitable for industrial mass production.

The invention provides a bone marrow mononuclear cell cryopreservation solution and a method for recovering cell viability through cryopreservation at a deep low temperature, and belongs to the technical field of cell cryopreservation. The method comprises the following steps: dividing bone marrow mononuclear cells into two parts, mixing one part with a cryopreservation solution containing Palbociclib, and performing cooling and cryopreservation to form cryopreserved bone marrow mononuclear cells; and culturing the other part of the cells until the primary cells grow to be full of the bottle bottom, and performing cryopreservation to form the cryopreserved bone marrow mesenchymal stem cells. When bone marrow mononuclear cells are resuscitated, firstly, cryopreserved bone marrow mesenchymal stem cells are resuscitated, and the mesenchymal stem cells BMSC-Evs are extracted; and then resuscitating the cryopreserved bone marrow mononuclear cells, and immediately adding mesenchymal stem cells (BMSC-Evs), so that the activity of the bone marrow mononuclear cells is recovered. According to the method, the survival rate of the recovered bone marrow mesenchymal stem cells reaches 80%, the recovery rate reaches 90%, the cell activity improvement rate is not lower than 30%, and the influence on the state of the recovered bone marrow mononuclear cells is small.

One embodiment of the present invention aims to provide a palbociclib tablet in which the formation of acetyl adducts of palbociclib is suppressed. [Solution] According to one embodiment of the present invention, a palbociclib-containing tablet is provided, comprising a core tablet containing palbociclib or a pharmaceutically acceptable salt thereof, and a film coat layer covering the core tablet, wherein the film coat layer contains an acetyl group-free plasticizer. The acetyl group-free plasticizer may be at least one selected from the group consisting of triethyl citrate, polyvinyl alcohol, polyethylene glycol, and hydroxypropyl cellulose.

The present application provides a bone marrow mononuclear cell freezing solution and a method for deep-cryopreservation and cell activity recovery, which belongs to the field of cell cryopreservation technology. In this method, bone marrow mononuclear cells are divided into two parts, one part is mixed with a freezing solution containing Palbociclib, cooled and frozen to form frozen bone marrow mononuclear cells; the other part is cultured until the primary cells grow to cover the bottom of the bottle and frozen to form frozen bone marrow mesenchymal stem cells. When resuscitating bone marrow mononuclear cells, the frozen bone marrow mesenchymal stem cells are first resuscitated, and the mesenchymal stem cells BMSC-Evs are extracted; then the frozen bone marrow mononuclear cells are resuscitated, and the mesenchymal stem cells BMSC-Evs are immediately added to restore the activity of the bone marrow mononuclear cells. This method can achieve a survival rate of 80%, a recovery rate of 90%, and a cell activity improvement rate of not less than 30% after the resuscitation of bone marrow mesenchymal stem cells, and has little effect on the state of the revived bone marrow mononuclear cells.

The present invention relates to a solid oral pharmaceutical dosage form comprising palbociclib as active pharmaceutical ingredient and succinic acid wherein the succinic acid has a surface area of more than 0.015 m2 / g.

The invention provides a method for treating tetra-negative breast cancer through combination of quercetin inhibiting CYP1B1 and Palbociclib, which comprises the following steps: verifying the influence of AR expression quantity on the curative effect of a CDK4 / 6 inhibitor in TNBC, screening related Chinese herbal medicine sets for treating TNBC by applying an HERB herbal medicine identification database, obtaining effective components and target spots thereof, analyzing the influence of quercetin inhibiting CYP1B1 expression in a QNBC cell line, and determining the curative effect of the CYP1B1 in the QNBC cell line. By knocking down an influence mechanism of CYP1B1 on AR expression in a QNBC cell line, analyzing a mechanism that the QNBC cell line is insensitive to Palbociclib and improving sensitivity, starting from the key target gene CYP1B1, how to improve the sensitivity of the QNBC cell line by regulating and controlling AR, Rb and other genes and related signal channels is deeply analyzed, so that the QNBC cell line is obtained. The multi-dimensional and multi-level research thought is beneficial to more comprehensive and deep understanding of the pathogenesis and the treatment target of QNBC; according to the present invention, the QNBC inhibition effect of quercetin is verified, and through the synergistic effect of the combination of the traditional Chinese medicine effective components and the clinical first-line western medicines, the new thought and the new drug selection are provided for the QNBC treatment, and the innovativeness and the practicability are provided;

