Office: 335 Sutherland Drive, 206 Salk Pavilion

Phone: 412-383-5276

Fax: 412-383-7436

Pager: 832-755-1268

Email: xix15@pitt.edu

URL: www.cdarcenter.org

Dr Xiang-Qun (Sean) Xie is an Associate Dean for Research Innovation at School of Pharmacy and a Professor of Pharmaceutical Sciences/Drug Discovery Institute, and a PI of an integrated Medicinal Chemistry Biology laboratory of CompuGroup, BioGroup and ChemGroup (www.CBLigand.org/XieLab) at University of Pittsburgh. He is a member of the Science Advisory Board to the US FDA. He is a Founding Director of Computational Chemical Genomics Screening Center (www.CBLigand.org/CCGS), and a Director/PI of NIH National Center of Excellence for CDAR (www.CDARCenter.org). He holds joint positions at Dept of Computational Biology and Dept of Structural Biology, and Pitt Cancer Institute MT/DD Program. He is an Editorial Advisory Board member for AAPS Journal and American Journal of Molecular Biology, and Associate Editor of BMC Pharmacology Toxicology.

He was a Charter Member of NIH BPNS Study Section, and an ad hoc expert reviewer for UK MRC foundation; the Wellcome Trust Fund; the Netherland Organization for Scientific Research Council; the Austrian Science Fund (FWF) Erwin Schrödinger Fellowship; and the Chinese Natural Science Foundation. He holds/held honorary professorship in top institutes and colleges of pharmacy in China, including Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Stem Cell Medical Center; and Shanghai Jiaotong University. He was an invited International Assessment Panelist for Fudan University, a member of the Board of Directors of the Chinese Association of Professionals in Science and Technology, and a Chair of the CAPST-Biomedical & Pharmaceutical Society.

Prof Xie and his team are known for their pioneering research for the development of internationally recognized diseases domain-specific chemogenomics knowledgebases, which is an integrated platform of “Big Data to Knowledge” computational chemogenomics-based target identification and system pharmacology for translational research. His recent work on Alzheimer’s disease specific chemogenomics database (www.CBLigand.org/AD/) was on 2014 coverpage story of a top peer-reviewed ACS journal. The innovation work includes GPU-accelerated cloud computing TargetHunter program for drug target identification (www.CBLigand.org/TargetHunter) (2013 AAPS special theme issue).

His lab was the first discovered/patented INK4C-targeting small molecule inhibitors for hematopoietic stem cell expansion (Nature Comm 2015), was the first discovered/patented p62ZZ chemical inhibitors for multiple myeloma (Nature Leukemia 2015), and also reported/patented novel ligands specific to cannabinoid CB2 receptor for osteoporosis and cancers. His invention discovery patents have been successfully licensed out to Biotech/Pharma. Overall, his developed integrated cloud computing knowledgebases help to bridge the knowledge gap between biology and chemistry, and to facilitate target identification, drug repurposing, and system pharmacology analyses in a chemogenomics scale for precision medicine drug discovery. As a result, he is a recipient of 2014 AAPS Award for Outstanding Research Achievements.

Dr Xie received MD in Pharmacy from the Second Military Medical University in Shanghai China, PhD in Medicinal Chemistry from the School of Pharmacy, University of Connecticut, and Executive MBA degree, and the Shared Leadership Cohort Development Experience Workshop Training by JPorcari & Associates.

http://www.cbligand.org/CCGS/people.php
http://www.cdarcenter.org/?page_id=50

Chemogenomics-knowledgebased small molecule probe design and development for target-specific neurodisorder, multiple myeloma, osteoporosis and hematopoietic stem cell drug discovery by using integrated approaches of computational system pharmacology and virtual screening,structural biophysics, HTS bioassay validation and medicinal chemistry.

Publications (last 5 years)

2016
1) Zhiwei Feng, Larry V. Pearce, Yu, Zhang, Changrui Xing, Brienna K.A. Herold, Shifan Ma, Ziheng Hu, Noe A. Turcios, Peng Yang, Qin Tong, Anna K. McCall, Peter M. Blumberg*, and Xiang-Qun Xie*."Multi-Functional Diarylurea Small Molecule Inhibitors of TRPV1 with Therapeutic Potential for Neuroinflammation". AASP.J, 2016 18(4):898-913. doi: 10.1208/s12248-016-9888-z. Epub 2016 Mar 21. PMID:27000851.

2) Wang LR, Xie XQ* “Cancer Genomics: Opportunities for Medicinal Chemistry?” Future Medicinal Chemistry, 2016, 8, 357-359 (doi:10.4155/fmc.16.1)
3) Zhang Y, Wang, LR, Cheng HZ, Ding YH, Feng ZW, Cheng T, Gao YD and Xie XQ* “StemCelldb: An Integrated Stem Cell-Specific Chemogenomics Knowledge base for Target Identification and Systems-Pharmacology Research”, JCIM, 2016 (accept with revision)
4) Zhiwei Feng҂, Yu Zhang҂, Shifan Ma, Ziheng Hu, Tao Cheng, Yingdai Gao*, Peng Yang* and Xiang-Qun Xie*."Protein-Protein Interface Based p18INK4C Inhibitors for Hematopoietic Stem Cell Expansion in Murine Bone Marrow and Human Cord Blood . ACS Chem.Biol, 2016(accept with revision).
5) Kai-Long Ji, Ping Zhang, Xiang-Qun Xie, Xiao-Nian Li, Juan Guo, Hua-Bin Hu, Chun-Fen Xiao, Xiang-Qun Xie and You-Kai Xu * “Cytotoxic limonoids from the leaves of Trichilia Americana” (美洲叶细胞毒类柠檬苦素). Phytochemistry. 2015 Oct;118:61-7. doi: 10.1016/j.phytochem.2015.08.014. Epub 2015 Aug 29.
6) Xie XQ*, Wang LR, Wang JM, Xie ZJ, Yang P, and Ouyang Q. “In Silico Chemogenomics Knowledgebase and Computational System Neuropharmacology Approach for Cannabinoid Drug Research” (Chapter 19). Neuropathology of Drug Addictions and Substance Misuse, 2016, Volume 3, chapter 19. http://dx.doi.org/10.1016/B978-0-12-800634-4.00019-6, Copyright © 2016 Elsevier Inc.
(2015)
7) Xie, XQ*, Yang P, Zhang Y, Zhang P, Wang L, Ding YH, Yang M, Tong Q, Cheng HZ, McGuire T, Yuan WP, Cheng T and Gao YD. “Discovery of novel INK4C small-molecule inhibitors to promote human and murine hematopoietic stem cell ex vivo expansion” Scientific Report (Nature), 2015, 5:18115, DOI: 10.1038/srep18115.

