Abstract:
OBJECTIVES:The aim of this study was to obtain antitumour molecules targeting to activate PKM2 through adequate computational methods combined with biological activity experiments. METHODS:The structure-based virtual screening was utilized to screen effective activator targeting PKM2 from ZINC database. Molecular dynamics simulations were performed to evaluate the stability of the small molecule-binding PKM2 complex systems. Then, cell survival experiments, glutaraldehyde crosslinking reaction, western blot, and qPCR experiments were used to detect the effects of top hits on various cancer cells and the targeting specificity of PKM2. RESULTS:Two small molecules in 1,5-2H-pyrrole-dione were obtained after virtual screening. In vitro experiments demonstrated that ZINC08383544 specifically activated PKM2 and affected the expression of upstream and downstream genes of PKM2 during glycolysis, leading to the inhibition of tumour cell growth. These results indicate that ZINC08383544 conforms to the characteristics of PKM2 activator and is potential to be a novel PKM2 activator as antitumour drug. DISCUSSION:This work proves that ZINC08383544 promotes the formation of PKM2 tetramer, effectively blocks PKM2 nuclear translocation, and inhibits the growth of tumour, and ZINC08383544 may be a novel activator of PKM2. This work may provide a good choice of drug or molecular fragments for the antitumour strategy targeting PKM2. Screening of targeted drugs by combination of virtual screening and bioactivity experiments is a rapid method for drug discovery.
journal_name
Cell Prolifjournal_title
Cell proliferationauthors
Li Y,Bao M,Yang C,Chen J,Zhou S,Sun R,Wu C,Li X,Bao Jdoi
10.1111/cpr.12509subject
Has Abstractpub_date
2018-12-01 00:00:00pages
e12509issue
6eissn
0960-7722issn
1365-2184journal_volume
51pub_type
杂志文章abstract::The cell cycle is controlled by numerous mechanisms ensuring correct cell division. This review will focus on these mechanisms, i.e. regulation of cyclin-dependent kinases (CDK) by cyclins, CDK inhibitors and phosphorylating events. The quality checkpoints activated after DNA damage are also discussed. The complexity ...
journal_title:Cell proliferation
pub_type: 杂志文章,评审
doi:10.1046/j.1365-2184.2003.00266.x
更新日期:2003-06-01 00:00:00
abstract:OBJECTIVE:Embryo implantation needs a reciprocal interaction between competent embryo and receptive endometrium. Adenosine triphosphate (ATP) produced by stressed or injured cells acts as an important signalling molecule. This study aims to investigate whether adenosine triphosphate (ATP) plays an important role in the...
journal_title:Cell proliferation
pub_type: 杂志文章
doi:10.1111/cpr.12737
更新日期:2020-02-01 00:00:00
abstract:OBJECTIVES:To evaluate the rapid repair potential of adipose-derived stem cells (ADSCs) co-overexpressing VEGF and GDNF on bilateral cavernous nerve injury (BCNI) in rat models. Progressive fibrosis of the penis that occurs shortly after BCNI is a key cause of clinical treatment difficulty of erectile dysfunction (ED)....
journal_title:Cell proliferation
pub_type: 杂志文章
doi:10.1111/cpr.12756
更新日期:2020-02-01 00:00:00
abstract:OBJECTIVES:Based on in vivo studies, low-intensity pulsed ultrasound (LIPUS) stimulation has been widely used in the clinic for advancing bone growth during healing of non-union alignment, fractures and other osseous defects. In this study, we have investigated osteogenic differentiation of adipose stem cells (ASCs) re...
journal_title:Cell proliferation
pub_type: 杂志文章
doi:10.1111/cpr.12035
更新日期:2013-06-01 00:00:00
abstract::The CD133 glycoprotein is a controversial cancer stem cell marker in the field of neuro-oncology, based largely on the now considerable experimental evidence for the existence of both CD133+ve and CD133-ve populations as tumour-initiating cells. It is thought that decreasing oxygen tension enhances the complex regulat...
