Abstract：
:Immunotherapy has been increasingly utilized for the treatment of cancer. Currently available cancer immunotherapies mainly involve the use of antibodies, which have advantages in terms of pharmacodynamics such as efficacy and specificity, however, they exhibit disadvantages in regard to the pharmacokinetics including but not limited to poor tissue and tumor penetration, very long half-life, and the lack of oral bioavailability. Also they are immunogenic and may cause undesired side effects. In addition, they are difficult and expensive to produce. In contrast to therapeutic antibodies, small molecule immuno-oncology agents generally have favorable pharmacokinetics, for example, better oral bioavailability, higher tissue and tumor penetration, reasonable half-lives etc. Furthermore, some small molecules are highly selective and efficacious with benign toxicity profiles. Therefore, small molecule immuno-oncology agents have the potential to overcome the drawbacks of therapeutic antibodies, and they can complement existing therapeutic antibodies and may also be used in combination with antibodies to achieve synergistic effects. In this article, we summarize the current advances in the field of small molecule approaches in tumor immunology which include the small molecules in clinical trials and preclinical studies, and the reported crystal structures of small molecules and their target proteins as well as the binding interactions between small molecules and the targets. The tumorigenesis mechanism of different targets (the programmed cell death 1/programmed cell death ligand 1(PD1/PD-L1), retinoic acid-related orphan receptor-gamma t (RORγt), Chemokine receptor, Stimulator of Interferon Genes (Sting), Indoleamine 2,3-dioxygenase (IDO), toll-like receptors (TLR) etc.) are also elucidated.
journal_name
Eur J Med Chemjournal_title
European journal of medicinal chemistryauthors
Cheng B,Yuan WE,Su J,Liu Y,Chen Jdoi
10.1016/j.ejmech.2018.08.028subject
Has Abstractpub_date
2018-09-05 00:00:00pages
582-598eissn
0223-5234issn
1768-3254pii
S0223-5234(18)30692-5journal_volume
157pub_type
杂志文章,评审abstract：:We investigated the antibacterial activity of some new steroidal thiosemicarbazone derivatives, prepared from the reaction of cholest-5-en-7-one with thiosemicarbazides, in ethanol in the presence of a few drops of HCl at 80 degrees C in high yield. All the compounds have been characterized by means of elemental analy...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2007.12.004
更新日期：2008-09-01 00:00:00
abstract：:Bicyclic polyprenylated acylphloroglucinols (BPAPs), the principal bioactive benzophenone products isolated from plants of genera Garcinia and Hypericum, have attracted noticeable attention from the synthetic and biological communities due to their fascinating chemical structures and promising biological activities. H...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章,评审
doi：10.1016/j.ejmech.2020.112646
更新日期：2020-11-01 00:00:00
abstract：:GSK805 (1) is a potent RORγt inverse agonist, but a drawback of 1 is its low solubility, leading to a limited absorption in high doses. We have explored detailed structure-activity relationship on the amide linker, biaryl and arylsulfonyl moieties of 1 trying to improve solubility while maintaining RORγt activity. As ...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2020.112536
更新日期：2020-09-15 00:00:00
abstract：:The trinuclear complex: [{trans-PtCl(NH(3))}(2)mu-{trans-Pt(NH(3))(2-hydroxypyridine)-(H(2)N(CH(2))(6)NH(2))(2)]Cl(4) (code named CH9) has been synthesized and characterized. The activity of the compound against human ovarian cancer cell lines: A2780, A2780(cisR) and A2780(ZD0473R), cell up take, level of binding with...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2005.03.009
更新日期：2005-08-01 00:00:00
abstract：:A new series of thiazole-2(3H)-thiones containing 4-(3,4,5-trimethoxyphenyl) moiety were synthesized as diaryl-heterocylic analogs of combretastatin A-4 with anticancer activity. The cytotoxicity evaluation of synthesized compounds against cancer cell lines (A549, MCF-7 and SKOV3) revealed that most of them had potent...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2019.111784
更新日期：2020-01-01 00:00:00
abstract：:As we are interested in synthetizing biologically active leads with dual anticancer and antibacterial activity, we adopted biology oriented drug synthesis (BIODS) strategy to synthesize a series of novel ciprofloxacin (CP) hybrids. The National Cancer Institute (USA) selected seventeen newly synthesized compounds for ...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2018.03.026
更新日期：2018-04-25 00:00:00
abstract：:Carbonic anhydrases (CA I, II, IX and XII) are known to be highly expressed in various human malignancies. CA IX is overexpressed in colorectal cancer specifically in hereditary nonpolyposis colorectal cancer. Inhibition of CA activity by small molecular CA inhibitor like sulphonamides, sulphonamide derivative (SU.D2)...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2016.01.001
