Nicholas Lawrence, PhD

Our research concerns the development of new anticancer drugs using a combination of synthetic chemistry and natural product isolation

Associations

• Drug Discovery
• Malignant Hematology
• Pentecost Family Myeloma Research Center
• Molecular Medicine Program
• Molecular Oncology & Drug Discovery Program

Education & Training

Graduate:

• Cambridge University, UK, PhD - Organic Chemistry

Our laboratory's efforts are focused on the synthesis of new anticancer agents. The goal of the laboratory is to design and develop synthetic methodology to provide small organic molecules to act as selective anticancer agents against a range of molecular targets. Our research concerns the development of new anticancer drugs using a combination of synthetic chemistry and natural product isolation; it involves a very productive collaborative program incorporating both chemistry and biology. One aspect of our research concerns the design and function of tumor vasculature targeting anticancer agents that interact with the elements of the cytoskeleton. We are investigating the nature of the colchicine-binding site of Beta-tubulin by the design of appropriate photo-affinity labeling agents and molecular modeling methods. Our laboratory is developing new anticancer agents based on agents related to combretastatins. These agents show potent activity in vitro and in vivo and are currently being prepared via serial and parallel synthesis for evaluation as tumor vasculature targeting drugs. The program also involves the structure activity study of complex derivatives of cucurbaticins. Natural products feature highly in our research, particularly as lead structures in the drug development process. The discovery of new bioactive natural products can often be a laborious venture. We are therefore developing novel natural product isolation techniques to help identify new structures with anticancer activity. In addition, we focus on the development of novel synthetic methodology. This has included methods for the clean asymmetric reduction of ketones using polymeric siloxanes. We are now developing new reagents for use in design and preparation of combinatorial libraries. Our a long-standing interest in multi-component reactions based on vicarious nucleophilic aromatic substitution now provides new processes for the rapid construction of molecular scaffolds for the development of combinatorial libraries for use in the high throughput screening lab.

• Walton K, Walker K, Riddle M, Koehn BH, Reff J, Sagatys EM, Linden MA, Pidala J, Kim J, Lee MC, Kiluk JV, Hui JYC, Yun SY, Xing Y, Stefanski H, Lawrence HR, Lawrence NJ, Tolar J, Anasetti C, Blazar BR, Sebti SM, Betts BC. Dual JAK2/Aurora kinase A inhibition prevents human skin graft rejection by allo-inactivation and ILC2-mediated tissue repair. Am J Transplant. 2022 Mar.22(3):717-730. Pubmedid: 34668635. Pmcid: PMC8897228.
• Sawant M, Mahajan K, Renganathan A, Weimholt C, Luo J, Kukshal V, Jez JM, Jeon MS, Zhang B, Li T, Fang B, Luo Y, Lawrence NJ, Lawrence HR, Feng FY, Mahajan NP. Chronologically modified androgen receptor in recurrent castration-resistant prostate cancer and its therapeutic targeting. Sci Transl Med. 2022 Jun.14(649):eabg4132. Pubmedid: 35704598.
• Bian Y, Alem D, Beato F, Hogenson TL, Yang X, Jiang K, Cai J, Ma WW, Fernandez-Zapico M, Tan AC, Lawrence NJ, Fleming JB, Yuan Y, Xie H. Development of SOS1 Inhibitor-Based Degraders to Target KRAS-Mutant Colorectal Cancer. J Med Chem. 2022 Dec.65(24):16432-16450. Pubmedid: 36459180. Pmcid: PMC10113742.
• Pidala J, Walton K, Elmariah H, Kim J, Mishra A, Bejanyan N, Nishihori T, Khimani F, Perez L, Faramand RG, Davila ML, Nieder ML, Sagatys EM, Holtan SG, Lawrence NJ, Lawrence HR, Blazar BR, Anasetti C, Sebti SM, Betts BC. Pacritinib Combined with Sirolimus and Low-Dose Tacrolimus for GVHD Prevention after Allogeneic Hematopoietic Cell Transplantation: Preclinical and Phase I Trial Results. Clin Cancer Res. 2021 May.27(10):2712-2722. Pubmedid: 33753457. Pmcid: PMC8127396.
