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Quantitative analysis of lab-to-lab variability in Caco-2 permeability assays (2017)
Journal Article
Lee, J. B., Zgair, A., Taha, D. A., Zang, X., Kagan, L., Kim, T. H., …Gershkovich, P. (2017). Quantitative analysis of lab-to-lab variability in Caco-2 permeability assays. European Journal of Pharmaceutics and Biopharmaceutics, 114, 38-42. https://doi.org/10.1016/j.ejpb.2016.12.027

In this study, Caco-2 permeability results from different laboratories were compared. Six different sets of apparent permeability coefficient (Papp) values reported in the literature were compared to experimental Papp obtained in our laboratory. The... Read More about Quantitative analysis of lab-to-lab variability in Caco-2 permeability assays.

Simple and sensitive HPLC-UV method for determination of bexarotene in rat plasma (2016)
Journal Article
Lee, J. B., Zgair, A., Kim, T. H., Kim, M. G., Yoo, S. D., Fischer, P. M., & Gershkovich, P. (2017). Simple and sensitive HPLC-UV method for determination of bexarotene in rat plasma. Journal of Chromatography B, 1040, 73-80. https://doi.org/10.1016/j.jchromb.2016.11.024

Bexarotene is currently marketed for treatment of cutaneous T-cell lymphoma and there has been growing interest in its therapeutic effectiveness for other cancers. Neuroprotective effects of bexarotene have also been reported. In this study, a simple... Read More about Simple and sensitive HPLC-UV method for determination of bexarotene in rat plasma.

Approved and experimental small-molecule oncology kinase inhibitor drugs: a mid-2016 overview (2016)
Journal Article
Fischer, P. M. (2017). Approved and experimental small-molecule oncology kinase inhibitor drugs: a mid-2016 overview. Medicinal Research Reviews, 37(2), 314-367. https://doi.org/10.1002/med.21409

Kinase inhibitor research is a comparatively recent branch of medicinal chemistry and pharmacology and the first small-molecule kinase inhibitor, imatinib, was approved for clinical use only 15 years ago. Since then, 33 more kinase inhibitor drugs ha... Read More about Approved and experimental small-molecule oncology kinase inhibitor drugs: a mid-2016 overview.

Design of nucleotide-mimetic and non-nucleotide inhibitors of the translation initiation factor eIF4E: Synthesis, structural and functional characterisation (2016)
Journal Article
Soukarieh, F., Nowicki, M. W., Bastide, A., Poyry, T., Jones, C., Dudek, K., …Fischer, P. M. (2016). Design of nucleotide-mimetic and non-nucleotide inhibitors of the translation initiation factor eIF4E: Synthesis, structural and functional characterisation. European Journal of Medicinal Chemistry, 124, 200-217. https://doi.org/10.1016/j.ejmech.2016.08.047

Eukaryotic translation initiation factor 4E (eIF4E) is considered as the corner stone in the cap-dependent translation initiation machinery. Its role is to recruit mRNA to the ribosome through recognition of the 50 - terminal mRNA cap structure (m7 G... Read More about Design of nucleotide-mimetic and non-nucleotide inhibitors of the translation initiation factor eIF4E: Synthesis, structural and functional characterisation.

GPCRs through the keyhole: the role of protein flexibility in ligand binding to ?-adrenoceptors (2016)
Journal Article
Emtage, A. L., Mistry, S. N., Fischer, P. M., Kellam, B., & Laughton, C. A. (2017). GPCRs through the keyhole: the role of protein flexibility in ligand binding to ?-adrenoceptors. Journal of Biomolecular Structure and Dynamics, 35(12), 2604-2619. https://doi.org/10.1080/07391102.2016.1226197

© 2016 Informa UK Limited, trading as Taylor & Francis Group. G protein-coupled receptors (GPCRs) are proteins of pharmaceutical importance, with over 30% of all drugs in clinical use targeting them. Increasing numbers of X-ray crystal (XRC) struct... Read More about GPCRs through the keyhole: the role of protein flexibility in ligand binding to ?-adrenoceptors.

Dietary fats and pharmaceutical lipid excipients increase systemic exposure to orally administered cannabis and cannabis-based medicines (2016)
Journal Article
Zgair, A., Wong, J. C., Lee, J. B., Mistry, J., Sivak, O., Wasan, K. M., …Gershkovich, P. (2016). Dietary fats and pharmaceutical lipid excipients increase systemic exposure to orally administered cannabis and cannabis-based medicines. American Journal of Translational Research, 8(8), 3448-3459

There has been an escalating interest in the medicinal use of Cannabis sativa in recent years. Cannabis is often administered orally with fat-containing foods, or in lipid-based pharmaceutical preparations. However, the impact of lipids on the exposu... Read More about Dietary fats and pharmaceutical lipid excipients increase systemic exposure to orally administered cannabis and cannabis-based medicines.

