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BACKGROUND Hepatocellular carcinoma (HCC) occurs frequently in China, with high morbidity and mortality. Cell division cycle 20 homolog (CDC20) is reportedly related to many cancers. In this study, we discuss a potential link of CDC20 expression to HCC patients' prognoses. MATERIAL AND METHODS Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to assess CDC20 expression in HCC and the paired noncancerous tissues. Chi-square analysis was used to assess potential association of CDC20 expression with clinicopathologic profiles among HCC patients. The overall survival for HCC patients with different CDC20 expressions was assessed using the Kaplan-Meier method. To evaluate the prognostic value for HCC patients, Cox regression analyses were performed. RESULTS The expression of CDC20 was elevated among HCC specimens compared with adjacent noncancerous ones (P

We have reached 25 years since the first molecular approaches to plant cell cycle. Fortunately, we have witnessed an enormous advance in this field that has benefited from using complementary approaches including molecular, cellular, genetic and genomic resources. These studies have also branched and demonstrated the functional relevance of cell cycle regulators for virtually every aspect of plant life. The question is - where are we heading? I review here the latest developments in the field and briefly elaborate on how new technological advances should contribute to novel approaches that will benefit the plant cell cycle field. Understanding how the cell division cycle is integrated at the organismal level is perhaps one of the major challenges.

Polyphenols are a widely used class of compounds in dermatology. While phenol itself, the most basic member of the phenol family, is chemically synthesized, most polyphenolic compounds are found in plants and form part of their defense mechanism against decomposition. Polyphenolic compounds, which include phenolic acids, flavonoids, stilbenes, and lignans, play an integral role in preventing the attack on plants by bacteria and fungi, as well as serving as cross-links in plant polymers. There is also mounting evidence that polyphenolic compounds play an important role in human health as well. One of the most important benefits, which puts them in the spotlight of current studies, is their antitumor profile. Some of these polyphenolic compounds have already presented promising results in either in vitro or in vivo studies for non-melanoma skin cancer and melanoma. These compounds act on several biomolecular pathways including cell division cycle arrest, autophagy, and apoptosis. Indeed, such natural compounds may be of potential for both preventive and therapeutic fields of cancer. This review evaluates the existing scientific literature in order to provide support for new research opportunities using polyphenolic compounds in oncodermatology.

Peptide motifs embedded within intrinsically disordered regions (IDRs) of proteins are often the sites of posttranslational modifications that control cell-signaling pathways. How do IDR sequences modulate the functionalities of motifs? We answer this question using the polyampholytic C-terminal IDR of the cell cycle inhibitory protein p27(Kip1) (p27). Phosphorylation of Thr-187 (T187) within the p27 IDR controls entry into S phase of the cell division cycle. Additionally, the conformational properties of polyampholytic sequences are predicted to be influenced by the linear patterning of oppositely charged residues. Therefore, we designed sequence variants of the p27 IDR to alter charge patterning outside the primary substrate motif containing T187. Computer simulations and biophysical measurements confirm predictions regarding the impact of charge patterning on the global dimensions of IDRs. Through functional studies, we uncover cryptic sequence features within the p27 IDR that influence the efficiency of T187 phosphorylation. Specifically, we find a positive correlation between T187 phosphorylation efficiency and the weighted net charge per residue of an auxiliary motif. We also find that accumulation of positive charges within the auxiliary motif can diminish the efficiency of T187 phosphorylation because this increases the likelihood of long-range intra-IDR interactions that involve both the primary and auxiliary motifs and inhibit their contributions to function. Importantly, our findings suggest that the cryptic sequence features of the WT p27 IDR negatively regulate T187 phosphorylation signaling. Our approaches provide a generalizable strategy for uncovering the influence of sequence contexts on the functionalities of primary motifs in other IDRs.

Cell division cycle 25 (CDC25) phosphatases, a kind of cell cycle regulators, have become an attractive target for drug discovery, as they have been found to be over-expressed in various human cancer cells. Several CDC25 inhibitors have achieved significant attention in clinical trials with possible mechanistic actions. Prompted by the significance of CDC25 inhibitors with medicinal chemistry prospect, it is an apt time to review the various drug discovery methods involved in CDC25 drug discovery including high throughput screening (HTS), virtual screening (VS), fragment-based drug design, substitution decorating approach, structural simplification approach and scaffold hopping method to seek trends and identify promising new avenues of CDC25 drug discovery.

