Sheng-Yong Yang's research while affiliated with Sichuan University and other places
What is this page?
This page lists the scientific contributions of an author, who either does not have a ResearchGate profile, or has not yet added these contributions to their profile.
It was automatically created by ResearchGate to create a record of this author's body of work. We create such pages to advance our goal of creating and maintaining the most comprehensive scientific repository possible. In doing so, we process publicly available (personal) data relating to the author as a member of the scientific community.
If you're a ResearchGate member, you can follow this page to keep up with this author's work.
If you are this author, and you don't want us to display this page anymore, please let us know.
It was automatically created by ResearchGate to create a record of this author's body of work. We create such pages to advance our goal of creating and maintaining the most comprehensive scientific repository possible. In doing so, we process publicly available (personal) data relating to the author as a member of the scientific community.
If you're a ResearchGate member, you can follow this page to keep up with this author's work.
If you are this author, and you don't want us to display this page anymore, please let us know.
Publications (168)
Background
The recruitment of a sufficient number of immune cells to induce an inflamed tumor microenvironment (TME) is a prerequisite for effective response to cancer immunotherapy. The immunological phenotypes in the TME of EGFR–mutated lung cancer were characterized as non-inflamed, for which immunotherapy is largely ineffective.
Methods
Global...
Doublecortin-like kinase 1 (DCLK1) is upregulated in many tumors and is a marker for tumor stem cells. Accumulating evidence suggests DCLK1 constitutes a promising drug target for cancer therapy. However, the regulation of DCLK1 kinase activity is poorly understood, particularly the function of its autoinhibitory domain (AID) and moreover, no physi...
The first potent and selective small‐molecule SETDB1 tandem tudor domain (TTD) inhibitor, (R,R)‐59, is reported. (R,R)‐59 is an endogenous binder‐competitive inhibitor and also showed activities in intact cells. The enantiomer (S,S)‐59 did not show any activity.
Abstract
SET domain bifurcated protein 1 (SETDB1) is a histone lysine methyltransferas...
Aberrant expression of protein arginine methyltransferases (PRMTs) has been implicated in a number of cancers, making PRMTs potential therapeutic targets. But it remains not well understood how PRMTs impact specific oncogenic pathways. We previously identified PRMTs as important regulators of cell growth in neuroblastoma, a deadly childhood tumor o...
Herein, we report the discovery of a series of thieno[2,3-d]pyrimidin-4(3H)-one derivatives as a new class of ROCK inhibitors. Structure-activity relationship studies of these compounds led to the identification of the most potent compound, 3-(3-methoxybenzyl)-6-(1H-pyrrolo[2,3-b]pyridin-4-yl)thieno[2,3-d]pyrimidin-4(3H)-one (8k), which showed IC50...
Since publication of this article, the authors have noticed that there were errors in Fig. 1b (the CT 26 cells colony formation images) and Fig. 7c (the vehicle group images). As a result of the misfiling of the data during preparation of figures, incorrect images were inadvertently inserted in these figures.
An amendment to this paper has been pub...
Determining chemical carcinogenicity in the early stages of drug discovery is fundamentally important to prevent the adverse effect of carcinogens on human health. There has been a recent surge of interest in developing computational approaches to predict chemical carcinogenicity. However, the predictive power of many existing approaches is limited...
Limited drug response and severe drug resistance confer the high mortality of non-small-cell lung cancer (NSCLC), a leading cause of cancer death worldwide. There is an urgent need for novel treatment against NSCLC. Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is aberrantly overexpressed and participats in NSCLC development and EGFR-TKIs-...
Peptidyl‐prolyl cis‐trans isomerase Pin1 plays a crucial role in the development of human cancers. Recently, we have disclosed that Pin1 regulates the biogenesis of miRNA, which is aberrantly expressed in HCC and promotes HCC progression, indicating the therapeutic role of Pin1 in HCC therapy. Here, 7‐(benzyloxy)‐3,5‐dihydroxy‐2‐(4‐methoxyphenyl)‐8...
Treatment of non-small-cell lung cancers (NSCLCs) harboring primary EGFR oncogenic mutations such as L858R and exon 19 deletion delE746_A750 (Del-19) using gefitinib/erlotinib ultimately fails due to the emergence of T790M mutation. Though WZ4002/CO-1686/AZD9291 are effective in overcoming EGFR T790M by targeting Cys797 via covalent bonding, their...