• McGuire JJ, Frieling JS, Lo CH, Li T, Muhammad A, Lawrence HR, Lawrence NJ, Cook LM, Lynch CC. Mesenchymal stem cell-derived interleukin-28 drives the selection of apoptosis resistant bone metastatic prostate cancer. Nat Commun. 2021 Feb.12(1):723. Pubmedid: 33526787. Pmcid: PMC7851397.
• Davis RR, Li B, Yun SY, Chan A, Nareddy P, Gunawan S, Ayaz M, Lawrence HR, Reuther GW, Lawrence NJ, Schönbrunn E. Structural Insights into JAK2 Inhibition by Ruxolitinib, Fedratinib, and Derivatives Thereof. J Med Chem. 2021 Feb.64(4):2228-2241. Pubmedid: 33570945. Pmcid: PMC8327781.
• Walton K, Fernandez MR, Sagatys EM, Reff J, Kim J, Lee MC, Kiluk JV, Hui JYC, McKenna D, Hupp M, Forster C, Linden MA, Lawrence NJ, Lawrence HR, Pidala J, Pavletic SZ, Blazar BR, Sebti SM, Cleveland JL, Anasetti C, Betts BC. Metabolic reprogramming augments potency of human pSTAT3-inhibited iTregs to suppress alloreactivity. JCI Insight. 2020 May.5(9). Pubmedid: 32255769. Pmcid: PMC7253027.
• Hesterberg RS, Beatty MS, Han Y, Fernandez MR, Akuffo AA, Goodheart WE, Yang C, Chang S, Colin C, Alontaga AY, McDaniel J, Mailloux AW, Billington JMR, Yue L, Russell S, Gillies RJ, Yun SY, Ayaz M, Lawrence NJ, Lawrence H, Yu XZ, Fu J, Darville LN, Koomen JM, Ren X, Messina J, Jiang K, Garrett TJ, Rajadhyaksha A, Cleveland JL, Epling-Burnette PK. Cereblon harnesses Myc-dependent bioenergetics and activity of CD8+ T lymphocytes. Blood. 2020 Aug.136(7):857-870. Pubmedid: 32403132. Pmcid: PMC7426646.
• Sun X, Ren Y, Gunawan S, Teng P, Chen Z, Lawrence HR, Cai J, Lawrence NJ, Wu J. Selective inhibition of leukemia-associated SHP2 mutant by the allosteric SHP2 inhibitor SHP099. Leukemia. 2018 May.32(5):1246-1249. Pubmedid: 29568093. Pmcid: PMC6166654.
• Mahajan NP, Coppola D, Kim J, Lawrence HR, Lawrence NJ, Mahajan K. Blockade of ACK1/TNK2 To Squelch the Survival of Prostate Cancer Stem-like Cells. Sci Rep. 2018 Jan.8(1):1954. Pubmedid: 29386546. Pmcid: PMC5792546.
• Nerlakanti N, Yao J, Nguyen DT, Patel AK, Eroshkin AM, Lawrence HR, Ayaz M, Kuenzi BM, Agarwal N, Chen Y, Gunawan S, Karim RM, Berndt N, Puskas J, Magliocco AM, Coppola D, Dhillon J, Zhang J, Shymalagovindarajan S, Rix U, Kim Y, Perera R, Lawrence NJ, Schonbrunn E, Mahajan K. Targeting the BRD4-HOXB13 Coregulated Transcriptional Networks with Bromodomain-Kinase Inhibitors to Suppress Metastatic Castration-Resistant Prostate Cancer. Mol Cancer Ther. 2018 Dec.17(12):2796-2810. Pubmedid: 30242092. Pmcid: PMC6528782.