The increasing Yezo sika deer (Cervus nippon yesoensis) population is creating a large problem. Yezo sika deer are an important blood meal source, and these deer contribute to the maintenance of tick populations. Theileria spp. infections in Yezo sika deer and T. orientalis infections in cows occur at high frequencies, and the same tick species infests both deer and cows. Therefore, a specific detection method to identify deer Theileria spp. is important. In this study, we establish a novel molecular detection method for identifying Theileria spp. from deer and tick samples using loop-mediated isothermal amplification (LAMP). This method targets a metalloprotease/cell division cycle protein gene homologue. Our LAMP protocol was able to detect deer Theileria and did not show cross reactivity with other closely related protozoan parasites, including T. orientalis. The LAMP method showed sensitivity and specificity equivalent to those of nested PCR performed on the same field samples from deer and ticks. These results demonstrate the applicability of LAMP to field surveys in which the detection of deer Theileria spp. is required. In conclusion, due to its simplicity, specificity, and reliability, we suggest our LAMP protocol as an appropriate method for routine surveys to detect Yezo sika deer and ticks infected with deer Theileria spp. parasites. Additionally, this LAMP method offers great promise as a useful tool to distinguish Yezo sika deer Theileria from related Theileria parasites present in livestock.

Regulation of plant root angle is critical for obtaining nutrients and water and is an important trait for plant breeding. A plant’s final, long-term root angle is the net result of a complex series of decisions made by a root tip in response to changes in nutrient availability, impediments, the gravity vector and other stimuli. When a root tip is displaced from the gravity vector, the short-term process of gravitropism results in rapid reorientation of the root toward the vertical. Here, we explore both short- and long-term regulation of root growth angle, using natural variation in tomato to identify shared and separate genetic features of the two responses. Mapping of expression quantitative trait loci mapping and leveraging natural variation between and within species including Arabidopsis suggest a role for PURPLE ACID PHOSPHATASE 27 and CELL DIVISION CYCLE 73 in determining root angle.

Background Cell division cycle associated 7 like (CDCA7L) belongs to the JPO protein family, which is recently identified as a target gene of c-Myc and is frequently dysregulated in multiple cancers. This study aimed to explore the clinicpathological value and biological role of CDCA7L in glioma. Methods CDCA7L expression in glioma patients was determined using the Oncomine database, and the prognostic role of CDCA7L expression was assessed in a retrospective cohort study. Moreover, the relationship of CDCA7L expression with the clinicopathological characteristics in glioma patients, including age, gender, tumor size, cystic change, Karnofsky performance scale (KPS) score, tumor location, extent of resection, WHO grade, adjuvant therapy and tumor recurrence, was analyzed in this study. In addition, the CDCA7L small interfering (si) RNA was constructed and transfected into the glioma U251 cells, so as to examine the role of CDCA7L in glioma patients. Besides, the changes in U251 cell invasion after transfection with CDCA7L siRNA were also monitored through Transwell assay. Results Our results suggested that CDCA7L expression was up-regulated in different glioma types, including glioblastoma, oligodendroglioma, diffuse astrocytoma and anaplastic astrocytoma. Moreover, the current retrospective cohort study indicated that high CDCA7L expression was associated with tumor size, WHO grade, adjuvant therapy and recurrence, as well as the poor overall survival (OS) and recurrence-free survival (RFS) in glioma patients. Lastly, CDCA7L expression was knocked down using CDCA7L siRNA, which could block the invasion abilities of glioma U251 cells. Conclusions CDCA7L is highly expressed in human glioma tissues and a high CDCA7L expression level predicts the dismal prognosis for glioma patients. Moreover, CDCA7L can promote glioma invasion, which can serve as an independent potential prognostic biomarker for glioma patients.

Understanding how cellular functions emerge from the underlying molecular mechanisms is a key challenge in biology. This will require computational models, whose predictive power is expected to increase with coverage and precision of formulation. Genome-scale models revolutionised the metabolic field and made the first whole-cell model possible. However, the lack of genome-scale models of signalling networks blocks the development of eukaryotic whole-cell models. Here, we present a comprehensive mechanistic model of the molecular network that controls the cell division cycle in Saccharomyces cerevisiae. We use rxncon, the reaction-contingency language, to neutralise the scalability issues preventing formulation, visualisation and simulation of signalling networks at the genome-scale. We use parameter-free modelling to validate the network and to predict genotype-to-phenotype relationships down to residue resolution. This mechanistic genome-scale model offers a new perspective on eukaryotic cell cycle control, and opens up for similar models—and eventually whole-cell models—of human cells., Whole-cell models hold great promise for fundamental and translational biology, but genome-scale modelling of signalling networks has been a challenge. Here, the authors present a genome-scale, mechanistic and executable model of the network controlling and executing the S. cerevisiae cell cycle.

