Jiashu Xie, PhD
Research Assistant Professor, Center for Drug Design (CDD)
Research Assistant Professor, Center for Drug Design (CDD)
South Dakota State University (Pharmaceutical Sciences), 2013
Shanghai Institute of Pharmaceutical Industry (Pharmaceutics), 2008
China Pharmaceutical University (Pharmaceutics), 2004
Current research in the Pharmacokinetics (PK) lab has focused on profiling the in vitro ADME (absorption, distribution, metabolism, and excretion) and in vivo PK properties of lead compounds from medicinal chemistry efforts. Our work can provide a basis for chemists to select and optimize the leads that have desirable “drug-like” properties, necessary for drug candidate selection before the preclinical and clinical development. A wide range of ADME/PK assays and techniques are employed in our research. These include:
- Microsomal stability, S9 stability, Plasma stability, Aqueous stability
- Cytochrome P450 inhibition, reaction phenotyping
- Plasma protein binding, brain tissue binding, blood to plasma ratio
- Caco-2, MDCK and PAMPA permeability
- Oral bioavailability and tissue distribution in rodent
- PK modeling and simulation using Phoenix WinNonlin®
- LC/MS/MS bioanalysis
Our other research focus is to improve drug response in combination chemotherapy and combat cancer drug resistance. Particularly, we devote a large portion of our research to identifying novel compounds that impact cellular uptake or inhibit drug efflux - the most common mechanism underlying acquired drug resistance in cancer, pinpointing the transporters or targets involved in these processes, and evaluating regimens to produce desirable anti-cancer responses.
Research Funding Grants
Discovery and development of novel anti-HCMV agents targeting the UL89 terminase protein
R01 AI136982 NIH/NIAID
Role: Co-Investigator (PIs: Robert Geraghty and Zhengqiang Wang)
Taking aim at HBV eradication using novel NRTIs and capsid effectors
R01 AI121315 NIH/NIAID
Role: Co-Investigator (PIs: Stefan Sarafianos and Zhengqiang Wang)
- Guanabenz Attenuates Acetaminophen-Induced Liver Toxicity and Synergizes Analgesia in Mice. Xie W.; Xie J.; Vince R.; More S. Chemical research in toxicology. 2019. Just Accepted: https://doi.org/10.1021/acs.chemrestox.9b00162
- Novel Deazaflavin Analogues Potently Inhibited Tyrosyl DNA Phosphodiesterase 2 (TDP2) and Strongly Sensitized Cancer Cells toward Treatment with Topoisomerase II (TOP2) Poison Etoposide. Kankanala J, Ribeiro CJA, Kiselev E, Ravji A, Williams J, Xie J, Aihara H, Pommier Y, Wang Z. Journal of medicinal chemistry.2019; 62 (9): 4669-4682.
- Discovery of Irreversible p97 Inhibitors. Ding R, Zhang T, Wilson DJ, Xie J, Williams J, Xu Y, Ye Y, Chen L. Journal of medicinal chemistry.2019; 62 (5):2814-2829.
- 5-Aminothiophene-2,4-dicarboxamide analogues as hepatitis B virus capsid assembly effectors. Tang J, Huber AD, Pineda DL, Boschert KN, Wolf JJ, Kankanala J, Xie J, Sarafianos SG, Wang Z. European journal of medicinal chemistry.2019; 164:179-192.
- Triazolopyrimidine and triazolopyridine scaffolds as TDP2 inhibitors. Ribeiro CJA, Kankanala J, Xie J, Williams J, Aihara H, Wang Z. Bioorganic & medicinal chemistry letters.2019; 29(2):257-261.
- 6-Arylthio-3-hydroxypyrimidine-2,4-diones potently inhibited HIV reverse transcriptase-associated RNase H with antiviral activity. Wang L, Tang J, Huber AD, Casey MC, Kirby KA, Wilson DJ, Kankanala J,Xie J, Parniak MA, Sarafianos SG, Wang Z. European journal of medicinal chemistry. 2018; 156:652-665.
- In Vitro and In Vivo Antimetastatic Effect of Glutathione Disulfide Liposomes. Sadhu SS, Wang S, Dachineni R, Averineni RK, Seefeldt T, Xie J, Tummala H, Bhat GJ, Guan X. Cancer growth and metastasis.2017; 10:1-11.
