PubChem (http://pubchem.ncbi.nlm.nih.gov) is a public repository for biological activity data of small molecules and RNAi reagents. The mission of PubChem is to deliver free and easy access to all deposited data, and to provide intuitive data analysis tools. The PubChem BioAssay database currently contains 500 000 descriptions of assay protocols, covering 5000 protein targets, 30 000 gene targets and providing over 130 million bioactivity outcomes. PubChem's bioassay data are integrated into the NCBI Entrez information retrieval system, thus making PubChem data searchable and accessible by Entrez queries. Also, as a repository, PubChem constantly optimizes and develops its deposition system answering many demands of both high- and low-volume depositors. The PubChem information platform allows users to search, review and download bioassay description and data. The PubChem platform also enables researchers to collect, compare and analyze biological test results through web-based and programmatic tools. In this work, we provide an update for the PubChem BioAssay resource, including information content growth, data model extension and new developments of data submission, retrieval, analysis and download tools.

Structure-based virtual screening (SBVS) has been widely applied in early-stage drug discovery. From a problem-centric perspective, we reviewed the recent advances and applications in SBVS with a special focus on docking-based virtual screening. We emphasized the researchers’ practical efforts in real projects by understanding the ligand-target binding interactions as a premise. We also highlighted the recent progress in developing target-biased scoring functions by optimizing current generic scoring functions toward certain target classes, as well as in developing novel ones by means of machine learning techniques.

Word count for text: 2779; abstract: 145, figure 7; reference count: 30 2 Key points• Functional mitochondria are transferred in-vivo from BMSC to the leukemic blast.• AML derived NOX-2 drives transfer of mitochondria via the generation of superoxide. AbstractImprovements in the understanding of the metabolic cross-talk between cancer and its micro-environment is expected to lead to novel therapeutic approaches. Acute myeloid leukemia (AML) cells have increased mitochondria compared to nonmalignant CD34+ hematopoietic progenitor cells. Furthermore, contrary to the Warburg hypothesis, (AML) relies on oxidative phosphorylation to generate ATP.Here we report that in human AML NOX2 generates superoxide, which stimulates bone marrow stromal cells (BMSC) to AML blast transfer of mitochondria through AML derived tunnelling nanotubes. Moreover, inhibition of NOX2 was able to prevent mitochondrial transfer, dramatically increase AML apoptosis and increase NSG mouse survival. Conversely, mitochondrial transfer could only be stimulated from BMSC to non-malignant CD34+ cells in response to oxidative stress. However, NOX2 inhibition had no detectable effect on non-malignant CD34+ cell survival.Taken together we identify tumor-specific dependence on NOX2 driven mitochondrial transfer as a novel therapeutic strategy in AML. 3Acute myeloid leukemia (AML) is an aggressive disease that originates in the bone marrow from malignant transformation of a myeloid progenitor cell. AML can occur at any age but primarily affects the elderly, with the average age at diagnosis of 72 years and three quarters of patients diagnosed after the age of sixty 1 . Despite existing cytotoxic treatments directly targeting the leukemic cell two-thirds of younger adults and 90% of older adults will die of their disease 2 . Moreover, current aggressive chemotherapy regimens are often poorly tolerated by the older less fit patients. Improved outcomes are expected to be achieved through novel therapies which are developed from an improved understanding of the biology of the disease.AML blasts cultured in vitro undergo high levels of apoptosis, however the tumor rapidly proliferates in vivo demonstrating that the tissue microenvironment plays a fundamental role in the development of AML disease 3,4 . . It is also established that AML cells have higher mitochondria levels compared to non-malignant haematopoietic stem cells 10,11 , which is entirely consistent with the observations that the tumor is dependent on a mitochondrial ATP production pathway. This proposes a key question; are the additional mitochondria in the AML blasts generated within the tumor cell or have they been acquired?For a long time mitochondria were thought to be retained in their somatic cell for their Monitoring Primer Set and the rLV.EF1.mCherry-mito-9 Lentivirus were purchased from Clontech Takara Bio Europe (Saint-Germain-en-Laye, France). Murine mitochondrial to nuclear DNA ratio kit was purchased from Detroit R&D (Detroit, MI, USA). All other reagents were obtained from Sigma-Aldr...