Principle Scientist

Darryl L. McDougald

* ******** ***** – Durham, NC 27713 – ********@*****.***

Work: 919-***-**** Home: 919-***-**** Cell: 919-***-****

Qualifications

Accomplished, multidiscipline Research Scientist with significant research experience in the fields of medicinal, synthetic and analytical chemistry. Background includes design and synthesis of a half dozen phase1 drug candidates of which I am personally responsible for or supervised as a manager. Process development of drug candidates in a GMP facility. Development of numerous analytical techniques designed to develop drug candidates, purify and isolate proteins, analyze unknown samples, develop radiopharmaceuticals and generate SOPs. I am also skilled in the area of nuclear medicine with experience working with numerous radioisotopes both synthetically and biologically. Additionally I am experienced in a host of biological techniques such as cell culture, cell assays, electrophoresis, western blot, flowcytometry and others. I am an enthusiastic teammate with great respect for team dynamics and professional growth.

Skills and Techniques

I am fluent in a number of skills and analytical techniques which include NMR(COSY, NOESY, TOCSY and HSQC), Mass Spec.(LCMS, GCMS, ESI, MALDI, FAB, CI, EI (high and low res.)) atomic absorption analysis, Raman IR, GC, Applied biosystems peptide synthesizer, HPLC(prep and analytical), TLC, ISCO and Biotage automated chromatography systems, Anton Parr and Biotage microwave reactors, flash chromatography, polarimeter, high vacuum distillations, high pressure reactors(Parr), MACS stem cell isolation technologies, Silver staining (gel), protein dialysis protocols, Aldefluor stemcell identification kits, flow cytometry, SDS PAGE gel electrophoresis, western blot, gamma and beta counter analysis, cellular assays, Bioscan radiomaging scanner, Capentec radio calibrators, Beckman radiodectector(HPLC), preparative TLC, Millipore gel readers and Hazmat training.

I am also proficient in most of the software routinely used in Lab and office settings including MS word, excel, powerpoint, Onenote, lotus notes, spotfire, scifinder, beistien, E-labnotebook, Outlook, chemdraw, isisdraw, ACD software, Labview.

Professional Experience

Sept. 2008-Present Research Scientist Duke Medical Center, Durham, NC 27710

I am presently serving as a research scientist with the Duke Radiology nuclear medicine group. The focus of our research is in translational stem cell resistance. I am currently working on a number of cancer chemotherapy projects as well as small molecule imaging projects. My duties include synthesis of small molecules and the evaluation of the SAR of these molecules as potential chemotherapeutic agents. It includes optimization of the cellular uptake of selected small and large molecules for tumor cell imaging. This work involves synthesis of small and large molecules (small peptides and antibodies) as well as measuring their cellular uptake in tumor cells. In concert with this work my duties include routinely performing cell assays, cell culture, protein identification and isolation via gel electrophoresis, western blot analysis, silver staining techniques and flowcytometry and others. My responsibilities also include labeling selected molecules with radioisotopes (123I, 124I, 125I, 131I and 18F) via radiosynthetic techniques. Ultimately these compounds are evaluated in mice and humans via PET (positron emission topography) imaging for tumor cells evaluation.

I am also responsible for monitoring exposure to chemical and radioactive materials. This includes Bicron analysis of work sites, Ludlum meters for thyroid analysis and measuring fume hood performance via flow meters.

July 2007-Jun2008 Principle Scientist GlaxoSmithKline Inc., Research Triangle Park, NC

I served as a principle scientist on the c-jun N-terminal kinase inhibitor project for diabetes under the supervision of Dr. David Deaton. I am primarily responsible for synthesizing analogs on the triazole templates, improving the chemical tractability of the series and development of SAR for the series.

Jan. 2007-Jun2007 Principle Scientist GlaxoSmithKline Inc., Research Triangle Park, NC

I served as a principle scientist on the POP inhibitor project for obesity. My responsibilities included design and synthesis of novel templates for the purpose of intellectual property creation and development of potent tool compounds for target validation. My responsibilities also included the direction of work carried out by an associate scientist.

Nov. 2005-Jan. 2007 Principle Scientist GlaxoSmithKline Inc., Research Triangle Park, NC

I served as a principle scientist on the SARM agonist project. My responsibilities included direction of work carried out on the pyrazole template. These duties included evaluating all chemistries carried out on the template, influencing direction of SAR development and monitoring of all literature around the series. Additionally I was also personally responsible for the synthesis of nearly 100 compounds. My responsibilities also included the direction of work carried out by an associate chemist on this series as well as direction of the work of my own direct report. This project is currently in phase1 drug development.