B cell lymphoma (BCL) is the most frequently diagnosed type of non-Hodgkin lymphoma (NHL), and accounts for about 4% of all cancers in the USA. Kinases spleen tyrosine kinase (Syk), Src, and Janus kinase 2 (JAK2) have been thought as potential targets for the treatment of BCL. We have recently developed a multikinase inhibitor, SKLB-850, which pote...
The RET tyrosine kinase is an important therapeutic target for medullary thyroid cancer (MTC), and drug resistance mutations of RET, particularly V804M and V804L, are a main challenge for the current targeted therapy of MTC based on RET inhibitors. In this investigation, we report the structural optimization and structure-activity relationship stud...
Autophagy inducers represent new promising agents for the treatment of a wide range of medical illnesses. However, safe autophagy inducers for clinical applications are lacking. Inhibition of cdc2-like kinase 1 (CLK1) was recently found to efficiently induce autophagy. Unfortunately, most of the known CLK1 inhibitors have unsatisfactory selectivity...
Small-molecule target identification is an important and challenging task for chemical biology and drug discovery. Structure-based virtual target identification has been widely used, which infers and prioritizes potential protein targets for the molecule of interest (MOI) principally via a scoring function. However, current ‘universal’ scoring func...
COMMUNICATION Crystallographic analyses of isoquinoline complexes reveal a new mode of metallo-β-lactamase inhibition
Herein we report the discovery of a series of new small molecule inhibitors of histone lysine demethylase 4D (KDM4D). Molecular docking was first performed to screen for new KDM4D inhibitors from various chemical databases. Two hit compounds were retrieved. Further structural optimization and structure-activity relationship (SAR) analysis were carr...
Crystallographic analyses of the VIM-5 metallo-β-lactamase (MBL) with isoquinoline inhibitors reveal non zinc ion binding modes. Comparison with other MBL-inhibitor structures directed addition of a zinc-binding thiol enabling identification of potent B1 MBL inhibitors. The inhibitors potentiate meropenem activity against clinical isolates harborin...
SIRT2, which is a NAD+ (nicotinamide adenine dinucleotide)-dependent deacetylase, has been demonstrated to play an important role in the occurrence and development of a variety of diseases such as cancer, ischemia-reperfusion, and neurodegenerative diseases. Small molecule inhibitors of SIRT2 are thought as potential interfering agents for relevant...
NMR-filtered virtual screening leads to non-metal chelating metallo-β-lactamase inhibitors A structure-based virtual screening approach combined with NMR filtering led to the identification of inhibitors of the clinically relevant Verona Integron-encoded MBL (VIM)-2. Crystallographic analyses reveal a new mode of MBL inhibition involving binding ad...
Colorectal carcinoma (CRC) is the one of the most common cancers with considerable metastatic potential, explaining the need for new drug candidates that inhibit tumor metastasis. The signal transducers and activators of the transcription 3 (Stat3) signaling pathway has an important role in CRC and has been validated as a promising anticancer targe...
There are no clinically useful inhibitors of metallo-β-lactamases (MBLs), which are a growing problem because they hydrolyse almost all β-lactam antibacterials. Inhibition by most reported MBL inhibitors involves zinc ion chelation. A structure-based virtual screening approach combined with NMR filtering led to the identification of inhibitors of t...
Herein we report the sophisticated process of structural optimization towards a previously disclosed Src inhibitor, compound 1, which showed high potency in the treatment of triple negative breast cancer (TNBC) both in vitro and in vivo, but had considerable toxicity. A series of 3-(phenylethynyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine derivatives wer...
PRMT5 is an important protein arginine methyltransferase that catalyzes the symmetric dimethylation of arginine resides on histones or non-histone substrate proteins. It has been thought as a promising target for many diseases, particularly cancer. Despite the potential applications of PRMT5 inhibitors in cancer treatment, very few of PRMT5i have b...
Psoriasis is a chronic T-cell-mediated autoimmune disease, and FMS-like tyrosine kinase 3 (FLT3) has been considered as a potential molecular target for the treatment of psoriasis. In this investigation, structural optimization was performed on a lead compound, 1-(4-(1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)phenyl)-3-(4-chloro-3- (trifluoromethyl)phenyl...
It is significantly challenging to collect more light and simultaneously avoid dye aggregation in dye-sensitized solar cells (DSSCs). This work addresses the significance of the intensity, rather than just the traditionally emphasized broadness, of the absorption band in developing DSSC sensitizers. With the assistance of calculating the oscillator...
