ApexScreen is a collection of 5,040 compounds that were selected to represent the diversity of TimTec stock of over 160,000 compounds in a smaller format as opposed to larger general screening collections. ApexScreen in a variety of formatting options tailored to customer requirements is a collection that allows You to jump-start any screening project.

ApexScreen was created by using TimTec's Diversity Analysis Software, that allows the assembly of libraries with maximized chemical diversity from databases of compounds that are currently available from TimTec US and/or overseas stock. Diversity libraries can be further filtered to include molecules that fall within designated MW, cLogP and Lipinski Rule parameters. TimTec can also provide a selection of compounds from its databases which will include only those compounds that will contribute to the diversity of an existing customer library.

In addition to diverse selection of compounds that represent variety of chemotypes in TimTec general stock collection, ApexScreen includes a number of pure natural compounds from TimTec Natural Product Library to suit current trends in screening.

ApexScreen is a perfect collection for starting a screening project and a valuable addition to existing compound libraries.

Various formatting option in terms of sample size or concentration are available.
Structural data and pricing information is available on request. Download data files

Receive a copy of TimTec compounds collections on a CDRom - please e-mail us your exact postal address.

Publications, Featured Screening Results for ApexScreen-5040

Chih‑Wei Sheen, Onur Alptürk, and Nicolas Sluis‑Cremer. Novel high-throughput screen identifies an HIV-1 reverse transcriptase inhibitor with a unique mechanism of action. Biochem. J. (2014) 462 (425–432) (Printed in Great Britain) doi:10.1042/BJ20140365

Abstract
HIV-1 resistance to zidovudine [AZT (azidothymidine)] is associated with selection of the mutations M41L, D67N, K70R, L210W, T215F/Y and K219Q/E in RT (reverse transcriptase). These mutations decrease HIV-1 susceptibility to AZT by augmenting RT's ability to excise the chain-terminating AZT-MP (AZT-monophosphate) moiety from the chain-terminated DNA primer. Although AZT-MP excision occurs at the enzyme's polymerase active site, it is mechanistically distinct from the DNA polymerase reaction. Consequently, this activity represents a novel target for drug discovery, and inhibitors that target this activity may increase the efficacy of nucleoside/nucleotide analogues, and may help to delay the onset of drug resistance. In the present study, we have developed a FRET (Förster resonance energy transfer)-based high-throughput screening assay for the AZT-MP excision activity of RT. This assay is sensitive and robust, and demonstrates a signal-to-noise ratio of 3.3 and a Z’ factor of 0.69. We screened three chemical libraries (7265 compounds) using this assay, and identified APEX57219 {3,3′-[(3-carboxy-4-oxo-2,5-cyclohexadien-1-ylidene)methylene]bis[6-hydroxybenzoic acid]} as the most promising hit. APEX57219 displays a unique activity profile against wild-type and drug-resistant HIV-1 RT, and was found to inhibit virus replication at the level of reverse transcription. Mechanistic analyses revealed that APEX57219 blocked the interaction between RT and the nucleic acid substrate.
 

Brandon M. Kenwood, Janelle L. Weaver, et.al. Identification of a novel mitochondrial uncoupler that does not depolarize the plasma  membrane. Mol Metabolism. Online Nov 27, 2013. http://dx.doi.org/10.1016/j.molmet.2013.11.005

View information about mitochondrial uncoupler and order BAM15

Abstract
Chemical mitochondrial uncouplers are lipophilic weak acids that increase proton transport into the mitochondrial matrix via a pathway independent of ATP synthase, thereby uncoupling nutrient oxidation from ATP production. These molecules enable determination of maximal  cellular respiration and have antioxidant effects that protect from ischemia-reperfusion injury. However, the most widely used proton transporter uncouplers have off-target activity that lead to a range of undesired effects including plasma membrane depolarization, mitochondrial inhibition, and cytotoxicity. To identify new mitochondrial uncouplers that lack off-target activity at the plasma membrane, we screened a small molecule chemical library. Herein we report the identification and validation of a novel mitochondrial protonophore uncoupler (2-fluorophenyl){6-[(2-fluorophenyl)amino](1,2,5-oxadiazolo[3,4-e]pyrazin-5-yl)}amine, named BAM15, that does not depolarize the plasma membrane and protects mice from acute renal ischemic-reperfusion injury. Thus, BAM15 represents a reliable new tool for the analysis of cellular bioenergetic function that has therapeutic potential by altering mitochondrial function in vivo.

