Prodrug approaches are often used to solve drug delivery *** doing so,the chemistry needed to bioreversibly derivatize the drug molecule is the *** this line,bioreversible derivatization of gasotransmitters such as ni...
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Prodrug approaches are often used to solve drug delivery *** doing so,the chemistry needed to bioreversibly derivatize the drug molecule is the *** this line,bioreversible derivatization of gasotransmitters such as nitric oxide,hydrogen sulfide and carbon monoxide are especially ***,the chemistry used to prepare antibody-drug conjugates also has much room for *** presentation will discuss some unique chemistry developed for the preparation of prodrugs of carbon monoxide and hydrogen sulfide as well as a new approach to prodrug activation through enrichment.
The first-generation JAK inhibitors Tofacitinib and Ruxolitinib are considered as promising therapeutics for the treatment of RA or ***,their side effects such as anemia limited their use possibly due to low selectivi...
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The first-generation JAK inhibitors Tofacitinib and Ruxolitinib are considered as promising therapeutics for the treatment of RA or ***,their side effects such as anemia limited their use possibly due to low selectivity of the drugs(dose-limiting) .Selective inhibition of JAK kinases within the JAK family may lead to maximum efficacy with minimized undesired off-target effects and to understanding the role of individual JAK isoforms in disease. We have discovered a class of novel,quinazoline derivatives as potent and selective JAK *** of SAR studies and profiling will be discussed in details.
Most lung cancer patients were diagnosed at advanced stage,therefore,local treatment for cure is often *** treatment is the mainstay for advanced stage nonsmall cell lung cancer ***-based chemotherapy has become stand...
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Most lung cancer patients were diagnosed at advanced stage,therefore,local treatment for cure is often *** treatment is the mainstay for advanced stage nonsmall cell lung cancer ***-based chemotherapy has become standard treatment *** new chemotherapy were designed and improved treatment outcome for *** year 2000,small molecules act as targeted therapy has changed the treatment paradigm
A series of novel gossypol Schiff bases were identified much potent(10-100 fold) than the gossypol and its known Schiff base derivatives for the anticancer activity.[1]This is the first example for Gossypol Schiff bas...
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A series of novel gossypol Schiff bases were identified much potent(10-100 fold) than the gossypol and its known Schiff base derivatives for the anticancer activity.[1]This is the first example for Gossypol Schiff bases with the increased activity.[2]The investigation of the Schiff base side chain of gossypol revealed the unique anticancer effect was achieved by the introduced hydrophobic ester *** molecular modeling analysis demonstrated the possible binding mode of these compounds with the Bcl-2,which could explain the good binding affinity of these novel gossypol Schiff bases with the proteins.
There is increasing interest in discovering HDAC6 selective inhibitors as chemical probes to elucidate the biological functions of HDAC6 and ultimately as new therapeutic ***-molecular fluorescent probes are widely us...
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There is increasing interest in discovering HDAC6 selective inhibitors as chemical probes to elucidate the biological functions of HDAC6 and ultimately as new therapeutic ***-molecular fluorescent probes are widely used to detect target protein location and function,identify protein complex composition in biological processes of *** the present study,structural modification of the previously reported compound 4 MS leads to two novel fluorescent HDAC inhibitors,6 a and 6 b(Figure 1 A).Determination of IC values against the panel of Zn dependent HDACs(HDACl-11) reveals that 6 b is a HDAC6 selective inhibitor,which can induce hyperacetylation of tubulin but not histone ***,fluorescent and immunofluorescent analyses of cells treated with the proteasome inhibitor MG132 demonstrates that 6 b can selectively target and image HDAC6 within the inclusion body,the aggresome(Figure IB).These results identify 6 b not only as a HDAC6 selective inhibitor but also as a fluorescent probe for imaging HDAC6 and investigating the roles of HDAC6 in various physiological and pathological contexts.
Chromones,which universally exist in nature,exhibit various pharmacological activities,such as antitumor,anti-inflammatory,antioxidant,cardioprotective,anti-HIV and antimicrobial *** were also favored due to low mamma...
