Abstract：
:We investigated the carbonic anhydrase (CA, EC 4.2.1.1) inhibitory activity of the clinically used antitumor agent bortezomib, a marketed proteasome inhibitor, against all the catalytically active mammalian isoforms CA I-VII, IX, XII-XV. Bortezomib effectively inhibited all these CAs in the micromolar range. hCA II, the physiologically dominant cytosolic isoform showed the highest affinity for the drug, with a KI of 1.16μM. The cytosolic slow isoform hCA I was also effectively inhibited, with a KI of 1.29μM, whereas the next best affinity was observed for the membrane-anchored form mCA XV, with a KI of 2.68μM, followed by two transmembrane isoforms, hCA IX and XIV (KIs of 3.28-3.38μM). The remaining cytosolic (CA III, VII and XIII), membrane-anchored (CA IV), mitochondrial (CA VA, VB), transmembrane (CA XII) and secreted (CA VI) isoforms were slightly less inhibited by bortezomib compared to isoforms discussed above, with KIs ranging between 4.38 and 8.45μM. These data may shed some light on possible side effects and novel antitumor mechanisms of action of this drug.
journal_name
Bioorg Med Chemjournal_title
Bioorganic & medicinal chemistryauthors
Supuran CTdoi
10.1016/j.bmc.2016.10.023subject
Has Abstractpub_date
2017-10-01 00:00:00pages
5064-5067issue
19eissn
0968-0896issn
1464-3391pii
S0968-0896(16)31021-5journal_volume
25pub_type
杂志文章abstract：:Compound libraries comprise an integral component of drug discovery in the pharmaceutical and biotechnology industries. While in-house libraries often contain millions of molecules, this number pales in comparison to the accessible space of drug-like molecules. Therefore, care must be taken when adding new compounds t...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2012.03.037
更新日期：2012-09-15 00:00:00
abstract：:12-O-β-D-glucopyranosyl jasmonic acid (JAG) shows unique biological activities, including leaf-closing of Samanea saman. It is expected that the mode of action for such regulation is distinct from that of other jasmonates. We developed high-performance compact molecular probes (CMPs) based on JAG that can be used for ...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2012.08.003
更新日期：2012-10-01 00:00:00
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journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2014.07.033
更新日期：2014-09-01 00:00:00
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journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2010.06.032
更新日期：2010-08-01 00:00:00
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journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2012.08.046
更新日期：2013-03-15 00:00:00
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journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2005.04.025
更新日期：2005-07-01 00:00:00
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journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2013.04.053
更新日期：2013-07-15 00:00:00
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journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2009.09.016
更新日期：2009-11-15 00:00:00
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journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2006.11.035
更新日期：2007-02-15 00:00:00
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journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2010.10.022
更新日期：2010-12-01 00:00:00
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journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2017.11.025
更新日期：2018-01-01 00:00:00
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journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2010.05.076
更新日期：2010-07-15 00:00:00
abstract：:Diacylhydrazine derivatives have been identified as one of the most important insect growth regulators. A variety of diacylhydrazine derivatives were designed and synthesized in recent years due to their unique action mechanism, simple structure, and environmental benign character. This paper describes the molecular d...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2007.01.008
更新日期：2007-03-01 00:00:00
abstract：:DNA methylation is an important epigenetic modification catalyzed by DNA methyltransferases (DNMTs). Abnormal expression of endogenous DNMTs in human causes alterations in the genome methylation patterns which subsequently lead to the development of cancers. Thus detection of endogenous DNMT activities and efficient i...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2015.03.006
更新日期：2015-06-15 00:00:00
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journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2005.05.012
更新日期：2005-08-15 00:00:00
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journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2013.07.017
更新日期：2013-09-15 00:00:00