Zhang S, Chen H, Webster J, Gerhard GS.Targeting heme for the identification of cytotoxic agents.Anticancer Agents Med Chem. 2013 Mar;13(3):515-22.

Abstract
Certain tumor types have an increased capacity for heme synthesis, which serves as the basis for photodynamic therapy. Heme also serves as the target for the anti-malaria drug artemisinin, which has also been used as an anti-cancer drug. We developed a high-throughput screening assay to identify heme interacting (HI) compounds, which included imidazole, pyridine, carbonitrile, isocyanide, and quinoline core structures that are known to interact with heme or hemin. The cytotoxicity of several of the compounds towards human leukemia cell lines could be modulated by increasing or decreasing heme synthesis. Spectral analysis indicated that distinct molecular interactions occurred with heme, suggesting that HI compounds appear to target heme with exquisite specificity. These studies suggest that heme may serve as a novel therapeutic target for cancer drug discovery.

LeVine H 3rd, Lampe L, Abdelmoti L, Augelli-Szafran CE. Dihydroxybenzoic acid isomers differentially dissociate soluble biotinyl-Aβ(1-42) oligomers. Biochemistry. 2012 Jan 10;51(1):307-15. doi: 10.1021/bi201288x

Abstract
Polyphenolic compounds including a number of natural products such as resveratrol, curcumin, catechin derivatives, and nordihydroguaiaretic  acid have effects on the assembly of Aβ fibrils and oligomers as well as on fibril morphology. Based on a lead structure obtained from a screen of a small molecule diversity library, simple benzoic acid derivatives distinguished by the number and position of hydroxyls on the aromatic ring displayed different abilities to dissociate preformed biotinyl-Aβ(1-42) oligomers.  The 2,3-, 2,5-, and 3,4-dihydroxybenzoic  acid (DHBA) isomers were active oligomer dissociators. The remaining DHBA isomers and the monohydroxy and unsubstituted benzoic acids were inactive and did not compete with the active compounds to block oligomer dissociation. None of the compounds blocked oligomer assembly, indicating that they do not interact with monomeric Aβ to shift the oligomer-monomer equilibrium. Dissociating activity was not associated with quinone redox cycling capacity of the compounds. Gallic acid (3,4,5-trihydroxybenzoic acid) stabilized biotinyl-Aβ(1-42) oligomers against intrinsic dissociation and blocked the effects of the active dissociators, independent of the concentration of dissociator. A model for the mechanism of action of the DHBA dissociators proposes that these compounds destabilize oligomer structure promoting progressive monomer dissociation rather than fissioning oligomers into smaller, but still macromolecular, species. Gallic acid blocks dissociation by stabilizing oligomers against this process.

Harry LeVine, III, Qunxing Ding,et.al. Clioquinol and other Hydroxyquinoline Derivatives Inhibit Aβ(1-42) Oligomer Assembly. Neurosci Lett. 2009 November 6; 465(1): 99–103. 10.1016/j.neulet.2009.08.002

Abstract
Soluble oligomeric amyloid-β (Aβ) species are toxic to many cell types and are a putative etiological factor in Alzheimer's disease. The NINDS-Custom Collection of 1040 drugs and biologically active compounds was robotically screened for inhibitors of Aβ oligomer formation with a single-site biotinylated Aβ(1-42) oligomer assembly assay. Several quinoline-like compounds were identified with IC50's < 10 μM, including the antiprotozoal clioquinol that has been reported to have effects on metal ion metabolism. The 2-OH, 4-OH, and 6-OH quinolines do not block Aβ oligomer formation up to a concentration of 100 μM. Analogs of clioquinol have shown activity in reducing Aβ levels and improving behavioral deficits in mouse models of Aβ pathology. The inhibitory effects of clioquinol and other 8-OH quinoline derivatives on oligomer formation in vitro are unrelated to their chelating activity. Crosslinking studies suggest that clioquinol acts at the stage of trimer formation. These preliminary data may suggest that 8-OH quinolines have the potential for suppressing Aβ oligomer formation which should be considered when assessing the effects of these compounds in animal models and clinical trials.

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Chem-TCM is the digital database of molecules from plants used in the traditional Chinese medicine
MyriaScreen II – diversity screening library from Sigma-Aldrich and TimTec
ApexScreen is a collection of 5,040 compounds that were selected to represent the diversity of TimTec stock
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