The invention discloses a multi-targeting photothermal-photodynamic-endocrine three-mode synergistic breast cancer treatment nano-drug and application thereof, and relates to the technical field of biology and new medicine. Growth and metastasis of breast cancer cells are effectively inhibited through the synergistic effect of three modes of photo-thermal, photodynamic and endocrine therapy, the amphiphilic polymer designed based on Tcpp (tetracarboxylphenylporphyrin) can be self-assembled to form a nanoscale hollow regular sphere, and by means of the high permeability and retention effect (EPR effect) of a tumor site, the tumor site can be effectively inhibited, and the tumor site can be effectively inhibited. The efficient accumulation of the medicine in the tumor tissue is realized; the prodrug BHP is combined with a photo-thermal group and palbociclib, so that the synergistic interaction of multiple action mechanisms is realized, and the treatment effect is improved. The nano-drug prepared by the invention has good safety and biocompatibility, shows a remarkable anti-tumor effect in a tumor-bearing nude mouse model, and provides a brand new strategy and thought for treatment of breast cancer.

One embodiment of the present invention aims to provide a highly stable palbociclib tablet with improved dissolution properties and suppressed generation of related substances after storage under open conditions susceptible to humidity. [Solution] According to one embodiment of the present invention, a palbociclib-containing tablet is provided, comprising palbociclib or a pharmaceutically acceptable salt thereof, and at least one water-soluble acid, adipic acid, and ascorbic acid. The palbociclib-containing tablet may further contain succinic acid.

This invention discloses a CDK4 / 6 inhibitor-loaded nanocarrier for targeting breast cancer, its preparation, and its application. Specifically, the nanoformulation of this invention contains: neutral phospholipids, anionic phospholipids, apolipoproteins and / or their mimic peptides, and a CDK4 / 6 inhibitor; wherein the CDK4 / 6 inhibitor is selected from the group consisting of abexicillin, ribociclib, palbociclib, dalcilib, or combinations thereof. The nanoparticles of this invention can efficiently kill breast cancer cells in vivo, inhibit breast cancer cell proliferation, and improve the prognosis of breast cancer.

The present invention relates to the use of a cyclin-dependent kinase inhibitor for the treatment of heart failure with preserved ejection fraction. The use is in particular the use of the cyclin-dependent kinase (CDK4 / 6) inhibitor palbociclib for the prevention and / or treatment of heart failure with preserved ejection fraction by oral administration.

The disclosure describes selective and potent CDK 4 / 6 inhibitors that show advantageous inhibition of cancer growth, even at low concentrations. A class of the CDK 4 / 6 inhibitors relates to substituted pyridopyrimidines compounds having a fatty acid moiety, and are namely derivatives of Palbociclib of general formula [2A], wherein R1 is hydrogen, aryl, alkyl, alkoxy, cycloalkyl, or heterocyclyl; R2 is hydrogen, halogen, alkyl, acyl, cycloalkyl, alkoxy, alkoxy alkyl, haloalkyl, hydroxy alkyl, alkenyl, alkynyl, nitrile, or nitro; R3 is hydrogen, halogen, alkyl, haloalkyl, hydroxy alkyl, or cycloalkyl; and n is an integer from 9 to 20. These compounds may be used as pharmaceutical compounds for anti-cancer therapies, and are useful for the treatment, prevention and / or amelioration of cancer.