P450 119 peroxygenase and its site-directed mutants are discovered to catalyze the enantioselective epoxidation of methyl-substituted styrenes. Two new site-directed P450 119 mutants, namely T213Y and T213M, which were designed to improve the enantioselectivity and activity for the epoxidation of styrene and its methyl substituted derivatives, were...
Herein we report the discovery of a series of new KDM5A inhibitors. A three-dimensional (3D) structure model of KDM5A jumonji domain was firstly established based on homology modeling. Molecular docking-based virtual screening was then performed against commercial chemical databases. A number of hit compounds were retrieved. Further structural opti...
Cancer cells activate autophagy in response to anticancer therapies. Autophagy induction is a promising therapeutic approach to treat cancer. In a previous study, YL4073 inhibited the growth of liver cancer and induced liver cancer cell apoptosis. Here, we demonstrated the anticancer activity and specific mechanisms of YL4073 in Lewis lung carcinom...
The development of amyloid-specific fluorophores allows the visualization of cerebral β-amyloid deposits using optical imaging technology. In the present study, a series of smart styrylpyran fluorophores with compact donor–acceptor architecture were designed and evaluated for noninvasive detection of cerebral β-amyloid deposits. Spectral behavior o...
Herein, we sought to discover new p300 HAT inhibitors from natural products by a customized structure-based virtual screening method. The natural compounds NP-2 (spinosine), NP-3 (palmatine), NP-9 (venenatine), and NP-15 (taxodione) were found to be potent p300 HAT inhibitors, of which IC50 values are 0.69 μM, 1.05 μM, 0.58 μM, 4.85 μM, respectivel...
Triple-negative breast cancer (TNBC) is the most aggressive and deadly breast cancer subtype. To date, chemotherapy is the only systemic therapy and prognosis remains poor. Herein, we report the preclinical evaluation of SKLB646 in the treatment of TNBC; SKLB646 is a novel multiple kinase inhibitor developed by us recently. This compound potently i...
Melanoma is a type of cancer arising from the melanocytes, which are the cells that make up the pigment melanin and are derived from the neural crest. There is no particularly effective therapy once the disease is metastatic, highlighting the need for discovery of novel potent agents. In this investigation, we adopted a zebrafish embryonic pigmenta...
Receptor interacting protein 1 (RIP1) kinase plays an important role in necroptosis and inhibitors of the RIP1 kinase are thought to have a potential therapeutic value in the treatment of diseases related to necrosis. Herein we report the structural optimization of a RIP1 kinase inhibitor, 1-(2,4-dichlorobenzyl)- 3-nitro-1H-pyrazole (1a). A number...
FLT3 has been identified as a valid target for the treatment of acute myeloid leukemia (AML), and some FLT3 inhibitors have shown very good efficacy in treating AML in clinical trials. Nevertheless, recent studies indicated that relapse and drug resistance are still difficult to avoid, and leukemia stem cells (LSCs) are considered one of the most i...
In this investigation, a series of 6-phenylimidazo[2,1-b]thiazole derivatives were synthesized. Structure-activity relationship (SAR) analysis of these compounds based on cellular assays led to the discovery of a number of compounds that showed potent activity against FLT3-dependent human acute myeloid leukemia (AML) cell line MV4-11, but very weak...
A series of novel teraryl oxazolidinone compounds was designed, synthesized and evaluated for their antimicrobial activity and toxicities. The compounds with aromatic N-heterocyclic substituents at the 4-position of pyrazolyl ring showed better antibacterial activity against the tested bacteria than other compounds with different pattern of substit...
Despite a potential application of PRMT1 inhibitors in cancer treatment, very few of PRMT1 inhibitors have been reported. To obtain novel potent PRMT1 inhibitors, structure optimizations towards a hit compound, 4-((6-chloro-5-nitropyrimidin-4-yl) amino) benzimidamide, were carried out. A series of 4-((5-nitropyrimidin-4-yl) amino) benzimidamide der...
Lysine specific demethylase 1 (LSD1) plays an important role in regulating histone lysine methylation at residues K4 and K9 on histone H3 and is recognized as an attractive therapeutic target in multiple malignancies. In this study, a series of novel (E)-N’-(2, 3-dihydro-1H-inden-1-ylidene) benzohydrazides were synthesized and biologically evaluate...