April 2004-Oct. 2005 Principle Scientist GlaxoSmithKline Inc., Research Triangle Park, NC

I served as a principle scientist on the DPP4/7 dual antagonist project. My responsibilities included direction of work carried out on the non-cyanopyrrolidine templates (Merck template and others). These duties included evaluating all chemistries carried out on the template, influencing direction of SAR development and monitoring of all literature around the series and other DPP4/7 antagonist. I was also personally responsible for the synthesis of discovery of other templates and analogs. My responsibilities also included the direction of work carried out by three other chemists on this series including my own direct report.

July 2003-April 2005 Principle Scientist GlaxoSmithKline Inc., Research Triangle Park, NC

I served as the chemistry lead for the AXOR 109 project. My role included being the chemical resource at the infancy stage of the project. My responsibilities included monitoring of the progress of high throughput biology in developing an assay, target validation work, monitoring of the high throughput assay and providing synthetic assistance when needed. My responsibilities later included development of a chemical strategy for lead optimization and facilitation of high throughput chemistry. Eventually this involved the scale-up of assay hits and lead compounds. The project is now in phase1.

August 2003-Oct. 2003 Principle Scientist GlaxoSmithKline Inc., Research Triangle Park, NC

I served as a member of the MCH project. My role was to assist in the scale-up of development candidates of interest (GSK 206827A) and synthesis of novel compounds to support back-up efforts. During this time I was able to provide scale-up support for GSK 206827A as well as synthesis of various novel compounds for patent support. My responsibilities also included the direction of work carried out by an associate scientist. The project is now in phase1.

July 2000-July 2003 Principle Scientist GlaxoSmithKline Inc., Research Triangle Park, NC

I served as a member of the DPP4 project. My responsibilities included design and synthesis of novel templates as well as improving the potency of the existing cyanopyrrolidine template. I was the chemistry leader for two the 4-Aminopiperidine and penicillamine templates. I was directly responsible for design and synthesis of two drug development candidates and oversaw the discovery of another. I provide a large scale chemical support to the project by synthesizing several hundred gram quantities of a number of compounds of interest. I developed procedures for the formation of various salts of drug candidates as well as providing metabolic support. I worked closely with the patent lawyers in constructing claims for the three different patents that were filed. During this period I also directed the work of an associate level scientist. The project eventually made it to phase3.

Jan. 1999-July 2000 Senior Scientist GlaxoWellcome, Research Triangle Park, NC

I am served as a senior scientist on the RXR project for diabetes under the supervision of Curt Haffner. I was primarily responsible for synthesizing analogs on the various templates, improving the chemical tractability of the series and development of SAR for different series. My work also included following up on hits from HTC.

Jan. 1995-Jan. 2000 Research Scientist GlaxoWellcome, Research Triangle Park, NC

I am served as a research scientist on the TNF project for rheumatoid arthritis under the supervision of Dr. Robert Andrews. My responsibilities included design and synthesis of novel reverse hydroximates. I was directly responsible for design and synthesis of three drug development candidates. I provide a large scale chemical support to the project by synthesizing several hundred gram quantities of intermediates and final compounds and I also was the chemical lead for the Aggrecanase project.

July 1992-Jan. 1995 Scientist GlaxoWellcome Research Triangle Park, NC

I am served as a scientist on the Amylin project for type 2 diabetes under the supervision of Dr. Jeff Cobb. My responsibilities included design and synthesis of amylin antagonist. I was directly responsible for design and synthesis of hundreds of novel analogs and templates. I provide a large scale chemical support to the project by synthesizing a number of intermediates. This work also included synthesis of various peptide that ranged from 2-11 amino acids in length via a peptide synthesizer.

June1987-July. 1992 Associate Scientist Glaxo Research Triangle Park, NC

I worked as a synthetic chemist chemical development. My responsibilities included working on milligram to kilogram scale as well as working under GLP and GMP guidelines. My responsibilities also required that I matrix with all other development organization to promote project all the way to phase3.