• Akuffo AA, Alontaga AY, Metcalf R, Beatty MS, Becker A, McDaniel JM, Hesterberg RS, Goodheart WE, Gunawan S, Ayaz M, Yang Y, Karim MR, Orobello ME, Daniel K, Guida W, Yoder JA, Rajadhyaksha AM, Schonbrunn E, Lawrence HR, Lawrence NJ, Epling-Burnette PK. Ligand-mediated protein degradation reveals functional conservation among sequence variants of the CUL4-type E3 ligase substrate receptor cereblon. J Biol Chem. 2018 Apr.293(16):6187-6200. Pubmedid: 29449372. Pmcid: PMC5912449.
• Ember SW, Lambert QT, Berndt N, Gunawan S, Ayaz M, Tauro M, Zhu JY, Cranfill PJ, Greninger P, Lynch CC, Benes CH, Lawrence HR, Reuther GW, Lawrence NJ, Schonbrunn E. Potent Dual BET Bromodomain-Kinase Inhibitors as Value-Added Multitargeted Chemical Probes and Cancer Therapeutics. Mol Cancer Ther. 2017 Jun.16(6):1054-1067. Pubmedid: 28336808. Pmcid: PMC5457702.
• Mahajan K, Malla P, Lawrence HR, Chen Z, Kumar-Sinha C, Malik R, Shukla S, Kim J, Coppola D, Lawrence NJ, Mahajan NP. ACK1/TNK2 Regulates Histone H4 Tyr88-phosphorylation and AR Gene Expression in Castration-Resistant Prostate Cancer. Cancer Cell. 2017 Jun.31(6):790-803.e8. Pubmedid: 28609657. Pmcid: PMC5512571.
• Betts BC, Veerapathran A, Pidala J, Yang H, Horna P, Walton K, Cubitt CL, Gunawan S, Lawrence HR, Lawrence NJ, Sebti SM, Anasetti C. Targeting Aurora kinase A and JAK2 prevents GVHD while maintaining Treg and antitumor CTL function. Sci Transl Med. 2017 Jan.9(372). Pubmedid: 28077684. Pmcid: PMC6368389.
• Lawrence HR, Mahajan K, Luo Y, Zhang D, Tindall N, Huseyin M, Gevariya H, Kazi S, Ozcan S, Mahajan N, Lawrence NJ. Development of novel ACK1/TNK2 inhibitors using a fragment-based approach. J Med Chem. 2015 Mar.58(6):2746-2763. Pubmedid: 25699576. Pmcid: PMC4605435.
• Schneeberger VE, Ren Y, Luetteke N, Huang Q, Chen L, Lawrence HR, Lawrence NJ, Haura EB, Koomen JM, Coppola D, Wu J. Inhibition of Shp2 suppresses mutant EGFR-induced lung tumors in transgenic mouse model of lung adenocarcinoma. Oncotarget. 2015 Mar.6(8):6191-6202. Pubmedid: 25730908. Pmcid: PMC4467431.
• Mahajan K, Lawrence HR, Lawrence NJ, Mahajan NP. ACK1 tyrosine kinase interacts with histone demethylase KDM3A to regulate the mammary tumor oncogene HOXA1. J Biol Chem. 2014 Oct.289(41):28179-28191. Pubmedid: 25148682. Pmcid: PMC4192474.
• Yang H, Lawrence HR, Kazi A, Gevariya H, Patel R, Luo Y, Rix U, Schonbrunn E, Lawrence NJ, Sebti SM. Dual Aurora A and JAK2 kinase blockade effectively suppresses malignant transformation. Oncotarget. 2014 May.5(10):2947-2961. Pubmedid: 24930769. Pmcid: PMC4102782.
• Ucar DA, Magis AT, He DH, Lawrence NJ, Sebti SM, Kurenova E, Zajac-Kaye M, Zhang J, Hochwald SN. Inhibiting the interaction of cMET and IGF-1R with FAK effectively reduces growth of pancreatic cancer cells in vitro and in vivo. Anticancer Agents Med Chem. 2013 May.13(4):595-602. Pubmedid: 23272972. Pmcid: PMC4052463.
