44 results about "Antileukemic agent" patented technology

The present invention relates to a new use of the compound chlorogenic acid isolated from the piper betel leaf extract or from any other sources for the treatment of acute and chronic myeloid leukemia and lymphoid leukemia, and the present invention also provides a pharmaceutical composition comprising chloregenic acid along with pharmaceutically acceptable additive for the treatment of acute and chronic myeloid leukemia and lymphoid leukemia.

The invention relates to an alpha, beta-unsaturated ketone compound containing a 1,2,4-oxadiazoles heterocycle, the structure of which is as shown in general formula 5, wherein R1 is hydrogen, methyl or chlorine; R2 is methyl, chlorine or bromine; R3 is methyl or ethyl; R4 is para-trifluoromethyl, ortho-methyl or para-nitro; and R5 is hydrogen or methyl. The invention also provides a preparation method of the compound and application thereof. The half-growth inhibitory concentration of the compound on HL-60 cells is less than or equal to 2.0 mu M, and the activity is obviously improved, thus the compound can be used for preparing antileukemie medicaments.

The invention relates to a dimensional flow liquid phase array detection method of fusion protein in leukemia cells, characterized in that: a microballoon 1 fluorescently labeled by FITC or Alexa Fluor 488 coated by fusion protein capture antibody and a microballoon 2 fluorescently labeled by FITC or Alexa Fluor 488 with another conentration coated by fusion protein capture antibody form a dimensional flow liquid phase array for detecting fusion protein in leukemia cells, after the co-incubation of the microballoon 1, the microballoon 2 , the fusion protein, a reported antibody and / or a secondary antibody fluorescently labeled by PE, a flow cytometry is used for detecting the dimensional flow liquid phase array, and the fusion protein expression value is expressed as a ratio of the PE fluorescence intensity of the microballoon 1 to the PE fluorescence intensity of the microballoon 2. The method can be applied in the biomedicine research fields, such as leukemia pathology, molecular diagnosis, and discovery of anti-leukemic medicines. The method has the advantages of effective elimination of system error, rapidness, and accuracy.

The invention discloses efficient targeting drug-loaded nano-micelle as well as a preparation method and application thereof. The preparation method comprises the following steps: (1) dissolving an amphiphilic block copolymer into an organic solvent, and then adding small molecule anti-leukemia drug hydrochloride; after the materials are fully dissolved and evenly mixed, adding triethylamine to remove hydrochloric acid so as to form a small molecule anti-leukemia drug; then, adding the small molecule anti-leukemia drug into a phosphate buffer solution (PBS) to form nano-micelle which has a hydrophilic shell and a core encapsulated with the drug; carrying out dialysis, and drying to obtain the drug-loaded nano-micelle; a polydopamine modification method is used for modifying a specific antibody against a leukemia cell surface antigen, thus realizing targeting. The drug-loaded nano-micelle prepared by the method has a particle size of 50-100nm, is very good in monodispersity, has a higher drug loading capacity and encapsulation efficiency, is simple in targeted modification step and good in targeted killing effect of leukemia cells, but is high in biosecurity for normal cells, and can realize slow release so as to avoid the defects caused by long-term and multiple dosing.

The invention belongs to the field of preparation of drugs, and discloses application of flavonoid GL-V9 in preparation of anti-leukemia drugs. The flavonoid GL-V9 can guide acute myeloid leukaemia cells to become into dendritic cells, and can be used for preparing anti-leukemia drugs.

The invention relates to an acute myeloid leukemia miRNA and transcription factor model and a construction method and application thereof. The construction method includes: acquiring differential expression miRNA and different expression transcription factors of marrow samples of acute myeloid leukemia patients and a healthy contrast group, constructing a miRNA-transcription factor regulatory network model to obtain core miRNA and core transcription factors, and the like. The constructed miRNA and transcription factor model can be used for construction of diagnosis probes, chips or reagents, equipment and the like to provide intermediate result information or reference information for diagnosis of the acute myeloid leukemia patients. By the acute myeloid leukemia miRNA and transcription factor model, microRNA mediated network regulation contents are enriched, and an action mechanism of a microRNA and transcription factor mediated regulation network in AML (acute myeloid leukemia) is revealed. Research results lay the foundation for development of anti-leukemia medicines or biological products, and high application value is achieved.