The application discloses a kind of multiple targeting photothermal-photo dynamic-endocrine three-mode synergistic treatment breast cancer nano-drug and its application, it is related to biological and new pharmaceutical technical field.The application is effectively inhibited the growth and metastasis of breast cancer cell by the three-mode synergistic effect of photothermal, photo dynamic and endocrine therapy, amphiphilic polymer based on Tcpp (four carboxyl phenyl porphyrin) It can be self-assembled to form nanoscale hollow regular sphere, using the high permeability and retention effect (EPR effect) of tumor site, realize the efficient accumulation of drug in tumor tissue;Prodrug BHP is realized by combining photothermal group and palbociclib, and the synergistic effect of multiple action mechanisms, so as to improve the treatment effect.The nano-drug prepared by the application has good safety and biocompatibility, and exhibits significant antitumor effect in tumor-bearing nude mouse model, which provides a new strategy and idea for the treatment of breast cancer.

Described herein are methods useful for the treatment of cancers in a canine subject with a pharmaceutical compositions with an anti-cancer agent (e.g., Olaparib, Toceranib, and Palbociclib).

The invention provides an isoindolone-containing CDK4 / 6 inhibitor and a preparation method and application thereof.The preparation method comprises the steps that ethyl bromoacetate is introduced to a piperazine group of a palbociclib structure to be hydrolyzed into acid, then amido bonds are generated to be linked with different isoindolone, and a series of compounds shown in the formula I are synthesized; the compound can be used for preventing or treating mammalian diseases related to abnormal expression of CDK4 / 6 and anti-tumor, anti-virus, antibacterial and anti-inflammatory related to CDK4 / 6. I.

The invention discloses an ROS response type polymer material, a drug-loaded nano-micelle and a preparation method of the ROS response type polymer material and the drug-loaded nano-micelle, and belongs to the technical field of medical materials. A CDK4 / 6 inhibitor Palbociclib which is approved to be used clinically is used as a model drug load, and the nano-micelle M-Pal loaded with the Palbociclib is prepared by utilizing an autonomously prepared ROS (reactive oxygen species) response type high polymer material MPEG113-b-PCL11-b-PB36 and using a solvent evaporation method. The drug-loaded nano-micelle can be stored for a long time after being freeze-dried; after the water phase is added and re-dispersed, the nano-micelle dispersion liquid is still clear and transparent. The ROS-responsive freeze-dried drug-loaded nano-micelle solves the long-term storage problem of conventional micelle-type drug-loaded nano-materials, provides an effective delivery platform for water-insoluble drugs, has ROS-responsive load release characteristics, and has a good application prospect.

This invention relates to the treatment of breast cancer in a subject, and the subject can be either a male or female subject. Including methods of: treating metastatic breast cancer; refractory breast cancer; AR-positive breast cancer; AR-positive refractory breast cancer; AR-positive metastatic breast cancer; AR-positive and ER-positive breast cancer; triple negative breast cancer; advanced breast cancer; breast cancer that has failed selective estrogen receptor modulator (SERM) (tamoxifen, toremifene, raloxifene), gonadotropin-releasing hormone (GnRH) agonist (goserelin), aromatase inhibitor (AI) (letrozole, anastrozole, exemestane), cyclin-dependent kinase 4 / 6 (CDK 4 / 6) inhibitor (palbociclib (Ibrance), ribociclib (Kisqali), lerociclib, abemaciclib (Vorzenio), trilaciclib, lerociclib), mTOR inhibitor (everolimus), trastuzumab (Herceptin, ado-trastuzumab emtansine), pertuzumab (Perjeta), alpelisib (Piqray) (an inhibitor of phosphatidylinositol-3-kinase subunit alpha (PI3Kα)), lapatinib, neratinib (Nerlynx), olaparib (Lynparza) (an inhibitor of the enzyme poly ADP ribose polymerase (PARP)), bevacizumab (Avastin), and / or fulvestrant treatments; metastasis in a subject suffering from breast cancer; HER2-positive; treating a subject suffering from ER mutant expressing breast cancer and / or treating breast cancer in a subject, by first determining the 18F-16β-fluoro-5α-dihydrotestosterone (18F-DHT) tumor uptake and identifying said subject as having AR-positive breast cancer based on 18F-DHT tumor uptake, comprising administering to the subject a therapeutically effective amount of a selective androgen receptor modulator (SARM) compound and a cyclin-dependent kinase 4 / 6 (CDK 4 / 6) inhibitor.