8) Teramachi J, Rebecca S, Yang P, Zhao W, Mohammad K, Guo JX, Anderson HL, Zhou D, Feng R, Myint KZ, Maertz N, Beumer JH, Eiseman, JL, Windle JL, Xie XQ*, Roodman D*, Kurihara N*. “Blocking the ZZ Domain of Sequestosome1/p62 Suppresses Myeloma Cell Growth and Osteoclast Formation In Vitro and Induces Dramatic New Bone Formation in Myeloma-Bearing Bones In Vivo” Leukemia (Nature) 2015, Aug 19. (doi: 10.1038/leu.2015.229) PMID:26286116 (*co-correspondent authors).
* Xie’s lab was the first to discover and develop p62ZZ chemical inhibitors with promising anti-multiple myeloma (MM) therapeutic index (Patent: Xie et al USSN 61/521,287, PCT/US2012/049911) in collaboration with Dr. David Roodman. Our innovation is based on the therapeutic knowledge and our data that the Sequestosome-1 (or p62) plays critical roles in the survival, growth and metastasis of MM cells. P62 is a key domain activating NF-B, and p38 MAPK, both of which are aberrantly activated in MM, thus it is a promising drug target for MM treatment. We have proved that the ZZ domain of p62 is responsible for increased MM cell growth and osteoclast (OCL) formation mediated by NF-B and p38 MAPK signaling. Our discovered lead compound XIE3P62ZZ (#3 or XRK3, 4.31 M) exhibited notable p62 antagonistic effects and significantly reduced survival of human MM cells and also inhibited osteoclastogenesis. The specificity was further confirmed by p62-/- experiments, in which effects of the inhibitor XRK3 on MM cells and tumor necrosis factor (TNF)-α-induced osteoclast (OCL) formation were lost upon p62-/- gene deficiency.
The most recent development of our preliminary chemistry modification of this lead produced more potent p62 inhibitor analogs (e.g., XIE1-10b: IC50 1.12, XIE1-62a: 0.63 M) with improved drug-like properties (t1/2 = 4.5 hrs, Bioavailability 43%). The in vivo MM xenograft murine model revealed significantly inhibited MM tumor growth (>75%) and increased mean survival time (53%) compared with the control group. This will be reported in Nature Chemical Biology.
9) Yingdai Gao, Peng Yang, Hongmei Shen, Hui Yu, Zhaojun Xie, Liyan Zhang, Patrick Bartlow, Qing Ji ,Yahui Ding, Lirong Wang, Haibin Liu, Shihui Ma, Sha Hao, Fang Dong, Yanxin Li, Peng Zhang, Haizi Cheng, Paulina H. Liang, Weimin Miao, YouzhongYuan, Tao Cheng* and Xiang-Qun Xie,* “Small-molecule inhibitors targeting INK4 protein p18INK4C enhance ex vivo expansion of haematopoietic stem cells”, Nature Communication, 2015 Feb 18;6:6328. doi: 10.1038/ncomms7328. PubMed PMID: 25692908; NIHMSID: 707327.
Xie’s Lab has discovered a first small chemical molecule that inhibits p18INK4C, a member of the cyclin-dependent kinase (CDK) inhibitors (CKI), and a potent negative regulator of human hematopoietic stem cells (HSC) self-renewal by using his developed computational chemical genomics screening approach and stem cells specific chemogenomics knowledgebase. The designed and synthesized p18-targeted small drug molecules are used as chemical probes to explore the mechanisms of activating HSC self-renewal in increasing the quantity of functional stem cells. Ultimately, our work is to developing HSC drugs for therapeutic uses. ( Xie - Invited speaker, Nov 2012, " Novel Small Chemical Inhibitors Targeting p18INK4C Protein for Hematopoietic Stem Cell Expansion”, 3rd International Forum on Stem Cells) (Patent pending)
10) Feng, ZW.; Hu, G.; Ma, S.; Xie*, X.-Q. Computational Advances for the Development of Allosteric Modulators and Bitopic Ligands in G Protein-Coupled Receptors. AAPS J. 2015: 1-16. May 5. PMID: 25940084; doi: 10.1208/s12248-015-9776-y