Education

1984-1987 Graduate Student University of North Carolina, Chapel Hill, NC

M.S. in Medicinal Chemistry

Research Director: Professor Steven D. Wyrick Dissertation: Synthesis of selective D1

dopamine antagonist

1980-1984 Undergraduate Student

B.A. in Chemistry University of North Carolina, Wilmington, NC

Selected Patents and Publications

Bennett B. Chin, Anita Hjelemand, Jeremy Rich, Haijing Song, Christopher Lascola, Robert Storms, Roger McLendon4, Robert Reiman, Kim L. Greer, Scott D. Metzler, Darryl McDougald, Diana Dai, Ganesan Vaidyanathan, Synthesis and preliminary evaluation of n.c.a. Iodoquine: A novel radiotracer with High uptake in cells with high ALDH expression, Current Radiopharmaceuticals (in press)

Vaidyanathan, Ganesan; McDougald, Darryl L.; Linda Grasfeder, Michael R. Zalutsky, and Bennett B. An Alternative and Expedient Synthesis of Radioiodinated

4-Iodophenylalanine, Applied Radiation and Isotopes (in press)

Vaidyanathan, Ganesan; Song, Haijing; Affleck, Donna; McDougald, Darryl L.; Storms, Robert W.; Zalutsky, Michael R.; Chin, Bennett B.

Targeting aldehyde dehydrogenase: a potential approach for cell labeling. Nuclear Medicine and Biology (2009), 36(8), 919-929. Language: English, Database: CAPLUS

Cadilla, Rodolfo; Larkin, Andrew; McDougald, Darryl Lynn; Randhawa, Amarjit Sab; Ray, John A.; Stetson, Katherine; Stewart, Eugene L.; Turnbull, Philip Stewart; Zhou, Huiquiang. Preparation of indole derivatives as modulators of androgen receptor. PCT Int. Appl. (2008), 369pp. CODEN: PIXXD2 WO 200-***-**** A2 20080410 CAN 148:449452 AN 2008:445054

Haffner, Curt D.; McDougald, Darryl L.; Reister, Steven M.; Thompson, Brian D.; Conlee, Christopher; Fang, Jing; Bass, Jonathan; Lenhard, James M.; Croom, Dallas; Secosky-Chang, Melissa B.; Tomaszek, Thaddeus; McConn, Donavon; Wells-Knecht, Kevin; Johnson, Paul R. 2-Cyano-4-fluoro-1-thiovalylpyrrolidine analogues as potent inhibitors of DPP-IV. Bioorganic & Medicinal Chemistry Letters (2005), 15(23), 5257-5261. CODEN: BMCLE8 ISSN:0960-894X. CAN 144:51883 AN 2005:1144496 CAPLUS

Lambert, Millard H.; Blackburn, R. Kevin; Seaton, Theresa D.; Kassel, Daniel B.; Kinder, Daniel S.; Leesnitzer, M. Anthony; Bickett, D. Mark; Warner, Janet R.; Andersen, Marc W.; Badiang, Jennifer G.; Cowan, David J.; Gaul, Michael D.; Petrov, Kimberly G.; Rabinowitz, Michael H.; Wiethe, Robert W.; Becherer, J. David; McDougald, Darryl L.; Musso, David L.; Andrews, Robert C.; Moss, Marcia L. Substrate specificity and novel selective inhibitors of TNF- converting enzyme (TACE) from two-dimensional substrate mapping. Combinatorial Chemistry and High Throughput Screening (2005), 8(4), 327-339. CODEN: CCHSFU ISSN:1386-2073. CAN 144:102782 AN 2005:452261 CAPLUS

Haffner, Curt D.; Lenhard, James M.; Miller, Aaron B.; McDougald, Darryl L.; Dwornik, Kate; Ittoop, Olivia R.; Gampe, Robert T., Jr.; Xu, H. Eric; Blanchard, Steve; Montana, Valerie G.; Consler, Tom G.; Bledsoe, Randy K.; Ayscue, Andrea; Croom, Dallas. Structure-Based Design of Potent Retinoid X Receptor Agonists. Journal of Medicinal Chemistry (2004), 47(8), 2010-2029. CODEN: JMCMAR ISSN:0022-2623. CAN 140:303476 AN 2004:202648 CAPLUS

Tippin, Timothy K.; Hamilton, Geraldine; Moore, Linda; Beaudet, Elizabeth J.; Jolley, Summer; Brodie, Thomas A.; Andrews, Robert C.; Becherer, J. David; McDougald, Darryl L.; Gaul, Michael D.; Hoivik, Debie J.; Mellon-Kusibab, Kathy; Lehmann, Jurgen; Kliewer, Steven; Novick, Steven; Laethem, Ron; Zhao, Zhiyang; LeCluyse, Edward L. CYP3A induction by N-hydroxyformamide tumor necrosis factor- converting enzyme/matrix metalloproteinase inhibitors: Use of a pregnane X receptor activation assay and primary hepatocyte culture for assessing induction potential in humans. Drug Metabolism and Disposition (2003), 31(7), 870-877. CODEN: DMDSAI ISSN:0090-9556. CAN 140:12429 AN 2003:512699 CAPLUS