更新日期：2016-02-15 00:00:00
abstract：:Drug therapy for Chagas disease remains a major challenge as potential candidate drugs have failed clinical trials. Currently available drugs have limited efficacy and induce serious side effects. Thus, the discovery of new drugs is urgently needed in the fight against Chagas' disease. Here, we synthesized and evaluat...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2019.111610
更新日期：2019-11-15 00:00:00
abstract：:Five series of novel thiophene-pyrimidine derivatives (9a-h, 10a-f, 11a-f, 12a-f, 13a-f) have been synthesized and tested for their anti-proliferative activity against several cancer cell lines in which EGF is highly expressed. Most of the target compounds showed excellent activity against one or more cancer cell line...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2020.112511
更新日期：2020-10-01 00:00:00
abstract：:A series of 6-chloro-3-phenyl-4-thioxo-2H-1,3-benzoxazine-2(3H)-ones 3 and a series of 6-chloro-3-phenyl-2H-1,3-benzoxazine-2, 4(3H)-dithiones 4 were synthesized by melting 6-chloro-3-phenyl-2H-1, 3-benzoxazine-2,4(3H)-dione and its derivatives substituted on the phenyl ring 2 with tetraphosphorus decasulfide. Compoun...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/s0223-5234(00)00174-4
更新日期：2000-07-01 00:00:00
abstract：:A small library of coumarins, carrying butynyl-amino chains, was synthesized continuing our studies in the field of MDR reverting ageEnts and in order to obtain multipotent agents to combat malignancies. In particular, the reported anticancer and chemopreventive natural product 7-isopentenyloxycoumarin was linked to d...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2017.01.020
更新日期：2017-02-15 00:00:00
abstract：:Structure-Activity Relationship (SAR) is a current approach in the design of new pharmacological agents. We previously reported the synthesis of a novel analogue of morphine, a 2-azabicyclo[3.3.1]nonane, which contains a β-amino acid. This bicyclic core exhibits two distinctive chemical handles for further elaboration...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2015.06.025
更新日期：2015-08-28 00:00:00
abstract：:Non-steroidal anti-inflammatory drugs are widely used therapeutic agents in the treatment of inflammation, pain and fever. Cyclooxygenase catalyzes the initial step of biotransformation of arachidonic acid to prostanoids, and exist as three distinct isozymes; COX-I, COX-II and COX-III. Selective COX-II inhibitors are ...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章,评审
doi：10.1016/j.ejmech.2010.07.045
更新日期：2010-11-01 00:00:00
abstract：:Current healthcare has significantly increased the average life expectancy, leading to a consequently greater incidence of age-related diseases, such as Alzheimer's disease. Following a multitarget approach, in this paper a series of polycyclic maleimide-based derivatives were designed and synthesized aimed at simulta...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2018.12.003
更新日期：2019-02-01 00:00:00
abstract：:Many known 5-HT7 ligands contain either a serotonin-like or an arylpiperazine structure that, in published SAR studies, are generally supposed to bind the same receptor pocket. Conversely, we explored the hypothesis that two such moieties can co-exist in the same ligand, binding to different pockets. We thus designed ...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2014.04.034
更新日期：2014-06-10 00:00:00
abstract：:The synthesis of (2RS)-1-(1H-indol-4-yloxy)-3-{[2-(2-methoxyphenoxy)ethyl]amino}propan-2-ol ((RS)-9) and its enantiomers has been described and tested for electrocardiographic, antiarrhythmic, hypotensive and spasmolytic activities as well as for alpha(1)-, alpha(2)- and beta(1)-adrenoceptors' binding affinities. All ...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2008.05.019
更新日期：2009-02-01 00:00:00
abstract：:Two novel series of 4-thiazolidinone derivatives, namely 2',4'-difluoro-4-hydroxybiphenyl-3-carboxylic acid [2-(5-nitro-2-furyl/substituted phenyl)-4-thiazolidinone-3-yl]amides (5a-g) and 2-(2',4'-difluoro-4-hydroxybiphenyl-3-carbonylhydrazono)-3-alkyl/aryl-4-thiazolidinones (6a-e) together with 5-(2',4'-difluoro-4-hy...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2005.11.005
更新日期：2006-03-01 00:00:00
abstract：:The term varicose vein refers to the twisted and swollen vein visible under the skin surface which occurs most commonly in the leg. Epidemiological studies report a varying percentage of incidences from 2 to 56% in men and <1-60% in women. Venous insufficiency is most often caused by the damage to the valves and walls...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章,评审
doi：10.1016/j.ejmech.2019.04.075
更新日期：2019-08-15 00:00:00