The invention discloses aloe-emodin quaternary ammonium salt alkyl iodoacetates with the multiple-related anti-cancer mechanism and a preparation method thereof. The preparation method comprises the steps that firstly, aloe-emodin reacts with phosphorus tribromide to obtain brominated aloe-emodin; secondly, brominated aloe-emodin reacts with N-methyldi-n-octylamine to generate aloe-emodin quaternary ammonium salt; lastly, the aloe-emodin quaternary ammonium salt reacts with chloroacetyl chloride to generate iodine acetylation in the presence of sodium iodide to obtain aloe-emodin quaternary ammonium salt alkyl iodoacetates shown as a structural formula (please see the structural formula in the description). In-vitro cancer cell inhibition tests of aloe-emodin quaternary ammonium salt alkyl iodoacetates show that aloe-emodin quaternary ammonium salt alkyl iodoacetates has the good inhibitory activity on hematopoietic cells, is expected to be developed into anti-leukemia drugs and has the great application prospect.

The invention discloses water-soluble realgar solid dispersions as well as a preparation method and an application thereof. The dispersions comprise the following components in parts by weight: 1 part of realgar, 1-20 parts of macromolecule, and 0-5 parts of a surfactant. The realgar solid dispersions solve the problem of low bioavailability due to difficult dissolution of realgar in water, effectively improve dissolution rate and accumulated dissolution of realgar in water, improve bioavailability of realgar, prolong cycling time of arsenic in blood, and therefore enhance efficacies of anti-leukemia drugs. The preparation processing process is simple, production efficiency is high, and the preparation process and a subsequent crushing or shaping process of the solid dispersions can be directly connected. In a clinic application, dosage of realgar can be effectively reduced, especially in an intensive treatment period or a consolidation treatment period, taking frequency and dosage can be reduced; compliance of patients can be improved, risks for health brought by toxic and side effects of large dosage of taking for a long time can be reduced, and treatment cost can be substantially reduced.

The invention discloses application of artesunate and podophyllotoxin conjugates in anti-leukemia drugs according to formula (I) and a preparation method. The preparation method includes using artesunate and podophyllotoxin as raw materials and esterifying to obtain artesunate and podophyllotoxin conjugates according to formula (I). The invention further discloses application of artesunate and podophyllotoxin in anti-leukemia drugs. The conjugates have anti-leukemia cell activity and can be used for preparing anti-leukemia drugs. The artesunate and podophyllotoxin has different degrees of anti-proliferation actions to leukemia K562 cell and leukemia Adriamycin persister K562 / Adr.

The invention discloses a small interfering RNA (Ribonucleic Acid) of an RALA (v-ral simian leukemia viral oncogene homolog A) gene and application thereof in preparing medicaments for resisting leukemia. The sequence of the small interfering RNA is as follows: the positive-sense strand is 5'-CGUGGAAACAUCUGCUAAATT-3', and the antisense strand is 5'-UUUAGCAGAU GUUUCCACGTA-3'. The small interfering RNA of the RALA gene can be used for preparing the medicaments for resisting the leukemia. The RALAsiRNA can suppress the growth of human leukemia k562 cells through down regulating the expression of a cancer RALA, has potential application values to oncogene treatment and is expected to be applied to the treatment of the leukemia. Moreover, on the basis of the small interfering RNA, new medicines for resisting the leukemia are developed to make a contribution to the prevention and cure of clinical leukemia.

The invention discloses an application of Vandetanib to preparation of a targeted EphB4 anti-tumor drug, and belongs to the technical field of medicines. Experiments verify the application of the Vandetanib, and a molecular docking method, an SPR (surface plasmon resonance) method and MST (modulated scatterer technique) experiment results indicate that the Vandetanib can interact with EphB4. EphB4kinase experiments display that the Vandetanib can obviously inhibit EphB4 kinase activity. Proliferation of leukemic cells K562, JLTRG and H9 is remarkably inhibited. Besides, the Vandetanib remarkably inhibits expression of signal molecules p-PI3K p85 / p55 and PI3K p85 at the downstream of the EphB4, and the phosphorylation level of MEK (methyl ethyl ketone) and ERK (extracellular signal-regulated kinase) is reduced. Therefore, the experiment results sufficiently support the application of the Vandetanib to an anti-leukemia drug and the targeted EphB4 anti-tumor drug.

