Success Stories

Menin-MLL Inhibitors Reverse Oncogenic Activity of MLL Fusion Proteins in Leukemia

Translocations involving the mixed lineage leukemia (MLL) gene result in human acute leukemias with very poor prognosis. The leukemogenic activity of MLL fusion proteins is critically dependent on their direct interaction with menin, a product of the multiple endocrine neoplasia (MEN1) gene. Here we present what are, to our knowledge, the first small-molecule inhibitors of the menin-MLL fusion protein interaction that specifically bind menin with nanomolar affinities.These compounds effectively reverse MLL fusion protein-mediated leukemic transformation by downregulating the expression of target genes required for MLL fusion protein oncogenic activity. (Grembecka et al Nat Chem Biol, 2012 http://www.ncbi.nlm.nih.gov/pubmed/22286128)

See Research Highlight in Nature Reviews Drug Discovery: http://www.nature.com/nrd/journal/v11/n3/full/nrd3689.html

 

Therapy for CNS-Based Lysosomal Storage Diseases

In collaboration with Professors James Shayman and Richard Keep, the VMCC has contributed to the development of inhibitors of an enzyme that causes several rare but devastating lipid storage diseases, including Tay-Sachs and Gaucher. The ability to inhibit this enzyme in the central nervous system (CNS) is crucial for treatment of CNS-based lipid storage diseases but has eluded researchers, leaving no treatment options for affected patients.

We have recently shown that one of our compounds is able to reduce lipid levels in the brains of mice, suggesting that it penetrates into the CNS. We are planning to progress this compound into animal models of CNS-based lipid storage diseases.

Larsen et al. J Lipid Res, 2012

http://www.ncbi.nlm.nih.gov/pubmed/22058426

 

Oral Antivirals for Neurotropic Arboviruses

Infections caused by insect-borne viruses (arboviruses) represent some of the most dramatic examples of disease re-emergence throughout the world. We recently reported the identification of a class of small molecules that inhibit RNA replication of the western equine encephalitis virus (WEEV), a neurotrophic alphavirus. The lead thienopyrrole compound 1 discovered via high throughput screening (HTS) in the University of Michigan Center for Chemical Genomics (CCG), possessed modest potency with low cytotoxicity.

In collaboration with Professors David Miller, David Irani, and Richard Keep, the VMCC has developed a novel series of indoles related to comound 1 that are more potent and more metabolically stable. One of these compounds was recently shown to improve survival in a mouse model of neuroadapted Sindbis virus infection.

Sindac et al. J Med Chem, 2012

http://www.ncbi.nlm.nih.gov/pubmed/22428985

 

All Patents and Publications

1. WO 2010014798: Preparation of pyrimidotriazinediones and pyrimidopyrimidinediones for treating cancer.
2. WO 201017312: Compositions and methods for the treatment and prevention of inflammatory bowel diseases; US Patent 8,293,776
3. WO 2010090860: Methods and compositions for treating bacterial infection. US Patent 8,501,722
4. WO 2011035143: Benzamides and related compounds as Rho GTPase inhibitors and their preparation and compositions for inhibiting Rho-mediated diseases and conditions.
5. US 20120252807: Preparation of pyrrolyl(or imidazolyl) piperidinyl methanone derivatives as arbovirus inhibitors. US Patent 8,846,684
6. WO2012149335: Preparation of thiadiazolidinone derivatives as inhibitors of RGS proteins
7. WO 2012040527: Preparation of WP1130 analogs as deubiquitinase inhibitors US Patent 8,809,377
8. US 20130095089: Glucosylceramide synthase inhibitors and therapeutic methods using the same. US Patent 8,961,959
9. WO 2013033392: Antitumor compounds.
10. WO 2013166282: Preparation of benzoquinazoline derivatives for treating bacterial infection.
11. WO 2013052943: Small Molecule Inhibitors of Mcl-1 and the Uses thereof.
12. WO 2013086415: Preparation of antimicrobial compounds related to rifalazil
13. WO 2014085485: Methods and compositions for targeting cancer stem cells.
14. WO 2014179734: Preparation of deuterated amlexanox derivatives for use as TBK1 or IKKε protein kinase inhibitors; Deuterated Amlexanox. US Patent 8,946,424.
15. WO 2015054555: Preparation of substituted acrylamides as deubiquitinase inhibitors