• Zhang X, Sun Y, Pireddu R, Yang H, Urlam MK, Lawrence HR, Guida WC, Lawrence NJ, Sebti SM. A novel inhibitor of STAT3 homodimerization selectively suppresses STAT3 activity and malignant transformation. Cancer Res. 2013 Mar.73(6):1922-1933. Pubmedid: 23322008. Pmcid: PMC4030628.
• Urlam MK, Pireddu R, Ge Y, Zhang X, Sun Y, Lawrence HR, Guida WC, Sebti SM, Lawrence NJ. Development of new N-Arylbenzamides as STAT3 Dimerization Inhibitors. Medchemcomm. 2013 Jun.4(6):932-941. Pubmedid: 24073326. Pmcid: PMC3780559.
• Pillai S, Szekeres K, Lawrence NJ, Chellappan SP, Blanck G. Regulation of interlocking gene regulatory network subcircuits by a small molecule inhibitor of retinoblastoma protein (RB) phosphorylation: cancer cell expression of HLA-DR. Gene. 2013 Jan.512(2):403-407. Pubmedid: 23041127.
• Trevino JG, Verma M, Singh S, Pillai S, Zhang D, Pernazza D, Sebti SM, Lawrence NJ, Centeno BA, Chellappan SP. Selective disruption of rb-raf-1 kinase interaction inhibits pancreatic adenocarcinoma growth irrespective of gemcitabine sensitivity. Mol Cancer Ther. 2013 Dec.12(12):2722-2734. Pubmedid: 24107447. Pmcid: PMC3858536.
• Blaskovich MA, Yendluri V, Lawrence HR, Lawrence NJ, Sebti SM, Springett GM. Lysophosphatidic acid acyltransferase beta regulates mTOR signaling. PLoS One. 2013.8(10):e78632. Pubmedid: 24205284. Pmcid: PMC3814986.
• Lawrence HR, Martin MP, Luo Y, Pireddu R, Yang H, Gevariya H, Ozcan S, Zhu JY, Kendig R, Rodriguez M, Elias R, Cheng JQ, Sebti SM, Schonbrunn E, Lawrence NJ. Development of o-chlorophenyl substituted pyrimidines as exceptionally potent aurora kinase inhibitors. J Med Chem. 2012 Sep.55(17):7392-7416. Pubmedid: 22803810. Pmcid: PMC4429609.
• Ucar DA, Kurenova E, Garrett TJ, Cance WG, Nyberg C, Cox A, Massoll N, Ostrov DA, Lawrence N, Sebti SM, Zajac-Kaye M, Hochwald SN. Disruption of the protein interaction between FAK and IGF-1R inhibits melanoma tumor growth. Cell Cycle. 2012 Sep.11(17):3250-3259. Pubmedid: 22894899. Pmcid: PMC3466524.
• Patel RA, Forinash KD, Pireddu R, Sun Y, Sun N, Martin MP, Schönbrunn E, Lawrence NJ, Sebti SM. RKI-1447 is a potent inhibitor of the Rho-associated ROCK kinases with anti-invasive and antitumor activities in breast cancer. Cancer Res. 2012 Oct.72(19):5025-5034. Pubmedid: 22846914. Pmcid: PMC3463757.
• Li R, Martin MP, Liu Y, Wang B, Patel RA, Zhu JY, Sun N, Pireddu R, Lawrence NJ, Li J, Haura EB, Sung SS, Guida WC, Schonbrunn E, Sebti SM. Fragment-based and structure-guided discovery and optimization of Rho kinase inhibitors. J Med Chem. 2012 Mar.55(5):2474-2478. Pubmedid: 22272748. Pmcid: PMC4516226.
• Mahajan K, Coppola D, Rawal B, Chen YA, Lawrence HR, Engelman RW, Lawrence NJ, Mahajan NP. Ack1-mediated androgen receptor phosphorylation modulates radiation resistance in castration-resistant prostate cancer. J Biol Chem. 2012 Jun.287(26):22112-22122. Pubmedid: 22566699. Pmcid: PMC3381169.
