37 results about "Mitoxantrone" patented technology

The invention relates to the technical field of medicines, and provides mitoxantrone-loaded ZIF-8 nanoparticles, a preparation method thereof and an application of the mitoxantrone-loaded ZIF-8 nanoparticles in tumor chemical-immunotherapy. Aiming at the defects of combined chemotherapy and immunotherapy clinically at the present stage, MIT ZIF-8 synthesized by a normal-temperature full-water-phase one-pot method is used as a novel chemical-immunotherapy scheme, and the capability of inducing cell immunogenic death of a chemotherapeutic drug mitoxantrone is enhanced by utilizing pyroptosis; the anti-tumor immune activation capability is enhanced while tumor cells are killed through chemotherapy, effective chemical-immune therapy is achieved, and the responsiveness of tumors to immune checkpoint inhibitor therapy is enhanced.

The invention discloses a novel nucleic acid delivery system based on phosphatidylmitoxantrone as well as a preparation method and application of the novel nucleic acid delivery system based on phosphatidylmitoxantrone, and phosphatidylmitoxantrone (PMA) is used as a novel cationic lipid to construct a novel lipidosome nano nucleic acid delivery system by utilizing the enzymatic response release property and ionizable cationic phospholipid characteristics of phosphatidylmitoxantrone (PMA). PMA not only can be used as a novel cationic lipid entrapped nucleic acid, but also can be used as an auxiliary lipid component to promote nucleic acid delivery, so that the synergistic anti-tumor effect of nucleic acid and mitoxantrone is realized. The system can respond to high expression of phospholipase D (PLD) in tumor tissues, promote hydrolysis of PMA and release chemotherapeutic drug mitoxantrone, dual functions of nucleic acid delivery and drug release are achieved, the purpose of double-target inhibition of tumor growth is achieved, and a new strategy is provided for cancer treatment.

The invention discloses application of mitoxantrone in preparation of an anti-rabies virus drug, reveals that clinical anti-tumor and immunosuppression drug mitoxantrone has remarkable anti-rabies virus activity for the first time, and opens up a new application field for mitoxantrone. The rigorous in-vitro and in-vivo tests prove that the mitoxantrone can inhibit virus replication in a dose-dependent manner, reduce virus gene and protein expression and remarkably improve the survival rate of infected mice in an animal model. The invention provides a new clinical application approach for mitoxantrone, provides a powerful candidate drug and a brand-new technical scheme for anti-rabies virus drugs, and has important practical significance and clinical application prospects for coping with rabies which is a major public health threat.

The invention discloses a mesoporous polydopamine (MPDA) nanoparticle which is loaded with a CeO2 nano enzyme and mitoxantrone mesylate (MitoQ) and is released by an intestinal tract, a preparation method of the mesoporous polydopamine (MPDA) nanoparticle, and an application of the mesoporous polydopamine (MPDA) nanoparticle, the preparation method of the mesoporous polydopamine (MPDA) nanoparticle, the preparation method of the mesoporous polydopamine (MPDA) nanoparticle and the preparation method of the mesoporous polydopamine (MPDA) nanoparticle, the preparation method of the mesoporous polydopamine (MPDA) nanoparticle, and the preparation method of the mesoporous polydopamine (MPDA) nanoparticle. The mesoporous polydopamine nanoparticle loaded with the CeO2 nano enzyme and the mitoxantrone mesylate and released by the intestinal tract comprises mesoporous polydopamine loaded with the CeO2 nano enzyme and MitoQ, and an enteric coating of chitosan and sodium alginate. The preparation method comprises the following steps: synthesizing mesoporous polydopamine by adopting a triblock copolymer as a template, then loading a small molecular drug MitoQ into MPDA through ultrasonic waves, and loading CeO2 nano-enzyme on the surface of MPDA through metal coordination to form MPDA (at) CeO2-MitoQ. And finally, coating chitosan and sodium alginate on the surfaces of the nanoparticles through electrostatic adsorption to obtain the final MPDA (at) CeO2-MitoQ (at) SA / CS. The drug-loaded nano-particles prepared by the preparation method disclosed by the invention have a good treatment effect on ulcerative colitis.