Chromoblastomycosis is found worldwide with higher incidence in tropical and subtropical regions. Fonsecaea spp. is one of the major causative agents of this disease. First case of chromoblastomycosis due to Fonsecaea nubica in Northern China is reported in a 75-year-old Chinese male. We firstly summarized molecular identification methods of Fonsecaea spp. and all the strains of F. nubica reported in the literature. Sequencing of internal transcribed spacer alone and/or combined with actin (ACT1), partial cell division cycle (CDC42) and partial beta-tubulin (BT2) were most commonly used to identify species, while lactase (Lac), homogentisate (HmgA) and polyketide synthase (PKS1) were also used in some cases. Most strains were isolated from South America and Eastern China. Five clinical cases of chromoblastomycosis due to F. nubica from Asia and Europe were also reviewed. All the five patients were male, over 30 years old, and their lesions occurred after trauma.

Purpose The postmortem interval (PMI) is the amount of time that has elapsed since the time of death. Over the years, many approaches have been developed to assess PMI, but their time frame of applicability has been only days to weeks. Our present pilot study aimed to find the sensitive mRNA marker if the degradation of mRNA could be used to estimate the early postmortem interval (up to 24 h). Methods In our study, we use the microarray to screen 217 mRNAs markers of rat cardiac tissue. Then, real-time fluorescent quantitative PCR (qPCR) was used to validate of the candidate markers at 7 time points within 24 h and at temperatures of 25 °C and 35 °C. Another 27 rats were then used to verify the model. Results Among all of the candidate markers, △Cq (cell division cycle 25 homolog B(Cdc25b)) had the best correlation coefficient with early postmortem interval and was used to build a new model using the R software. The results of verification testing demonstrated that the error rate was less than 15%, demonstrating the high predictive power of our mathematical model. Conclusion In this study, Cdc25b was found to be the sensitive marker to estimate early postmortem interval, and Rpl27 was found to be suitable for use as the endogenous control. Our work provided new leads for molecular approaches to early postmortem interval estimation using the significant mRNA markers established here.

Heat shock protein 90 (Hsp90) is a critical molecular chaperone protein that regulates the folding, maturation, and stability of a wide variety of proteins. In recent years, the development of Hsp90-directed inhibitors has grown rapidly, and many of these inhibitors have entered clinical trials. In parallel, the functional dissection of the Hsp90 chaperone machinery has highlighted the activity disruption of Hsp90 co-chaperone as a potential target. With the roles of Hsp90 co-chaperones being elucidated, cell division cycle 37 (Cdc37), a ubiquitous co-chaperone of Hsp90 that directs the selective client proteins into the Hsp90 chaperone cycle, shows great promise. Moreover, the Hsp90-Cdc37-client interaction contributes to the regulation of cellular response and cellular growth and is more essential to tumor tissues than normal tissues. Herein, we discuss the current understanding of the clients of Hsp90-Cdc37, the interaction of Hsp90-Cdc37-client protein, and the therapeutic possibilities of targeting Hsp90-Cdc37-client protein interaction as a strategy to inhibit Hsp90 chaperone machinery to present new insights on alternative ways of inhibiting Hsp90 chaperone machinery. Electronic supplementary material The online version of this article (10.1186/s13045-018-0602-8) contains supplementary material, which is available to authorized users.

Despite decades of research, it remains unclear how mammalian cell growth varies with cell size and across the cell division cycle to maintain size control. Answers to this question have been limited by the difficulty of directly measuring growth at the single cell level. Here, using a variety of cultured mammalian cell lines, we report direct measurement of single cell volumes over a complete cell division cycle. We show that the volume added across the cell cycle is independent of cell birth size, a size homeostasis behavior called “adder”. We propose a mathematical framework that can be used to characterize the full spectrum of size homeostasis mechanisms from bacteria to mammalian cells. This reveals that a near-adder is the most common type of size regulation, but shows that it can arise from various types of coupling between cell size, cell growth rate and cell cycle progression.