1. Showalter HDH, Denny WA. A Roadmap for Drug Discovery and its Translation to Small Molecule Agents in Clinical Development for Tuberculosis Treatment. Tuberculosis, 2008; 88: Suppl 1:S3-S17.
2. Turbiak AJ, Showalter HDH. A Novel Synthesis of N1-(Substituted)-pyrimido[5,4-e]-1,2,4-triazine-5,7(1H,6H)-diones. Tet. Lett., 2009, 50:1996-1997; PMID: 3105757
3. Aminoff D, Bochar DA, Fuller AA, Mapp AK, Showalter HDH, Kirchhoff PD. Research into Selective Biomarkers of Erythrocyte Exposure to Organophosphorus Compounds. Anal. Biochem. 2009, 392:155-161. PMID: 19497294
4. Turbiak AJ, Showalter HDH. A New Route to Substituted Pyrimido[5,4-e]-1,2,4-triazine-5,7(1H,6H)-diones and Facile Extension to 5,7(6H,8H) Isomers. Synthesis, 2009, 4022-4026; PMID: 3021411.
5. Turbiak AJ, Kampf JW, Showalter HDH. A Novel Synthesis of 3-(Substituted)pyrimido[4,5-c]pyridazine-5,7(1H,6H)-diones. Tet. Lett., 2010, 51:1326-1328.Peng, W.; Peltier, D.C.; Larsen, M.J.; Kirchhoff, P.D.; Larsen, S.D.; Neubig, R.R.; Miller, D.J. “The Identification of Thieno[3,2-b]pyrrole Derivatives as Novel Small Molecule Inhibitors of Neurotropic Alphaviruses”, J. Infect. Diseases 2009, 199, 950-57.
6. Aristoff PA, Garcia GA, Kirchhoff PD, and Showalter HDH, Rifamycins – Obstacles and Opportunities. Tuberculosis, 2010; 90: 94-118
7. Evelyn, C.R.; Bell, J.L., Ryu, J.G.; Wade, S.M., Kocab A., Harzdorf, N.L., Showalter, H.D.H., Neubig, R.R., Larsen, S.D. “Design, synthesis and prostate cancer cell-based studies of analogs of the Rho/MKL1 transcriptional pathway inhibitor, CCG-1423”, Bioorg. Med. Chem. Lett 2010, 20, 665-72.
8. Chen Y-C, Brooks AF, Goodenough-Lashua DM, Kittendorf JD, Showalter HD, Garcia GA. Evolution of tRNA Guanine Transglycosylase: Insight Gained from the Heterocyclic Substrate Recognition by the Wild-type and Mutant Human and E. coli tRNA Guanine Transglycosylases. Nucleic Acids Research, 2011, 39:2834-2844.
9. Yep A, Sorenson RJ, Wilson MR, Showalter HDH, Larsen SD, Keller PR, Woodard RW. Enediol Mimics as Inhibitors of the D-arabinose 5-phosphate Isomerase (KdsD) from Francisella tularensis. Bioorg. Med. Chem. Lett., 2011, 21:2679-2682. PMID: 21236668.
10. Kapuria V, Peterson LF, Showalter HDH, Kirchhoff PD, Talpaz M, Donato NJ. Novel Protein Cross-linking Activity of a Ubiquitin-activating Enzyme Inhibitor. Biochem. Pharmacol., 2011, 82:341-349.
11. Okawada M, Koga H, Larsen SD, Showalter HD, Turbiak AJ, Jin X, Lucas PC, Lipka, E, Hillfinger J, Kim JS, Teitelbaum DH. Use of Enterally-delivered Angiotensin II Type Ia Receptor Antagonists to Reduce the Severity of Colitis. Dig. Dis. Sci., 2011, 56:2553-2565.