The application discloses a kind of endoplasmic reticulum of tumor cell can be targeted N -(2-hydroxypropyl) methacrylamide (HPMA) polymer-drug conjugate. The chemotherapeutic drug carried by the HPMA polymer is at least one of doxorubicin, epirubicin, pirarubicin, cisplatin, oxaliplatin, camptothecin, paclitaxel, gemcitabine, methotrexate, vinblastine, mitoxantrone, irinotecan, and the linker for connecting the drug and the HPMA polymer is at least one of hydrazone bond, amide bond, ester bond, disulfide bond, and ketosulfenyl bond. The HPMA polymer-drug conjugate targets the drug to the endoplasmic reticulum through receptor-ligand interaction, can cause severe endoplasmic reticulum stress, thereby transporting a large amount of calnexin to the tumor cell membrane surface, greatly improving the immunogenicity of tumor cells, and promoting tumor immunotherapy.

The invention belongs to the technical field of biological medicine, and discloses application of mitoxantrone liposome (LipoMIT) in preparation of a medicine for inhibiting ovarian cancer stem cells and / or improving ovarian cancer relapse and / or drug resistance. It is found for the first time that LipoMIT has a good inhibiting effect on the ovarian cancer stem cells; the medicine can be used for improving the problems of relapse and drug resistance of ovarian cancer, not only can fill the blank of the problems of drug resistance and relapse in ovarian cancer treatment, but also can fill the technical blank of LipoMIT in the field of ovarian cancer treatment in the prior art. Lipo-MIT plays a role through targeting tumor stem cells, the risk of ovarian cancer recurrence and drug resistance is reduced fundamentally, the bottleneck that only tumor cells are killed but tumor stem cells cannot be eradicated in traditional treatment is broken through, and the clinical problems of high recurrence and high drug resistance of ovarian cancer in the prior art are solved.

The application belongs to the field of new adjuvants and new dosage forms of pharmaceutical preparations, and particularly relates to a type I and type II immunogenic cell death inducer ion pairing engineered nanoassemblies as well as construction and application thereof. The nanoassemblies are composed of type I ICD inducers, type II ICD inducers, hydrophobic auxiliary counterions and amphiphilic lipid ion pairing. The type I ICD inducer is selected from mitoxantrone, doxorubicin, oxaliplatin or cyclophosphamide; the type II ICD inducer is selected from hypericin; and the hydrophobic auxiliary counterion is selected from cholesteryl sodium sulfate, cholic acid, deoxycholic acid, chenodeoxycholic acid, lithocholic acid, glycolcholic acid, taurocholic acid, glycochenodeoxycholic acid, taurochenodeoxycholic acid, deoxycholic acid lysine derivative, oleanolic acid and ursolic acid. The type I and type II ICD inducers are combined in the application, and have a synergistic tumor treatment effect.

The invention is suitable for the technical field of biological medicine, and provides a preparation method and application of a high heat treatment cell drug delivery system. Mitoxantrone (MTX) is loaded in human umbilical cord mesenchymal stem cells (PD-MSCs) derived on the basis of high heat treatment to prepare the drug delivery system PD-MTX, drugs can be accurately delivered to tumor sites, release is controlled through a pH sensitive mechanism, the treatment effect is improved, and the side effects of chemotherapy are reduced. The PD-MSCs are inactivated through high heat treatment, so that the safety is ensured. PD-MTX and alphaPD-L1 are combined for use, so that a synergistic effect of chemotherapy and immunization is formed, and accurate and safe treatment is realized. The method for high heat treatment of cells and drug loading is not limited to human umbilical cord mesenchymal stem cells and mitoxantrone, and can be popularized to other cells and drugs. The composition has a remarkable effect in treatment of prostatic cancer and prostatic cancer osseous metastasis, can be popularized to treatment of other diseases, and has wide application potential.

The invention discloses a pharmaceutical composition containing a polysialic acid-melittin polyion compound and sialic acid modified anthracycline anti-tumor drug liposome and application of the pharmaceutical composition. The invention belongs to the technical field of biological medicine, and particularly relates to a targeted delivery pharmaceutical composition for treating cold tumors through immunotherapy, and the pharmaceutical composition comprises a polysialic acid-melittin polyion compound and sialic acid modified anthracycline antitumor drug liposome. The anthracycline antitumor drug is selected from one or more of the following components: doxorubicin, epirubicin, pirarubicin, idarubicin, daunorubicin or mitoxantrone. The pharmaceutical composition shows a remarkable synergistic effect in tumor inhibition index, can stimulate congenital immunity and adaptive immunity, induce multiple release of tumor-associated antigens and specific antigens, trigger tumor immune circulation and recover immune control of a body on tumors, and also can enable the body to generate immune memory, so that the tumor inhibition effect is improved. And a new combined treatment strategy is provided for cold tumor treatment.