Since the early 1970's, investigators at Station Biologique de Roscoff (SBR), France, have been using marine organisms as models to describe molecular pathways conserved through evolution in mammalian cells (e.g. the cyclin-dependent kinases involved in the control of the cell division cycle). Some kinases are misregulated in various human pathologies, including cancers. Using a specialized screening approach, chemical libraries were analysed, using on-site facilities at Roscoff, in order to identify small chemical inhibitors of protein kinases. Eight chemical scaffolds produced by marine organisms were characterized as candidate drugs by our screening facility, some of which are being considered as chemical tools to pinpoint specific cellular functions of the targeted kinases. In this review, we describe our existing screening facilities and we discuss new perspectives related to marine bioprospecting.

Social stress has a high impact on many biological systems in the brain, including serotonergic (5-HT) system—a major drug target in the current treatment for depression. Hyperactivity of hypothalamic-pituitary-adrenal (HPA) axis and monoamine oxidase A (MAO-A) are well-known stress responses, which are involved in the central 5-HT system. Although, many MAO-A inhibitors have been developed and used in the therapeutics of depression, effective management of depression by modulating the activity of MAO-A has not been achieved. Identifying the molecular pathways that regulate the activity of MAO-A in the brain is crucial for developing new drug targets for precise control of MAO-A activity. Over the last few decades, several regulatory pathways of MAO-A consisting of Kruppel like factor 11 (KLF11), Sirtuin1, Ring finger protein in neural stem cells (RINES), and Cell division cycle associated 7-like protein (R1) have been identified, and the influence of social stress on these regulatory factors evaluated. This review explores various aspects of these pathways to expand our understanding of the roles of the HPA axis and MAO-A regulatory pathways during social stress. The first part of this review introduces some components of the HPA axis, explains how stress affects them and how they interact with the 5-HT system in the brain. The second part summarizes the novel regulatory pathways of MAO-A, which have high potential as novel therapeutic targets for depression.

Despite decades of research, how mammalian cell size is controlled remains unclear because of the difficulty of directly measuring growth at the single-cell level. Here we report direct measurements of single-cell volumes over entire cell cycles on various mammalian cell lines and primary human cells. We find that, in a majority of cell types, the volume added across the cell cycle shows little or no correlation to cell birth size, a homeostatic behavior called “adder”. This behavior involves modulation of G1 or S-G2 duration and modulation of growth rate. The precise combination of these mechanisms depends on the cell type and the growth condition. We have developed a mathematical framework to compare size homeostasis in datasets ranging from bacteria to mammalian cells. This reveals that a near-adder behavior is the most common type of size control and highlights the importance of growth rate modulation to size control in mammalian cells., The size of cells fluctuates but there are limited experimental methods to measure live mammalian cell sizes. Here, the authors track single cell volume (FXm) over the cell cycle and generate a mathematical framework to compare size homeostasis in datasets ranging from bacteria to mammalian cells.

// Li-Li Ma 1, 2, 3, * , Lan Shen 1, 2, * , Gui-Hui Tong 1, 2, * , Na Tang 4, * , Yang Luo 5, * , Li-Li Guo 1, 2 , Chun-Ting Hu 6 , Ying-Xin Huang 1, 2 , Guan Huang 1, 2, 7 , Fang-Yan Jing 8 , Chao Liu 9 , Zhuo-Yi Li 3 , Na Zhou 1, 2 , Qian-Wen Yan 1, 2 , Yan Lei 1, 2 , Shi-Jie Zhu 1, 2 , Zhi-Qiang Cheng 4 , Guang-Wen Cao 10 , Yong-Jian Deng 1, 2 and Yan-Qing Ding 1, 2 1 Department of Pathology, Nanfang Hospital and School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China 2 Guangdong Provincial Key Laboratory of Molecular Tumor Pathology, Guangzhou 510515, China 3 Department of Cardiothoracic Surgery, Taishan City People’s Hospital, Taishan 529200, China 4 Department of Pathology, Shenzhen People’s Hospital, Second Clinical Medical College of Jinan University, Shenzhen 518020, China 5 Department of Urinary Surgery, Nanfang Hospital and the Fifth Affiliated Hospital of Southern Medical University, Guangzhou 510900, China 6 Pathology Center, Shanghai General Hospital Faculty of Basic Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China 7 Department of Pathology, Longgang District Central Hospital of Shenzhen, Shenzhen 518116, China 8 Department of Anorectal Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China 9 Department of Pathology and Laboratory Medicine, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou 510080, China 10 Department of Epidemiology, Second Military Medical University, Shanghai 200433, China * These authors have contributed equally to this work Correspondence to: Yong-Jian Deng, email: dengyj@smu.edu.cn Yan-Qing Ding, email: dyq@smu.edu.cn Keywords: colorectal cancer, migration directionality, prohibitin, vascular endothelial growth factor, cell division cycle 42 Received: April 07, 2017 Accepted: June 20, 2017 Published: July 19, 2017 ABSTRACT Directional migration is a cost-effective movement allowing invasion and metastatic spread of cancer cells. Although migration related to cytoskeletal assembly and microenvironmental chemotaxis has been elucidated, little is known about interaction between extracellular and intracellular molecules for controlling the migrational directionality. A polarized expression of prohibitin (PHB) in the front ends of CRC cells favors metastasis and is correlated with poor prognosis for 545 CRC patients. A high level of vascular endothelial growth factor (VEGF) in the interstitial tissue of CRC patients is associated with metastasis. VEGF bound to its receptor, neuropilin-1, can stimulate the activation of cell division cycle 42, which recruits intra-mitochondrial PHB to the front end of a CRC cell. This intracellular relocation of PHB results in the polymerization and reorganization of filament actin extending to the front end of the cell. As a result, the migration directionality of CRC cells is targeted towards VEGF. Together, these findings identify PHB as a key modulator of directional migration of CRC cells and a target for metastasis.

