34 results about "Ribociclib" patented technology

The present disclosure is directed to oral tablet of ribociclib including its salt(s). One embodiment of the present disclosure is directed to tablet of ribociclib with high drug load with an immediate release profile. One embodiment of the present disclosure is directed to coated tablet of ribociclib. Another embodiment of the present disclosure is directed to coated tablet of ribociclib where the coating is an aqueous moisture barrier coating (e.g., Opadry® amb II coating where the coating is PVA based).

The invention belongs to the technical field of biological medicines, and particularly relates to a ferrozirconium bimetallic nano-material, a preparation method and application of the ferrozirconium bimetallic nano-material in preparation of medicines for treating breast cancer. The ferrozirconium bimetallic nano material is formed by loading a CDK4 / 6 inhibitor on a nano carrier; wherein the nano carrier is an organic framework material Zr-Fe MOF containing double metals of Zr and Fe, and the CDK4 / 6 inhibitor is preferably ribociclib. A product ZFRH for treating breast cancer is obtained based on coupling of the ferrozirconium bimetallic nano-material provided by the invention with a targeted drug such as trastuzumab. The ZFRH provides a new method for developing a nano platform with an antibody function, and realizes a treatment strategy of combined anti-tumor of trastuzumab and a CDK4 / 6 inhibitor. As a safe and effective tumor treatment strategy, the ZFRH has huge clinical transformation potential.

The present invention refers to a crystalline form of Ribociclib dihydrochloride (dihydrate) designated as Form A and a process for its preparation, a pharmaceutical composition comprising it, and its use for the the treatment of breast cancer.

The invention relates to the technical field of medicinal chemistry, radiopharmaceutical chemistry and clinical nuclear medicine, in particular to a CDK4 / 6-targeted molecular imaging probe labeling precursor, a probe and a preparation method and application thereof. According to the molecular imaging probe [68Ga] Ga-PY03 provided by the invention, on the basis of a Ribociclib structure, a PEG1 chain and proline with envelope conformation are introduced, so that a hydrophobic region in a protein binding pocket can be filled, Van der Waals force can be enhanced, the molecular imaging probe [68Ga] Ga-PY03 can be stably bound with CDK4 / 6, and the targeting of the molecular imaging probe to the CDK4 / 6 is further ensured; the hydrophilicity of the molecular imaging probe can be adjusted, and kidney uptake is reduced; and the compound has excellent tumor / liver and tumor / muscle ratio, and can effectively improve tumor uptake.

The present disclosure relates to methods of treating breast cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a radiopharmaceutical compound having a GRPR antagonist moiety, such as [177Lu] Lu-NeoB, in combination with a CDK4 / 6 inhibitor, such as ribociclib, and a therapeutically effective amount of an endocrine therapy, such as fulvestrant.

This invention provides a combination for use in treating cancers that express prostate-specific membrane antigen (PSMA). [Solution] A combination comprising a PD-1 inhibitor, a CTLA-4 inhibitor, and a radiolabeled compound of formula Ia for use in treating PSMA-expressing cancer in the subject. JPEG2026049728000042.jpg45132 The aforementioned combination comprises one or more further anticancer agents, wherein the further anticancer agents are selected from octreotide, lanreotide, vapreotide, pasireotide, satreotide, everolimus, temozolomide, telotristat, sunitinib, sulfatinib, ribociclib, entinostat, and pazopanib.

The present disclosure is directed to oral tablet of ribociclib including its salt(s). One embodiment of the present disclosure is directed to tablet of ribociclib with high drug load with an immediate release profile. One embodiment of the present disclosure is directed to coated tablet of ribociclib. Another embodiment of the present disclosure is directed to coated tablet of ribociclib where the coating is an aqueous moisture barrier coating (e.g., Opadry® amb II coating where the coating is PVA based).

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.

