- Screening of the small molecule library of Meinox enables the identification of anticancer compounds in pathologically distinct cancers. - Small molecule libraries accelerate the exploration of chemical leads that act as a starting point for novel therapeutics (Coussens et al., 2017. - Bayram et al., 2018;. - Demirel et al., 2018. - Beksac et al., 2020. - With this approach, biologically and physiologically relevant assays can be rapidly tested, with the complex chemical space of thousands of small molecules. - The discovery techniques for small molecules are commonly defined in phenotypic cell-based tests and biochemical target-based tests (Mohammadi et al., 2020).. - A commonly used paradigm for the treatment of various human malignancies is combination drug therapy (Boztas et al., 2013. - Bakhshaliyev et al., 2020). - Karpuz et al., 2018. - Kacı et al., 2020). - This can be explained in part by the interdependence of receptors that are important for the growth and survival of cancer (Gökbulut et al., 2015). - However, because of the intricate molecular machinery that underlies tumor growth and progression, recognition of multiple interdependencies is difficult (Kaymaz et al., 2015). - Further experiments are also required to eradicate these pathways of interdependence and drug resistance (Kara et al., 2021). - This also requires development of new small molecule library that is suitable for high-throughput testing ( Zaka et al., 2018. - Kanan et al., 2020).. - Meinox small molecule library includes over a thousand distinct and pharmacological molecules, and it is likely to be expanding to tens of thousands compounds soon with NCEs.. - Abstract: Small molecules are widely used for the modulation of the molecular basis of diseases. - In this work, we have established a library of small molecules in house and characterized its molecular and druglike properties. - We have shown that most small molecules have molecular weights less than 450. - In addition, Meinox’s small molecule library contained small molecules with polar surface areas that are less than 60 square angstroms, suggesting their potent ability to cross the blood- brain barrier. - Meinox’s small molecule library was also tested in vitro for pathologically distinct forms of cancer, including pancreatic adenocarcinoma PANC1, breast carcinoma MCF7, and lymphoblastic carcinoma RS4-11 cell lines. - This study shows that in vitro analysis of different cancers or other phenotypic assays with Meinox small molecule library may generate novel and potent bioassay-specific compounds.. - Key words: Screening, small molecules, Meinox small molecule library, cytotoxicity. - In this work, a novel library of small molecules has been developed and its molecular and druglike properties have been characterized. - Around a thousand small molecules from the Meinox repository were tested for their effect on cancer viability at a dosage of 1 μM for three different cancers. - This study suggests that in vitro screening with the small molecule library of Meinox may generate novel and effective compounds related to the bioassays or cancer used.. - Small molecule library preparations. - The Meinox small molecule library chemicals are dissolved dimethyl sulfoxide (DMSO) as 10 mM main stocks. - List of compounds is provided on the http://www.meinoxtech.com/meinox- small-molecule-library.html.. - Computational analysis of Meinox library of small molecules. - Meinox small molecule library includes over thousand druglike compounds in house, which is established with the support of medical chemists in Turkey, and antiparasitic/. - pandemic small molecule projects. - Small molecules were characterized for their general molecular and lead/. - Briefly MCF7 and PANC cells were seeded into 96-well plates/well the day before small molecule treatments. - A total of RS4-11 cells/well were passaged in the growth medium and treated with 1 μM of small molecules from Meinox library on the same day. - After four days of treatments, cancer viability was assessed by CellTiter (Promega) according to manufacturer’s protocol as we have done previously (Boztas et al., 2013. - Turan et al., 2020).. - Statistical analysis was carried out by comparing chosen hits to the entire library of small molecules using the Student’s t-test. - Analysis of molecular and lead/druglike properties of Meinox small molecule library. - We established a library of small molecules with the support of medical chemists and molecular biologist who provided small molecules that are biologically relevant and subject to further characterization for drug discovery and development. - First version of the Meinox small molecule library included 1000 small molecules. - We have found that majority of Meinox small molecule library demonstrated cLogP values smaller than 5.0, similar to pool of traded small molecule drugs in the market (Figure 2B). - Furthermore, druglikeness based on the assessment of fragment-based approach in Meinox small molecule library showed that about 70% of the compounds have a positive druglikeness value (i.e. - Meinox small molecule library allows identification of compounds specifically could block breast, pancreas and leukemia growth. - Meinox small molecule library compounds are maintained in DMSO as 10 mM stocks and diluted to 100X working. - Small Molecule Library. - Meinox small molecule library was tested and validated in pancreatic adenocarcinoma (PANC1), breast carcinoma (MCF7), and lymphoblastic leukemia (RS4-11) in 1 μM final concentrations for cancer viability.. - Analysis of cell viability posttreatment of PANC1 pancreatic adenocarcinoma cell line with the Meinox small molecule library.. - Meinox Small Molecule Library in PANC1 Pancreatic Adenocarcinoma. - Meinox Small Molecule IDs. - The PANC1 pancreatic adenocarcinoma cell line, MCF7 breast carcinoma cell line, and the RS4-11 lymphoblastic leukemia cell line were used to determine potent anticancer compound in the Meinox small molecule library. - Cancer cells were seeded into 96-well plates and treated with 1 μM of small molecules from the Meinox library. - Treatment