Haffner, Curt Dale; Kaldor, Istvan; McDougald, Darryl Lynn; Miller, Aaron Bayne. Preparation of retinoid analogs that have selectivity as RXR agonists. PCT Int. Appl. (2003), 82 pp. CODEN: PIXXD2 WO 200-***-**** A2 20030403 CAN 138:287846 AN 2003:261825 CAPLUS

Haffner, Curt Dale; McDougald, Darryl Lynn; Lenhard, James Martin. Preparation of fluoropyrrolidinecarbonitrile derivatives as dipeptidyl peptidase inhibitors. PCT Int. Appl. (2003), 133 pp. CODEN: PIXXD2 WO 200-***-**** A2 20030109 CAN 138:90072 AN 2003:22868 CAPLUS

Haffner, Curt Dale; McDougald, Darryl Lynn; Randhawa, Amarjit Sab; Reister, Steven Michael; Lenhard, James Martin. Preparation of fluoropyrrolidinecarbonitrile derivatives as dipeptidyl peptidase inhibitors. PCT Int. Appl. (2003), 186 pp. CODEN: PIXXD2 WO 200-***-**** A2 20030109 CAN 138:90071 AN 2003:22848 CAPLUS

Haffner, Curt Dale; McDougald, Darryl Lynn; Randhawa, Amarjit Sab; Reister, Steven Michael; Deaton, David N.; Lenhard, James Martin. Preparation of pyrrolidine- or thiazolidinecarbonitrile derivatives as dipeptidyl peptidase inhibitors. PCT Int. Appl. (2003), 48 pp. CODEN: PIXXD2 WO 200-***-**** A2 20030109 CAN 138:73532 AN 2003:22847 CAPLUS

Rabinowitz, Michael H.; Andrews, Robert C.; Becherer, J. David; Bickett, D. Mark; Bubacz, Dulce G.; Conway, James G.; Cowan, David J.; Gaul, Micheal; Glennon, Kimberly; Lambert, Millard H.; Leesnitzer, M. Anthony; McDougald, Darryl L.; Moss, Marcia L.; Musso, David L.; Rizzolio, Michele C. Design of Selective and Soluble Inhibitors of Tumor Necrosis Factor- Converting Enzyme (TACE). Journal of Medicinal Chemistry (2001), 44(24), 4252-4267. CODEN: JMCMAR ISSN:0022-2623. CAN 136:79266 AN 2001:752302 CAPLUS

Conway, James G.; Andrews, Robert C.; Beaudet, Beth; Bickett, D. Mark; Boncek, Virginia; Brodie, Thomas A.; Clark, Richard L.; Crumrine, R. Christian; Leenitzer, Michael A.; McDougald, Darryl L.; Han, Bajin; Hedeen, Kevin; Lin, Peiyuan; Milla, Marcos; Moss, Marcia; Pink, Heather; Rabinowitz, Michael H.; Tippin, Timothy; Scates, Phillip W.; Selph, Jeffrey; Stimpson, Stephen A.; Warner, Janet; Becherer, J. David. Inhibition of tumor necrosis factor- (TNF- ) production and arthritis in the rat by GW3333, a dual inhibitor of TNF- -converting enzyme and matrix metalloproteinases. Journal of Pharmacology and Experimental Therapeutics (2001), 298(3), 900-908. CODEN: JPETAB ISSN:0022-3565. CAN 135:352507 AN 2001:616531

Musso, D. L.; Andersen, M. W.; Andrews, R. C.; Austin, R.; Beaudet, E. J.; Becherer, J. D.; Bubacz, D. G.; Bickett, D. M.; Chan, J. H.; Conway, J. G.; Cowan, D. J.; Gaul, M. D.; Glennon, K. C.; Hedeen, K. M.; Lambert, M. H.; Leesnitzer, M. A.; McDougald, D. L.; Mitchell, J. L.; Moss, M. L.; Rabinowitz, M. H.; Rizzolio, M. C.; Schaller, L. T.; Stanford, J. B.; Tippin, T.; Warner, J. R.; Whitesell, L. G.; Wiethe, R. W. N-Hydroxyformamide peptidomimetics as TACE/Matrix metalloprotease inhibitors: oral activity via P1' isobutyl substitution. Bioorganic & Medicinal Chemistry Letters (2001), 11(16), 2147-2151. CODEN: BMCLE8 ISSN:0960-894X. CAN 135:358135 AN 2001:612029

