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    Xiangqun (Sean) Xie’s Laboratory publications and patents for the past five years
    Publications for past 5 years:


    • 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.
    • 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 VivoLeukemia (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-kB, 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-kB and p38 MAPK signaling.Our discovered lead compound XIE3P62ZZ (#3 or XRK3, 4.31 mM) 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 mM) 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.

    • 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/ncomms732. 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)

    • 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
    • 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).

    • 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.
    • 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.
    • 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.
    • 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.


    • 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.

    • 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.
    • 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.
    • 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.
    • 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”. 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.

    • 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.
    • 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.
    • 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.

    • 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.
    • 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 in Caenorhabditis elegans. Experimental Gerontology. (In press).(I.F. 3.911)
    • 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).
    • 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).
    • Sheng S, Wang J, Wang L, Xie, X-Q* et al. Network pharmacology analyses of the antithrombotic pharmacological mechanism of Fufang Xueshuantong Capsule 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.
    • 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.

    • 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.

    • 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.


    • 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.

    • 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.
    • 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

    • 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.
    • 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 Lett2013, 4(4):387-392. DOI: 10.1021/ml3004236. NIHMSID: 451185.  ml3004236.
    • 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.
    • 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
    • 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.


    • 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.
    • 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
    •  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.

    • 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
    • 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.

    • 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.
    • 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.
    • 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.
    • 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.
    • 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


    • 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).
    • 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.

    • 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

    • 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.
    • 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.

    • 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.

    • 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.

    • 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)
    • 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
    • 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


    Invention drug discovery patents and patent disclosure filed for the past five years:

    • Xie, X-Q*., J.Z. Chen and Y.X. Zhang. “Ligands Specific for Cannabinoid Receptor Subtype 2”. Patent No: US8466131 B2, Application No. US 12/740,099; PCT No: PCT/US2008/012395; Publication date: Jun 18, 2013; Filing date: Oct 31, 2008. https://www.google.com/patents/US8466131?dq=20110118214
    • Xie, X-Q*., J.Z. Chen and Y.X. Zhang. “Ligands Specific for Cannabinoid Receptor Subtype 2”. Publication No: US20110118214 A1, Application No. US 12/740,099; PCT No: PCT/US2008/012395; Publication date: May 19, 2011; Filing date: Oct 31, 2008.
    • Xie, X-Q*., J.Z. Chen and Y.X. Zhang. “Ligands Specific for Cannabinoid Receptor Subtype 2”. Publication No: WO2009058377 A1, Application No. PCT No: PCT/US2008/012395; Publication date: May 7, 2009; Filing date: Nov 1, 2007.
    • Xie, X-Q*., Myint, K., Kurihara, N., Roodman, D. “P62-ZZ Chemical Inhibitor” (This is the first p62 chemical inhibitor with therapeutic potential for multiple myeloma). Publication No: US 20150175607 A1 (Application No.US No14/237,494);  PCT Publication No: WO2013022919 A1 (Application No: PCT/US2012/049911); Provisional USSN 61/521,287. Filing date: Aug 8, 2012; Publication date: June 25, 2015.  ) Publication No: CN103930166 A (Application No: CN 201280048718). http://www.google.com/patents/US20150175607?cl=en
    • Xie, X-Q*., Myint, K., Kurihara, N., Roodman, D. “P62-ZZ Chemical Inhibitor” (This is the first p62 chemical inhibitor with therapeutic potential for multiple myeloma). Publication No: US 20150175607 A1, Application No.US 14/237,494, PCT/US2012/049911, Publication date: June 25, 2015, Filing date: Aug 8, 2012.
    • Xie, X-Q*., Myint, K., Kurihara, N., Roodman, D. “P62-ZZ Chemical Inhibitor” (This is the first p62 chemical inhibitor with therapeutic potential for multiple myeloma). Publication No: WO2013022919 A1, PCT/US2012/049911, Publication date: Feb 14, 2013, Filing date: Aug 8, 2012; Provisional USSN 61/521,287.
    • Xie, X-Q* “P62-ZZ Chemical Inhibitor” (This is the first p62 chemical inhibitor with therapeutic potential for multiple myeloma). Publication No: CN103930166 A, Application No: CN 201280048718, PCT No: PCT/US2012/049911; Publication date: June 16, 2014. Filing date: Aug 8, 2012. 
    • Xie, X-Q.*, Feng, RT, and Peng Yang “Preparation of phenylacetamide compounds as cannabinoid receptor 2 (CB2) inverse agonists and therapeutic potential for multiple myeloma and osteoporosis bone diseases”. Patent No. US 8772541 B2 (Appl No: 13/715603, Publication date: July 8, 2014); Patent No. US20140296294 A1 ( Appl No: 14/305,941. Filing date: 06/16/2014); US20130172388 A1 (Appl No: US 13/715,603, Filing date: 12/14/2012) ; Provisional US Application No: 61/576,041; Pitt No: 02549. https://www.google.com/patents/US8772541?dq=US+8772541
    • Xie, X-Q.*, Feng, RT, and Peng Yang “Cannabinoid receptor 2 (CB2) inverse agonists and therapeutic potential for multiple myeloma and osteoporosis bone diseases” Patent No. US 8772541 B2; Appl No: 13/715603; Publication date: July 8, 2014.
    • Xie, X-Q.*, Feng, RT, and Peng Yang “Novel cannabinoid receptor 2 (cb2) inverse agonists and therapeutic potential for multiple myeloma and osteoporosis bone diseases” Patent No. US20140296294 A1; Appl No: 14/305,941; Filing date:  Jun 16,2014.
    • Xie, X-Q.*, Feng, RT, and Peng Yang “Novel cannabinoid receptor 2 (cb2) inverse agonists and therapeutic potential for multiple myeloma and osteoporosis bone diseases” US20130172388 A1; Appl No: US 13/715,603, Filing date: Dec 14, 2012); Provisional US Application No: 61/576,041; Pitt No: 02549
    • Xie X-Q: New provisional patent application No. 62/174,465: “p62-ZZ CHEMICAL INHIBITOR”. Filed on June 11, 2016.
    • Cheng, T, Xie, XQ, Gao, YD, and Yang P. “p18 small molecule chemical inhibitor and human hematopoietic stem cell expansion ex vivo”. 专利号Patent No. 201510081641. Publication No: 2015061001183450. Classification No. C07C303/38(2006.01) (300457). 2015-06-12, 17:27 (http://www.aptchina.com/zhuanli/11599713/).
    • Xie, X-Q.*, Feng Z. Human transient receptor potential vanilloid type 1 (hTRPV1) Chemical Agents. (2015) Pitt Ref.:  03491. Attorney Ref.:  076333-0673. Application No.:  62/113,429
    • Xie, X-Q.*, Yang P, Almehizia A. Novel Cannabinoid Receptor CB2 Ligand 4-(aminomethyl)- N,N-diethylanilines Innovator(s). Pitt Ref No.: 03493, 2015.
    • Gold, B. and Xie, X-Q, Srinivasan, A and Wang, L.R. “Compounds and Methods for Inhibition of AP endonuclease-1/redox factor-1 (hAPE1) activity.” International Appl No.: PCT/US2013/023653, WO2013/116228; USSN: 61/593,276, Pitt Ref. No. 02385
    • Yin, XM and Xie, X-Q, “Modulation of Autophagy by Atg4B inhibitors” Int. Reference 02204 (patent pending).
    • Xie, X-Q, Mu, Ying and Xie, ZJ “CD1X on Dendritic Cells: A Novel Biomarker of Metallic Allergens and Metallic Non-Allergens”. Int. Reference 03156 (Patent Pending).




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