A series of quinoline derivatives was synthesized and biologically evaluated as Enhancer of Zeste Homologue 2 (EZH2) inhibitors. Structure-activity relationship (SAR) studies led to the discovery of 5-methoxy-2-(4-methyl-1,4-diazepan-1-yl)-N-(1-methylpiperidin-4-yl)quinolin-4-amine (5k), which displayed an IC50 value of 1.2 μM against EZH2, decreas...
Microemulsion-based organogels (MBGs) were effectively employed for the immobilization of four commonly used lipases. During the asymmetric hydrolysis of ketoprofen vinyl ester at 30 °C for 24 h, lipase from Rhizomucor miehei and Mucor javanicus immobilized in microemulsion-based organogels (RML MBGs and MJL MBGs) maintained good enantioselectiviti...
A series of 3-(phenylethynyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine derivatives were designed and synthesized. Structure-activity relationship (SAR) analysis of these compounds led to the discovery of compound 1j, which showed the highest inhibitory potency against the Src kinase and the most potent anti-viability activity against the typical TNBC ce...
The design, synthesis and SARs studies of novel inhibitors of HCV NS4B which based on imidazo[2,1-b]thiazole scaffold were described. Optimization of potency with respect to genotype 1b resulted in the discovery of two potent leads 26f (EC50=16 nM) and 28g (EC50= 31 nM). The resistance profile studies revealed that 26f and 28g targeted at HCV NS4B,...
Lead optimization is one of the key steps in drug discovery, and currently it is carried out mostly based on experiences of medicinal chemists, which often suffers from low efficiency. In silico methods are thought to be useful in improving the efficiency of lead optimization. Here we describe a new in silico automatic tool for structure-based lead...
The clinical prognosis of pancreatic cancer remains rather disappointing despite tremendous efforts in exploring medical treatments in the past two decades. Development of more effective treatment strategies is still desperately needed to improve outcomes in patients with pancreatic cancer. SKLB261 is a multi-kinase inhibitor obtained recently thro...
Hepatocellular carcinoma (HCC) is a serious life-threatening malignant disease of liver. Molecular targeted therapies are considered a promising strategy for the treatment of HCC. Sorafenib is the first, and so far the only targeted drug approved by the U.S. Food and Drug Administration (FDA) for clinical therapy of HCC. Despite being effective in...
Epigenetic modifications are critical mechanisms that regulate many biological processes and establish normal cellular phenotypes. Aberrant epigenetic modifications are frequently linked to the development and maintenance of several diseases including cancer, inflammation and metabolic diseases and so on. The key proteins that mediate epigenetic mo...
Lipase-catalyzed direct vinylogous Michael addition reactions of electron-deficient vinyl malononitriles to nitroalkenes are reported for the first time. A series of nitroalkenes reacting with vinyl malononitriles generate the corresponding products with moderate to high yields in the presence of Lipozyme (R) (immobilized lipase from Mucor miehei)...
Most of the scoring functions currently used in structure-based drug design belong to “universal” scoring functions, which often give a poor correlation between the calculated scores and experimental binding affinities. In this investigation, we proposed a simple strategy to construct target-specific scoring functions based on known “universal” sco...
Drug-induced ototoxicity, as a toxic side effect, is an important issue needed to be considered in drug discovery. Nevertheless, current experimental methods used to evaluate drug-induced ototoxicity are often time-consuming and expensive, indicating that they are not suitable for a large-scale evaluation of drug-induced ototoxicity in the early st...
- [...]
New CYP 119 T213G mutants were constructed and characterized. Introduction of the T213G mutation into the wild-type CYP 119 significantly enhances the turnover rate for the peroxide-dependent styrene epoxidation 4.4-fold to 346.2 min−1, and the double T213G/T214V mutant improves the ratio of the S- and R-enantiomers of the epoxide products 2- fold...
A fast large-scale synthesis of fluorescent carbon dots (CDs) has been developed in this work without high temperature or high pressure. Using benzenediols (catechol, resorcinol and hydroquinone) as the carbon precursor and sulfuric acid as the catalyst, three distinct CDs with strong and stable luminescence were prepared via a microwave-assisted m...
Psoriasis is a common chronic T-cell-mediated autoimmune skin disease, and traditional immunotherapies for psoriasis have focused on the direct inhibition of T cells, which often causes toxicity and lacks long-term effectiveness. Safe and effective therapeutic strategies are strongly needed for psoriasis. In this study, we show for the first time a...