Moss, M. L.; Becherer, J. D.; Conway, J. G.; Warner, J. R.; Bickett, D. M.; Leesnitzer, M. A.; Seaton, T. M.; Mitchell, J. L.; McConnell, R. T.; Tippin, T. K.; Whitesell, L. G.; Rizzolio, M. C.; Hedeen, K. M.; Beaudet, E. J.; Andersen, M.; Lambert, M. H.; Austin, R.; Stanford, J. B.; Bubacz, D. G.; Chan, J. H.; Schaller, L. T.; Gaul, M. D.; Cowan, D. J.; Boncek, V. M.; Rabinowitz, M. H.; Musso, D. L.; McDougald, D. L.; Kaldor, I.; Glennon, K.; Wiethe, R. W.; Guo, Y.; Andrews, R. C. Screening and design of tumor necrosis factor- converting enzyme inhibitors. Cytokine Inhibitors (2001), 163-176. CODEN: 69BACA CAN 135:162023 AN 2001:214187

Andrews, Robert Carl; Anderson, Marc W.; Stanford, Jennifer Badaing; Bubacz, Dulce Garrido; Chan, Joseph H.; Cowan, David J.; Gaul, Michael D.; McDougald, Darryl Lynn; Musso, David Lee; Rabinowitz, Michael H.; Wiethe, Robert W. Preparation of N-formyl-N-hydroxypeptide analogs as metalloprotease inhibitors. Brit. UK Pat. Appl. (2000), 127 pp. CODEN: BAXXDU GB 2348198 A 20000927 CAN 134:42444 AN 2001:12831

Andrews, Robert Carl; Andersen, Marc Werner; Stanford, Jennifer Badiang; Babacz, Dulce Garrido; Chan, Joseph Howing; Cowan, David John; Gaul, Michael David; Mcdougald, Darryl Lynn; Musso, David Lee; Rabinowitz, Michael Howard; Wiethe, Robert William. Preparation of peptidyl formamide compounds as therapeutic agents. PCT Int. Appl. (2000), 115 pp. CODEN: PIXXD2 WO 200******* A1 20000309 CAN 132:208133 AN 2000:161247

Andrews, Robert Carl; Andersen, Marc Werner; Stanford, Jennifer Badiang; Bubacz, Dulce Garrido; Chan, Joseph Howing; Cowan, David John; Gaul, Michael David; Mcdougald, Darryl Lynn; Musso, David Lee; Rabinowitz, Michael Howard; Wiethe, Robert William. Preparation of peptidyl formamide compounds as therapeutic agents. PCT Int. Appl. (2000), 171 pp. CODEN: PIXXD2 WO 200******* A1 20000309 CAN 132:208132 AN 2000:161126

Andrews, Robert Carl; Andersen, Marc Werner; Stanford, Jennifer Badiang; Bubacz, Dulcie Garrido; Chan, Joseph Howing; Cowan, David John; Gaul, Michael David; McDougald, Darryl Lynn; Musso, David Lee; Rabinowitz, Michael Howard; Wiethe, Robert William. Preparation of peptidyl reverse hydroxamate derivatives as metalloprotease inhibitors. PCT Int. Appl. (1998), 164 pp. CODEN: PIXXD2 WO 9838179 A1 19980903 CAN 129:216923 AN 1998:608610

Fang, Francis G.; Bankston, Donald D.; Huie, Edward M.; Johnson, M. Ross; Kang, Kyung-Chol; LeHoullier, Craig S.; Lewis, George C.; Lovelace, Thomas C.; Lowery, Melissa W.; McDougald, Darryl L.; Meerholz, Clive A.; Partridge, John J.; Sharp, Matthew J.; Xie, Shiping. Convergent catalytic asymmetric synthesis of camptothecin analog GI147211C. Tetrahedron (1997), 53(32), 109**-*****. CODEN: TETRAB ISSN:0040-4020. CAN 127:262890 AN 1997:553117

Charifson, Paul S.; Wyrick, Steven D.; Hoffman, Andrew J.; Simmons, Rosa M. Ademe; Bowen, J. Phillip; McDougald, Darryl L.; Mailman, Richard B. Synthesis and pharmacological characterization of 1-phenyl-, 4-phenyl-, and 1-benzyl-1,2,3,4-tetrahydroisoquinolines as dopamine receptor ligands. Journal of Medicinal Chemistry (1988), 31(10), 1941-6. CODEN: JMCMAR ISSN:0022-2623. CAN 109:128804 AN 1988:528804

Wyrick, Steven D.; McDougald, Darryl L.; Mailman, Richard B. Multiple tritium labeling of (+)-7-chloro-8-hydroxy-1-phenyl-3-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SCH23390). Journal of Labelled Compounds and Radiopharmaceuticals (1986), 23(7), 685-92. CODEN: JLCRD4 ISSN:0362-4803. CAN 106:138235 AN 1987:138235

Contact this candidate