- Reversing the undesirable pH-profile of doxorubicin: Via activation of a di-substituted maleamic acid prodrug at tumor acidity
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The acid-labile behavior of di-substituted maleamic acid (DMA) and its equilibrium with di-substituted maleimide (DMI) are exploited to build an ultra acid-sensitive, small molecule prodrug that can be activated by tumor extracellular pH (pHe) in the range of 6.5-6.9. Such a DMA prodrug reversed the unfavorable pH-profile of doxorubicin (Dox), which may improve its therapeutic window.
- Zhang, Anqi,Yao, Lan,An, Ming
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- ADIPOCYTE MEDIATED DELIVERY OF ANTICANCER THERAPEUTICS
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Disclosed are compositions and methods related to the use of adipocytes for sustained release of anti-cancer therapeutics and treatment of cancer.
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Page/Page column 29
(2020/05/28)
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- FAP-ACTIVATED THERAPEUTIC AGENTS, AND USES RELATED THERETO
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Disclosed are prodrugs of cytotoxic anthracyclines (such as doxorubicin) and other therapeutic agents that are selectively cleaved and activated by fibroblast activating protein (FAP). The prodrugs are useful for targeted delivery of cytotoxic and other agents to FAP- expressing tissues, including cancer (e.g., solid tumors). Also provided are pharmaceutical compounds comprising the prodrugs, as well as methods of using the prodrugs to treat a disorder characterized by FAP upregulation, e.g., cancer, fibrosis, and inflammation.
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Page/Page column 86
(2016/01/01)
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- CHANNEL PROTEIN ACTIVATABLE LIPOSOMES
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Disclosed is a liposome, comprising a lipid bilayer enclosing a cavity, wherein the bilayer comprises a channel protein releasably linked to an eight-membered non-aromatic cyclic alkenylene group, preferably a cyclooctene group, and more preferably a trans-cyclooctene group. The liposomes are used in a kit comprising the liposome, the liposomal membrane of which comprises a channel protein linked to a Trigger, and an Activator for the Trigger, wherein the Trigger comprises the eight- membered non-aromatic cyclic alkenylene group, and the Activator comprises a diene.
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Page/Page column 112
(2014/06/11)
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- ACTIVATABLE LIPOSOMES
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Disclosed are reactive liposome, comprising a lipid bilayer enclosing a cavity, wherein the bilayer comprises a linkage to an eight-membered non-aromatic cyclic alkenylene group, preferably a cyclooctene group, and more preferably a trans-cyclooctene group. The liposomes are use in a kit comprising the liposome linked, directly or indirectly, to a Trigger, and an Activator for the Trigger, wherein the Trigger comprises an eight-membered non-aromatic cyclic alkenylene group, and the Activator comprises a diene.
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Page/Page column 129
(2014/06/11)
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- Method for identifying an enzyme to design anti-cancer compounds
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The present invention relates to a method for identification of enzymes that are preferentially expressed in certain tumor tissue as compared with rapidly growing normal cells or tissue, use of said enzymes for the compound design to generate an active anti-cancer substance selectively in tumor tissue, compounds designed based on said enzymes, their pharmaceutically acceptable salts as well as pharmaceutical composition thereof.
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- Crystallization of doxorubicin hydrochloride
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Disclosed are a crystallizing method of doxorubicin hydrochloride from a doxorubicin hydrochloride-containing solution, particularly a method for carrying out the crystallization under a condition of 40° C. or higher, and a doxorubicin hydrochloride crystalline aggregate having particularly an excellent solubility in water.
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Page/Page column 6-10
(2008/06/13)
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- NOVEL PROTEIN AND DNA THEREOF
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Because the protein of the present invention has in its amino acid sequence a homology with, for example, ribonucleotide reductase, the protein of the present invention, its DNA, antibodies to these and the like are useful in the prevention, treatment and diagnosis, etc. of cancer.
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- Prodrugs activated by targeted catalytic proteins
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Prodrugs that are activated by and conjugated to a catalytic antibody conjugated to a moiety that binds to a tumor cell population are provided.
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- Elongated multiple electronic cascade and cyclization spacer systems in activatible anticancer prodrugs for enhanced drug release
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The design and synthesis of several novel elongated self-elimination spacer systems for application in prodrugs is described. These elongated spacer systems can be incorporated between a cleavable specifier and the parent drug. Naphthalene- and biphenyl-containing spacers were synthesized but did not eliminate. Prodrugs of the anticancer agents doxorubicin and paclitaxel are reported that contain two or three electronic cascade spacers. A novel catalytic application of HOBt was found for the synthesis of N-aryl carbamates through reacting a 4-nitrophenyl carbonate with an aniline derivative, to connect the 1,6-elimination spacers via a carbamate linkage. In addition, a double spacer-containing paclitaxel prodrug was synthesized, comprising a 1,6-elimination spacer and a bis-amine linker connected to paclitaxel via a 2′-carbamate linkage. Prodrugs in which the novel spacer systems were incorporated between a specific tripeptide specifier and the parent drug doxorubicin or paclitaxel proved to be significantly faster activated by plasmin in comparison with prodrugs containing conventional spacer systems. It is expected that the generally applicable novel spacer systems reported herein will contribute to future development of improved enzymatically activated prodrugs.
- De Groot,Loos,Koekkoek,Van Berkom,Busscher,Seelen,Albrecht,De Bruijn,Scheeren
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p. 8815 - 8830
(2007/10/03)
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- Amine derivatives of anthracycline antibodies
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Novel antineoplastic amine-containing derivatives and methods for synthesizing such derivatives of anthracycline antibiotics are disclosed. The derivatives are useful to anthracycline antibiotic conjugates which retain substantial immunospecificity of the unconjugated antibody molecule. Using the conjugates, targeted delivery of the attached antibiotics is achieved in vivo. Such conjugates are thus therapeutically effective against a variety of neoplastic cellular disorders when administered in vivo. Methods for preparing the antibody conjugates and for use of the conjugates in vivo are also disclosed.
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- Amine derivatives of anthracycline antibiotics
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Novel antineoplastic amine-containing derivatives and methods for synthesizing such derivatives of anthracycline antibiotics are disclosed. The derivatives are useful to prepare site-selectively attached therapeutic antibody-anthracyline antibiotic conjugates which retain substantial immunospecificity of the unconjugated antibody molecule. Using the conjugates, targeted delivery of the attached antineoplastic amine derivatives of anthracycline antibiotics is achieved in vivo. Such conjugates are thus therapeutically effective against a variety of neoplastic cellular disorders when administered in vivo. Methods for preparing the antibody conjugates and for use of the conjugates in vivo are also disclosed.
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