12. Jin Y, Gill SK, Kirchhoff PD, Wan B, Franzblau SG, Garcia GA, Showalter HDH. Synthesis and Structure-Activity Relationships of Novel Substituted 8-Amino, 8-Thio, and 1,8-Pyrazole Congeners of Antitubercular Rifamycin S and Rifampin. Bioorg. Med. Chem. Lett., 2011, 21:6094-6099.
13. Fribley AM, Cruz PG, Miller JR, Callaghan MU, Cai P, Narula N, Neubig RR, Showalter HD, Larsen SD, Kirchhoff PD, Larsen MJ, Burr DA, Schultz PJ, Jacobs RR, Tamayo-Castillo G, Ron D, Sherman DH, Kaufman RJ. Complementary Cell-Based High Throughput Screens Identify Novel Modulators of the Unfolded Protein Response. J Biomed. Screen., 2011, 16:825-835.
14. Kapuria V, Levitzki A, Bornmann WG, Maxwell D, Priebe W, Sorenson RJ, Showalter HD, Talpaz M, Donato NJ. A Novel Small Molecule Deubiquitinase Inhibitor Blocks Jak2 Signaling Through Jak2 Ubiquitination. Cell. Signal., 2011, 23:2076-2085.
15. Burkholder K, Perry J, Wobus C, Donato N, Showalter H, Kapuria V, O'Riordan M, A Small Molecule Deubiquitinase Inhibitor Increases Localization of Inducible Nitric Oxide Synthase to the Macrophage Phagosome and Enhances Bacterial Killing. Infect. Immun., 2011, 79:4850-4857.
16. Puliyappadamba T, Wu W, Polin L, Kilkuskie R, Finley R, Larsen SD, Levi E, Miller FR, Wali A, Rishi AK. Antagonists of Anaphase Promoting Complex (APC)-2-Cell Cycle and Apoptosis Regulatory Protein (CARP)-1 Interaction Are Novel Regulators of Cell Growth and Apoptosis. J. Biol. Chem., 2011, 286:38000-17.
17. Larsen SD, Wilson MW, Abe A, Shu L, George CH, Kirchhoff P, Showalter HD, Xiang J, Keep RF, Shayman JA. Property-Based Design of a Substrate-Based Glucosylceramide Synthase Inhibitor that Reduces Glucosylceramide Levels in the Central Nervous System. J. Lipid Res., 2012, 53:282-291.
18. Grembecka J, He S, Shi A, Purohit T, Muntean AG, Sorenson RJ, Showalter HD, Murai M, Belcher A, Hartley T, Hess JL, Cierpicki T. Menin-MLL Inhibitors Reverse Oncogenic Activity of MLL Fusion Proteins in Leukemia. Nat. Chem. Biol., 2012, 8:277-284.
19. Clifford-Nunn B, Showalter HDH, Andrews PC. Cyclic Diamines as Mass Spectrometry Cleavable Crosslinkers for Protein Interactions. J. Am. Soc. Mass Spectr., 2012, 23:201-212.
20. Sun H, Xu Y, Sitkiewicz I, Ma Y, Wang X, Yestrepsky BD, Huang Y, Lapadatscu MC, Larsen MJ, Larsen SD, Musser JM, Ginsburg D. Inhibitor of Streptokinase Gene Expression Improves Survival After Group A Streptococcus Infection in Mice. Proc. Nat. Acad. Sci., 2012, 109:3469-74.
21. Sindac JS, Yestrepsky BD, Barraza SJ, Bolduc KL, Blakely PK, Keep RF, Irani DN, Miller DJ, Larsen SD. Novel Inhibitors of Neurotropic Alphavirus Replication That Improve Host Survival in a Mouse Model of Acute Viral Encephalitis. J. Med. Chem., 2012, 55, 3535-45.