11) Feng, R, Tong, Q, Xie, ZJ, Cheng, HZ, Wang, LR, Lentzsch, S, Roodman, GD, Sfeir, C and Xie, X-Q * “Targeting cannabinoid receptor-2 pathway by phenylacetylamide suppresses the proliferation of human myeloma cells through mitotic dysregulation and cytoskeleton disruption”, Molecular Carcinogenesis, 16 Jan 2015, DOI: 10.1002/mc.22251
Xie’s lab is the first discovered novel Cannabinoid receptor CB2 ligands with new chemical scaffolds and also first report the new therapeutic application of CB2 ligands to human myltiple myeloma intervention (US patent: Xie, X-Q., Myint, K., Kurihara, N., Roodman, D. “P62-ZZ Chemical Inhibitor and Therapeutic Potential for Multiple Myeloma” PCT/US2012/049911; WO2013/022919A1; USSN 61/521,287, Application No. 14/237,494, filed February 6, 2014).
12) Zhang H,Sun S, Zhang W, Xie XQ, Zhu Z, Chai Y, Zhang G.”Biological activities and pharmacokinetics of aconitine, benzoylaconine, and aconine after oral administration in rats.” Drug Test Anal. 2015 Sep 11. doi: 10.1002/dta.1858. [Epub ahead of print]
13) Zhiwei Feng, Larry V. Pearce, Xiaomeng Xu, Xiaole Yang, Peng Yang, Peter M. Blumberg*, and Xiang-Qun Xie*."Structural Insight into Tetrameric hTRPV1 from Homology Modeling, Molecular Docking, Molecular Dynamics Simulation, Virtual Screening and Bioassay Validations". J. Chem. Inf. Model, 2015, 55(3), 572-588. PMID: 25642729 DOI: 10.1021/ci5007189.
14) Zhiwei Feng, Shifan Ma, Guanxing Hu, and Xiang-Qun Xie*. "Allosteric Binding Site and Activation Mechanism of Class C G-Protein Coupled Receptors: Metabotropic Glutamate Receptor Family". AAPS J, 2015, 17(3): 737-753. PMID: 25762450 DOI: 10.1208/s12248-015-9742-8.
15) Zhiwei Feng, Stanton Kochanek, David Close, LiRong Wang, Ajay Srinivasan, Abdulrahma A. Almehizia, Prema Iyer, Xiang-Qun Xie*, Paul Johnston* and Barry Gold*. "Design and Activity of AP Endonuclease-1 Inhibitors". J. Chem Biol. 2015. 19 Apr 10.1007/s12154-015-0131-7
16) Myint KZ, Xie XQ*. “Ligand biological activity predictions using fingerprint-based artificial neural networks (FANN-QSAR)”. Methods Mol Biol. 2015;1260:149-64. PMID: 25502380. doi: 10.1007/978-1-4939-2239-0_9.

(2014)
17) Feng, Zhiwei; Alqarni, Mohammed; Tong, Qin; Chowdhury, Ananda; Wang, Lirong; Xie, Xiang-Qun*, "Modeling, Molecular Dynamics Simulation and Mutation Validation for Structure of Cannabinoid Receptor 2 Based on Known Crystal Structures of GPCRs", J. Chem. Inf. Model. 2014, 54(9), 2483–2499. PubMed ID: 25141027,DOI: 10.1021/ci5002718.
Xie is the first author published first 3D structure model of Cannabinoid Receptor CB2 in 2003 (Xie et al Proteins). With such predicted 3D CB2 model, his group has in silico screened and published/patented several new CB2 ligands with therapeutic potential. This new 3D structure model of CB2 is further improvement and a new discovery of a potential allosteric binding site for the G-protein coupled CB2 receptor (GPCR), a very important drug target but no experimental structure.
18) Feng, RT, Milcarek, C, and Xie, X-Q*. Antagonism of cannabinoid receptor 2 pathway suppresses IL-6-induced immunoglobulin IgM secretion. BMC Pharmacol Toxicol. 2014, 15:30 PMID:24913620, PMCID: PMC4062519; doi:10.1186/2050-6511-15-30.
19) Alqarni, MH, Myint KZ, Tong Q, Yang P, Bartlow P, Wang L, Feng R, and Xie XQ*. Examining the critical roles of human CB2 receptor residues Valine 3.32 (113) and Leucine 5.41 (192) in ligand recognition and downstream signaling activities. Biochem. Biophys. Res. Commun., 2014; 452(3):334-9. doi: 10.1016/j.bbrc.2014.08.048. PMID: 25148941
20) Wang NZ, Bartlow P, Ouyang Q, Xie XQ. “Recent advance in antimultiple myeloma drug development.” Pharm Pat Anal. 2014 May; 3(3):261-77. doi: 10.4155/ppa.14.18.
21) Chen XF, Gao Y, Zhang H, Zhu ZY, Liu M, Liu HB, Hong ZY, Liu WH, Lv DY, Wang LR, Zhuo XY, Zhang JP, Xie X-Q* and Chai YF*. “Comparative Normal/Failing Rat Myocardium Cell Membrane Chromatographic Analysis System for Screening Specific Components That Counteract Doxorubicin-Induced Heart Failure from Acontium carmichaeli (附子)”. Anal Chem. 2014 May 20;86(10):4748-57. PMID:24731167; PMCID:PMC4033634. doi: 10.1021/ac500287e. Epub 2014 Apr 30.
*Cell membrane chromatography (CMC) derived from pathological tissues is ideal for screening specific components acting on specific diseases from complex medicines owing to the maximum simulation of in vivo drug receptor interactions. The developed online high throughput comparative CMC analysis method is suitable for screening specific active components from herbal medicines by increasing the specificity of screened results and can also be applied to other biological chromatography models.
22) Lirong Wang, Xiang-Qun Xie* "Computational target fishing: what should chemogenomics researchers expect for the future of in silico drug design and discovery?" Future Medicinal Chemistry, March 2014, Vol. 6, No. 3, Pages 247-249. PMID:24575960
23) Abdulrahman Almehizia, Peng Yang, Lirong Wang, Xiang-Qun Xie* “Latest Advances in the Multiple Myeloma Drug Research: From Molecular Signaling Pathways to Small Molecules Development” Current Trends in Medicinal Chemistry (2013) 7:105-133.
24) Liu, HB, Wang, L, Su, WW and Xie* X.-Q., ALzPlatform: An Alzheimer’s Disease Domain-Specific Chemogenomics Knowledgebase for Polypharmacology and Target Identification Research. J Comput Info Modeling. 2014, 54(4):1050-60. PMID:24597646; PMCID: PMC4010297; doi: 10.1021/ci500004h. Epub 2014 Mar 20. (Invited Journal Coverpage of the issue).
* This article was selected by Dr. Professor Kenneth M. Merz, Jr., Editor-in-Chief, Journal of Chemical Information and Modeling for the journal cover page. This is a first Alzheimer’s disease knowledgebase reported with integrated chemical genomics information and built-in computing tools/algorithms to facilitate the Alzheimer’s drug discovery and target identification as well as polypharmacology signaling pathway studies..
Coverpage caption: AlzPlatform (www.CBLigand.org/AD/) is an Alzheimer’s Disease (AD) domain-specific chemogenomics knowledge base, featuring a large repertoire of AD drugs and small chemical molecules as well as related genes and protein targets. The comprehensive database and powerful computational algorithms and tools implemented have been developed and maintained by Xie’s laboratory (www.CBLigand.org/XieLab) to facilitate target identification, drug repurposing, and system polypharmacology analyses in a chemogenomics scale for new anti-AD drug discoveries.