Manned spaceflight continues to be in the agenda of most of the countries involved in space research. Development of human settlements in planets and sustainable space ecosystems where crops can be grown and waste recycled are the exciting aims of some of the future space missions. There is considerable concern on the health of the space travelers during long term travel and stay in these unexplored terrains. Astronauts may be exposed to ionizing radiations and weightlessness due to alterations in gravitational force. Studies on astronauts during and after space travel indicate effects on the immune system, cardiovascular system, bone density etc. It is not clearly known how the space missions may influence DNA replication, transcription, and translation and cell division cycle in humans. Information on these will be vital. Experiments on humans and animals could be cumbersome in space. As such use of eukaryotic models like Saccharomyces cerevisiae could be rewarding. The yeast S. cerevisiae is considered as an excellent model for studying eukaryotic biology and has contributed significantly to our understanding of cancer biology and fundamental metabolic processes in humans. In this review, the potential of S. cerevisiae as a model for space biology has been discussed.

Mean cell size at division is generally constant for specific conditions and cell types, but the mechanisms coupling cell growth and cell cycle control with cell size regulation are poorly understood in intact tissues. Here we show that the continuously dividing fields of cells within the shoot apical meristem of Arabidopsis show dynamic regulation of mean cell size dependent on developmental stage, genotype and environmental signals. We show cell size at division and cell cycle length is effectively predicted using a two-stage cell cycle model linking cell growth and two sequential cyclin dependent kinase (CDK) activities, and experimental results concur in showing that progression through both G1/S and G2/M is size dependent. This work shows that cell-autonomous co-ordination of cell growth and cell division previously observed in unicellular organisms also exists in intact plant tissues, and that cell size may be an emergent rather than directly determined property of cells., The mechanistic coupling of cell growth and cell cycle control with cell size regulation in tissues is not well understood. Here, the authors show that within the shoot apical meristem of Arabidopsis cell size depends on developmental stage, genotype and environmental signals; however cell growth and cell division are cell-autonomously coordinated.

This chapter briefly reviews the cell division cycle in Mycobacterium tuberculosis . The symmetrical binary fission and unusual type of growth (ie, asymmetrical, budding, and multibranching types of cell divisions) is discussed and presented using atomic and electron micrographs.

Cell cycle control in galls provoked by root-knot nematodes involves the activity of inhibitor genes like the Arabidopsis ICK/KRP members. Ectopic KRP1, KRP2 and KRP4 expression resulted in decreased gall size by inhibiting mitotic activity, whereas KRP6 induces mitosis in galls. Herein, we investigate the role of KRP3, KRP5 and KRP7 during gall development and compared their role with previously studied members of this class of cell cycle inhibitors. Overexpression of KRP3 and KRP7 culminated in undersized giant cells, with KRP3(OE) galls presenting peculiar elongated giant cells. Nuclei in KRP3(OE) and KRP5(OE) lines presented a convoluted and apparently connected phenotype. This appearancemay be associated with the punctuated protein nuclear localization driven by specific common motifs. As well, ectopic expression of KRP3(OE) and KRP5(OE) affected nematode development and offspring. Decreased mitotic activity in galls of KRP3(OE) and KRP7(OE) lines led to a reduced gall size which presented distinct shapes-from more elongated like in the KRP3(OE) line to small rounded like in the KRP7(OE) line. Results presented strongly support the idea that induced expression of cell cycle inhibitors such as KRP3 and KRP7 in galls can be envisaged as a conceivable strategy for nematode feeding site control in crop species attacked by phytopathogenic nematodes.