Current treatment for hepatitis C is barely satisfactory, there is an urgent need to develop novel agents for combating hepatitis C virus infection. This study discovered a new class of thieno[2,3-b]pyridine derivatives as HCV inhibitors. First, a hit compound characterized by a thienopyridine core was identified in a cell-based screening of our pr...
Here, we describe the structural optimization of a known EGFR inhibitor (compound 1) that showed weak off-target activity against RET. Twenty-six analogs of 1 were synthesized. SAR analysis led to the discovery of several compounds that showed considerable potency against the RET-dependent thyroid cancer cell line TT. Kinase inhibitory potency was...
This chapter describes a pharmacophore-based de novo ligand design method, called PhDD. The algorithm generates new molecules under the constraints of a given pharmacophore hypothesis, followed by the assessment of the drug-likeness, bioactivity, and synthetic accessibility of the designed compounds. Both algorithms of the previous version (v1.0) o...
S6K1 has emerged as a potential target for the treatment for obesity, type II diabetes and cancer diseases. Discovery of S6K1 inhibitors has thus attracted much attention in recent years. In this investigation, a hybrid virtual screening method that involves pharmacophore hypothesis, genetic function approximation (GFA) model, and molecular docking...
Herein, a combined molecular docking-based and pharmacophore-based target prediction strategy is presented, in which a probabilistic fusion method is suggested for target ranking. Establishment and validation of the combined strategy are described. A target database, termed TargetDB, was firstly constructed, which contains 1105 drug targets. Based...
Background:
Melanoma is considered as one of the most aggressive and deadliest cancers and current targeted therapies of melanoma often suffer limited efficacy or drug resistance. Discovery of novel multikinase inhibitors as anti-melanoma drug candidates is still needed.
Methods:
In this investigation, we assessed the in vitro and in vivo anti-m...
Background and purpose:
Targeted chemotherapy using small-molecule inhibitors of angiogenesis and proliferation is a promising strategy for cancer therapy.
Experimental approach:
YL529 was developed via computer-aided drug design, de novo synthesis and high-throughput screening. The biochemical, pharmacodynamic and toxicological profiles of YL52...
Scoring functions have been widely used to assess protein-ligand binding affinity in structure-based drug discovery. However, currently commonly used scoring functions face some challenges including a poor correlation between calculated scores and experimental binding affinities, target-dependent performance, and low sensitivity to analogues. In th...
We performed molecular dynamics simulations on complexes of ABL to investigate the binding of imatinib, P16 (binding at the ATP pocket), and STJ, MS7, MS9, 3YY, and MYR (binding at the myristoyl pocket). The calculated binding energies were then decomposed to determine the ligand-residue pair interactions, using the generalized Born surface area (G...
We describe the structural optimization of a hit compound, 1-(4-(1H-pyrazolo[3,4-d]pyrimidin-4-ylamino)phenyl)-3-(3-methoxyphenyl)urea (1), which exhibits inhibitory activity but low potency against FLT3 and VEGFR2. A series of pyrazolo[3,4-d]pyrimidine derivatives were synthesized, and SAR analysis using cell- and transgenic zebrafish-based assays...
We describe the structural optimization of a hit compound, N2-(4-(4-methylpiperazin-1-yl)phenyl)-N8-phenyl-9H-purine-2,8-diamine (1), which is a reversible kinase inhibitor targeting both EGFR-activating and drug-resistance (T790M) mutations, but has poor binding affinity. Structure-activity relationship studies led to the identification of 9-cyclo...
In this investigation, a common feature pharmacophore model of anaplastic lymphoma kinase (ALK) inhibitors was developed based on several known ALK inhibitors that were co-crystallized with ALK. The established pharmacophore model Hypo1 was carefully validated, and then adopted to screen two in silico chemical databases, Specs (202 408 compounds) a...
Combination therapies are urgently needed for optimal clinical benefit, but an efficient strategy for rational discovery of drug combinations, especially combinations of experimental drugs, is still lacking. Consequently, we proposed here a network-based computational method to identify novel synergistic drug combinations. A large-scale drug combin...
Aberrant activation of casein kinase 1 (CK1) has been demonstrated to be implicated in the pathogenesis of cancer and various central nervous system disorders. Discovery of CK1 inhibitors has thus attracted much attention in recent years. In this account, we describe the discovery of N6-phenyl-1H-pyrazolo[3,4-d]pyrimidine-3,6-diamine derivatives as...