The present invention relates to the use of compounds of formula (I) as RAS inhibitors and as a medicament, in particular for use in treating proliferative disorders, inflammatory diseases and / or genetic disorders. The present invention relates further to a pharmaceutical composition comprising the compounds of formula (I). Moreover, the present invention relates to a method of inhibiting growth, proliferation or metastasis of cancer cells in a subject in need thereof, in particular which may encompass subsets of patients defined by their mutational status of the RAS oncogene or patients who might have developed resistance to the standard of care or treatment with RAS mutation specific inhibitors. The present invention also relates to a method of inhibiting RAS molecules in treating genetic disorders like RASopathies or inflammatory disorders like Adenomyosis where KRAS gene is mutationally activated. In addition, the present invention relates to a method of inhibiting proliferation and / or secretion of factors from a cell population sensitive towards inhibiting RAS activation in vitro, in particular sensitive towards inhibiting KRAS, HRAS and NRAS activation in vitro. Furthermore, the present invention relates to a kit containing a formulation comprising a pharmaceutical composition comprising a compound of formula (I).

This invention discloses a non-cationic polymer siRNA and chemical drug co-delivery system, comprising a non-cationic polymer and a complex of siRNA and drug loaded on the polymer; the complex is composed of a target siRNA and a corresponding drug; the non-cationic polymer contains several branches with aromatic rings, the aromatic rings being selected from one or more of 5- to 15-membered aromatic rings or 5- to 15-membered heteroaromatic rings; the drug is selected from one or more of gemcitabine, mitoxantrone, topotecan, beloteccan, irinotecan, doxorubicin, camptothecin, and derivatives of any of the above drugs. This invention enables the synergistic delivery of siRNA and chemical drugs, effectively overcoming the cytotoxicity problems caused by cationic delivery systems, and demonstrates promising application prospects in the field of modern drug delivery.

This invention discloses a supramolecular carrier-free self-delivery system, its preparation method, and its application in tumor treatment, belonging to the field of biomedical technology. The supramolecular carrier-free self-delivery system is prepared by non-covalent self-assembly of mitoxantrone, dihydroporphyrin (Ce6), and ultrasmall iron oxide nanoparticles in an aqueous phase. This invention utilizes the co-assembly of mitoxantrone (MTX), dihydroporphyrin (Ce6), and ultrasmall iron oxide nanoparticles (IONP) to form a supramolecular carrier-free self-delivery system CMIOs. This system is simple to prepare, stable in performance, and highly biosafety. It can synergistically inhibit cancer through multiple mechanisms, achieving highly efficient inhibition of breast cancer, providing a new strategy for tumor treatment, and has broad application prospects in solving clinical problems.

The invention provides an application of MCU (Microprogrammed Control Unit) in treating addictive diseases. By means of a conditional knockout dopamine system mouse model, it is observed that motonous nerve excitability caused by heroin, morphine and methamphetamine is remarkably reduced due to deficiency of MCU. In addition, behavioral experiments further prove that the MCU knockout significantly reduces the addiction desire of mice to heroin and methamphetamine. By applying MCU inhibitors, namely mitoxantrone (MTX) and Ru265, the inhibitors are found to be capable of remarkably inhibiting motor nerve excitability caused by heroin and reducing addiction and relapse behaviors of mice on heroin. Mechanism research reveals that MCU knockout inhibits dopamine release caused by opioids and methamphetamine in a nucleus septum (NAc) area, and it is indicated that MCU may serve as an effective target for treating addiction of multiple drugs. The invention provides a brand-new treatment strategy for inhibiting MCU as a clinical treatment for opioid (morphine) or drug (heroin) and methamphetamine addiction for the first time.

The invention discloses an Au-coated Ag / C-CNF / PEGDA hydrogel SERS (Surface Enhanced Raman Scattering) sensor as well as a preparation method and application thereof, and belongs to the technical field of analysis and detection. Gold and silver nanoparticles with a core-shell structure, polyethylene glycol diacrylate and carboxylated cellulose react to form an Au-coated Ag / C-CNF / PEGDA hydrogel prepolymer solution, and the hydrogel prepolymer solution is subjected to ultraviolet crosslinking under the action of a photoinitiator to form the porous three-dimensional network structure Au-coated Ag / C-CNF / PEGDA hydrogel SERS sensor with a synergistic effect. The hydrogel sensor provided by the invention not only can accurately detect 10 <-9 > M-10 <-5 > M Raman signal molecule rhodamine 6G (R6G), but also has good sensitivity and excellent uniformity, the RSD is as low as 4.92%, and the detection limits on anthracycline antitumor drugs doxorubicin (DOX) and mitoxantrone (MTO) respectively reach 3.4 * 10 <-8 > M and 3.6 * 10 <-9 > M.