Discovery, synthesis and biochemical profiling of purine-2,6-dione derivatives as inhibitors of the human poly(A)-selective ribonuclease Caf1 (2015)
Journal Article
Winkler, S., Jadhav, G. P., Kaur, I., Maryati, M., Airhihen, B., & Fischer, P. M. (2015). Discovery, synthesis and biochemical profiling of purine-2,6-dione derivatives as inhibitors of the human poly(A)-selective ribonuclease Caf1. Bioorganic and Medicinal Chemistry Letters, 25(19), 4219-4224. https://doi.org/10.1016/j.bmcl.2015.07.095

Eukaryotic mRNA contains a 3? poly(A) tail, which plays important roles in the regulation of mRNA stability and translation. Well-characterized enzymes involved in the shortening of the poly(A) tail include the multi-subunit Ccr4-Not deadenylase, whi... Read More about Discovery, synthesis and biochemical profiling of purine-2,6-dione derivatives as inhibitors of the human poly(A)-selective ribonuclease Caf1.

Development of a simple and sensitive HPLC-UV method for the simultaneous determination of cannabidiol and ?(9)-tetrahydrocannabinol in rat plasma (2015)
Journal Article
Zgair, A., Wong, J., Sabri, A., Fischer, P., Barrett, D., Constantinescu, C., & Gershkovich, P. (2015). Development of a simple and sensitive HPLC-UV method for the simultaneous determination of cannabidiol and ?(9)-tetrahydrocannabinol in rat plasma. Journal of Pharmaceutical and Biomedical Analysis, 114, 145-151. doi:10.1016/j.jpba.2015.05.019

Mutations in a translation initiation factor identify the target of a memory-enhancing compound (2015)
Journal Article
Sekine, Y., Zyryanova, A., Crespillo-Casado, A., Fischer, P., Harding, H. P., & Ron, D. (2015). Mutations in a translation initiation factor identify the target of a memory-enhancing compound. Science, 348(6238), 1027-1030. https://doi.org/10.1126/science.aaa6986

The integrated stress response (ISR) modulates messenger RNA translation to regulate the mammalian unfolded protein response (UPR), immunity, and memory formation. A chemical ISR inhibitor, ISRIB, enhances cognitive function and modulates the UPR in... Read More about Mutations in a translation initiation factor identify the target of a memory-enhancing compound.

Partial restoration of protein synthesis rates by the small molecule ISRIB prevents neurodegeneration without pancreatic toxicity (2015)
Journal Article
Halliday, M., Ortori, C., Radford, H., Barrett, D., Sekine, Y., Fischer, P., …Mallucci, G. (2015). Partial restoration of protein synthesis rates by the small molecule ISRIB prevents neurodegeneration without pancreatic toxicity. Cell Death and Disease, 6, https://doi.org/10.1038/cddis.2015.49

© 2015 Macmillan Publishers Limited All rights reserved. Activation of the PERK branch of the unfolded protein response (UPR) in response to protein misfolding within the endoplasmic reticulum (ER) results in the transient repression of protein synth... Read More about Partial restoration of protein synthesis rates by the small molecule ISRIB prevents neurodegeneration without pancreatic toxicity.

Coagulation factor XII protease domain crystal structure (2015)
Journal Article
Pathak, M., Wilmann, P., Awford, J., Li, C., Hamad, B., Fischer, P., …Emsley, J. (2015). Coagulation factor XII protease domain crystal structure. Journal of Thrombosis and Haemostasis, 13(4), 580-591. https://doi.org/10.1111/jth.12849

Background: Coagulation factor XII is a serine protease that is important for kinin generation and blood coagulation, cleaving the substrates plasma kallikrein and FXI. Objective: To investigate FXII zymogen activation and substrate recognition by d... Read More about Coagulation factor XII protease domain crystal structure.

A facile approach to tryptophan derivatives for the total synthesis of argyrin analogues (2014)
Journal Article
Chen, C., Genapathy, S., Fischer, P. M., & Chan, W. C. (2014). A facile approach to tryptophan derivatives for the total synthesis of argyrin analogues. Organic and Biomolecular Chemistry, 12(48), 9764-9768. https://doi.org/10.1039/c4ob02107j

A facile route has been established for the synthesis of indole-substituted (S)-tryptophans from corresponding indoles, which utilizes a chiral auxiliary-facilitated Strecker amino acid synthesis strategy. The chiral auxiliary reagents evaluated were... Read More about A facile approach to tryptophan derivatives for the total synthesis of argyrin analogues.

Design, synthesis and SAR exploration of tri-substituted 1,2,4-triazoles as inhibitors of the annexin A2–S100A10 protein interaction (2014)
Journal Article
Reddy, T. R., Li, C., Guo, X., Fischer, P. M., & Dekker, L. V. (2014). Design, synthesis and SAR exploration of tri-substituted 1,2,4-triazoles as inhibitors of the annexin A2–S100A10 protein interaction. Bioorganic and Medicinal Chemistry, 22(19), 5378-5391. https://doi.org/10.1016/j.bmc.2014.07.043

Recent target validation studies have shown that inhibition of the protein interaction between annexin A2 and the S100A10 protein may have potential therapeutic benefits in cancer. Virtual screening identified certain 3,4,5-trisubstituted 4H-1,2,4-tr... Read More about Design, synthesis and SAR exploration of tri-substituted 1,2,4-triazoles as inhibitors of the annexin A2–S100A10 protein interaction.