22. Shen D, Wang X, Li X, Zhang X, Yao Z, Dibble S, Dong X-P, Yu T, Lieberman A, Showalter HD, Xu H. Lipid Storage Disorders Block Lysosomal Trafficking by Inhibiting TRP Channel and Calcium Release. Nat. Commun., 2012, 3:1735/1.
23. Gill SK, Xu H, Kirchhoff PD, Cierpicki T, Turbiak AJ, Wan B, Zhang N, Peng K-W, Franzblau SG, Garcia GA, Showalter HDH. Structure-based Design of Novel Benzoxazinorifamycins with Potent Binding Affinity to Wild-type and Rifampin-resistant Mutant Mycobacterium Tuberculosis RNA Polymerases. J. Med. Chem., 2012, 55: 3814-3826. Wang Y, Cesena TI, Ohnishi Y, Burger-Caplan R, Lam V, Kirchhoff PD, Larsen SD, Larsen MJ, Nestler EJ, Rudenko G. Small Molecule Screening Identifies Regulators of the Transcription Factor deltaFosB. ACS Chem. Neuroscience, 2012, 3, 546-56.
24. Jacob RT, Larsen MJ, Larsen SD, Kirchhoff PD, Sherman DH, Neubig RR. MScreen: An Integrated Compound Management and High Throughput Screening (HTS) Data Storage and Analysis System. J. Biomol. Screening, 2012, 17, 1080-87.
25. Lall MS, Hoge G, Tran T, Kissel W, Murphy ST, Taylor C, Hutchings K, Samas B, Ellsworth E, Curran T, Showalter HDH. Stereoselective Synthesis of (S)-3-(Methylamino)-3-((R)-pyrrolidin-3-yl)propanenitrile. J. Org. Chem., 2012, 77: 4732-4739.
26. Asangani IA, Ateeq B, Cao Q, Dodson L, Pandhi M, Kandarpa M, Townsend E, Kunju LP, Mehra R, Lonigro RJ, Siddiqui J, Palanisamy N, Wu Y-M, Cao X, Kim JH, Zhao M, Qin ZS, Iyer MK, Maher CA, Barker PL, Larsen SD, Dou Y, Lauring J, Kuehl MW, Kuman-Sinha C, Varambally S, Chinnaiyan AM. Characterization of the EZH2-MMSET Histone Methyltransferase Regluatory Axis in Cancer. Cell, submitted.
27. Perry JW, Ahmed M, Chang K-O, Donato NJ, Showalter HD, Wobus CE. Antiviral Activity of a Small Molecule Deubiquitinase Inhibitor Occurs via Induction of the Unfolded Protein Response. Plos. Pathog., 2012, 8: e1002783. Brooks AF, Velez-Martinez CS, Showalter HDH, Garcia GA. Investigating the Prevalence of Queuine in Escherichia coli RNA via Incorporation of the Tritium Labeled Precursor, PreQ1. Biochem. Bioph. Res. Com., 2012, 425:83-88. Bolduc KL, Larsen SD, Sherman DH. Efficient, Divergent Synthesis of Cryptophycin Unit A Analogues. JCS Chem. Comm., 2012, 17, 1080-87.
28. Ma, Y.; Xu, Y.; Yestrepsky, B.D.; Sorenson, R.J.; Chen, M.; Larsen, S.D.; Sun, H. “Novel inhibitors of Staphylococcus aureus virulence gene expression and biofilm formation”, PLoS ONE 2012, 7, e47225.
29. Yestrepsky, B.D.; Xu, Y.; Sorenson, R.J.; Wilson, M.W.; Ryu, J.; Rajaswaran, W.; Breen, M.E.; Tsume, Y.; Zhang, W.; Li, X.; Sun, D.; Sun, H.; Larsen, S.D. “Novel Inhibitors of Bacterial Virulence: Development of 5,6-Dihydrobenzo[h]quinazoline-4(3H)-ones for the Inhibition of Group A Streptococcal Streptokinase Expression”, Bioorg. Med. Chem. 2013, 21, 1880-97.