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Chromones,which universally exist in nature,exhibit various pharmacological activities,such as antitumor,anti-inflammatory,antioxidant,cardioprotective,anti-HIV and antimicrobial *** were also favored due to low mammalian toxicity,which attracted many researchers' interest for structural modification of *** oxide has great potential in inhibiting carcinogenesis and tumor ***,due to its instability and short half-life,it is not really *** predicament inspired us to design and synthesize a series of chromones derivatives bearing nitric oxide *** biological activities of this series of compounds are under evaluation.
Spurred by the encouraging clinical treatment of cancers with antibody drug conjugates(ADC),an emerging strategy with the use of small molecule drug conjugates(SMDC)manifests several advantageous properties,such as be...
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Spurred by the encouraging clinical treatment of cancers with antibody drug conjugates(ADC),an emerging strategy with the use of small molecule drug conjugates(SMDC)manifests several advantageous properties,such as better in vitro and in vivo stability,lower antigenicity,facile conjugation chemistry,lower manufacturing costs,and enhanced ability to
Thrombotic disease is one of the most serious threats to human ***,available antithrombotic drugs have a common side effect:the risk of bleeding during *** show that selective inhibition of the intrinsic coagulation p...
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Thrombotic disease is one of the most serious threats to human ***,available antithrombotic drugs have a common side effect:the risk of bleeding during *** show that selective inhibition of the intrinsic coagulation pathway may distinguish thrombosis from hemostasis ,offering promise *** development of safer anticoagulants without serious bleeding *** chondroitin sulfate(FuCS) is a structurally distinct glycosaminoglycan with excellent anticoagulant *** studies showed that FuCS and its depolymerized fragments selectively inhibited the intrinsic coagulation pathway,and nonasacchande was the minimum structural unit that retained the potent activity .To achieve a large-scale preparation and explore further optimization,here we report a facile method for the synthesis of structurally homogeneous FuCS hexa-and nonasacchande for the first time over 12 linear steps from commercially available chondroitin *** studies showed that the synthetic nonasacchande displayed promising APTT activity and strong FXase inhibition activity,which may promote the discovery of novel anticoagulant candidates.
An interesting class of cyclic boron-containing compounds,benzoxaboroles,were first synthesized in 1957 while its medicinal usage had remained unknown for fifty years until tavaborole(Kerydin) was approved in 2014 f...
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An interesting class of cyclic boron-containing compounds,benzoxaboroles,were first synthesized in 1957 while its medicinal usage had remained unknown for fifty years until tavaborole(Kerydin) was approved in 2014 for the treatment of fungal infection of the toenails. To date,benzoxaboroles have been investigated for their antifungal,antibacterial,anti-parasite,antiviral,and anti-inflammatory properties. However,an investigation of their anticancer activity has been *** this talk,I will discuss our recent work on the anticancer activity and mechanism of action study of a series of interesting benzoxaboroles.
Liposomes provide stable encapsulation and local tumor-specific release for cancer therapy based on enhanced permeability and retention effects to increase therapy outcome and reduce side effect of antitumor ***,the e...
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Liposomes provide stable encapsulation and local tumor-specific release for cancer therapy based on enhanced permeability and retention effects to increase therapy outcome and reduce side effect of antitumor ***,the encapsulation efficiency and stable retention of drugs in liposomes is drug dependent Many potent antitumor drags are difficult to encapsulate and retain in liposomes,thus causing side effect and decreasing the dose of drugs at tumor ***,we propose a glycosidic switch technology to adjust lipid/water solubility of drugs to increase drug loading and stability within *** strategy is to conjugate drugs with a methyl glucuronide via a self—immolative linker to generate a lipid soluble methyl drug glucoronate(Drug-GL) that can directly pass through the lipid bilayer of *** Drug-GL then is converted to water-soluble drug glucuronide(Drug-Gw) via spontaneous saponification within liposomes that increase drug retention and *** extend this concept to create highly potent anticancer agents,we synthesis of the glycosidic switch analog of *** is suitable for an extensive range of drugs and provides a new method to improve the loading and retention of drugs in liposome to increase accumulation of anticancer drugs at target cancer cells and produce greater cytotoxicity for improved therapeutic outcome.
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