The invention discloses an indoledione piperazine type alkaloid and a preparing method and application thereof. The alkaloid is obtained from fermentation products of a garcinia multiflora endophyticfungus through separation and purification, wherein the endophytic fungus has the name of Aspergillus sp.GZWMJZ-258, is preserved in the China Center for Type Culture Collection on April 28th, 2019 atthe address of Wuhan, China, and has the preservation number of CCTCC NO:M 2019305. The indoledione piperazine type alkaloid is a compound with a new framework. It is shown through a pharmacologicalexperiment that the alkaloid has a certain selective retraining effect on a leukemia cell line MV4-11 and can be applied in an anti-leukemia medicine.

The invention belongs to the field of antineoplastic medicaments and discloses a composition comprising oroxylin and used for treating leukemia and application of the composition. Active ingredients of the medicine composition contain the oroxylin and tumor necrosis factors. The medicine composition has an excellent therapeutic effect on the leukemia, can be used to prepare anti-leukemia medicines and is high in clinical value.

The invention discloses a podophyllotoxin isatin derivative as shown in a formula (I) which is described in the specification. The invention also discloses a preparation method for the derivative and application of the derivative to preparation of an anti-leukemia drug.

The invention discloses an N-(2-chloro-6-methyl phenyl)-2-(phenyl acrylamide)thiazole-5-formamide derivative, and a preparation method of the derivative and use of the derivative, wherein the general structural formula of the N-(2-chloro-6-methyl phenyl)-2-(phenyl acrylamide)thiazole-5-formamide derivative is as follows: wherein R1, R2, R3 and R4 are independently selected from hydrogen, chlorine, fluorine, methyl, methoxyl or trifluoromethyl; at least two of R1, R2, R3 and R4 are hydrogen. In comparison with the existing anti-leukemia drug dasatinib, the compound disclosed by the invention has remarkable inhibitory effect on K562 leukemia cells and is suitable for being further chosen as an anti-leukemia drug; the condition required for synthesis of the compound is mild, and the yield of the compound is high.

The invention provides pyrrolo[2,3-b]pyrazine derivatives. The structural formula of the derivatives are disclosed as Formula (I), wherein R1 is hydrogen, hydroxyl, heterocyclic radical, phenyl or substituted phenyl, and amido or substituted amido; R2 is cyano, methyl or hydrogen; n=1, 2, 3, 4, 5, 6, 7 or 8; Y is NH, O, S or N(CH2)mR5; m=1, 2, 3, 4, 5 or 6; and R5 is hydrogen, amido or substituted amido. The derivatives provided by the invention can obviously inhibit activity of DNA topoismerase II and inhibit high expression of the DNA topoismerase II in tumor cell strains, and is an important target for antineoplastic drugs. Meanwhile, the derivatives have obvious inhibiting actions on proliferation of multiple tumor cell strains, have obvious capacity for inducing apoptosis of leukaemia cells, and have wide application prospects in preparing antitumor and anti-leukaemia drugs.

The invention relates to succinyl hydrazine compounds derivative and medical compound containing them; and the application of it in preparing medicine that resists leukemia. The succinyl hydrazine compounds derivative shows inhibiting action to BCR-Ab1 tyrosine kinase activity through pharmacological test. It is characterized by high effecivity and low toxicity, and can be widly used to prepare medicine that treats chronic granulocytic leukemia (CML) and philadelphia chromosome positive acute lymphoblastic leukemia, especially medicine treating patient that generates drug resistance to Gleevec.

The invention belongs to the technical field of medicines, and relates to two caryophyllene type sesquiterpenoids with anti-tumor activity, which are separated from Ascotricha sp., and a preparation method of the sesquiterpenoids. The structure of the sesquiterpenoids is described in the specification. The sesquiterpenoids related in the invention are novel in structure, and remarkable in anti-tumor activity in vitro, can be easily massively obtained by liquid fermentation and a simple and convenient extraction and separation method, and can be an active lead compound for developing a novel anti-leukemia medicine. The general formula is described in the specification, wherein R is H or CH3.

The invention discloses an siRNA inhibiting the PPFIA1 gene expression, and its application. The positive-sense strand sequence of the siRNA is 5'-CCACAAAGCUCUGGAUGAA-3', the antisense strand sequence of the siRNA is 5'-UUCAUCCAGAGCUUUGUGG-3', and dTdT is dangled at the 3' segment of the siRNA seuqnce. The siRNA inhibiting the PPFIA1 gene expression can effectively silence the PPFIA1 gene and provides a technical scheme for researches on the functions of the PPFIA1 gene, and the silenced PPFIA1 gene can inhibit the cell growth and promote the cell apoptosis; and the siRNA can be used for preparing anti-leukemia medicines.