The present application relates to a kind of isoquinoline alkaloid derivatives for reversing tumor multidrug resistance by inhibiting autophagy and preparation method and application.The derivative can efficiently reverse the multidrug resistance of various solid tumor cells such as gastric cancer, lung cancer and esophageal cancer, the derivative can inhibit the autophagy flow of tumor cells, it is combined with vincristine, mitoxantrone, colchicine, docetaxel and various chemotherapeutic drugs, can efficiently reverse tumor multidrug resistance in vivo and in vitro, this kind of derivative has excellent oral bioavailability and lower toxic side effects, provides a kind of alternative strategy for autophagy inhibitor as antitumor chemosensitizer, can be used as lead compound for the research and development of new drug-resistant tumor reversing agent.

The invention relates to the technical field of functional dyes, and particularly discloses a high-weather-resistance blue dye and a preparation method and application thereof.The preparation method of the high-weather-resistance blue dye comprises the following steps that S1, mitoxantrone, 3-bromine-1-amidonaphthalene, a catalyst and an organic solvent are mixed and then heated and stirred for a reaction, a solid is obtained through filtering, and the solid is dried; washing with water and ethanol, and drying to obtain a dye intermediate A; and S2, mixing the dye intermediate A with 2-amino-4 '-methoxybenzophenone, a catalyst and an organic solvent, heating, stirring and reacting, extracting, carrying out rotary evaporation to obtain a solid, recrystallizing, and drying to obtain the high-weather-resistance blue dye. The benzophenone structure is introduced into the anthraquinone dye, so that the light resistance and the heat resistance of the anthraquinone dye are synchronously improved fundamentally.

The invention relates to a nano drug delivery system co-carrying a pyruvate dehydrogenase kinase inhibitor and mitoxantrone as well as a preparation method and application of the nano drug delivery system, and belongs to the technical field of pharmaceutical preparations. A pyruvate dehydrogenase kinase inhibitor and mitoxantrone are jointly loaded on the metal organic framework ZIF-90 nano material in sequence through a simple and rapid method, and the nano drug delivery system is prepared. The nano drug delivery system can target tumor cell mitochondria, responds to release drugs in an acidic tumor microenvironment, realizes multi-mode synergistic treatment of chemotherapy-glycometabolism treatment through the synergistic effect of metabolism reprogramming and redox imbalance, and significantly enhances the anti-tumor effect.

The present invention relates to the use of compounds of formula (I) as RAS inhibitors and as pharmaceutical agents, particularly for the treatment of proliferative, inflammatory, and / or genetic disorders. The present invention also relates to pharmaceutical compositions comprising the compounds of formula (I). Furthermore, the present invention relates to methods for inhibiting the growth, proliferation, or metastasis of cancer cells in a subject in need thereof, which may include, in particular, a subset of patients defined by their RAS oncogene mutation status, or patients who have developed resistance to standard treatment or treatment with RAS mutation-specific inhibitors. The present invention also relates to methods for inhibiting RAS molecules in the treatment of genetic disorders such as RAS syndromes or inflammatory diseases such as adenomyosis in which the KRAS gene is activated by mutations. The present invention also relates to methods for inhibiting the proliferation and / or secretion of factors from cell populations sensitive to in vitro inhibition of RAS activation, particularly cell populations sensitive to in vitro inhibition of KRAS, HRAS, and NRAS activation. Furthermore, the present invention relates to kits containing formulations of pharmaceutical compositions containing compounds of formula (I).

The invention provides an application of mitoxantrone and / or a pharmaceutical salt thereof in preparation of a lymphatic tracer, and the lymphatic tracer is used for lymph node tracing in gastric resection related diseases and has a good dyeing effect on gastric cancer lymph nodes.