30. Xu H, Sabit H, Amidon GL, Showalter HDH. An Improved Synthesis of a Fluorophosphonate –polyethyleneglycol-biotin Probe and its Use against Competitive Substrates. Beilstein J. Org. Chem., 2013, 9: 89-96.
31. Showalter HDH. Progress in the Synthesis of Canthine Alkaloids and Ring-Truncated Congeners. J. Nat. Prod., 2013; 76: 455 – 467
32. Arthur, J.R.; Wilson, M.W.; Larsen, S.D.; Shayman, J.A.; Seyfried, T.N. “Ethylenedioxy-PIP2 oxalate reduces ganglioside storage in brain and liver of mice with Sandhoff disease”, Neurochem. Res. 2013, 38, 866-75.
33. Bell, J.L.; Haak, A.J.; Wade, S.M.; Sun, Y.; Neubig, R.R.; Larsen, S.D. “Design and synthesis of tag-free photoprobes for the identification of the molecular target for CCG-1423, a novel inhibitor of the Rho/MKL1/SRF signaling pathway”, Beilstein J. Org. Chem. 2013, 9, 966-73.
34. Titchenell PM, Showalter HDH, Pons J-F, Barber AJ, Jin Y, Antonetti DA. Synthesis and Structure-activity Relationships of 2-Amino-3-carboxy-4-phenylthiophenes as Novel Atypical Protein Kinase C Inhibitors. Bioorg. Med. Chem. Lett., 2013, 23:3034-3038.
35. Bell, J.L.; Haak, A.J.; Wade, S.M., Kirchhoff, P.D.; Neubig, R.R.; Larsen, S.D. “Optimization of Novel Nipecotic Bis(amide) Inhibitors of the Rho/MKL1/SRF Transcriptional Pathway as Potential Anti-metastasis Agents”, Bioorg. Med. Chem. Lett. 2013, 23, 3826-32.
36. Molodtsov V, Nawarathne IN, Scharf NT, Kirchhoff PD, Showalter HDH, Garcia GA, Murakami KS. X-ray Crystal Structures of the Escherichia coli RNA Polymerase in Complex with Benzoxazinorifamycins. J. Med. Chem., 2013, 56: 4758-4763.
37. Sindac, J.A.; Barraza, S.J.; Dobry, C.J.; Xiang, J.; Blakely, P.K.; Irani, D.N.; Keep, R.F.; Miller, D.J.; Larsen, S.D. “Optimization of Novel Indole-2-carboxamide Inhibitors of Neurotropic Alphavirus Replication”, J. Med. Chem. 2013, 56, 9222-41.
38. Zeller J, Turbiak AJ, Powelson IA, Lee S, Sun D, Showalter HDH, Fearon ER. Investigation of 3-Aryl-pyrimid[5,4-e][1,2,4]triazine-5,7-diones as Small Molecule Antagonists of β-catenin/TCF Transcription. Bioorg. Med. Chem. Lett., 2013, 23:5814-5820.
39. Johnson, L.A.; Rodansky, E.; Haak, A.; Larsen, S.D.; Neubig, R.R.; Higgins, P.D.R. “Novel Rho/MRTF-A Inhibitors Block Matrix-stiffness and TGF-Induced Fibrogenesis in Human Colonic Myofibroblasts”, Inflamm. Bowel Dis. 2014, 20, 154-65.
40. Winters T, Sercel A, Suto C, Elliott W, Leopold W, Leopold J, Showalter H. Design and Synthesis of 2-Nitroimidazoles with Variable Alkylating and Acylating Functionality. Chem. Pharm. Bull., 2014, 62:301-303.
41. Lundquist, M.R.; Storaska, A.; Liu, T.-C.; Larsen, S.D.; Evans, T.; Neubig, R.R.; Jaffrey, S.R. “Redox modification of nuclear actin by MICAL-2 regulates SRF signaling”, Cell 2014, 156, 563-76.