A solid oral pharmaceutical dosage form comprises palbociclib as active pharmaceutical ingredient and succinic acid wherein the succinic acid has a surface area of more than 0.015 m 2 / g.

The invention provides a palbociclib derivative, a preparation method and application thereof, a pharmaceutical composition and application thereof, and relates to the technical field of biological medicines. Palbociclib can achieve the effect of inhibiting proliferation of human cancer cells by promoting tumor cell cycle arrest, and can effectively inhibit growth of in-vivo tumors and prolong the lifetime of patients. The piperazine ring position of palbociclib is structurally optimized and modified, and short-chain carboxylic acid, carboxylic ester or substituted benzoyl structure is introduced to the piperazine position through amido bond, so that the water solubility or fat solubility of the compound is improved, the fat-water partition coefficient is improved, and the bioavailability of the compound is improved. Meanwhile, the introduction of the substituted benzoyl group can enhance the binding force between the compound and a receptor (such as CDK protein), prolong the half-life period of the compound, improve the anti-tumor activity of the compound and promote the rapid research and development of anti-cancer drugs, and has very good clinical application value.

The present application relates to a kind of combination drug for treating kras mutant ovarian cancer and its application.The present application proves by experiment that RB7LP can inhibit the proliferation of ovarian cancer cells, further, can promote the senescence and apoptosis of part kras mutant ovarian cancer cells, simultaneously, it also proves that KRAS inhibitor or EGFR inhibitor can synergistically Palbociclib combined lethal KRAS mutant ovarian cancer, compared with the treatment effect of Palbociclib or sotoracib alone, it is superior, the combination drug of the present application can synergistically induce kras mutant ovarian cancer cell apoptosis, increase cancer cell inhibition rate, curative effect is good, with very strong clinical application value.

The invention relates to the field of cell engineering, in particular to a human hypopharyngeal carcinoma tissue block PDX-HPC1 and application thereof. The invention provides a human hypopharyngeal carcinoma tissue block PDX-HPC1 or a cancer cell derived from the tissue block. The preservation number of the human hypopharyngeal carcinoma tissue block PDX-HPC1 is CCTCC (China Center For Type Culture Collection) No: C2025106. The tumor tissue of the patient is directly inoculated to the mouse, sample pretreatment and cell digestion processes are not involved, operation is easy, the tumor formation rate is high, the constructed hypopharyngeal carcinoma PDX model can make up the huge vacancy of domestic and overseas transformation research of the hypopharyngeal carcinoma PDX model, and the development of the hypopharyngeal carcinoma PDX model is promoted. And research on the anti-tumor effect of palbociclib on the basis of the constructed hypopharyngeal carcinoma PDX model is helpful for determining the anti-tumor mechanism of palbociclib in hypopharyngeal carcinoma.

Provided are a combination therapy comprising inavolisib, palbociclib and fulvestrant and methods of treating PIC3CA-mutant, hormone receptor positive (HR+) and HER2 negative (HER2−) locally advanced or metastatic breast cancer comprising administering a therapeutically effective amount of inavolisib, palbociclib and fulvestrant. The combination therapy produces a statistically significant and clinically meaningful improvement to the patient as compared to administering palbociclib and fulvestrant alone to a comparable patient.

The invention provides a drug-drug salt of palbociclib and a non-steroidal anti-inflammatory drug containing a carboxylic acid group, a crystal of the drug-drug salt, a preparation method of the crystal, a pharmaceutical composition containing the crystal and application of the pharmaceutical composition. In the drug-drug salt, palbociclib is connected with a non-steroidal anti-inflammatory drug containing a carboxylic acid group through an intermolecular ionic bond. The drug-drug salt obtained by the invention can realize the synergistic interaction of palbociclib and a non-steroidal anti-inflammatory drug containing a carboxylic acid group, improves the antitumor activity of palbociclib, and can improve the solubility, dissolution rate, dissolution concentration and dissolution rate of palbociclib and improve the bioavailability of palbociclib.