The application of mitoxantrone in inducing IRF4 protein degradation through autophagy-lysosome pathway belongs to the field of biological medicine. Mitoxantrone can specifically bind to IRF4 protein and significantly reduce the level of IRF4 protein. Mitoxantrone mainly binds to the DNA binding domain of IRF4, shortens the half-life of IRF4 protein, and promotes its degradation through the autophagy-lysosome pathway rather than the proteasome pathway. Mitoxantrone can interact with IRF4 protein and autophagy receptor p62 at the same time, promote the formation of IRF4 and p62 complex, enhance the ubiquitination modification of IRF4 and recruit it to the autophagy degradation pathway, thereby playing the role of molecular glue. Mitoxantrone treatment can inhibit the transcriptional activation function mediated by IRF4, down-regulate the expression of its downstream target genes, inhibit the proliferation of multiple myeloma cells and tumor growth, and provide a new technical approach for the development of anti-tumor drugs targeting transcription factors.

The present invention discloses the use of mitoxantrone in the preparation of a drug for treating head and neck squamous cell carcinoma with high IL6R expression. The present invention discovers for the first time that IL6R can be used as a biomarker for mitoxantrone in the treatment of head and neck squamous cell carcinoma. The higher the expression level of IL6R, the more sensitive the head and neck squamous cell carcinoma cells are to mitoxantrone. Based on this, the present invention provides a new use of mitoxantrone: mitoxantrone can be used to prepare a drug for treating head and neck squamous cell carcinoma with high IL6R expression. At the same time, the present invention also provides a kit for detecting the sensitivity of head and neck squamous cell carcinoma patients to mitoxantrone. The kit can pre-detect whether the head and neck squamous cell carcinoma patient is suitable for treatment with mitoxantrone before treatment, so that personalized treatment plans can be formulated for different patients, improving the treatment effect and the patient's quality of life.

The invention belongs to the field of new auxiliary materials and new dosage forms of pharmaceutical preparations, and particularly relates to an I-type and II-type immunogen cell death inducer ion pairing engineering nano assembly and construction and application thereof. The nano assembly is formed by pairing an I-type ICD inducer, an II-type ICD inducer, hydrophobic auxiliary counter ions and amphiphilic lipid ions; the I-type ICD inducer is selected from mitoxantrone, adriamycin, oxaliplatin or cyclophosphamide; the type II ICD inducer is selected from hypericin; the hydrophobic auxiliary counter ions are selected from sodium cholesterol sulfate, cholic acid, deoxycholic acid, chenodeoxycholic acid, lithocholic acid, glycocholic acid, taurocholic acid, glycochenodeoxycholic acid, taurochenodeoxycholic acid, deoxycholic acid lysine derivatives, oleanolic acid and ursolic acid. The I-type ICD inducer and the II-type ICD inducer are combined for use, and the synergistic tumor treatment effect is achieved.

The application is a metabolic regulation medium and a method for inhibiting diploidization of haploid embryonic stem cells by using the same, which comprises a basic medium and a metabolic regulation functional component, and the metabolic regulation functional component comprises Mitoquinone mesylate, Emricasan, Forsfructose, 2-Deoxy-D-glucose, UK5099 and VLX600. A new culture system of mouse haploid embryonic stem cells is established, and the haploid maintenance effect, cell pluripotency, differentiation ability and genomic stability of the system are systematically verified. The application can significantly improve the haploid maintenance ability of haploid embryonic stem cells and reduce the culture cost, and provides a simple and economical culture strategy for the popularization and application of haploid embryonic stem cells.

The invention discloses a pharmaceutical composition and a liposome. The pharmaceutical composition comprises emidine with the concentration not lower than 0.01 M and mitoxantrone with the concentration not lower than 0.003 M, and is used for treating breast cancer. The liposomes include at least three lipids (including DPPC, DSPE-PEG (2000) amine, and cholesterol) and comprise the composition.

The invention belongs to the technical field of nano biology, and discloses a hypoxia responsive lipid nano delivery system as well as a preparation method and application thereof. The method comprises the following steps: mixing and stirring 2-(4-chloro-2-nitrophenyl) acetic acid, 2-(7-azabenzotriazole)-N, N, N ', N'-tetramethylurea hexafluorophosphate, N, N-diisopropylethylamine and pyridine to react, adding mPEG-NH2 to stir and react, then adding distearoyl phosphatidyl ethanolamine, palladium acetate, 4, 5-bis (diphenylphosphine-9, 9-dimethyl xanthene and cesium carbonate to stir and react, and finally adding a catalyst to stir and react, so as to obtain a target product. Carrying out reflux reaction at 120 DEG C overnight, dialyzing, centrifuging, collecting supernatant, and freeze-drying to obtain DNP; the preparation method comprises the following steps: dissolving distearoyl phosphatidylcholine, cholesterol, DNP, sorafenib and mitoxantrone in absolute ethyl alcohol, and stirring and dissolving in a dark place; spin-drying to form a film, adding PBS, hydrating, and carrying out ultrasonic treatment in an ice-water bath; and extruding a film to obtain the hypoxia responsive lipid nano delivery system.