International audience; Aurora kinases are key effectors of mitosis. Plant Auroras are functionally divided into two clades. The alpha Auroras (Aurora1 and Aurora2) associate with the spindle and the cell plate and are implicated in controlling formative divisions throughout plant development. The beta Aurora (Aurora3) localizes to centromeres and likely functions in chromosome separation. In contrast to the wealth of data available on the role of Aurora in other kingdoms, knowledge on their function in plants is merely emerging. This is exemplified by the fact that only histone H3 and the plant homolog of TPX2 have been identified as Aurora substrates in plants. Here we provide biochemical, genetic, and cell biological evidence that the microtubule-bundling protein MAP65-1-a member of the MAP65/Ase1/PRC1 protein family, implicated in central spindle formation and cytokinesis in animals, yeasts, and plants-is a genuine substrate of alpha Aurora kinases. MAP65-1 interacts with Aurora1 in vivo and is phosphorylated on two residues at its unfolded tail domain. Its overexpression and down-regulation antagonistically affect the alpha Aurora double mutant phenotypes. Phospho-mutant analysis shows that Aurora contributes to the microtubule bundling capacity of MAP65-1 in concert with other mitotic kinases.

Isolated ruminal epithelia from caudal blind sacs of dairy goats were incubated with butyrate and insulin-like growth factor-1 (IGF-1) at different concentrations. Proportions of ruminal epithelium in different phases of the cell division cycle were determined by flow cytometric analysis. The proportion of epithelial cells in S phase and G2-M phase (PS&G2-M) increased significantly (P

Introduction: Lung cancer is the leading cause of cancer-related mortality worldwide a survival rate of 14%. While platinum-based chemotherapy remains the most effective non-small cell lung cancer (NSCLC) treatment, less than 35% of patients have an objective partial response. Novel approaches are needed to best identify the patients who will derive the most benefit and prevent unnecessary treatment and toxicity. Herein we describe cell division cycle associated protein-3 (CDCA3) as a novel prognostic factor to delay or prevent platinum resistance in NSCLC.

Gram-negative rod-shaped bacteria have different approaches to position the cell division initiating Z-ring at the correct moment in their cell division cycle. The subsequent maturation into a functional division machine occurs in vastly different species in two steps with appreciable time in between these. The function of this time delay is unclear, but may partly be explained by competition for Lipid-II between proteins involved in length growth that interact directly with the Z-ring early in the maturation phase and the proteins involved in septum synthesis. A second possible activity of the early Z-ring might be the monitoring of or the active involvement in DNA segregation through proteins such as ZapA and ZapB/MatP and their homologues.

A series of pyrrolopyridinone derivatives as specific inhibitors towards the cell division cycle 7 (Cdc7) was taken into account, and the efficacy of these compounds was analyzed by QSAR and docking approaches to gain deeper insights into the interaction mechanism and ligands selectivity for Cdc7. By regression analysis the prediction models based on Grid score and Zou-GB/SA score were found, respectively with good quality of fits (r(2)=0.748, 0.951; r(cv)(2)=0.712, 0.839). The accuracy of the models was validated by test set and the deviation of the predicted values in validation set using Zou-GB/SA score was smaller than that using Grid score, suggesting that the model based on Zou-GB/SA score provides a more effective method for predicting potencies of Cdc7 inhibitors.

Several mitotic kinases and kinesins are currently considered as cancer targets based on their critical role during the cell division cycle and their significant level of expression in human tumors. Yet, their use is limited by the lack of selectivity against tumor cells, the low percentage of mitotic cells in many human tumors, and dose-limiting side-effects. As a consequence, initial clinical trials have shown limited responses. Despite these drawbacks, inhibiting mitosis is a promising strategy that deserves further development. Future advances will benefit from more specific inhibitors with better pharmacodynamic properties, a clear physiological characterization and cell-type-specific requirements of old and new mitotic targets, and rational strategies based on synthetic lethal interactions to improve selectivity against tumor cells.