• Pireddu R, Forinash KD, Sun NN, Martin MP, Sung SS, Alexander B, Zhu JY, Guida WC, Schönbrunn E, Sebti SM, Lawrence NJ. Pyridylthiazole-based ureas as inhibitors of Rho associated protein kinases (ROCK1 and 2). Medchemcomm. 2012 Jun.3(6):699-709. Pubmedid: 23275831. Pmcid: PMC3531244.
• Win-Piazza H, Schneeberger VE, Chen L, Pernazza D, Lawrence HR, Sebti SM, Lawrence NJ, Wu J. Enhanced anti-melanoma efficacy of interferon alfa-2b via inhibition of Shp2. Cancer Lett. 2012 Jul.320(1):81-85. Pubmedid: 22306001. Pmcid: PMC3319810.
• Davis R, Pillai S, Lawrence N, Sebti S, Chellappan SP. TNF-α-mediated proliferation of vascular smooth muscle cells involves Raf-1-mediated inactivation of Rb and transcription of E2F1-regulated genes. Cell Cycle. 2012 Jan.11(1):109-118. Pubmedid: 22185776. Pmcid: PMC3272234.
• Johnson JL, Pillai S, Pernazza D, Sebti SM, Lawrence NJ, Chellappan SP. Regulation of matrix metalloproteinase genes by E2F transcription factors: Rb-Raf-1 interaction as a novel target for metastatic disease. Cancer Res. 2012 Jan.72(2):516-526. Pubmedid: 22086850. Pmcid: PMC3261351.
• Alamanda V, Singh S, Lawrence NJ, Chellappan SP. Nicotine-mediated induction of E-selectin in aortic endothelial cells requires Src kinase and E2F1 transcriptional activity. Biochem Bioph Res Co. 2012 Feb.418(1):56-61. Pubmedid: 22240023. Pmcid: PMC3273677.
• Li X, Gilkes D, Li B, Cheng Q, Pernazza D, Lawrence N, Chen J. Abnormal MDMX degradation in tumor cells due to ARF deficiency. Oncogene. 2012 Aug.31(32):3721-3732. Pubmedid: 22120712. Pmcid: PMC3290737.
• Caceres G, Robey RW, Sokol L, McGraw KL, Clark J, Lawrence NJ, Sebti SM, Wiese M, List AF. HG-829 is a potent noncompetitive inhibitor of the ATP-binding cassette multidrug resistance transporter ABCB1. Cancer Res. 2012 Aug.72(16):4204-4213. Pubmedid: 22761337. Pmcid: PMC4557794.
• Mahajan K, Coppola D, Chen YA, Zhu W, Lawrence HR, Lawrence NJ, Mahajan NP. Ack1 tyrosine kinase activation correlates with pancreatic cancer progression. Am J Pathol. 2012 Apr.180(4):1386-1393. Pubmedid: 22322295. Pmcid: PMC3349895.
• Martin MP, Zhu JY, Lawrence HR, Pireddu R, Luo Y, Alam R, Ozcan S, Sebti SM, Lawrence NJ, Schönbrunn E. A novel mechanism by which small molecule inhibitors induce the DFG flip in Aurora A. Acs Chem Biol. 2012 Apr.7(4):698-706. Pubmedid: 22248356. Pmcid: PMC4429595.
• Scott LM, Chen L, Daniel KG, Brooks WH, Guida WC, Lawrence HR, Sebti SM, Lawrence NJ, Wu J. Shp2 protein tyrosine phosphatase inhibitor activity of estramustine phosphate and its triterpenoid analogs. Bioorg Med Chem Lett. 2011 Jan.21(2):730-733. Pubmedid: 21193311. Pmcid: PMC3034307.