42. Homan, K.T.; Wu, E.; Wilson, M.W.; Singh, P.; Larsen, S.D.; Tesmer, J.J.G. “Structural and Functional Analysis of G Protein-Coupled Receptor Kinase Inhibition by Paroxetine and a Rationally Designed Analog”, Mol. Pharmacol. 2014, 85, 237-48.
43. Peng Z, Maxwell D, Sun D, Pal A, Ying Y, Han D, Gao L, Wang S, Kapuria V, Talpaz M, Young M, Showalter HD, Donato NJ, Bornmann W. Tyrphostin-like Compounds with Deubiquitinase Inhibitory Activity as Possible Therapeutic Agents for Multiple Myeloma (II). Bioorg. Med. Chem., 2014, 22:1450–1458.
44. Yestrepsky, B.D.; Kretz, C.; Xu, Y.; Holmes, A.; Sun, H.; Ginsburg, D.; Larsen, S.D. “Development of tag-free photoprobes for studies aimed at identifying the target of novel Group A Streptococcus antivirulence agents”, Bioorg. Med. Chem. Lett. 2014, 24, 1538-44.
45. Larsen, M.J.; Larsen, S.D.; Fribley, A.; Grembecka, J.; Haak, A; Homan, K.; Mapp, A.; Nikolovska-Coleska, Z.; Stuckey, J.A.; Sun, D.; Sherman, D.H. “The Role of HTS in Drug Discovery at University of Michigan”, Combi. Chem. & High Throughput Screening 2014, 17, 210-30.
46. Baez-Santos, Y.M.; Barraza, S.J.; Wilson, M.W.; Agius, M.P.; Mielech, A.; Davis, N.M.; Baker, S.C.; Larsen, S.D.; Mesecar, A.D. “X-Ray Structural and Biological Evaluation of a Series of Potent and Highly Selective Inhibitors of Human Coronavirus Papain Like-Proteases”, J. Med. Chem., 2014, 57, 2393-2412.
47. Haak, A.; Tsou, P.-S.; Amin, M.A.; Ruth, J.H.; Campbell, P.; Fox, D.A.; Khanna, D.; Larsen, S.D.; Neubig, R.R. “Targeting the myofibroblast genetic switch: inhibitors of MRTF/SRF-regulated gene transcription prevent fibrosis in a murine model of skin injury”, J. Pharmacol. Exp. Ther. 2014, 349, 480-86.
48. Shayman, J.A.; Larsen, S.D. “The Development and Use of Small Molecule Inhibitors of Glycosphingolipid Metabolism for the Treatment of Lysosomal Storage Disease”, J. Lipid Res. 2014, 55, 1215-25.
49. Lenhart JS, Brandes ER, Schroeder JW, Sorenson RJ, Showalter HD, Simmons LA. RecO and RecR are Necessary for RecA Loading in Response to DNA Damage and Replication Fork Stress in Bacillus Subtilis. J. Bacteriology, 2014, 196:2851-2860.
50. Abulwerdi FA, Liao C, Mady AS, Shen C, DiBernardo J, Gavin J, Cierpicki T, Stuckey JA, Showalter HDH, Nikolovska-Coleska Z. Structure-Based Design and Synthesis of 3-Substituted-N-(4-Hydroxynaphthalen-1-yl)arylsulfonamides as Potent, Selective Inhibitors of the Anti-apoptotic Protein Mcl-1. J. Med. Chem., 2014, 57:4111-4133.
51. Delekta, P.C.; Dobry, C.J.; Sindac, J.A.; Barraza, S.J.; Blakely, P.K.; Xiang, J.; Kirchhoff, P.D.; Keep, R.F.; Irani, D.N.; Larsen, S.D.; Miller, D.J. “Novel indole-2-carboxamide compounds are potent broad spectrum antivirals active against western equine encephalitis virus in vivo”, J. Virology 2014, 88, 11199-11214.