journal_title:Cell proliferation
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2184.2012.00842.x
更新日期:2012-12-01 00:00:00
abstract:OBJECTIVES:We previously reported that Golgi phosphoprotein 3 (GOLPH3) promotes glioma progression by inhibiting EGFR endocytosis and degradation, leading to EGFR accumulation and PI3K-AKT pathway over-activation. In the current study, we examine whether GOLPH3 affects the response of glioma cells to gefitinib, an EGFR...
journal_title:Cell proliferation
pub_type: 杂志文章
doi:10.1111/cpr.12636
更新日期:2019-07-01 00:00:00
abstract::Studies on growth regulation in vitro to a large extent rely on comparison of growth curves. However, these do not discriminate between the relative contributions of the mitotic rate and the apoptotic rate to the net growth rate. In the present study, differential effects of 17beta-oestradiol (E2, 10(-8) M) and/or tam...
journal_title:Cell proliferation
pub_type: 杂志文章
doi:10.1046/j.1365-2184.1999.3250289.x
更新日期:1999-10-01 00:00:00
abstract:OBJECTIVES:miR-21 can promote osteoblast differentiation of periodontal ligament stem cells. However, the effect of miR-21 on bone remodelling in the midpalatal suture is unclear. This study aimed to elucidate the effects of miR-21 on the midpalatal suture bone remodelling by expanding the palatal sutures. MATERIALS A...
journal_title:Cell proliferation
pub_type: 杂志文章
doi:10.1111/cpr.12697
更新日期:2020-01-01 00:00:00
abstract:OBJECTIVES:In peripheral neuropathy, the underlying mechanisms of nerve and muscle degeneration include chronic inflammation and oxidative stress in fibrotic tissues. (-)-Epigallocatechin gallate (EGCG) is a major, active component in green tea and may scavenge free radical oxygen and attenuate inflammation. Conservati...
journal_title:Cell proliferation
pub_type: 杂志文章
doi:10.1111/cpr.12730
更新日期:2020-01-01 00:00:00
abstract:OBJECTIVES:Creation of functional, durable vasculature remains an important goal within the field of regenerative medicine. Engineered biological vasculature has the potential to restore or improve human tissue function. We hypothesized that the pleotropic effects of insulin-like growth factor 1 (IGF1) would enhance th...
journal_title:Cell proliferation
pub_type: 杂志文章
doi:10.1111/cpr.12387
更新日期:2018-02-01 00:00:00
abstract:OBJECTIVES:Glucagon-like peptide 2 (GLP2) is involved in the regulation of energy absorption and metabolism. Despite the importance of the GLP2 signalling mechanisms on osteoclast, little has been studied on how GLP2 works during osteoclastogenesis. MATERIALS AND METHODS:RAW264.7 cells were infected with rLV-Green-GLP...
journal_title:Cell proliferation
pub_type: 杂志文章
doi:10.1111/cpr.12443
更新日期:2018-08-01 00:00:00
abstract::Atherosclerosis is an inflammatory-fibroproliferative response of the arterial wall involving a complex set of interconnected events where cell proliferation (lymphomonocytes, and endothelial and smooth-muscle cells) and substantial perturbations of intracellular cholesterol metabolism are considered to be among the m...
journal_title:Cell proliferation
pub_type: 杂志文章
doi:10.1046/j.1365-2184.2002.00231.x
更新日期:2002-06-01 00:00:00
abstract::We have developed a mathematical model based on proliferation and infiltration of neoplastic cells that allows predictions to be made concerning the life expectancies following various extents of surgical resection of gliomas of all grades of malignancy. The key model parameters are the growth rate and the diffusion r...