C5aR antagonists have been thought as potential immune mediators in various inflammatory and autoimmune diseases, and discovery of C5aR antagonists has attracted much attention in recent years. The discovery of C5aR antagonists was usually achieved through high-throughput screening, which usually suffered a high cost and a low success rate. Current...
In the title compound, C(21)H(16)FN(3)OS, the thieno[2,3-b]pyridine system forms dihedral angles of 10.57 (12) and 83.87 (5)° with the fluoro-phenyl ring at the 6-position and the phenyl ring of the benzyl group, respectively. In the crystal, mol-ecules are linked by weak N-H⋯N anf N-H⋯O hydrogen bonds and π-π stacking inter-actions involving fluor...
Bruton's tyrosine kinase has emerged as a potential target for the treatment for B-cell malignancies and autoimmune diseases. Discovery of Bruton's tyrosine kinase inhibitors has thus attracted much attention recently. In this investigation, we introduced a hybrid protocol of virtual screening methods including support vector machine model-based vi...
Aromatic π-π stacking inter-actions stabilize the crystal structure of the title compound, C(10)H(12)N(2)O(3), the perpendic-ular distance between parallel planes being 3.7721 (8) Å. The morpholine ring adopts a chair comformation.
Aromatic π–π stacking interactions stabilize the crystal structure of the title compound, C10H12N2O3, the perpendicular distance between parallel planes being 3.7721 (8) Å. The morpholine ring adopts a chair comformation.
Structure-activity relationship (SAR) studies of 2-(quinazolin-4-ylthio)thiazole derivatives, which are for optimizing the in vitro and in vivo antiacute myeloid leukemia (AML) activity of a previously identified FLT3 inhibitor 2-(6,7-dimethoxyquinazolin-4-ylthio)thiazole (1), are described. SAR studies centering around the head (thiazole) and tail...
Protein kinase casein kinase 2 (CK2), a member of the serine/threonine kinase family, has been established as one of the most attractive targets for molecularly targeted cancer therapy. The discovery of CK2 inhibitors has thus attracted much attention in recent years. In this investigation, a hybrid virtual screening approach based on Bayesian clas...
Anti-epidermal growth factor receptor (EGFR) treatment has been successfully applied in clinical cancer therapy. However, the clinical efficacy of first-generation reversible EGFR inhibitors, such as gefitinib and erlotinib, is limited by the development of drug-resistant mutations, including the gatekeeper T790M mutation and upregulation of altern...
The title compound, C(17)H(13)ClN(2)OS, crystallizes with three independent mol-ecules (A, B and C) in the asymmetric unit which differ slightly in their conformations. In mol-ecule A, the thiazole ring makes dihedral angles of 27.44 (14) and 66.05 (6)° with the phenyl and chloro-benzene rings. In mol-ecule B, the respective angles are 29.09 (10) a...
The mol-ecule of the title compound, C(7)H(6)ClNO(2), is almost planar, with a dihedral angle of 3.34 (14)° between the COOMe group and the aromatic ring. In the crystal, the mol-ecules are arranged into (1[Formula: see text]2) layers by C-H⋯N hydrogen bonds and there are π-π stacking inter-actions between the aromatic rings in adjacent layers [cen...
ROS levels in H460 cells with or without gefitinib treatment. The ROS probe signals as well as the DAPI nuclear localization in H460 cells were presented alone or merged (merge).
(TIF)
Biochemical reactions involved in the computational model together with corresponding parameters.
(DOC)
Initial conditions of the computational model.
(DOC)
Despite many evidences supporting the concept of "oncogene addiction" and many hypotheses rationalizing it, there is still a lack of detailed understanding to the precise molecular mechanism underlying oncogene addiction. In this account, we developed a mathematic model of epidermal growth factor receptor (EGFR) associated signaling network, which...
In a cell-based screen of novel anticancer agents, the hit compound 1a which bears a pyrazolo[3,4-d]pyrimidine scaffold exhibited high inhibitory activity against a panel of four different types of tumor cell lines. In particular, the IC₅₀ for A549 cells was 2.24 µM, compared with an IC₅₀ of 9.20 µM for doxorubicin, the positive control. Four synth...
Citations
... Ablation or blockade of PKCδ will promote ICB sensitivity significantly. 122 Lysine demethylase 5B (KDM5B) suppresses endogenous retroelements and promotes immune evasion via recruiting SET domain bifurcated histone lysine methyltransferase 1 (SETDB1). Depletion of KDM5B may induce robust adaptive immune responses and overcome resistance in mouse melanoma models. ...