52. Gonzalez-Hernandez MJ, Gyan KE, Charbonneau M-E, Showalter HD, Donato NJ, O’Riordan M, Wobus CE. Chemical Derivatives of a Small Molecule Deubiquitinase Inhibitor have Antiviral Activity against Several RNA Viruses. Plos One, 2014, 9:e94491
53. Deng, X.; Agnihothram, S.; Mielech, A.M.; Nichols, D.B.; St. John, S.; Wilson, M.W.; Larsen, S.D.; Mesecar, A.D.; Lenschow, D.J.; Baric, R.; Baker, S.C. “A Chimeric Virus-Mouse Model System for Evaluating the Function and Inhibition of Papain-like Proteases of Emerging Coronaviruses”, J. Virology 2014, 88, 11825-33.
54. Charbonneau M-E, Gonzalez-Hernandez MJ, Showalter HD, Donato NJ, Wobus CE, O’Riordan MXD. Small Molecule Deubiquitinase Inhibitors Promote Macrophage Anti-infective Capacity. Plos One, 2014, 9:e104096.
55. Gibbons GS, Showalter HD, Nikolovska-Coleska Z. Novel Carboxaldehyde Mediated Synthetic Pathway for 5’-Amino Adenosine Analogues. Nucleosides, Nucleotides and Nucleic Acids, 2015, 34:348-360
56. Barraza, S.J.; Delekta, P.C.; Sindac, J.A.; Dobry, C.J.; Xiang, J.; Keep, R.F.; Miller, D.J.; Larsen,S.D. “Discovery of Anthranilamides as a Novel Class of Inhibitors of Neurotropic Alphavirus Replication”, Bioorg. Med. Chem 2015, 23, 1569-87.
57. Sisson, T.H.; Ajayi, I.O.; Subbotina, N.; Dodi, A.E.; Rodansky, E.S.; Chibucos, L.N.; Kim, K.K.; Keshamouni, V.G.; White, E.S.; Zhou, Y.; Higgins, P.D.R.; Larsen, S.D.; Neubig, R.R.; Horowitz, J.C. “Inhibition of MRTF/SRF Signaling Decreases Lung Fibrosis and Promotes Mesenchymal Cell Apoptosis”, Am. J. Pathology, 2015, 185, 969-86.
58. Peterson LF, Sun H, Liu Y, Potu H, Kandarpa M, Ermann M, Courtney SM, Young MA, Showalter HD, Sun D, Jakubowiak AJ, Malek SN, Talpaz M, Donato NJ. Targeting Deubiquitinase Activity with a Novel Small Molecule Inhibitor as Therapy for B-cell Malignancies, Blood, DOI: http://dx.doi.org/10.1182/blood-2014-10-605584.
59. Min, K.A.; Rajeswaran, W.G.; Oldenbourg, R.; Harris, G.; Keswani, R.K.; Chiang, M.; Hafeez, M.; Horobin, R.W.; Larsen, S.D.; Stringer, K.A.; Rosania, G.R. “Macrophages Preferentially Accumulate Chiral Phenazine Compounds as Ordered Molecular Aggregates within an Optically Anisotropic Cytoplasmic Phase”, Advanced Science 2015, in press.
60. Homan, K.T.; Waldschmidt, H; Glukhova, A.; Cannavo, A.; Koch, W.J.; Larsen, S.D.; Tesmer, J.J.G. “Crystal Structure of G Protein-Coupled Receptor Kinase 5 in Complex with a Rationally Designed Inhibitor “, J. Biol. Chem. 2015 in press.
61. Xu H, Majmudar JD, Ghanakota P, Davda D, Kim KH, Carlson HA, Showalter HD, Martin BR, Amidon GL. Substrate-competitive Activity-based Profiling of Ester Prodrug Activating Enzymes. Molecular Pharmaceutics, 2015. in press.