journal_title:Cell proliferation
pub_type: 杂志文章
doi:10.1111/j.1365-2184.1996.tb01580.x
更新日期:1996-06-01 00:00:00
abstract:OBJECTIVES:Nonylphenol (NP) is present ubiquitously in both aquatic and terrestrial environments. This compound is considered an important endocrine disruptor and its toxic/oestrogenic activity has been investigated in a number of in vitro and in vivo studies. Human exposure to NP may occur by cutaneous absorption, ing...
journal_title:Cell proliferation
pub_type: 杂志文章
doi:10.1111/j.1365-2184.2011.00774.x
更新日期:2011-10-01 00:00:00
abstract::The R- cell line is a 3T3-like cell line originating from mouse embryos with a homozygous disruption of the type 1 insulin-like growth factor receptor (IGF-IR) genes. Although R- cells cannot grow at all in serum-free medium (SFM) supplemented by several known growth factors, either singly or in combination, they are ...
journal_title:Cell proliferation
pub_type: 杂志文章
doi:
更新日期:1997-06-01 00:00:00
abstract:OBJECTIVE:To determine the inhibitory effect and mechanism of Notch signalling on adipogenesis of mouse adipose-derived stem cells (mASCs). MATERIALS AND METHODS:Varied concentrations of N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butylester (DAPT) were added to mASCs 3 days before adipogenic induction w...
journal_title:Cell proliferation
pub_type: 杂志文章
doi:10.1111/j.1365-2184.2009.00661.x
更新日期:2010-04-01 00:00:00
abstract:OBJECTIVE:Five-year survival rate at early lung tumour was about 70%; however, its early diagnosis rate was still at a low level, so the enhancement of diagnosis level for early lung tumour is the key factor to increase the survival rate. Diagnosis and therapy of early lung tumour are still challenged. METHODS:The mag...
journal_title:Cell proliferation
pub_type: 杂志文章
doi:10.1111/cpr.12486
更新日期:2018-12-01 00:00:00
abstract:OBJECTIVES:The present study aimed to investigate overall effect of quercetin on proliferation and osteogenic differentiation of mouse adipose stem cells (mASCs) in vitro. MATERIALS AND METHODS:Mouse adipose stem cells were isolated from subcutaneous fat pads and induced into the osteogenic lineage. Effects of quercet...
journal_title:Cell proliferation
pub_type: 杂志文章
doi:10.1111/cpr.12097
更新日期:2014-04-01 00:00:00
abstract::A number of techniques, including autoradiography after in vivo administration of tritiated thymidine ([3H]dT), immunohistochemistry after in vivo administration of bromodeoxyuridine (BrdUrd), and flow cytometry (FCM) with and without BrdUrd detection were compared in the epithelium of ventral mouse tongue. Investigat...
journal_title:Cell proliferation
pub_type: 杂志文章
doi:10.1111/j.1365-2184.1994.tb01429.x
更新日期:1994-06-01 00:00:00
abstract::On 31 May 2010, 14 072 567 bone marrow/apheresis donors registered in 44 countries and 426 501 cord blood units banked in 26 countries for public use were available to treat candidates to haemopoietic stem cell transplant lacking a family related compatible donor. Despite these impressive numbers, additional efforts a...
journal_title:Cell proliferation
pub_type: 杂志文章
doi:10.1111/j.1365-2184.2010.00720.x
更新日期:2011-04-01 00:00:00
abstract:OBJECTIVES:Oestrogen is known to inhibit osteoclastogenesis, and numerous studies have identified it as an autophagic activator. To date, the role of oestrogen in the autophagy of osteoclast precursors (OCPs) during osteoclastogenesis remains unclear. This study aimed to determine the effect of autophagy regulated by t...
journal_title:Cell proliferation
pub_type: 杂志文章
doi:10.1111/cpr.12789
更新日期:2020-04-01 00:00:00
abstract::Extracellular vesicles (EVs), a heterogeneous group of vesicles differing in size and shape, cargo content and function, are membrane-bound and nano-sized vesicles that could be released by nearly all variations of cells. EVs have gained considerable attention in the past decades for their functions in modulating inte...