abstract：:The interaction of organic compounds with apoptosis regulatory proteins is an attractive field of research because of its relevance in the development of new chemotherapeutic agents for cancer treatment. Our group designed four new adamantane thiadiazole derivatives (ATDs). The four ATDs were theoretically tested for ...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2016.10.040
更新日期：2017-01-01 00:00:00
abstract：:Poly(ADP-ribose) glycohydrolase (PARG) plays an essential role in poly(ADP-ribose) (PAR) turnover, and thereby regulating DNA transactions, such as DNA repair, replication, transcription and recombination. Here, we examined the inhibitory activities of 6-hydroxy-3H-xanthene-3-one (HXO) derivatives and analyzed their b...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2019.115249
更新日期：2020-02-01 00:00:00
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journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2011.08.003
更新日期：2011-09-15 00:00:00
abstract：:Bovine plasma amine oxidase (BPAO) was previously shown to be irreversibly inhibited by propargylamine and 2-chloroallylamine. 1,4-Diamine versions of these two compounds are here shown to be highly potent inactivators, with IC50 values near 20 microM. Mono-N-alkylation or N,N-dialkylation greatly lowered the inactiva...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/s0968-0896(03)00521-2
更新日期：2003-10-15 00:00:00
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journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2013.02.039
更新日期：2013-05-01 00:00:00
abstract：:Retinoids comprise a group of compounds each composed of three basic parts: a trimethylated cyclohexene ring that is a bulky hydrophobic group, a conjugated tetraene side chain that functions as a linker unit, and a polar carbon-oxygen functional group. Biochemical conversion of carotenoid or other retinoids to retino...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章,评审
doi：10.1016/j.bmc.2013.11.025
更新日期：2014-01-15 00:00:00
abstract：:A series of novel pyrazolo[1,5-a]pyrazin-4(5H)-one derivatives were synthesized by the reaction of ethyl 3-aryl-1-(2-bromoethyl)-1H-pyrazole-5-carboxylate and amine in the general heating condition and microwave-assisted condition. The structures of the compounds were determined by IR, (1)H NMR and mass spectroscopy, ...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2008.10.066
更新日期：2008-12-15 00:00:00
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journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2013.09.014
更新日期：2013-11-15 00:00:00
abstract：:Human enterovirus (EV) belongs to the picornavirus family, which consists of over 200 medically relevant viruses. A peptidomimetic inhibitor AG7088 was developed to inhibit the 3C protease of rhinovirus (a member of the family), a chymotrypsin-like protease required for viral replication, by forming a covalent bond wi...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2008.06.015
更新日期：2008-08-01 00:00:00
abstract：:Skin penetration enhancers are used in the formulation of transdermal delivery systems for drugs that are otherwise not sufficiently skin-permeable. We generated two series of esters by multi-step synthesis with substituted 6-aminohexanoic acid as potential transdermal penetration enhancers by multi-step synthesis. Th...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2010.10.025
更新日期：2010-12-15 00:00:00
abstract：:Methylation of histone arginine residues is an epigenetic mark related to gene expression that is implicated in a variety of biological processes and can be reversed by small-molecule modulators of protein arginine methyltransferases (PRMTs). A series of symmetrical ureas, designed as analogues of the known PRMT1 inhi...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2013.01.017
更新日期：2013-04-01 00:00:00
abstract：:Thiazolyl peptides are a class of thiazole-rich macrocyclic potent antibacterial agents. Recently, we described thiazomycin, a new member of thiazolyl peptides, discovered by a thiazolyl peptide specific chemical screening. This method also allowed for the discovery of a new thiazolyl peptide, thiazomycin A, which car...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2008.08.079
更新日期：2008-10-01 00:00:00
abstract：:Histamine H(1) and serotonin 5-HT(2A) receptors present in the CNS have been implicated in various neuropsychiatric disorders. 9-Aminomethyl-9,10-dihydroanthracene (AMDA), a conformationally constrained diarylalkyl amine derivative, has affinity for both of these receptors. A structure-affinity relationship (SAFIR) st...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2009.08.016
更新日期：2009-09-15 00:00:00
abstract：:A codrug approach for simultaneous treatment of alcohol abuse and tobacco dependence is considered as very desirable because of substantial evidence that smoking is increased significantly during drinking, and that smoking is regarded as a behavioral 'cue' for the urge to consume alcohol. The purpose of this study was...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2006.06.018
更新日期：2006-10-15 00:00:00