• Fragale A, Stellacci E, Ilari R, Remoli AL, Lanciotti A, Perrotti E, Shytaj I, Orsatti R, Lawrence HR, Lawrence NJ, Wu J, Rehli M, Ozato K, Battistini A. Critical role of IRF-8 in negative regulation of TLR3 expression by Src homology 2 domain-containing protein tyrosine phosphatase-2 activity in human myeloid dendritic cells. J Immunol. 2011 Feb.186(4):1951-1962. Pubmedid: 21220691. Pmcid: PMC4053178.
• Chen L, Pernazza D, Scott LM, Lawrence HR, Ren Y, Luo Y, Wu X, Sung SS, Guida WC, Sebti SM, Lawrence NJ, Wu J. Inhibition of cellular Shp2 activity by a methyl ester analog of SPI-112. Biochem Pharmacol. 2010 Sep.80(6):801-810. Pubmedid: 20510203. Pmcid: PMC2906681.
• Mahajan K, Challa S, Coppola D, Lawrence H, Luo Y, Gevariya H, Zhu W, Chen YA, Lawrence NJ, Mahajan NP. Effect of Ack1 tyrosine kinase inhibitor on ligand-independent androgen receptor activity. Prostate. 2010 Sep.70(12):1274-1285. Pubmedid: 20623637. Pmcid: PMC3953126.
• Berndt N, Yang H, Trinczek B, Betzi S, Zhang Z, Wu B, Lawrence NJ, Pellecchia M, Schönbrunn E, Cheng JQ, Sebti SM. The Akt activation inhibitor TCN-P inhibits Akt phosphorylation by binding to the PH domain of Akt and blocking its recruitment to the plasma membrane. Cell Death Differ. 2010 Nov.17(11):1795-1804. Pubmedid: 20489726. Pmcid: PMC2952662.
• Scott LM, Lawrence HR, Sebti SM, Lawrence NJ, Wu J. Targeting protein tyrosine phosphatases for anticancer drug discovery. Curr Pharm Des. 2010 Jun.16(16):1843-1862. Pubmedid: 20337577. Pmcid: PMC3076191.
• Singh S, Davis R, Alamanda V, Pireddu R, Pernazza D, Sebti S, Lawrence N, Chellappan S. Rb-Raf-1 interaction disruptor RRD-251 induces apoptosis in metastatic melanoma cells and synergizes with dacarbazine. Mol Cancer Ther. 2010 Dec.9(12):3330-3341. Pubmedid: 21139044. Pmcid: PMC3058238.
• Ducki S, Rennison D, Woo M, Kendall A, Chabert JF, McGown AT, Lawrence NJ. Combretastatin-like chalcones as inhibitors of microtubule polymerization. Part 1: synthesis and biological evaluation of antivascular activity. Bioorg Med Chem. 2009 Nov.17(22):7698-7710. Pubmedid: 19837593.
• Ducki S, Mackenzie G, Greedy B, Armitage S, Chabert JF, Bennett E, Nettles J, Snyder JP, Lawrence NJ. Combretastatin-like chalcones as inhibitors of microtubule polymerisation. Part 2: Structure-based discovery of alpha-aryl chalcones. Bioorg Med Chem. 2009 Nov.17(22):7711-7722. Pubmedid: 19837594.
• Lawrence HR, Li Z, Yip ML, Sung SS, Lawrence NJ, McLaughlin ML, McManus GJ, Zaworotko MJ, Sebti SM, Chen J, Guida WC. Identification of a disruptor of the MDM2-p53 protein-protein interaction facilitated by high-throughput in silico docking. Bioorg Med Chem Lett. 2009 Jul.19(14):3756-3759. Pubmedid: 19457663. Pmcid: PMC2754843.
• Butler LC, Blanchard GB, Kabla AJ, Lawrence NJ, Welchman DP, Mahadevan L, Adams RJ, Sanson B. Cell shape changes indicate a role for extrinsic tensile forces in Drosophila germ-band extension. Nat Cell Biol. 2009 Jul.11(7):859-864. Pubmedid: 19503074.