The present invention provides the compound Ormeloxifene [3,4-trans-2,2-dimethyl-3-phenyl-4-p-(beta-pyrrolidinoethoxy)phenyl-7-methoxy chroman] as useful in inducing differentiation in wide range of myeloid leukemias including acute promyelocytic leukemia, acute myeloid leukemia and chronic myeloid leukemia where block in differentiation is common feature. Ormeloxifene induced differentiation that is marked by increase in differentiation marker proteins like C / EBPα and surface proteins such as cd11b and granulocyte colony stimulating factor receptor (GCSFr). Differentiated cells having neutrophil like morphology were observed when treated with 1.0 uM to 7.5 uM ORM which clearly indicates that ORM can induce differentiation in myeloid leukemia cells. At higher doses (5 uM to 7.5 uM) there is early onset of myeloid differentiation (24 to 48 h) with reduced no. of cells which is likely due to apoptotic effects of ORM at higher does. In contrary, lower doses (1 uM) induce differentiation after longer duration (6-15 days) with quite reduced apoptotic effect.

The invention discloses an application of ORP4L (Oxsterol binding protein-related protein, 4L) in preparation of a product for treating acute myeloid leukemia. According to specific expression of an ORP4L gene in a leukemia stem cell, the specific energy support mechanism of a leukemia stem cell is discovered, that is, oxidative phosphorylation depends on existence of the ORP4L gene. The novel application of the ORP4L gene is provided, that is, the ORP4L gene taken as a target site for selectively killing the leukemia stem cell is applied to new product development and treatment of acute myeloid leukemia. A novel ORP4L inhibitor is screened and has greater practical significance and a broad application prospect in leukemia treatment through blocking of LSC (leukemia stem cell) energy supply. Small interfering RNA (ribonucleic acid) has a remarkable inhibition effect on ORP4L gene expression, LSC energy generation and cell viability can be inhibited by silent ORP4L genes, and the ORP4L gene can be taken as a novel target site in drugs for treating leukemia and resisting leukemia.

The invention relates to the field of drug synthesis and biological activity evaluation, in particular to an aminomethylpyridine derivative, a preparation method and application thereof. The aminomethylpyridine derivative adopts aminomethylpyridine and substituted benzaldehyde as the raw materials, and the obtained aminomethylpyridine derivative has a general structural formula shown as the specification. The aminomethylpyridine derivative provided by the invention has mild synthesis conditions, and simple and easily operable post-treatment method, thus being suitable for industrial production. Compared with the existing anti-leukemia drug imatinib, the aminomethylpyridine derivative has significant inhibitory effect on human chronic granulocytic leukemia cell line K562, and is suitable for further screening as an anti-leukemia drug.

The invention discloses an siRNA inhibiting the PPFIA1 gene expression, and its application. The positive-sense strand sequence of the siRNA is 5'-CCACAAAGCUCUGGAUGAA-3', the antisense strand sequence of the siRNA is 5'-UUCAUCCAGAGCUUUGUGG-3', and dTdT is dangled at the 3' segment of the siRNA seuqnce. The siRNA inhibiting the PPFIA1 gene expression can effectively silence the PPFIA1 gene and provides a technical scheme for researches on the functions of the PPFIA1 gene, and the silenced PPFIA1 gene can inhibit the cell growth and promote the cell apoptosis; and the siRNA can be used for preparing anti-leukemia medicines.

The invention discloses new application of mercaptopurine and derivatives thereof, namely application of mercaptopurine and derivatives thereof in preparation of drugs for removing malignant tumor immunosuppression, mercaptopurine and thioguanine act on tumor cells of human lung cancer, colorectal cancer, liver cancer, melanoma, breast cancer and the like. The expression of glycosyltransferase GLT8D1 can be remarkably reduced. Further, the protein level and glycosylation level of PDL1 are inhibited, so that the killing effect of peripheral blood mononuclear cells on tumor cells is improved, and the purpose of inhibiting tumors is achieved; the invention finds that mercaptopurine / thioguanine which interferes with nucleic acid biosynthesis and is widely applied to anti-leukemia drugs can inhibit glycosyltransferase GLT8D1 and a programmed cell death ligand 1 (PDL1) in a targeting manner to enhance tumor killing of T cells so as to achieve the purpose of drugs for treating various tumors; The invention provides a new therapeutic drug for treating various tumors.