Disclosed are a use of Mitoxantrone or an isomer, nitrogen oxide, solvate, metabolite, pharmaceutically acceptable salt thereof, a prodrug thereof, or a derivative thereof in the preparation of a drug for treating or preventing neuroendocrine tumor, and a method for treating or preventing neuroendocrine tumor. Research shows that Mitoxantrone can inhibit the growth of neuroendocrine tumor in a dose-dependent manner, has high drug sensitivity and significant tumor inhibition effect, is a new candidate drug for the clinical treatment of neuroendocrine tumor, and has high clinical value.

The invention discloses a tetrahydroisoquinoline-indole-pyrimidine compound and preparation and application thereof.The tetrahydroisoquinoline-indole-pyrimidine compound has good biological activity, can inhibit the activity of P-gp protein and BCRP protein at the same time, has an excellent MDR reversing effect and enhances the sensitivity of malignant tumor cells to anti-tumor drugs doxorubicin hydrochloride and mitoxantrone, and has a good application prospect. The compound can be used for development and utilization of drugs for treating multidrug resistance of malignant tumor cells caused by P-gp protein and BCRP protein, and is expected to become a potential multidrug resistance protein inhibitor for treating MDR.

Pharmaceutical compositions comprising oil as a vehicle, a suspending agent, and a surfactant are disclosed to be used in conjunction with active pharmaceutical ingredients which are water soluble or insoluble, or which are sensitive to water but insoluble in oil. Such active pharmaceutical ingredients may include temozolomide, lenalidomide, Oxaliplatin, Cisplatin, Carboplatin, 5-fluorouracil, irinotecan, topotecan, cyclophosphamide, doxorubicin, vincristine, vinblastine, Melphalan, Chlorambucil, Dacarbazine, Daunorubicin, Epirubicin, Mitoxantrone, Etoposide, Teniposide, Azacitidine, Cytarabine, Gemcitabine, vinoralbine, Pemetrexed, a derivative thereof, or a combination thereof. The pharmaceutical compositions may be administered as an oral suspension. Other embodiments are directed towards methods of using and methods of making such formulations.

(3R, 4S)-3-(4-hydroxy-3,5-dimethoxyphenyl)-4-(4-hydroxyphenyl)-8-methyl-3,4-dihydro-2H- chromen-7-ol (TRX-E-002-1) for use in a method of treatment for a hematological cancer being acute myeloid leukemia or multiple myeloma in a subject in need thereof, the method comprising administering to the subject an effective amount of TRX-E-002-1. The method may further comprise administering to the subject an effective amount of a second compound selected from the group consisting of (i) a BCL-2 inhibitor such as venetoclax, navitoclax or obatoclax, (ii) a deoxycytidine analogue chemotherapeutic such as cytarabine or gemcitabine, (iii) a hypomethylating agent such as azacitidine or decitabine, (iv) an anthracycline chemotherapeutic such as daunorubicin, doxorubicin, epirubicin, idarubicin, valrubicin or mitoxantrone, (v) a proteasome inhibitor such as carfilzomib, bortezomib, and ixazomib, (vi) an immunomodulatory drug such as pomalidomide, lenalidomide, and thalidomide and(vii) a corticosteroid drug such as dexamethasone or prednisone, and (viii) an alkylator such as bendamustine, cyclophosphamide, melphalan, and melflufen. Corresponding combination pharmaceutical compositions.

The invention discloses an N, 4-diphenylpyrimidine-2-amine compound and preparation and application thereof.The N, 4-diphenylpyrimidine-2-amine compound can remarkably reverse tumor MDR, enhance the sensitivity of malignant tumor cells to anti-tumor drugs such as doxorubicin hydrochloride and mitoxantrone and improve the drug-resistant tumor apoptosis rate, has good potential in the aspect of MDR reversing and has important development prospects.