25) Ouyang Q, Wang LR, My Y and Xie XQ* Modeling skin sensitization potential of mechanistically hard-to-be-classified aniline and phenol compounds with quantum mechanistic properties” BMC Pharmacology & Toxicology, 2014, 15: 76; doi:10.1186/2050-6511-15-76.

26) Liu, HB, Liang, FY, Su, WW, Xie, X-Q, et al, Significant attenuation of A myloid-β induced pathological behaviors by n-butanol extract from seed of Platycladus orientalis侧柏in Caenorhabditis elegans. Experimental Gerontology. (In press).(I.F. 3.911)
27) Liu, HB, Wang, LR, Su, WW and Xie, X-Q* Advance in Alzheimer disease Drug development. Patents and Clinical trials. Pharm. Pat. Anal. (2014) 3(4), 429–447 (I.F. 2.323)
28) Liu, HB, Liang, FY, Su, WW, Xie, X-Q et al, Lifespan extensionby n-butanol extract from seed of Platycladus orientalis in Caenorhabditis elegans. Journal of Ethnopharmacology. 2013, 147: 366-372. (I.F. 3.014).
29) Sheng S, Wang J, Wang L, Xie, X-Q* et al. Network pharmacology analyses of the antithrombotic pharmacological mechanism of Fufang Xueshuantong Capsule (复方血栓通胶) with experimental support using disseminated intravascular coagulation rats[J]. Journal of ethnopharmacology, 2014, 154(3): 734-744. PMID: 24832112. doi: 10.1016/j.jep.2014.04.048. Epub 2014 May 14
30) Xie X-Q*, Wang L, Liu H, Ouyang Q, Fang C and Su W. “Chemogenomics Knowledgebased Polypharmacology Analyses of Drug Abuse Related G-Protein Coupled Receptors and Their Ligands”. Front. Pharmacol.(Neuropharmacology), 2014, 5:3. PMID:24567719; PMCID: PMC3915241 doi: 10.3389/ fphar.2014.00003.
* * * This is the first research article reported by Xie Lab about chemogenomics knowledge database and integrated polypharmacology analysis tools for GPCRs-related drug abuse targets and associated ligands. Such public knowledgebase will facilitate information exchange and new medicine design and discovery for treatment of drug abuse and addiction.

31) Zeng D, Ouyang Q, Cai Z, Xie XQ, Anderson CJ. New cross-bridged cyclam derivative CB-TE1K1P, an improved bifunctional chelator for copper radionuclides. Chem Commun (Camb). 2014, 4;50(1):43-5. PubMed PMID: 24141371; NIHMSID: 562664. DOI: 10.1039/C3CC45928D (journal coverpage)
* The article was selected by Editor-in-Chief as a coverpage of the journal. With collaborative research work by Dr. Anderson and Dr. Xie labs, innovative image material, CBTE1K1P, was developed and it can serve as an improved BFC for conjugation to small molecules, peptide and protein-based biomolecules, for labelling with 64Cu or other copper radionuclides with applications in diagnostic imaging, radiotherapy, and/or theranostics.
32) Zhang, SJ, Jia, NY, Shao, P, Tong, Q, Xie, X-Q and Bai, Mingfeng “Target-Selective Phototherapy Using a Ligand-Based Photosensitizer for Type 2 Cannabinoid Receptor” Chemistry & Biology, 2014 21(3):338-44. PMID: 24583052; PMCID: PMC3989837; doi:10.1016/j.chembiol.2014.01.009.