The invention relates to the field of drug synthesis and biological activity evaluation, in particular to an aminomethylpyridine derivative, a preparation method and application thereof. The aminomethylpyridine derivative adopts aminomethylpyridine and substituted benzaldehyde as the raw materials, and the obtained aminomethylpyridine derivative has a general structural formula shown as the specification. The aminomethylpyridine derivative provided by the invention has mild synthesis conditions, and simple and easily operable post-treatment method, thus being suitable for industrial production. Compared with the existing anti-leukemia drug imatinib, the aminomethylpyridine derivative has significant inhibitory effect on human chronic granulocytic leukemia cell line K562, and is suitable for further screening as an anti-leukemia drug.

The invention relates to a dimensional flow liquid phase array detection method of fusion protein in leukemia cells, characterized in that: a microballoon 1 fluorescently labeled by FITC or Alexa Fluor 488 coated by fusion protein capture antibody and a microballoon 2 fluorescently labeled by FITC or Alexa Fluor 488 with another conentration coated by fusion protein capture antibody form a dimensional flow liquid phase array for detecting fusion protein in leukemia cells, after the co-incubation of the microballoon 1, the microballoon 2 , the fusion protein, a reported antibody and / or a secondary antibody fluorescently labeled by PE, a flow cytometry is used for detecting the dimensional flow liquid phase array, and the fusion protein expression value is expressed as a ratio of the PE fluorescence intensity of the microballoon 1 to the PE fluorescence intensity of the microballoon 2. The method can be applied in the biomedicine research fields, such as leukemia pathology, molecular diagnosis, and discovery of anti-leukemic medicines. The method has the advantages of effective elimination of system error, rapidness, and accuracy.

The invention provides the application of a two-dimensional carbon-based nano material for killing leukemia cells. The two-dimensional carbon-based nanomaterials include graphdiyne derivatives such as Graphdiyne (GDY) and Graphdiyne Oxide (GDYO). The leukemia cells are DNMT3A-mutated acute myeloid leukemia (Acute Myeloid Leukemia, AML) cell lines. The GDY and GDYO are nano-sheet structures with a size range of 50nm-500nm. They are added to different types of AML cells cultured in vitro or injected into AML mouse models at a certain dose, which can achieve the effect of targeting only DNMT3A mutant cells. Specific killing, but no obvious effect on normal cells. The invention has great application potential in clinical and scientific research fields such as research and development of anti-leukemia drugs, drug efficacy research and drug resistance research of leukemia cells.

The invention discloses a high-efficiency, targeted drug-loaded nano-micelle and its preparation method and application. The preparation steps are: (1) dissolving the amphiphilic block copolymer in an organic solvent, and then adding a small-molecule anti-leukemia drug Hydrochloride, after fully dissolved and mixed, add triethylamine to remove hydrochloric acid to form a small molecule anti-leukemia drug, and then add it to PBS buffer to form nanomicelles with inner core encapsulated drug and outer shell hydrophilic; after dialysis, dry , to obtain drug-loaded nanomicelles; the polydopamine modification method is used to modify the specific antibody against the leukemia cell surface antigen to achieve targeting. The particle size of the drug-loaded nano-micelle prepared by the invention is 50-100nm, showing good monodispersity, high drug-loading capacity and encapsulation efficiency, simple targeting modification steps, and good targeting leukemia cell killing effect , while for normal cells, it has high biological safety and can achieve slow release, avoiding the disadvantages of long-term and multiple administrations.

The invention belongs to the field of medicine technology, and relates to a polyketone compound with antitumor activity which is separated from a strain of Ascotricha sp. and a preparation method thereof. The compound has a novel structure, and has substantial effects for inhibiting growth of a human acute promyelocytic leukemia HL-60 cell line and a human leukemia K562 cell line; a fermentation process as well as an extracting and separation method are simple, which are good for carrying out further pharmacological and clinic researches, and developing applications to preparation of medicaments for preventing and treating leukemia.

The invention discloses application of tubeimoside in preparing a medicine for treating special subtype leukemia. Pharmacodynamic tests show that tubeimoside separated and purified from bolbostemma paniculatum has a very remarkable function of inhibiting special subtype leukemia cell proliferation, meanwhile has a treatment function on common types of leukemia such as acute leukemia cell and chronic leukemia cell, and in addition has a good effect in inhibiting activity of subtype leukemia cells when being compared with that of a leukemia treatment medicine, namely Imatinib in the market.