30 results about "Palbociclib" patented technology

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

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 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 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.

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.

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 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.

Provided are a method for treating a cancer by a CDK4 / 6 inhibitor and a corresponding pharmaceutical use. The cancer is glioblastoma or non-small cell lung cancer, and the inhibitor shows a better tumor suppression effect compared with positive control drugs Palbociclib and Abemaciclib.

Provided are a pharmaceutical combination and a pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable form thereof and at least one other anticancer agent, and use thereof in the preparation of a medicine for treating a malignant tumor disease. The other anticancer agent is a CDK inhibitor or a pharmaceutically acceptable salt thereof (such as palbociclib), lenvatinib or a pharmaceutically acceptable salt thereof, sorafenib or a pharmaceutically acceptable salt thereof, or any combination of the above.

This invention introduces a stable oral tablet dosage form comprising palbociclib or its pharmaceutically acceptable salts, along with at least one excipient. By adjusting the amount of excipients, the formulation enhances the flow and granulation properties, ensuring uniform die filling and precise weight control during tablet production. Specifically, it involves a process for producing without flow and adhesive problems that can be dry granulated powder comprising palbociclib, to prepare storage-stable tablets having an acceptable in-vitro dissolution profile.

Provided are combination therapies comprising a PI3K inhibitor (e.g., inavolisib), a CDK4 / 6 inhibitor (e.g., palbociclib), and fulvestrant; and methods of treating hormone receptor positive and HER2 negative (HR+ / HER2−) locally advanced or metastatic breast cancer in a patient (preferably a patient with a PIC3CA mutant patient) comprising administering a therapeutically effective amount of inavolisib, or a pharmaceutically acceptable salt thereof, a CDK4 / 6 inhibitor (e.g., palbociclib), and fulvestrant or letrozole.

The present invention relates to a solid oral pharmaceutical for Axitinib, Ibrutinib and / or Palbociclib (API) or any other Kinase Inhibitor API with a novel, well defined method to enhance solubility of active pharmaceutical ingredients (API) with low solubility in aqueous media and use those enhanced API in a new approach of preparing modified and / or sustained release pharmaceutical formulation for API which are regularly not suitable for sustained release formulations because of their low solubility. This invention is applicable for small molecule API (molecular weight < 1000) for which the solubility can be enhanced by formation of a e.g., Cyclodextrin Complex regardless which Cyclodextrin or derivate thereof is employed according to the method described in this invention. Axitinib, Ibrutinib and / or Palbociclib and other Kinase Inhibitors can be found for treatment of malign tumor diseases and others.

Disclosed herein are methods of inhibiting tumor growth or producing tumor regression in a subject by administering to the subject a therapeutically effective amount of a combination of palbociclib and RAD1901.

The present invention relates to combination therapies for treating KRas G12C cancers. In particular, the present invention relates to methods of treating cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a combination of a CDK 4 / 6 inhibitor and a KRAS G12C inhibitor of Formula (I), Formula (I-A) or Formula (I-B), pharmaceutical compositions comprising a therapeutically effective amounts of the inhibitors, kits comprising the compositions and methods of use therefor.

Provided herein are compositions and methods of treating cancer with combinations of cell cycle inhibitors and LSD1 inhibitors. In some aspects, the cell cycle inhibitor is a CDK4 / 6 inhibitor, e.g., palbociclib. In some aspects, the LSD1 inhibitor is MC2580 or DDP38003. The compositions and methods of the disclosure may be used to treat cancers including, but not limited to, leukemia, lung cancer, melanoma, or breast cancer. The cancers may be, for example, LSD1-inhibitor-resistant and / or comprise cells having a reduced level of p21 expression or a loss of p21 function.

A combination therapy comprising enoxacin, palbociclib, and fulvestrant is provided, along with a method for treating locally advanced or metastatic breast cancer with PIC3CA mutations, hormone receptor-positive (HR+), and HER2-negative (HER2-), the method comprising administering therapeutically effective amounts of enoxacin, palbociclib, and fulvestrant. The combination therapy produced statistically significant and clinically meaningful improvements in comparable patients compared to administration of palbociclib and fulvestrant alone.

To provide a tablet or the like comprising palbociclib or a pharmaceutically acceptable salt thereof together with an organic acid or a salt thereof, ensuring that the stability of palbociclib or the pharmaceutically acceptable salt thereof is maintained even when the content of palbociclib or the pharmaceutically acceptable salt thereof is high.SOLUTION: The tablet of the present disclosure comprises granules containing palbociclib or a pharmaceutically acceptable salt thereof together with an organic acid or a salt thereof. The content of palbociclib or the pharmaceutically acceptable salt thereof in the tablet is 35 mass% or more. The particle diameter (D50) of the organic acid or the salt thereof is 180 μm or more.SELECTED DRAWING: None

The present disclosure relates to a process for the preparation of Palbociclib intermediate. Particularly, the present disclosure relates to a process for the preparation of 6-bromo-2-chloro- 8-cyclopentyl-5-methylpyrido[2,3-d]pyrimidin-7(8H)-one. The process of the present 5 disclosure is simple, cost effective and environment friendly; and provides 6-bromo- 2-chloro-8-cyclopentyl-5-methylpyrido[2,3-d]pyrimidin-7(8H)-one with a comparatively better purity and better yield.

The application discloses application of XPO7 in treatment of esophageal squamous carcinoma, and the XPO7 is applied to treatment of the esophageal squamous carcinoma as a sensitization target of a CDK4 / 6 inhibitor, and after XPO7 knockdown, the growth inhibition of the esophageal squamous carcinoma to the CDK4 / 6 inhibitor can be significantly increased; meanwhile, after the XPO7 inhibitor is combined with the CDK4 / 6 inhibitor, the XPO7 inhibitor can down-regulate a cell cycle related pathway, further promote expression down-regulation of a cell cycle related gene and inhibition of the cell cycle, so that the sensitivity of the esophageal squamous carcinoma to palbociclib is increased; moreover, by combining the XPO7 inhibitor with the CDK4 / 6 inhibitor, the drug resistance of the esophageal squamous carcinoma to palbociclib can be effectively reduced, the growth of the esophageal squamous carcinoma can be continuously and effectively inhibited, the applicable patient population is wider, and the application has wide popularization value.

The invention discloses an application of palbociclib in mucosal malignant melanoma. In particular, the present invention provides the therapeutic use of palbociclib in mucosal malignant melanoma known for the treatment of ER + / HER2-advanced postmenopausal breast cancer. Different from common skin malignant melanoma treatment, palbociclib has a very good tumor inhibition effect on multi-source mucous membrane malignant melanoma which is extremely high in malignant degree and does not have an exact treatment drug, fills the blank of drug treatment for mucous membrane malignant melanoma, and has a very great application prospect.

Palbociclib free base has a pH-dependent solubility, resulting in a problem of significantly reduced dissolution in the neutral pH range of 5.5 or higher compared to dissolution in the acidic range. To address this issue, the use of a water-soluble acid such as succinic acid is known. However, it is also known that palbociclib is decomposed by the water-soluble acid, resulting in the formation of related substances in the formulation. Therefore, there is a need for a pharmaceutical tablet containing palbociclib and a water-soluble acid and having excellent storage stability. In particular, the objective is to provide a pharmaceutical tablet in which the formation of related substances is suppressed after storage. [Solution] By adding adipic acid to pharmaceutical tablets containing palbociclib as an active ingredient, it is possible to prepare pharmaceutical tablets that suppress the production of related substances during storage.