• Wei S, Chen X, Rocha K, Epling-Burnette PK, Djeu JY, Liu Q, Byrd J, Sokol L, Lawrence N, Pireddu R, Dewald G, Williams A, Maciejewski J, List A. A critical role for phosphatase haplodeficiency in the selective suppression of deletion 5q MDS by lenalidomide. Proc Natl Acad Sci U S A. 2009 Aug.106(31):12974-12979. Pubmedid: 19470455. Pmcid: PMC2722346.
• Wei J, Kitada S, Rega MF, Emdadi A, Yuan H, Cellitti J, Stebbins JL, Zhai D, Sun J, Yang L, Dahl R, Zhang Z, Wu B, Wang S, Reed TA, Wang HG, Lawrence N, Sebti S, Reed JC, Pellecchia M. Apogossypol derivatives as antagonists of antiapoptotic Bcl-2 family proteins. Mol Cancer Ther. 2009 Apr.8(4):904-913. Pubmedid: 19372563. Pmcid: PMC2750823.
• Kinkade R, Dasgupta P, Carie A, Pernazza D, Carless M, Pillai S, Lawrence N, Sebti SM, Chellappan S. A small molecule disruptor of Rb/Raf-1 interaction inhibits cell proliferation, angiogenesis, and growth of human tumor xenografts in nude mice. Cancer Res. 2008 May.68(10):3810-3818. Pubmedid: 18483265. Pmcid: PMC3233839.
• Lawrence HR, Pireddu R, Chen L, Luo Y, Sung SS, Szymanski AM, Yip ML, Guida WC, Sebti SM, Wu J, Lawrence NJ. Inhibitors of Src homology-2 domain containing protein tyrosine phosphatase-2 (Shp2) based on oxindole scaffolds. J Med Chem. 2008 Aug.51(16):4948-4956. Pubmedid: 18680359. Pmcid: PMC2744494.
• Siddiquee K, Zhang S, Guida WC, Blaskovich MA, Greedy B, Lawrence HR, Yip ML, Jove R, McLaughlin MM, Lawrence NJ, Sebti SM, Turkson J. Selective chemical probe inhibitor of Stat3, identified through structure-based virtual screening, induces antitumor activity. Proc Natl Acad Sci U S A. 2007 May.104(18):7391-7396. Pubmedid: 17463090. Pmcid: PMC1863497.
• Lawrence N, Patterson R, Ooi L, Cook D, Ducki S. Effects of alpha-substitutions on structure and biological activity of anticancer chalcones. Bioorg Med Chem Lett. 2006 Nov.16(22):5844-5848. Pubmedid: 16949281.
• Chen L, Sung SS, Yip ML, Lawrence HR, Ren Y, Guida WC, Sebti SM, Lawrence NJ, Wu J. Discovery of a novel shp2 protein tyrosine phosphatase inhibitor. Mol Pharmacol. 2006 Aug.70(2):562-570. Pubmedid: 16717135.
• Guo F, Rocha K, Bali P, Pranpat M, Fiskus W, Boyapalle S, Kumaraswamy S, Balasis M, Greedy B, Armitage ES, Lawrence N, Bhalla K. Abrogation of heat shock protein 70 induction as a strategy to increase antileukemia activity of heat shock protein 90 inhibitor 17-allylamino-demethoxy geldanamycin. Cancer Res. 2005 Nov.65(22):10536-10544. Pubmedid: 16288046.
• Hadfield J, Gaukroger K, Hirst N, Weston A, Lawrence N, McGown A. Synthesis and evaluation of double bond substituted combretastatins. Eur J Med Chem. 2005 Jun.40(6):529-541. Pubmedid: 15922837.
• Ducki S, Mackenzie G, Lawrence N, Snyder JP. Quantitative structure-activity relationship (5D-QSAR) study of combretastatin-like analogues as inhibitors of tubulin assembly. J Med Chem. 2005 Jan.48(2):457-465. Pubmedid: 15658859.
