The Translational Core commonly engages in assay development/validation/implementation, screening, hit identification, hit/lead candidate first in animal studies, preliminary in vitro and in vivo ADMET analysis, bioanalytical and preliminary formulation development, and/or basic PK and MTD studies. Screening activities in the core employ both commercially available libraries and our exclusive UK-based collections (see Compound Collections). In the context of translational research and lead development, the core provides experimental validation for computational models (Computational Core) and emphasizes studies to illuminate potential liabilities of early stage hits/leads and set the stage for in vivo evaluation in the relevant disease models. The core operates under the directorship of Professor Jon Thorson with a current staff of one Ph.D. level and one M.S. level scientist.
Ye Q, Zhang Y, Cao Y, Wang X, Guo Y, Chen J, Horn J, Ponomareva LV, Chaiswing L, Shaaban KA, Wei Q, Anderson BD, St Clair DK, Zhu H, Leggas M, Thorson JS, She QB (2019). Frenolicin B targets peroxiredoxin 1 and glutaredoxin 3 to trigger ROS/4E-BP1-mediated antitumor effects. Cell Chemical Biology 2019, 26(3):366-377. PMCID: PMC6557261
Mitra P, Eckenrode JM, Mandal A, Jha AK, Salem SM, Leggas M, Rohr J (2018). Development of mithramycin analogues with increased selectivity toward ETS transcription factor expressing cancers. Journal of Medicinal Chemistry, 61(17):8001-8016. PMCID: In Process
El-Refai SM, Brown JD, Arnold SM, Black EP, Leggas M, Talbert JC (2017). Epidemiologic analysis along the mevalonate pathway reveals improved cancer survival in patients who receive statins alone and in combination with bisphosphonates. JCO Clinical Cancer Informatics 1:1-12. PMCID: PMC6467073
Wang Y, Liu X, Pijut SS, Li J, Horn J, Bradford EM, Leggas M, Barrett TA, Graf GA (2015). The combination of ezetimibe and ursodiol promotes fecal sterol excretion and reveals a G5G8-independent pathway for cholesterol elimination. Journal of Lipid Research 56(4):810-820. PMCID: PMC4373739
Bada HS, Sithisarn T, Gibson J, Garlitz K, Caldwell R, Capilouto G, Li Y, Leggas M, Breheny P (2015). Morphine versus clonidine for neonatal abstinence syndrome. Pediatrics 135(2):e383-391.
Ahmed TA, Hayslip J, Leggas M (2014). Simvastatin interacts synergistically with tipifarnib to induce apoptosis in leukemia cells through the disruption of RAS membrane localization and ERK pathway inhibition. Leukemia Research 38(11):1350-1357. PMCID: PMC5628615
Rinehart J, Arnold S, Kloecker G, Lim A, Zaydan MA, Baeker T, Maheshwari JG, Carloss H, Slone S, Shelton B, Croley J, Kvale E, Brooks M, Leggas M (2013). Phase II randomized trial of carboplatin and gemcitabine with or without dexamethasone pre-treatment in patients with stage IV non-small cell lung cancer. Cancer Chemotherapy and Pharmacology 71(5):1375-1383.
The Translational Studies Core welcomes inquiries from UK investigators with an interest in assay development, new ligand/probe discovery, and/or early preclinical evaluation of small molecules, delivery modalities, and/or biologics. For more information and to request services, please contact us.
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This work was supported by the Center for Pharmaceutical Research and Innovation (CPRI, NIH P20 GM130456) and the National Center for Advancing Translational Sciences (UL1 TR001998).