- A fluorescence-based high-throughput assay to identify inhibitors of tyrosylprotein sulfotransferase activity. Zhou W, Wang Y, Xie J, Geraghty RJ. Biochemical and biophysical research communications.2017; 482(4):1207-1212.
- N-(1-Benzyl-3,5-dimethyl-1H-pyrazol-4-yl)benzamides: Antiproliferative Activity and Effects on mTORC1 and Autophagy. Ai T, Willett R, Williams J, Ding R, Wilson DJ, Xie J, Kim DH, Puertollano R, Chen L. ACS medicinal chemistry letters.2017; 8(1):90-95.
- Eeyarestatin I derivatives with improved aqueous solubility. Ding R, Zhang T, Xie J, Williams J, Ye Y, Chen L. Bioorganic & medicinal chemistry letters.2016; 26(21):5177-5181.
- Glutathione Disulfide Liposomes - a Research Tool for the Study of Glutathione Disulfide Associated Functions and Dysfunctions. Sadhu SS, Xie J, Zhang H, Perumal O, Guan X. Biochemistry and biophysics reports.2016; 7:225-229.
- 3-Hydroxypyrimidine-2,4-dione-5-N-benzylcarboxamides Potently Inhibit HIV-1 Integrase and RNase H. Wu B, Tang J, Wilson DJ, Huber AD, Casey MC, Ji J, Kankanala J, Xie J, Sarafianos SG, Wang Z. Journal of medicinal chemistry.2016; 59(13):6136-48.
- Synergistic reduction of HIV-1 infectivity by 5-azacytidine and inhibitors of ribonucleotide reductase. Rawson JM, Roth ME, Xie J, Daly MB, Clouser CL, Landman SR, Reilly CS, Bonnac L, Kim B, Patterson SE, Mansky LM. Bioorganic & medicinal chemistry.2016; 24(11):2410-22.
- 5-((3-Amidobenzyl)oxy)nicotinamides as Sirtuin 2 Inhibitors. Ai T, Wilson DJ, More SS, Xie J, Chen L. Journal of medicinal chemistry.2016; 59(7):2928-41.
- 5-Azacytidine Enhances the Mutagenesis of HIV-1 by Reduction to 5-Aza-2'-Deoxycytidine. Rawson JM, Daly MB, Xie J, Clouser CL, Landman SR, Reilly CS, Bonnac L, Kim B, Patterson SE, Mansky LM. Antimicrobial agents and chemotherapy.2016; 60(4):2318-25.
- Dual anti-HIV mechanism of clofarabine. Daly MB, Roth ME, Bonnac L, Maldonado JO, Xie J, Clouser CL, Patterson SE, Kim B, Mansky LM. Retrovirology.2016; 13:20.
- Design and synthesis of an activity-based protein profiling probe derived from cinnamic hydroxamic acid. Ai T, Qiu L, Xie J, Geraghty RJ, Chen L. Bioorganic & medicinal chemistry.2016; 24(4):686-92.
- Discovery of 1-hydroxypyridine-2-thiones as selective histone deacetylase inhibitors and their potential application for treating leukemia. Muthyala R, Shin WS, Xie J, Sham YY. Bioorganic & medicinal chemistry letters.2015; 25(19):4320-4.
- Evaluation of a dithiocarbamate derivative as a model of thiol oxidative stress in H9c2 rat cardiomyocytes. Xie J, Potter A, Xie W, Lynch C, Seefeldt T. Free radical biology & medicine. 2014; 70:214-22.
- Simultaneous determination of ginkgolides A, B, C and bilobalide in plasma by LC-MS/MS and its application to the pharmacokinetic study of Ginkgo Biloba extract in rats. Xie J, Ding C, Ge Q, Zhou Z, Zhi X. Journal of chromatography. B, Analytical technologies in the biomedical and life sciences. 2008; 864(1-2):87-94.
- Matrix effects in bioanalysis by LC/MS. Xie J, Ge Q. Chinese Journal of Pharmaceutical Analysis. 2008; 28(8):1386-1389.