• Lawrence N, McGown A. The chemistry and biology of antimitotic chalcones and related enone systems. Curr Pharm Des. 2005.11(13):1679-1693. Pubmedid: 15892668.
• Lawrence NJ, Davies CA, Gray M. Synthesis of diaryl acetates and oxindoles via a sequential VNS(Ar)-S(N)Ar three-component coupling reaction. Org Lett. 2004 Dec.6(26):4957-4960. Pubmedid: 15606109.
• Gaukroger K, Hadfield J, Lawrence N, Nolan S, McGown A. Structural requirements for the interaction of combretastatins with tubulin: how important is the trimethoxy unit?. Org Biomol Chem. 2003 Sep.1(17):3033-3037. Pubmedid: 14518125.
• Lawrence N, Rennison D, McGown A, Hadfield J. The total synthesis of an aurone isolated from Uvaria hamiltonii: aurones and flavones as anticancer agents. Bioorg Med Chem Lett. 2003 Nov.13(21):3759-3763. Pubmedid: 14552774.
• Lawrence N, Liddle J, Bushell S, Jackson D. A three-component coupling process based on vicarious nucleophilic substitution (VNS(AR))-alkylation reactions: an approach to indoprofen and derivatives. J Org Chem. 2002 Jan.67(2):457-464. Pubmedid: 11798318.
• Gaukroger K, Hadfield JA, Hepworth LA, Lawrence NJ, McGown AT. Novel syntheses of cis and trans isomers of combretastatin A-4. J Org Chem. 2001 Nov.66(24):8135-8138. Pubmedid: 11722216.
• Lawrence NJ, Rennison D, Woo M, McGown AT, Hadfield JA. Antimitotic and cell growth inhibitory properties of combretastatin A-4-like ethers. Bioorg Med Chem Lett. 2001 Jan.11(1):51-54. Pubmedid: 11140732.
• Lawrence N, McGown A, Nduka J, Hadfield J, Pritchard R. Cytotoxic Michael-type amine adducts of alpha-methylene lactones alantolactone and isoalantolactone. Bioorg Med Chem Lett. 2001 Feb.11(3):429-431. Pubmedid: 11212128.
• Lawrence N, McGown A, Ducki S, Hadfield J. The interaction of chalcones with tubulin. Anticancer Drug Des. 2000 Apr.15(2):135-141. Pubmedid: 10901301.
• Ducki S, Forrest R, Hadfield JA, Kendall A, Lawrence NJ, McGown AT, Rennison D. Potent antimitotic and cell growth inhibitory properties of substituted chalcones. Bioorg Med Chem Lett. 1998 May.8(9):1051-1056. Pubmedid: 9871706.
• Jordan A, Hadfield JA, Lawrence NJ, McGown AT. Tubulin as a target for anticancer drugs: agents which interact with the mitotic spindle. Med Res Rev. 1998 Jul.18(4):259-296. Pubmedid: 9664292.
• Ducki S, Hadfield JA, Zhang X, Lawrence NJ, McGown AT. Isolation of aurantiamide acetate from Arisaema erubescens. Planta Med. 1996 Jun.62(3):277-278. Pubmedid: 8693046.
• Ducki S, Hadfield JA, Lawrence NJ, Zhang X, McGown AT. Isolation of paeonol from Arisaema erubescens. Planta Med. 1995 Dec.61(6):586-587. Pubmedid: 8824957.
• Lawrence NJ, Parkinson EK, Emmerson A. Benzoyl peroxide interferes with metabolic co-operation between cultured human epidermal keratinocytes. Carcinogenesis. 1984 Mar.5(3):419-421. Pubmedid: 6705146.

• Title: Developing ULK3 inhibitors for Multiple Myeloma
  Sponsor: Moffitt Cancer Center
  PI (Contact): Lynch, C., PI: Lawrence, N.
• Title: Targeting ULK3 in Cutaneous Squamous Cell Carcinoma
  Sponsor: Moffitt Cancer Center
  PI (Contact): Lawrence, N., PI: Lynch, C.