(2013)
33) Wang L, Ma C, Wipf P, Liu H, Su W and Xie X-Q*. “TargetHunter: An In Silico Target Identification Tool for Predicting Therapeutic Potential of Small Organic Molecules Based on Chemogenomic Database”. AAPS J. 2013, 15, 395-406 PMID:23292636; PMCID: PMC3675739 (AAPS Special theme issue)
* This is a peer-reviewed article of special theme issue of AAPS Journal: “New Paradigms in Pharmaceutical Sciences: In Silico Drug Discovery” (Dr. Xiang-Qun (Sean) Xie as a Guest Editor). TargetHunter© developed by Xie Lab represents a powerful cloud computing tool with attractive features: (i) ease of use to identify the drug targets and predict therapeutic potential of small molecules; (ii) powerful query data retrieval function; (iii) user choices of desired fingerprints and databases; (iv) high accuracy; and (v) implemented BioassayGeoMap function to easily find the laboratories who have published a bioassay for validation. Such a tool will help to bridge the knowledge gap between biology and chemistry and can significantly boost the productivity of chemogenomics researchers for drug design and discovery.
34) Xie, X.Q*., Chowdhury, A., “ Advances in methods to characterize ligand-induced ionic lock and rotamer toggle molecular switch in G protein-coupled receptors”. Methods Enzymol 2013, 520, 153-174. PMID: 23332699; NIHMSID: 562667. doi: 10.1016/B978-0-12-391861-1.00007-1.
35) Yang P, Wang L, Feng R, Almehizia AA, Tong Q, Myint K-Z, Qin Ouyang, Alqarni MH, Wang L, Xie* X-Q , “Novel Triaryl Sulfonamide Derivatives as Selective Cannabinoid Receptor 2 Inverse Agonists and Osteoclast Inhibitors: Discovery, Optimization, and Biological Evaluation”, J Med Chem 2013, 56(5):2045-2058. PMID:23406429, NIHMSID: 449514. doi: 10.1021/jm3017464
* Xie Lab reported a novel CB2 receptor selective ligands, N,N′-((4-(Dimethylamino)phenyl)methylene)bis(2-phenylacetamide), that was discovered by using 3D pharmacophore database searches and was biologically confirmed as a new class of CB2 inverse agonists. Among the 52 derivatives designed/synthesized, five compounds were developed and also confirmed as CB2 inverse agonists with the highest CB2 binding affinity (CB2 Ki of 22 to 85 nM, EC50 of 4 to 28 nM) and best selectivity (CB1/CB2 of 235- to 909-fold). Furthermore, osteoclastogenesis bioassay indicated that PAM compounds showed great inhibition of osteoclast formation. Especially, compound 26 showed 72% inhibition activity even at the low concentration of 0.1 μM. The cytotoxicity assay suggested that the inhibition of PAM compounds on osteoclastogenesis did not result from its cytotoxicity. Overall, the data presented in this paper show that PAM is a new scaffold different from the existing CB2 ligands and is promising for the design of new selective CB2 receptor inverse agonists for further CB2 signaling and antiosteoclast studies. The work also led to two patents: (i) Xie, X-Q., et al “Novel CB2 Inverse Agonists and Therapeutic Potential for Multiple Myeloma and Osteoporosis Bone Diseases”. Patent USSN: 61/576,041. (ii) Xie, X-Q*., Jet al. “Ligands Specific for Cannabinoid Receptor Subtype 2”. PCT/US2008/012395; WO 2009/058377; US20110118214 A1. Application No. 12/740,099; Patent No. 8466131

36) Ma C, Wang LR, Yang P, Tong Q, Myint KZ, and Xie X-Q*. “LiCABEDS II. Modeling of Ligand Selectivity for G-protein Coupled Cannabinoid Receptors”, J. Chem. Inf. Model., 2013, 53(1):11-26. PMID:23278450; NIHMSID: 433009. PMID: 23278450. doi: 10.1021/ci3003914.
37) Ouyang Q, Tong Q, Peng RT, Myint KZ, Yang P, Xie* X-Q: Trisubstituted Sulfonamides: A New Chemotype for Development of Potent and Selective CB2 Receptor Inverse Agonists. ACS Med Chem Lett 2013, 4(4):387-392. DOI: 10.1021/ml3004236. NIHMSID: 451185. ml3004236.
38) Gao X, Huang Y, Makhov AM, Epperly M, Lu J, Grab S, Zhang P, Rohan L, Xie XQ, Wipf P, Greenberger J, Li S. “Nanoassembly of surfactants with interfacial drug-interactive motifs as tailor-designed drug carriers.” Mol Pharm. 2013,10(1):187-98. PMID:23244299
39) Liu, HB, Liang,FY, Su, WW, Wang,N, Lv,ML, Li, PB, Pei,Z, Zhang,Y and Xie, X-Q,, Wang, LR, Wang, YG, “Lifespan extension by n-butanol extract from seed of Platycladus orientalis in Caenorhabditis elegans”, J Ethnopharmacol. 2013 May 20;147(2):366-72. doi: 10.1016/j.jep.2013.03.019. Epub 2013 Mar 21.PMID: 23523941

40) Laporte MG, Tsegay S, Hong KB, Lu C, Fang C, Wang L, Xie X-Q, Floreancig PE. Construction of a Spirooxindole Amide Library through Nitrile Hydrozirconation-Acylation-Cyclization Cascade. ACS Comb Sci. 2013, 15(7):344-9. PMID: 23731121; PMCID: PMC3800499. (Journal Coverpage)
* This peer-reviewed research article was invited by Dr. M.G. Finn, ACS Editor-in-Chief as a cover page issue of ACS Comb Sci Journal. Xie group applied his developed powerful 3D chemistry-matrix compound library profiling algorithm tool to evaluate and visualize structural and stereochemical diversity of compound library. The program has been extensively used by chemists (including Dr. MG Laporte and PE Floreancig groups here as an example) in combinatorial chemistry to design structurally-divesed drug chemical molecules for diversity oriented synthesis.

(2012)
41) Peng Yang, Lirong Wang and Xiang-Qun Xie*. Latest advances in novel cannabinoid CB2 ligands for drug abuse and their therapeutic potential. Future Med Chem 2012, 4(2):187-204. PMID: 22300098
42) Manuj Tandon, Lirong Wang, Qi Xu, Xiang-Qun Xie, Peter Wipf and Q. Jane Wang. “A Targeted Library Screen Reveals a New Selective Inhibitor Scaffold for Protein Kinase D”. Plos One 2012;7(9):e44653. doi: 10.1371/journal.pone.0044653 (*these authors contributed equally) PMID: 23028574

43) Srinivasan, A; Wang, L; Cline, C.J.; Xie, Z.J. Sobol, R. W.; Xie, Xiang-Qun; Gold, B*. “The Identification and Characterization of Human AP Endonuclease-1 Inhibitors”. Biochemistry 2012 (51), 6246-6259. PMID: 22788932
* Xie Lab applied his developed computational chemogenomics virtual screening approach and successfully discovered novel DNA damage repair protein APE inhibitors. The research has resulted in a joint patent: Gold, B. and Xie, X-Q, “Inhibitors of AP endonuclease-1/redox factor-1 (hAPE1) activity.” PCT/US2013/023653, USSN: 61/593,276, Pitt Ref. No. 02385, and a joint publication “The Identification and Characterization of Human AP Endonuclease-1 Inhibitors”. Biochemistry 2012 (51), 6246-6259. PMID: 22788932.