journal_title:Cell proliferation
pub_type: 杂志文章,评审
doi:10.1111/cpr.12659
更新日期:2019-11-01 00:00:00
abstract:OBJECTIVE:Accumulating data show that dysregulation of long noncoding RNAs (lncRNAs) acts a critical role in a variety of malignancies. Among these lncRNAs, small nucleolar RNA host genes (SNHGs) are associated with tumour growth and progression. But, the molecular mechanisms by which SNHG4 contributes to osteosarcoma ...
journal_title:Cell proliferation
pub_type: 杂志文章
doi:10.1111/cpr.12515
更新日期:2018-12-01 00:00:00
abstract::This study examines epithelial cell streaming and turnover in normal rat bulbar conjunctiva. Twenty seven male adult random-bred Hebrew rats weighing between 250-300 g, were injected i.p. with [3H]-thymidine. Three rats were killed at various times, thereafter from 1 h to 28 days. The enucleated eyes were fixed in for...
journal_title:Cell proliferation
pub_type: 杂志文章
doi:10.1111/j.1365-2184.1995.tb00066.x
更新日期:1995-04-01 00:00:00
abstract::Intra-erythrocytic Plasmodium species can be stained with the DNA binding dye, Hoechst 33342, and the distribution of DNA content determined for parasite populations by flow cytometric measurement of fluorescence. Analysis of this distribution will determine the parasitaemia (percentage of erythrocytes infected), and ...
journal_title:Cell proliferation
pub_type: 杂志文章
doi:10.1111/j.1365-2184.1992.tb01452.x
更新日期:1992-09-01 00:00:00
abstract:OBJECTIVES:Small aromatic compounds like flavonoids can intercalate with DNA molecules bringing about conformational changes leading to reduced replication and transcription. Here, we have examined one dietary flavonoid, quercetin (found in many fruit and vegetables), for possible anti-cancer effects, on HeLa cells ori...
journal_title:Cell proliferation
pub_type: 杂志文章
doi:10.1111/cpr.12017
更新日期:2013-04-01 00:00:00
abstract::Nerous system diseases, both central and peripheral, bring an incredible burden onto patients and enormously reduce their quality of life. Currently, there are still no effective treatments to repair nerve lesions that do not have side effects. Stem cell-based therapies, especially those using dental stem cells, bring...
journal_title:Cell proliferation
pub_type: 杂志文章,评审
doi:10.1111/cpr.12572
更新日期:2019-05-01 00:00:00
abstract::RAIDD (RIP-associated ICH-1 homologous protein with a death domain) is an adaptor molecule that mediates the action of cysteine proteases involved in apoptosis. To study the possibility of a novel system of cell ablation mediated by RAIDD, a preadipocyte cell line (3T3L1) was stably transfected with a plasmid containi...
journal_title:Cell proliferation
pub_type: 杂志文章
doi:10.1046/j.1365-2184.2003.00253.x
更新日期:2003-02-01 00:00:00
abstract:OBJECTIVES:Accumulating evidence demonstrated that the long noncoding RNA (lncRNA) HOTAIR (Hox transcript antisense intergenic RNA) plays key role in renal cell carcinoma (RCC) malignancy, while microRNA-124 (miR-124) is a tumour suppressor in RCC. The aim of this work was to assess the biological function of HOTAIR an...
journal_title:Cell proliferation
pub_type: 杂志文章
doi:10.1111/cpr.12507
更新日期:2018-12-01 00:00:00
abstract:OBJECTIVES:Mesenchymal stem cells (MSCs) are frequently used for bone regeneration, however, they are limited in quantity. Moreover, their proliferation and differentiation capabilities reduce during cell culture expansion. Potential application of induced pluripotent stem cells (iPSCs) has been reported as a promising...
journal_title:Cell proliferation
pub_type: 杂志文章,评审
doi:10.1111/cpr.12321
更新日期:2017-04-01 00:00:00