- λ-Radiolysis of mitomycin C derivatives
-
The λ-Radiolysis reactions of mitomycin C (1) and its derivatives were studied in the hope of developing a radiation-induced drug (RID). The λ- radiolysis reactions were carried out in aqueous solutions under the condition where hydrated electron (e-(aq)) was generated as a principal reactive species. The competitive λ-radiolysis studies revealed that the rate constants for the reactions of 1 with e-(aq) at room temperature was 3.6 x 1010 dm3 mol-1s-1. Among mitomycin C derivatives, the 5H-6- alkoxyimino derivatives 11 and 12, and compound 13 in which ring A of 1 has the 4-hydroxy-6-hydroxyimino structure cleaved to give 1. The mechanic aspect of these λ-radiolysis reactions is discussed.
- Kuroda,Hisamura,Nakamizo,Otsuji
-
-
Read Online
- Degradation kinetics and mechanism of N6-[(dimethylamino)methylene]mitomycin C in aqueous solutions
-
The degradation of N6-[(dimethylamino)methylene]mitomycin C, a semisynthetic analogue of mitomycin C, was studied in aqueous solution. The compound degraded rapidly and followed pseudo-first-order kinetics in both acidic (pH 6-(formyl)mitomycin C. The latter compound subsequently hydrolyzed to mitomycin C.
- Chen,Coppola,Johns,Bogardus,Lipper
-
-
Read Online
- MITOMYCIN C PRODRUG LIPOSOME FORMULATIONS AND USES THEREOF
-
The present invention provides MMC prodrug compounds and liposomal MMC prodrugs and compositions thereof for the treatment of cancer. The compositions include liposomes containing a phosphatidylcholine lipid, a sterol, a PEG-lipid and a MMC prodrug. The present invention also provides liposomal compositions for the treatment of cancer comprising administering to a patient in need thereof a liposome, wherein the liposome comprises: a phosphatidylcholine lipid; a sterol; a PEG-lipid and a MMC prodrug or a pharmaceutically-acceptable salt thereof.
- -
-
Paragraph 0110
(2018/05/27)
-
- An oral redox-sensitive self-immolating prodrug strategy
-
We report a novel oral prodrug approach where a solubilizing polymer conjugated to the drug is designed to be released by the action of an exogenously administered agent in the intestine. A redox-sensitive self-immolating design was implemented, and the reconversion kinetics were studied for three reducible prodrugs.
- Sun, Tao,Morger, Andrea,Castagner, Bastien,Leroux, Jean-Christophe
-
supporting information
p. 5721 - 5724
(2015/03/30)
-
- THERAPEUTIC FOR HEPATIC CANCER
-
A novel pharmaceutical composition for treating or preventing hepatocellular carcinoma and a method of treatment are provided. A pharmaceutical composition for treating or preventing liver cancer is obtained by combining a chemotherapeutic agent with an anti-glypican 3 antibody. Also disclosed is a pharmaceutical composition for treating or preventing liver cancer which comprises as an active ingredient an anti-glypican 3 antibody for use in combination with a chemotherapeutic agent, or which comprises as an active ingredient a chemotherapeutic agent for use in combination with an anti-glypican 3 antibody. Using the chemotherapeutic agent and the anti-glypican 3 antibody in combination yields better therapeutic effects than using the chemotherapeutic agent alone, and mitigates side effects that arise from liver cancer treatment with the chemotherapeutic agent.
- -
-
-
- Anti-Claudin 3 Monoclonal Antibody and Treatment and Diagnosis of Cancer Using the Same
-
Monoclonal antibodies that bind specifically to Claudin 3 expressed on cell surface are provided. The antibodies of the present invention are useful for diagnosis of cancers that have enhanced expression of Claudin 3, such as ovarian cancer, prostate cancer, breast cancer, uterine cancer, liver cancer, lung cancer, pancreatic cancer, stomach cancer, bladder cancer, and colon cancer. The present invention provides monoclonal antibodies showing cytotoxic effects against cells of these cancers. Methods for inducing cell injury in Claudin 3-expressing cells and methods for suppressing proliferation of Claudin 3-expressing cells by contacting Claudin 3-expressing cells with a Claudin 3-binding antibody are disclosed. The present application also discloses methods for diagnosis or treatment of cancers.