44) Yang P, Myint K-Z, Tong Q, Cao H, Almehizia AA, Feng R, Hamed AM, Wang L, Gertsch J, Teramachi, J, Kurihara, N, Roodman, D and Xie* X-Q. “Lead Discovery, Chemistry Optimization, and Biological Evaluation Studies of Novel Biamide Derivatives as CB2 Receptor Inverse Agonists and Osteoclast Inhibitors. “ J. of Med. Chem. 55(2012), 9973-9987. PMID:23072339

45) Myint, K., Wang, LR, Tong, Q and Xie, X-Q*. “Molecular Fingerprint-based Artificial Neural Networks QSAR (FANN-QSAR) for Ligand Biological Activity Predictions”. Molecular Pharmaceutics 9(2012), 2912-23. PMID:22937990.
* This is the first report about a fingerprint-based artificial neural network (FANN) approach in QSAR research field developed by Xie Lab. The FANN-QSAR algorithm can be used as a robust virtual screening tool in screening large structurally diverse databases for novel lead discovery. It could benefit biologists/chemists a lot for the development/identification of ligands with high potency.
46) Wang, L.R.; Ma, C.; Wipf, P. and Xie, X.-Q.* “ Linear and Non-linear Support Vector Machine for the Classification of Human 5-HT1A Ligand Functionality”, Molecular Informatics, 31(2012), 85-95
47) Gold, B; Iyer, P; Srinivasan, A; and Xie, X.-Q., “Selective formation of N3-Methyladenine lesions in DNA and their removal by base excision repair”. 64th Southeast Regional Meeting of the American Chemical Society, Raleigh, NC, United States, November 14-17 (2012), SERM-888
48) Chowdhury A, Feng RT, Tong Q, Zhang Y, Xie X-Q*. “Mistic and TarCF as fusion protein partners for functional expression of the cannabinoid receptor 2 in Escherichia coli” Protein Expr & Purif 83(2012),128-134.
49) Lu, Dujuan; Chambers, Peter; Wipf, Peter; Xie, X-Q; Englert, Danielle; Weber, Stephen, “Lipophilicity screening of novel drug-like compounds and comparison to clog P.” J. of Chromatography, A (2012), 1258, 161-167.
50) Brummond, Kay M.; Goodell, John R.; LaPorte, Matthew G.; Wang, Lirong; Xie, Xiang-Qun “Synthesis and in silico screening of a library of β-carboline-containing compounds.” Beilstein Journal of Organic Chemistry (2012), 8, 1048-1058. PMID:23019432
(2011)
51) Painter, TO.; Wang, LR; Majumder, S; Xie, X.-Q.*; Brummond, K M. “Diverging DOS Strategy Using an Allene-Containing Tryptophan Scaffold and a Library Design that Maximizes Biologically Relevant Chemical Space While Minimizing the Number of Compounds. “ ACS Combinatorial Science 13(2011), 166-174. (*Xie is the co-correspondent).
52) Ma, C, Wang, LR, Xie, XQ* “GPU Accelerated Chemical Similarity Calculation for Compound Library Comparison” JCIM, 51 (2011), 1521–1527
*This is one of the pioneer researches conducted on the application of high performance computational unit (GPU) in cheminformatics research. The novel GPU-accelerated Tanimoto calculation significantly speeds up similarity search and data mining of large chemical databases. The source code was publicly available. The scientific community may immediately take advantages of this new technology for computer-aided drug design with GPU-acceleration technology. The GPU program developed here are well-liked by computational chemistry communities at academics and pharma industries. Merck Serono company at Boston invited Xie group to implement the GPU program into the company’s computing systems.
53) Teramachi J, Myint KZY, Feng RT, Xie XQ, Windle JJ, Roodman D, Kurihara N. “Blocking the ZZ Domain of Sequestosome 1/p62 Suppress the Enhancement of Myeloma Cell Growth and Osteoclast Formation by Marrow Stromal Cells”. Blood, 2011, 118(21):406
* In collaboration with UPMC clinician David Roodman, MD, Xie’s lab discovered the first small chemical molecule inhibitor targeting an important protein, Sequestosome 1/p62, that involves in tumor cell autophagy signaling pathway. The research led to a new patent invention for a promising drug for filing pre-IND drug for multiple myeloma treatment. Xie, X-Q., et al. “P62-ZZ Chemical Inhibitor and Therapeutic Potential for Multiple Myeloma” PCT/US2012/049911; WO2013/022919 A1; USSN 61/521,287.
54) Zhang, YX, Xie, ZJ, Wang, LR, Lazo, JS, Gertsch, J, Schribeit B, Xie X-Q*: Mutagenesis and computer modeling studies of a GPCR conserved residue W5.43(194) in ligand recognition and signal transduction for CB2 receptor. International Immunopharmacology 11(2011), 1303-10
55) Ma, C, Lazo, JS, and Xie, X-Q*: Compound Acquisition and Prioritization (CAP) Algorithm for Constructing Structurally Diverse Chemical Libraries. J. Comb. Chem. 13(2011), 223-231.
* The Compound Acquisition and Prioritization (CAP) algorithm developed by Xie Lab helps to identify the to-be-acquired candidate compounds and demonstrate the diversity increment by importing the acquired/purchased compounds. As a rational approach for drug library design, the distance-based selection rule exhibits certain advantages in prioritizing compound selection to enhance the overall structural diversity of an existing in-house compound collection or virtual combinatorial library for in silico drug screening, diversity oriented synthesis and high-throughput screening.
56) Ma C, Wang L, Xie X-Q*: LiCABEDS (Ligand Classifier of Adaptively Boosting Ensemble Decision Stumps). A Machine Learning Based Algorithm for GPCR ligand selectivity and functionality predictions (patent pending). . J. of Chem. Inf. and Modelings 51(2011), 521-531.
* This is a powerful machine learning tool developed by Xie Lab for modeling of the functionality and selectivity bioactivities of structural diverse compounds. Its advantage includes free-of-structure alignment, free-of-receptor homologue, high computation efficiency, etc. Results are validated both retrospectively and perceptively. LiCABEDS shows great potential to enhance the productivity of drug screening projects.
57) Wang, L.R. Xie, ZJ, Wipf, Peter, and Xie*, X.-Q.* “Residue Preference Mapping of Ligand Fragments in PDB” . J. of Chem. Inf. and Modelings, 51(2011), 807-815.
*This is the first report about analysis and interpretation of the interaction of ligand fragments with 20 ammonia acids in a large scale. LigFrag-RMP algorithm is expected not only to promote the understanding of the preferred determinant of ligand binding but also be used as primary filtering processes in virtual screening to remove ineligible compounds, thus as a potential tool for fragment-based drug design.
58) Xie, X.-Q. (Sean)*, “Exploiting PubChem for Virtual Screening”, Expert Opin. Drug Discov. 5(2010), 1205-1220. 1458330 NIHMSID23741 (invited review for NIH PubChem library)
59) Chen, J-Z., Myint, K-Z. and Xie, X-Q.* A Novel QSAR Approach for GPCR CB2-Antagonistic Triaryl Bis-Sulfone Analogs: A Combined Molecular Morphological and Pharmacophoric Approach, SAR and QSAR in Environmental Research 22 (2011), pp. 525-44
60) Kyaw Myint, Chao Ma, Lirong Wang and Xiang-Qun Xie*. “Fragment-based QSAR Algorithm Development for Compound Bioactivity Prediction”, SAR QSAR Environ Res. 2011, 22(3):385-410