... It has also been linked to tumor immunosuppression via M2-macrophage polarization [103]. An important caveat to these types of overexpression studies with kinases is that these studies represent unfettered kinase activity that may obscure the subtle aspects of kinase regulation [104]. ...
![[object Object]](https://i1.rgstatic.net/ii/profile.image/891397968261122-1589537245652_Q64/Q-Chen-5.jpg)
... SETDB1-TTD-IN-1 is a selective inhibitor of SETDB1-TTD. 369 At present, no specific inhibitor of SETDB1 has been found. The SET domain of SETDB1 is split, so it is more difficult to develop specific inhibitors of SETDB1. ...
... A recent study has linked ATF5 with neuroblastoma cell survival [42]. The study has shown that inhibition of protein arginine methyltransferases 1 (PRMT1) induces apoptosis of human neuroblastoma cells and that ATF5 acts as a downstream effector of PRMT1-mediated survival signaling. ...
... ANNs have previously used molecular structure relationships to classify substances as carcinogenic [4][5][6] or to predict molecular properties [7,8]. In cheminformatics, molecular structures are often represented using specific notations, such as InChI [9] (International Chemical Identifier) or SMARTS [10] (SMILES ARbitrary Target Specification), or, more popularly, with SMILES [11] (Simplified Molecular Input Line Entry Specification) representations, which are a subset of SMARTS. ...
... STAT3 is also a convergence point for multiple signaling pathways. In cases of CRC, evidence has demonstrated that the activation of STAT3 and overexpression of cyclin D1 have a relationship and that STAT3 is correlated with both survivin and bcl-x [222] . TPs have the ability to suppress the JAK/STAT pathway [223] . ...
![[object Object]](https://i1.rgstatic.net/ii/profile.image/642464964689926-1530186992426_Q64/Yongxia-Zhu.jpg)
... On the other hand, previous studies [27] have shown that ROR1 is also a potential target for improving EGFR-TKIs resistance. Liu et al. [28] demonstrated that ARI-1, a ROR1 inhibitor, can improve the resistance of NSCLC to EGFR-TKIs by modulating the PI3K/AKT/mammalian target of rapamycin (mTOR) signaling pathway. Notably, targeting ROR1 can also improve EGFR resistance by inhibiting EMT [29]. ...
![[object Object]](https://i1.rgstatic.net/ii/profile.image/618929869299736-1524575788857_Q64/Wenchen-Pu.jpg)
... PKs are involved in anaerobic glycolysis and provide 50% of ATP to mature red blood cells. Dysfunctional PKLR can lead to PKs deficiency (PKD) and ATP deficiency, shortening the lifespan of red blood cells (8). The Warburg effect (aerobic glycolysis) is a well-defined metabolic change that is relevant to cancerous phenotypes, including the accelerated proliferative, invasive and migratory potentials (9). ...
... Because of its presence in a variety of pharmacologically active molecules and natural products, such as citrus fruit and vegetables [5][6][7][8], the chromone moiety is believed to represent a key structural class in the field of drug design and discovery [9,10]. Natural and synthetic 2-arylchroman-4-ones are known to possess antioxidant [11][12][13][14][15], neuroprotective [16], antiallergic [17], cardioprotective [8,18], antitumor [5,[19][20][21][22][23][24][25][26][27][28][29][30][31][32][33], antiviral [34], antibacterial [11,35,36] activities, etc. The structures of some 2-aryl-chromane-4-one derivatives with pronounced antiviral activity and their assumed mode of inhibitory action are shown in Fig. 1. ...
![[object Object]](https://i1.rgstatic.net/ii/profile.image/644664411566088-1530711381740_Q64/Shen-Xianyan-2.jpg)
... Based on the literature, EGFR was selected as a drug target for pancreatic cancer 17 . The X-ray crystal structure of EGFR and its co-crystallized ligand (PDB ID: 5X2A) 18 was obtained from the Protein Data Bank. The protein and the 3D structure of Cucurbita-5(10),6,23-triene-3β,25-diol were prepared using the structure preparation wizard in MOE (version 2019.01) ...
![[object Object]](https://i1.rgstatic.net/ii/profile.image/273515999920128-1442222704104_Q64/Cai-Hong-Yun.jpg)