abstract：:Naturally occurring saponins 3 and 4 have a normal type F ring and alpha-arranged CH(3)-21 group. Treatments of pseudosaponin peracetates 18 and 19 derived from 3 and 4, respectively, with alcoholic KOH, followed by acidification with acetic acid, gave spirostanols 20 and 22 having iso type F rings as major products. ...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/s0223-5234(00)00151-3
更新日期：2000-05-01 00:00:00
abstract：:Glycogen synthase kinase 3β (GSK-3β) is widely recognised as a relevant player in the pathogenesis of several highly prevalent disorders such as Alzheimer's disease, mood disorders, diabetes and cancer. Therefore, this enzyme constitutes a highly attractive therapeutic target for the development of selective inhibitor...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2012.12.014
更新日期：2013-02-01 00:00:00
abstract：:Synthesis of a new series of 1,3,4-oxadiazole derivatives possessing sulfonamide moiety is described. Their in vitro antiproliferative activities against NCI-58 human cancer cell lines of nine different cancer types were tested. Compound 1k with p-methoxybenzenesulfonamido moiety showed the highest mean %inhibition va...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2014.11.011
更新日期：2015-01-27 00:00:00
abstract：:African trypanosomiasis is a neglected parasitic disease that is still of great public health relevance, and a severe impediment to agriculture in endemic areas. The pathogens possess certain unique metabolic features that can be exploited for the development of new drugs. Notably, they rely on an essential, mitochond...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2018.02.075
更新日期：2018-04-25 00:00:00
abstract：:Modified purine derivatives exemplified by pyrazolopyrimidines have emerged as highly selective inhibitors of several angiogenic receptor tyrosine kinases. Herein, we designed and synthesized a new series of substituted pyrazolopyridines and explored their ability to influence crucial pro-angiogenic attributes of endo...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2016.05.035
更新日期：2016-10-04 00:00:00
abstract：:A series of novel γ-(triazolyl ethylidene)butenolides (4-23) were prepared from commercially available l-ascorbic acid in good yields. These butenolides on reaction with ethanolic ammonia/amines led to formation of respective 5-hydroxy pyrrolinones (24-33). The two of these pyrrolinones on dehydration with p-toluenesu...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2014.05.042
更新日期：2014-07-23 00:00:00
abstract：:Structure-based pharmacophore models were built by using LigandScout and used for virtual screening of the SPECS database to identify new potential 11beta-HSD1 inhibitors. As a refinement of the results obtained from virtual 3D pharmacophore screening, the best fitting virtual hits were subjected to docking study. The...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2008.06.005
更新日期：2009-03-01 00:00:00
abstract：:A series of pyrazine-2-carboxylic acid hydrazide derivatives were synthesized and screened for their activity against Mycobacterium tuberculosis. The results show that pyrazine-2-carboxylic acid hydrazide-hydrazone derivatives 3a-l were less active than pyrazinamide. In contrast, the N(4)-ethyl-N(1)-pyrazinoyl-thiosem...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2010.04.025
更新日期：2010-08-01 00:00:00
abstract：:A series of 6-acylureido derivatives containing a 3-(pyrrol-2-ylmethylidene)indolin-2-one scaffold were synthesized as potential dual Aurora B/FLT3 inhibitors by replacing the 6-arylureido moiety in 6-arylureidoindolin-2-one-based multi-kinase inhibitors. (Z)-N-(2-(pyrrolidin-1-yl)ethyl)-5-((6-(3-(2-fluoro-4-methoxybe...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2014.07.108
更新日期：2014-10-06 00:00:00
abstract：:During a screening for compounds that could act against Mycobacterium tuberculosis, a series of new cellular antiproliferative agents was identified. The most cytotoxic molecules were evaluated against a panel of human cell lines derived from hematological and solid human tumors. In particular, (E)-2-(1H-benzo[d] [1,2...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2011.06.018
更新日期：2011-09-01 00:00:00
abstract：:A series of 3-N-aryl substituted-2-heteroarylchromones was efficiently synthesized via Pd-mediated oxidative coupling under the influence of hetero-atoms neighboring group participation. Synthesized molecules were evaluated against human microtubule affinity regulating kinase 4 (MARK4) enzyme inhibitors, a recently id...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2018.09.030
更新日期：2018-11-05 00:00:00
abstract：:Purple acid phosphatases (PAPs) are binuclear hydrolases that catalyze the hydrolysis of phosphorylated substrates under acidic to neutral conditions. Elevated serum concentrations of PAP are observed in patients suffering from osteoporosis, identifying this enzyme as a potential target for the development of novel th...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2019.111611
更新日期：2019-11-15 00:00:00