(Active)
P30DA035778
Project Title: NIDA Center of Excellence OF Computational Drug Abuse Research (CDAR)
Funding Agency: National Institutes of Health (NIH, NIDA)
Investigator Relationship: P.I. and Center Director (X.-Q. Xie)
Dates of Funding 07/01/2014-06/31/2019
Annual Direct Costs and Overall Direct Costs: $1,126,949,000 and $5,960,391
Grant or Contract Research Grant
** To develop/integrate tools for DA-domain-specific chemical-to-protein-to-genomics mapping using cheminformatics, computational biology and computational genomics methods by centralizing computational chemical genomics (or chemogenomics) resources while also making them available on a cloud server. Overall, the Center will strive to achieve the long-term goal of translating advances in computational chemistry, biology and genomics toward the development of novel personalized DA therapeutics.

(Active)
R01DA025612 P.I.: X.-Q. Xie 4/1/2010-03/31/2016
Project Title: Structure/Function of the GPCR CB2 binding Pockets and G-protein Recognition Sites
Funding Agency: National Institutes of Health (NIDA)
Investigator Relationship: P.I. (X.-Q. Xie)
Dates of Funding 04/01/2010-03/31/2015 (active)
Annual Direct Costs and Overall Direct Costs: $250,000 and $1,250,000
Grant or Contract Research Grant
**The objective is to identify/characterize the key residues/functional domains and elucidate their 3D structures of recognition pockets important to agonist and antagonist binding as well as G-protein coupling recognitions in the CB2 receptor by the combined biophysical and biochemical approaches.

NIH R21 HL109654 P.I. X.-Q. Xie 7/1/2011-6/30/2014
Screen/Design the CKl p18 Inhibitors for Hematopoietic Stem Cell Self-Renewal
“This project is to screen/design small molecules targeting CKI p18, and use them as chemical probes for characterization of p18 protein binding and p18/CDK6 disruption, and further exploration of the mechanisms of activating HSC self-renewal in increasing the quantity of functional stem cells. Ultimately, our work will lead to developing HSC drugs for therapeutic uses.”

NIGMS P50 GM067082 (active) (Dr. Peter Wipf, Director)
Project Title: New Concepts, Methodologies and Scaffolds for Diversity-Oriented Organic Synthesis
Funding Agency: National Institutes of Health, NIGM
Investigator Relationship: Co-P.I./Core Co-Director (X.-Q. Xie)
Dates of Funding 10/01/08-09/30/14 (active)
Annual Direct Costs: $2,126,233, five years
Grant or Contract Research Grant
**The objective is to build a Pitt Center for Chemical Methodologies and Library Development (PCMLD) and design/develop diverse chemical library for NIH SML deposite.

 NIH NCI/SAIC Contract No. 29XS127 (active) Co-PI X.-Q. Xie 9/1/2011-12/31/2013
University of Pittsburgh Chemical Diversity Center” (Donna M. Huryn, PI) (UP-CDC Project ID#1015)
The project is to conduct computational chemical genomics approach for STAT3 lead discovery and structurally-diverse library design.

Invited speakers/meeting presentations (last 5 years):
1) (Invited speaker) Xie, XQ, 2016 May 27, “Clinical System Pharmacology by Chemogenomics Knowledgebase”, 2016 Sino-America Forum of Clinical Pharmacy at Fudan University, China

2) (Invited speaker) Xie, XQ, 2016 June 4 “Benchtop to Bedside” Precision System Pharmacology by Chemogenomics Knowledgebases and TargetHunter©” Tasly R&D Institute, China

3) (Invited speaker) Xie, XQ, 2016 June 3, “Precision System Pharmacology. A Case Study “Benchtop to Bedside” of Alzheimer’s Disease (AD) via Chemogenomics Knowledgebases and TargetHunter©”, Medicinal Chemistry Biology Key Laboratory, Nankai University, China

4) (Invited speaker) Xie, XQ, 2016 June 13, “Stem Cells-specific Chemogenomics Knowledgebase and Discovery of First INK4C Chemical Modulator for Hematopoietic Stem Cell Expansion”, Seoul National University, South Korea.