of Meinox small molecules with PANC1 cells at 1 μM final dose revealed twenty-one compounds that decrease cell viability at least 50% (Figures 3 and S1). - With the PANC1 cell viability assay, we obtained an overall viability of with Meinox small molecules. - Treatment of MCF7 cells with Meinox small molecules (800 compounds) at 1 μM final dose showed five compounds that decrease cell viability more than 50%. - We achieved an overall average of viability with MCF7 cells and Meinox small molecule treatments. - The treatment of Meinox small molecules (800 compounds) in RS4-11 cells at 1 μM final dose showed. - with the small molecules of Meinox. - Analysis of common anticancer compounds from Meinox small molecule library demonstrates potential druglike compounds. - Analysis of cell viability posttreatment of MCF7 breast carcinoma cell line with the Meinox small molecule library.. - Meinox Small Molecule Library in MCF7 Breast Carcinoma. - Analysis of cell viability posttreatment of in RS4-11 lymphoblastic leukemia cell line with the Meinox small molecule library.. - Meinox Small Molecule Library in RS4-11 Lymphoblastic Leukemia. - Analysis of small molecules in cell viability in the Meinox small molecule library. - A) Distribution of common and cancer type specific small molecules identified with at least 40% reduction in cell viability in MCF7, PANC1 or RS4-11 cancers. - B) Percent viabilities of common thirteen small molecules.. - from Meinox small molecule library that lowered cell viability at least 50%. - Furthermore, when we compared average cell viability of whole small molecule library with selected hits in each cancer types, we have found significant difference (p <. - B Common anti-cancer small molecules. - We have calculated cell viability of whole small molecule library treatments and compared to selected hits for each cancer. - In short, we have established a library of small molecules with potentially and biologically active new chemical entities. - This research also indicates that in vitro analysis of different cancers or resistant disease models or other phenotypic assays with Meinox small molecule library could yield and recognize novel potent compounds unique to the utilized bioassay.. - Pharmaceutical modulation of small molecule diseases follows a variety of common features that allow us to foresee when a novel chemical agent with potent biological activity could become a medicine in the future. - To this end, Meinox small molecule library contains 818 compounds (81.8%) with a molecular weight less than 450.. - To this end, the small molecule library of Meinox established in this study has been examined for cLogP values found to have 926 compounds (90.26%) of cLogP values less than 5.. - In comparison, Meinox small molecule library established in this study contains 375 compounds (37.5%) with a value greater than –4 and 641 compounds (64.1%) with a value greater than –5 cLogS.. - It seems that newly established Meinox small molecule library in this study includes compounds with PSA values below 140, and compounds with PSA values below 60. - B) Structures of identified anticancer compounds from Meinox library of small molecules. - We ran a number of toxic compounds and a set of possibly nontoxic compounds through the forecast to test the efficiency of the toxicity prediction in the newly established Meinox small molecule library in this study. - Identified small molecules from Meinox library of compounds were analyzed for their MW, cLogP, cLogS, Polar surface area, druglikeness, and predicted for mutagenicity, tumorigenicity, reproductive effect, and irritation.. - Meinox small molecule library allowed us to identified both new (i.e. - Mx00691, also known as Topotecan, has been used in the treatment of colorectal, ovarian and nonsmall cell lung cancer as antineoplastic agents (Noronha et al., 2020).. - Mx00737, also known as Fludarabine, is an antimetabolite analog of vidarabine that poses antineoplasty (Barreca et al., 2020). - Mx00771, also known as Miglustat, is analogue of D-glucose and used in the therapy of type 1 Gaucher disease (Stirnemann et al., 2017). - Intriguingly, to delay the development of multiple myeloma, researchers have recently repurposed the licensed drug miglustat (Ersek et al., 2015). - the prevention of canine tumors including lymphoma is being investigated (Sadowski et al., 2018).. - In brief, we have developed a library of small molecules with theoretical and biologically active chemical entities.. - This research also shows that in vitro analysis of different cancers or disease-resistant models or other phenotypic assays with the Meinox small molecule library could yield and define novel potent compounds unique to the bioassay used.. - Tumor Targeting of Polymeric Nanoparticles Conjugated with Peptides, Saccharides, and Small Molecules for Anticancer Drugs.. - Boztas AO, Karakuzu O, Galante G, Ugur Z, Kocabas F et al.. - Boztas AO, Karakuzu O, Galante G, Ugur Z, Kocabas F et al. - Small-Molecule Screens: A Gateway to Cancer Therapeutic Agents with Case Studies of Food and Drug Administration–Approved Drugs. - A Structural Perspective on the Modulation of Protein-Protein Interactions with Small Molecules. - Small molecule inhibitors and stimulators of inducible nitric oxide synthase in cancer cells from natural origin (phytochemicals, marine compounds, antibiotics). - Development of Small Molecule MEIS Inhibitors that modulate HSC activity. - Novel tumor necrosis factor-α (TNF-α) inhibitors from small molecule library screening for their therapeutic activity profiles against rheumatoid arthritis using target-driven approaches and binary QSAR models.. - Small molecules in the Meinox small molecule library that inhibits PANC1 pancreatic adenocarcinoma growth at least 50% at 1 μM dose.. - Small molecules in the Meinox small molecule library that inhibits MCF7 breast carcinoma growth at least 50% at 1 μM dose.. - Small molecules in the Meinox small molecule library that inhibits RS4-11 lymphoblastic leukemia growth at least 50%
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