The invention provides a ribociclib intermediate compound as well as a preparation method and application thereof, and the intermediate compound V has the following structural formula: # imgabs0 #, in the formula, R1 is alkoxy or dimethylamino; r2 is a C1-C6 alkyl group; and R3 is alkyl with 1 to 12 carbon atoms.

The ribociclib intermediate compound and the preparation method thereof have the advantages that raw materials and auxiliary materials are cheap, atom economy is high, the ribociclib intermediate compound is green and safe, substrate universality is high, technological operation is simple, the ribociclib intermediate compound is suitable for industrial production, and the ribociclib intermediate compound has great potential in the field.

Pharmaceutical compositions of ribociclib ora pharmaceutically acceptable salt thereof are disclosed, wherein the compositions are substantially free of nitrosamines. Pharmaceutical products containing said compositions are also disclosed, as well as methods for preparing and storing said pharmaceutical compositions and pharmaceutical products.

The present invention relates to a pharmaceutical combination comprising TNO155 and ribociclib; pharmaceutical compositions comprising the same; and methods of using such combinations and compositions in the treatment or prevention of conditions in a SHP2 inhibitor combined with CDK4 / 6 inhibition is beneficial in, for example, the treatment of cancers.

The invention provides a drug-drug salt of ribociclib (English name Ribociclib) 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, ribociclib 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 ribociclib and a non-steroidal anti-inflammatory drug containing a carboxylic acid group, improves the anti-tumor activity of ribociclib, can improve the solubility of ribociclib, and improves the physical stability and bioavailability.

The invention belongs to the technical field of medicinal chemistry and nuclear medicine, and particularly relates to a PET probe based on radioactive metal labeling and a preparation method and application of the PET probe. Comprising a compound with a result shown in a formula (I). The radioactive probe disclosed by the invention has an obvious target to non-target ratio, can be used as a candidate probe for targeting CDK4 / 6, realizes precise positioning of tumors, and provides visual guidance for subsequent targeted therapy; due to the high specificity of the CDK4 / 6 gene, the CDK4 / 6 gene is expected to be developed into an accompanying diagnosis medicine, a clinical medication scheme is guided by quantitatively analyzing the CDK4 / 6 expression level in tumor tissue, and personalized treatment is achieved; and meanwhile, a new drug screening means and an analysis approach are provided for revealing the drug resistance mechanism of piperisib, ribociclib or abelsib and the like in breast cancer treatment.

The present invention relates to a preparation method and use of a ribociclib intermediate, specifically, the compound of formula A6 is prepared by a substitution reaction of the compound of formula A3 and the compound of formula B under the action of an acid-binding agent, selectively followed by a thiolation reaction, selectively followed by a condensation reaction, and then a ring-closing reaction. The compound of formula A6 of the present invention is prepared into ribociclib after an oxidation reaction, a substitution reaction, a deprotection reaction and a salt formation reaction, which is a process route with significant technical advantages, high reaction efficiency and industrial application prospects.

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.

Pharmaceutical compositions of ribociclib or a pharmaceutically acceptable salt thereof are disclosed, wherein the compositions are substantially free of nitrosamines. Pharmaceutical products containing said compositions are also disclosed, as well as methods for preparing and storing said pharmaceutical compositions and pharmaceutical products.

The present invention relates to a ribociclib intermediate compound and a preparation method thereof, which has the advantages of cheap raw and auxiliary materials, high atom economy, green and safe, high substrate universality, simple process operation, and suitability for industrial production, and has great potential in this field.

The present disclosure relates to Ribociclib solid state forms, Ribociclib salts including Ribociclib succinate and solid state forms thereof, as well as processes for preparation thereof and pharmaceutical compositions thereof.