Investigation of the flexibility of protein kinases implicated in the pathology of Alzheimer's Disease (2014)
Journal Article
Laughton, C., Mazanetz, M., & Fischer, P. (2014). Investigation of the flexibility of protein kinases implicated in the pathology of Alzheimer's Disease. Molecules, 19(7), 9134-9159. https://doi.org/10.3390/molecules19079134

The pathological characteristics of Alzheimer’s Disease (AD) have been linked to the activity of three particular kinases—Glycogen Synthase Kinase 3β (GSK3β), Cyclin-Dependent Kinase 5 (CDK5) and Extracellular-signal Regulated Kinase 2 (ERK2). As a c... Read More about Investigation of the flexibility of protein kinases implicated in the pathology of Alzheimer's Disease.

Targeting RNA transcription and translation in ovarian cancer cells with pharmacological inhibitor CDKI-73 (2014)
Journal Article
Lam, F., Abbas, A. Y., Shao, H., Teo, T., Adams, J., Li, P., …Wang, S. (2014). Targeting RNA transcription and translation in ovarian cancer cells with pharmacological inhibitor CDKI-73. Oncotarget, 5(17), 7691–7704. https://doi.org/10.18632/oncotarget.2296

Dysregulation of cellular transcription and translation is a fundamental hallmark of cancer. As CDK9 and Mnks play pivotal roles in the regulation of RNA transcription and protein synthesis, respectively, they are important targets for drug developme... Read More about Targeting RNA transcription and translation in ovarian cancer cells with pharmacological inhibitor CDKI-73.

A novel Cdk9 inhibitor preferentially targets tumor cells and synergizes with fludarabine (2013)
Journal Article
Walsby, E., Pratt, G., Shao, H., Abbas, A. Y., Fischer, P., Bradshaw, T. D., …Pepper, C. (2013). A novel Cdk9 inhibitor preferentially targets tumor cells and synergizes with fludarabine. Oncotarget, 5, 375-385

Cdk9 is a key elongation factor for RNA transcription and functions by phosphorylating the C-terminal domain of RNA polymerase II. Here we present direct evidence that cdk9 is important for cancer cell survival and describe the characterization of th... Read More about A novel Cdk9 inhibitor preferentially targets tumor cells and synergizes with fludarabine.

A fluorescence-based assay suitable for quantitative analysis of deadenylase enzyme activity (2013)
Journal Article
Maryati, M., Kaur, I., Jadhav, G. P., Olotu-Umoren, L., Oveh, B., Hashmi, L., …Winkler, G. S. (2014). A fluorescence-based assay suitable for quantitative analysis of deadenylase enzyme activity. Nucleic Acids Research, 42(5), https://doi.org/10.1093/nar/gkt972

In eukaryotic cells, the shortening and removal of the poly(A) tail of cytoplasmic mRNA by deadenylase enzymes is a critical step in post-transcriptional gene regulation. The ribonuclease activity of deadenylase enzymes is attributed to either a DEDD... Read More about A fluorescence-based assay suitable for quantitative analysis of deadenylase enzyme activity.

Synthesis and in vitro and in vivo characterization of highly ?1-Selective ?-Adrenoceptor partial agonists (2013)
Journal Article
Mistry, S. N., Baker, J. G., Fischer, P. M., Hill, S. J., Gardiner, S. M., & Kellam, B. (2013). Synthesis and in vitro and in vivo characterization of highly ?1-Selective ?-Adrenoceptor partial agonists. Journal of Medicinal Chemistry, 56(10), https://doi.org/10.1021/jm400348g

β-Adrenoceptor antagonists boast a 50-year use for symptomatic control in numerous cardiovascular diseases. One might expect highly selective antagonists are available for the human β-adrenoceptor subtype involved in these diseases, yet few truly β1-... Read More about Synthesis and in vitro and in vivo characterization of highly ?1-Selective ?-Adrenoceptor partial agonists.

Three-dimensional pharmacophore design and biochemical screening identifies substituted 1,2,4-triazoles as inhibitors of the annexin A2-S100A10 protein interaction (2012)
Journal Article
Reddy, T. R., Li, C., Fischer, P. M., & Dekker, L. V. (2012). Three-dimensional pharmacophore design and biochemical screening identifies substituted 1,2,4-triazoles as inhibitors of the annexin A2-S100A10 protein interaction. ChemMedChem, 7(8), https://doi.org/10.1002/cmdc.201200107

Protein interactions are increasingly appreciated as targets in small-molecule drug discovery. The interaction between the adapter protein S100A10 and its binding partner annexin A2 is a potentially important drug target. To obtain small-molecule sta... Read More about Three-dimensional pharmacophore design and biochemical screening identifies substituted 1,2,4-triazoles as inhibitors of the annexin A2-S100A10 protein interaction.