- -
-
-
- Pigs and pig cells having an inactivated α 1,3-galactosyl transferase gene
-
Human pre-formed xenoantibodies play an important role in the hyperacute rejection response in human xenotransplantation. Disclosed are materials and methods for removing or neutralizing such antibodies. Also disclosed are materials and methods for reducing or eliminating the epitopes in the donor organs that are recognized by such antibodies. Such epitopes are formed as the result of activity by the enzyme α-1,3 galactosyltransferase. The porcine gene encoding α-1,3 galactosyltransferase is disclosed, as are materials and methods for inactivating (“knocking out”) the α-1,3 galactosyltransferase gene in mammalian cells and embryos. Included are nucleic acid constructs useful for inactivating the α-1,3 galactosyltransferase gene in a target cell. Also disclosed is a novel leukemia inhibitory factor (T-LIF) that is useful for maintenance of embryonic stem cells and primordial germ cells in culture.
- -
-
-
- Method for treating multi-drug resistant tumors
-
Methods for administering mitomycin C to a multi-drug resistant cell and for reducing the toxicity of the compound are described. In the methods, mitoymic C is provided in the form of a prodrug conjugate, where the drug is linked to a hydrophobic moiety, such as a lipid, through a cleavable dithiobenzyl linkage. The dithiobenzyl linkage is susceptible to cleavage by mild thiolysis, resulting in release of mitomycin C in its original form. The linkage is stable under nonreducing conditions. The prodrug conjugate can be incorporated into liposomes for administration in vivo and release of mitomycin C in response to endogenous in vivo reducing conditions or in response to administration of an exogenous reducing agent.
- -
-
-
- Compositions containing piperine
-
A pharmaceutical composition having increased bioavailability characterized by piperine of the formula STR1 and a drug for treating a disease or condition of the human cardiovascular system, central nervous system, gastrointestinal tract, respiratory tract, endocrine system, genito urinary tract or haemopoietic system.
- -
-
-
- Drug carriers
-
A drug carrier useful for improved drug delivery upon administration comprising a fat or fatty emulsion as a core and a surface layer thereover wherein the core amounts to 30% to 65% and the surface layer amounts to 35% to 70%. The constituents of the core and surface layer are detailed together with the improved drug delivery obtained. The emulsion has a mean particle diameter less than 100 nm.
- -
-
-
- Carboxymethylmannoglucans and derivatives thereof
-
A carboxymethylmannoglucan comprising tetrasaccharide units represented by the following general formula (I) and salt thereof. Further, the invention discloses a carboxymethylmannoglucan derivative and salt thereof produced by subjecting part or the whole of mannose of the tetrasaccharide units to ring opening and subjecting part or the whole of glucose which constitute the main chain but have no mannose as a branch STR1 wherein R1 to R12 each represent a hydrogen atom or a carboxymethyl group. The compounds are useful as carrier for delaying the disappearance of a drug in the blood and for enhancing the organotropism of the drug for a carcinoma.
- -
-
-
- Compositions containing piperine
-
A pharmaceutical composition having increased bioavailability characterized by piperine of the formula and a drug for treating a disease or condition of the human cardiovascular system, central nervous system, gastrointestinal tract, respiratory tract, endocrine system, genito urinary tract or haemopoietic system.
- -
-
-
- Liposome composition and its production
-
The liposome compositions entrapping a drug are prepared by constituting the liposomal membrane with a saturated phospholipid and a glycolipid having sulfo group. Thus obtained compositions circulate stably in blood for a long time after intravenous administration.
- -
-
-
- 7-(diphenylmethyl)oxy-9a-methoxymitosane
-
7-(Diphenylmethyl)oxy-9a-methoxymitosane is a novel intermediate for conversion into 7-amino and 7-oxy-9a-methoxymitosanes and is also useful for inhibiting mammalian tumor growth. The compound is prepared by reacting 7-hydroxy-9a-methoxymitosane with diazodiphenylmethane. In a preferred reaction, the compound is prepared from mitomycin C via 7-hydroxy-9a-methoxymitosane without drying (water removal). The intermediate is advantageously converted to the very effective anti-tumor agent 7-[2-(4-nitrophenyldithio)ethylamino]-9a-methoxymitosane in unexpectedly high yields using a two step process where the first step constitutes conversion to 7-[2-(2-pyridyldithio)ethylamino]-9a-methoxymitosane or 7-[2-(3-nitro-2-pyridyldithio)ethylamino]-9a-methoxymitosane.