5) (Invited speaker) Xie, XQ, 2016 June 16, “Precision Pharmacology. Thinking inside Precision Medicine via Diseases-Specific Chemogenomics Knowledgebases and TargetHunter©”. 2016 Bit’s 14th Annual Congress of International Drug Discovery Science and Technology, June 16-18, Gyeonggi, South Korea.

6) (Invited speaker) Xie, XQ, 2016 June 20, “GPU-accelerated Cloud Computing Chemogenomics Knowledgebases and TargetHunter© for Precision System Pharmacology and Drug Discovery” Guangzhou Branch of Chinese Academy of Sciences, Guangdong, China

7) Invited Speaker, 2016 Jan 20 “Short-Term and Long-Term Strategic Plans and Execution”, College of Pharmacy, University of Hawaii, Hilo, Hawaii.

8) Invited speaker, 2016, January 27, “Precision System Pharmacology for Multiple Myeloma and Osteoporosis: Thinking Inside Precision Medicine via Diseases-Specific Chemogenomics Knowledgebases and TargetHunter©”, Pittsburgh Center for Bone & Mineral Research Seminar Series, University of Pittsburgh.

9) Speaker and organizing committee chair, symposium “Pharmaceutical Sciences in the Era of Big Data” 2015 AAPS Annual meeting, Orlando, Florida, USA. October 21-26, 2015

10) Speaker/Chair, “Computational Chemogenomics Knowledgebase for Drug Abuse Research”, National Center for Computational Drug Abuse Research (CDAR), May 14, 2015

11) Invited Speaker 2015 April 10, “Diseases-Specific Chemogenomics Knowledgebases and TargetHunter© for System Pharmacology and Alzheimer’s Disease Drug Discovery Research”, FDA - Center for Devices and Radiological Health, Office of Science and Engineering Laboratories , Division of Biology, Chemistry, and Materials Science, Silver Spring, MD, USA

12) Invited Speaker 2015 March 12, “Diseases-Specific Chemogenomics Knowledgebases and TargetHunter© for System Pharmacology and Alzheimer’s Disease Drug Discovery Research” Alzheimer’s Disease Clinical Research Center, School of Medicine, University of Pittsburgh, PA

13) Invited Speaker 2015 Feb “Diseases-Specific Chemogenomics Knowledgebases and Drug TargetHunter© Center for Drug Discovery (CDD), School of Pharmacy, Northeastern University, Boston, MA USA

14) Invited Speaker 2015 Jan 30, “Diseases-Specific Chemogenomics Knowledgebases and TargetHunter© for Quantitative System Pharmacology” Department of Informatics, University of Pittsburgh, PA

15) Invited Speaker 2014 “Cloud Computing and Diseases-Specific Chemogenomics Knowledgebase for System Pharmacology Drug Discovery and Personalized Medicine” at New Frontiers in Therapeutic Agents – Successes in Drugging the Undruggable Conference, jointly sponsored by the John S. Dunn Gulf Coast Consortium for Chemical Genomics (GCCCG) and the Texas Screening Alliance for Cancer Therapeutics (TxSACT). April 16-17, 2014, The University of Texas MD Anderson Cancer Center, Houston, Texas. USA.

16) Invigted Speaker 2014 ”Manipulation of Hematopoietic Stem Cell Expansion by INK4C Chemical Inhibitors” December 18, 2014, Stem Cell Research Center, University of Pittsburgh, Pittsburgh USA

17) In vited Speaker 2014 ”Cloud Computing Target Hunter and Disease-Specific Chemogenomics Knowledgebase for System Pharmacology Drug Discovery and Personalized Medicine”. June 23, 2014 University of Florida, Gainseville, Florida, USA

18) Invited 2013 ”Cloud Computing and Diseases Domain-Specific Chemogenomics Knowledgebases for Systems Pharmacotherapy and Personalized Medicine.” Workshop on Quantitative Systems Pharmacology in Personalized Medicine. Nov. 2013, Pittsburgh, USA.

19) Invited seminar speaker, April 24, 2012, “Computational Chemical Genomics Screening Center” Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

20) Invited speaker, March, 28, 2012, “Computational Chemical Genomics Screening Center”, Department of Developmental Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

21) Invited speaker, December 19, 2011 “GPCR Chemical Genomics for Drug Discovery”, Shanghai JiaoTong University, College of Pharmacy, Shanghai, China

22) Invited speaker, December 28, 2011 “Computational GPCR Chemical Genomics for Drug Discovery”, Sun-Yat Sen University, College of Life Sciences, Guangzhou, China

23) Invited speaker, July 28, 2011 “GPCR Chemical Genomics for Drug Discovery”, Shanghai NanKai University, College of Pharmacy, Tianjin, China

24) Invited speaker, June, 10, 2012, “Cloud computing and High Throughput Experimental Chemical Genomics Screening Approaches for Lead Discovery”, Jinan University, GuangZhou, China

25) Invited speaker, June, 20, 2012, “Cloud computing and High Throughput Experimental Chemical Genomics Screening Approaches for Natural Product Target Identification and Lead Discovery”, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, China

26) Invited speaker, June, 23, 2012, “Computational Chemical Genomics Screening Approaches for Natural Product Target Identification and Lead Discovery”, XiShuanBanNan Tropical Botanic Garden, Chinese Academy of Sciences, XiShuanBanNan, China

(Active)
NIH NIDA P30 DA035778-01A1 (Xie and PI/Center Director)
7/1/2014 - 6/30/2019 $5,960,391
NIDA Center of Excellence for Computational Drug Abuse Research (CDAR)

New awarded DOD grant AZ150100   (PI Dr. Xiang-Qun Xie) letter of award received.
9/1/2016-8/31/2019
Chemogenomics Systems Pharmacology Approach for TBI and AD Research