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 utility model discloses preparation equipment for ribociclib tablets, which belongs to the technical field of tablet preparation and comprises a base, the upper surface of the base is fixedly connected with a plurality of support rods, the upper ends of the support rods are fixedly connected with a same storage tank, one side of the surface of the storage tank is fixedly connected with a processing component, and the processing component is fixedly connected with a plurality of blades. The upper end of the storage tank is fixedly connected with a tank cover, the lower surface of the tank cover is rotatably connected with a mixing assembly, the middle end of the upper surface of the base is fixedly connected with a transfer box, and the front surface of the transfer box is fixedly connected with a drying assembly. The ribociclib tablet crushing device is provided with the processing assembly, raw materials of ribociclib tablets are effectively and rapidly crushed, the uniformity of raw material particles is ensured, the mixing process of the raw materials, auxiliary materials and additives is accelerated by arranging the mixing assembly, the materials are prevented from being adhered to the inner wall of the tank body, excessive moisture in the materials is effectively removed by arranging the drying assembly, and the drying efficiency is improved. The hardness and the stability of the tablet are improved.

Provided herein are new crystalline form(s) of succinate salt(s) of 7-Cyclopentyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide (also known as ribociclib), pharmaceutical compositions comprising the same, methods of treatment using the same and methods of making the same.

The present invention discloses novel crystalline Ribociclib succinate polymorph Form-C and process for preparation thereof.

A method for treating adenoid cystic carcinoma (ACC) is provided, comprising co-administering at least inhibitor of cyclin-dependent kinase 4 / 6 (CDK 4 / 6) and at least one multi-targeted receptor tyrosine kinase inhibitor (mtRTKI). The CDK 4 / 6 inhibitor may be at least one of palbociclib, abemaciclib and ribociclib and the mtRTKI may be at least one of sunitinib, sorafenib and pazopanib. A combination therapy with palbociclib and sunitinib provides a synergic effect in treatment of ACC.

The invention relates to a preparation method and application of a ribociclib intermediate. The preparation method specifically comprises the following steps: carrying out substitution reaction, selective sulfhydrylation reaction and selective condensation reaction on a compound shown in a formula A3 and a compound shown in a formula B under the action of an acid-binding agent, and then carrying out ring closing reaction to prepare a compound shown in a formula A6. The ribociclib is prepared from the compound as shown in the formula A6 through an oxidation reaction, a substitution reaction, a deprotection reaction and a salt forming reaction, and the method is a process route which has remarkable technical advantages, is efficient in reaction and has industrial application prospects.

Provided herein are new crystalline form(s) of succinate salt(s) of 7-Cyclopentyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide (also known as ribociclib), pharmaceutical compositions comprising the same, methods of treatment using the same and methods of making the same.

The invention discloses a JQ1-ribociclib heterocomplex, a synthesis method thereof and application of the JQ1-ribociclib heterocomplex as an anti-gastric cancer drug. The structural formula of the JQ1-ribociclib heterocomplex is # imgabs0 #. The invention also specifically discloses a synthesis method of the JQ1-ribociclib heterocomplex and application of the JQ1-ribociclib heterocomplex in preparation of the anti-gastric cancer drug. The JQ1-ribociclib heterocomplex provided by the invention has relatively high gastric cancer inhibition activity, and a new way is provided for treatment of gastric cancer. The JQ1-ribociclib heterocomplex provided by the invention has the advantages of simple synthesis method, cheap and easily available raw materials, and easy industrial production and clinical conversion.

The present application relates to the fields of medicinal chemistry, radiopharmaceutical chemistry and clinical nuclear medicine technology, in particular to a kind of molecular imaging probe targeting CDK4 / 6 labeled precursor, probe and preparation method and application thereof.The molecular imaging probe provided by the present application [68 Ga]Ga-PY03 is based on Ribociclib structure, by introducing PEG1 chain and proline with envelope conformation, not only can fill the hydrophobic region in protein binding pocket, enhance van der waals force, so that the molecular imaging probe [68 Ga]Ga-PY03 can be stably combined with CDK4 / 6, thereby ensuring the targeting of the molecular imaging probe to CDK4 / 6;It can also regulate the hydrophilicity of the molecular imaging probe, reduce kidney uptake;And excellent in tumor / liver and tumor / muscle ratio, can effectively improve tumor uptake.