- -
-
-
- Liposome composition and production thereof
-
The liposome compositions entrapping a drug are prepared by constituting the liposomal membrane with a saturated phospholipid and a glycolipid having sialic acid group. Thus obtained compositions circulate stably in blood for a long time after intravenous administration.
- -
-
-
- Substituted hydrazine mitomycin analogs
-
7-substituted hydrazine mitomycin analogs are provided having anti-tumor activity in experimental animal tumors. The compounds are made by treating mitomycin A with a substituted acid hydrazide or alkyl carbazate. Acyl substituted hydrazine mitomcyin analogs are disclosed.
- -
-
-
- Amino acid and hydroxyamino acid transporter compounds for therapeutic applications, process and use
-
Amino acid and hydroxyamino acid transporter compounds are provided, in which an amino acid or hydroxyamino acid as a carrier is linked via an ester linkage to a therapeutic compound, and having one of the general formulae: in which AA represents the amino acid or hydroxyamino acid, HAA represents the hydroxyamino acid, and Z1 and Z2 represent a therapeutic compound, or a linking compound attached to COOH or OH of the hydroxyamino acid and to the therapeutic compound, as well as a process for preparing the same, and a process for administration of the same to animals, to obtain the benefit of the therapeutic effect of the therapeutic compound.
- -
-
-
- Method of treating nausea and vomiting with certain substituted-phenylalkylamino (and aminoacid) derivatives and other serotonin depleting agents
-
A method for the treatment of emesis in a mammal, which method comprises administering to said mammal an emesis inhibiting amount of a compound which depletes serotonin in the brain of mammals; among which are compounds having the formula: STR1 wherein, R is selected from hydrogen, loweralkyl, trifluoromethyl, carboxyl, or loweralkoxycarbonyl; R1 and R2 are hydrogen or loweralkyl; Z is trifluoromethyl or halogen; the optical isomers and pharmaceutically acceptable salts thereof; two of the preferred compounds of the invention are fenfluramine and norfenfluramine.
- -
-
-
- Novel Mitomycin C Amidines: Synthesis and Their Reactions with Amines
-
Reactions of formamide acetals (e.g.DMFDMA, 10, 12) with mitomycin C (1) has afforded novel amidine derivatives (e.g. 7-9, 11, 13).Investigation of reactions of amines with bisamidine 8 in both polar and nonpolar solvents (e.g.MeOH vs CHCl3) has led to the discovery that 8, in its reactions with primary amines in methanol, behaves as a mitomycin A (2) equivalent to afford 7-N-substituted mitosanes (e.g. 16-19).In contrast, bisamidine 8 undergoes a selective deamidination reaction with primary amines in chloroform to afford monoamidine 14.
- Vyas, D. M.,Chiang, Y.,Benigni, D.,Doyle, T. W.
-
p. 5601 - 5605
(2007/10/02)
-
- Fibronectin-physiologically active substance complex and method of preparation thereof
-
Physiologically active substances such as antibiotics can preferentially be carried to a morbid part, for example, injured tissue and neoplastic cell proliferation site by administering its complex with fibronectin to repair the morbid part. The complex is prepared by the reaction between the physiologically active substance and the fibronectin with or without intervention of a protein cross-linking agent.
- -
-
-
- Derivatives of mitomycin C
-
1A-Higher aliphatic acyl derivatives of mitomycin C have been found to have superior anti-tumor activity and lipid-solubility as compared with known 1a-acyl derivatives of mitomycin C. Also, the new derivatives exhibit far lower toxicity than mitomycin C. These derivatives are represented by the following formula: STR1 wherein R is an aliphatic hydrocarbon group having 9-29 carbon atoms or a group wherein a hydrogen atom of the aliphatic hydrocarbon group is substituted by a hydroxy group.
- -
-
-