Patents

1. WO 2010014798: Preparation of pyrimidotriazinediones and pyrimidopyrimidinediones for treating cancer.
2. WO 201017312: Compositions and methods for the treatment and prevention of inflammatory bowel diseases; US Patent 8,293,776
3. WO 2010090860: Methods and compositions for treating bacterial infection. US Patent 8,501,722
4. WO 2011035143: Benzamides and related compounds as Rho GTPase inhibitors and their preparation and compositions for inhibiting Rho-mediated diseases and conditions.
5. US 20120252807: Preparation of pyrrolyl(or imidazolyl) piperidinyl methanone derivatives as arbovirus inhibitors. US Patent 8,846,684
6. WO2012149335: Preparation of thiadiazolidinone derivatives as inhibitors of RGS proteins
7. WO 2012040527: Preparation of WP1130 analogs as deubiquitinase inhibitors US Patent 8,809,377
8. US 20130095089: Glucosylceramide synthase inhibitors and therapeutic methods using the same. US Patent 8,961,959
9. WO 2013033392: Antitumor compounds.
10. WO 2013166282: Preparation of benzoquinazoline derivatives for treating bacterial infection.
11. WO 2013052943: Small Molecule Inhibitors of Mcl-1 and the Uses thereof.
12. WO 2013086415: Preparation of antimicrobial compounds related to rifalazil
13. WO 2014085485: Methods and compositions for targeting cancer stem cells.
14. WO 2014179734: Preparation of deuterated amlexanox derivatives for use as TBK1 or IKKε protein kinase inhibitors; Deuterated Amlexanox. US Patent 8,946,424.
15. WO 2015054555: Preparation of substituted acrylamides as deubiquitinase inhibitors

Publications

1. Showalter HDH, Denny WA. A Roadmap for Drug Discovery and its Translation to Small Molecule Agents in Clinical Development for Tuberculosis Treatment. Tuberculosis, 2008; 88: Suppl 1:S3-S17.
2. Turbiak AJ, Showalter HDH. A Novel Synthesis of N1-(Substituted)-pyrimido[5,4-e]-1,2,4-triazine-5,7(1H,6H)-diones. Tet. Lett., 2009, 50:1996-1997; PMID: 3105757
3. Aminoff D, Bochar DA, Fuller AA, Mapp AK, Showalter HDH, Kirchhoff PD. Research into Selective Biomarkers of Erythrocyte Exposure to Organophosphorus Compounds. Anal. Biochem. 2009, 392:155-161. PMID: 19497294
4. Turbiak AJ, Showalter HDH. A New Route to Substituted Pyrimido[5,4-e]-1,2,4-triazine-5,7(1H,6H)-diones and Facile Extension to 5,7(6H,8H) Isomers. Synthesis, 2009, 4022-4026; PMID: 3021411.
5. Turbiak AJ, Kampf JW, Showalter HDH. A Novel Synthesis of 3-(Substituted)pyrimido[4,5-c]pyridazine-5,7(1H,6H)-diones. Tet. Lett., 2010, 51:1326-1328.Peng, W.; Peltier, D.C.; Larsen, M.J.; Kirchhoff, P.D.; Larsen, S.D.; Neubig, R.R.; Miller, D.J. “The Identification of Thieno[3,2-b]pyrrole Derivatives as Novel Small Molecule Inhibitors of Neurotropic Alphaviruses”, J. Infect. Diseases 2009, 199, 950-57.
6. Aristoff PA, Garcia GA, Kirchhoff PD, and Showalter HDH, Rifamycins – Obstacles and Opportunities. Tuberculosis, 2010; 90: 94-118
7. Evelyn, C.R.; Bell, J.L., Ryu, J.G.; Wade, S.M., Kocab A., Harzdorf, N.L., Showalter, H.D.H., Neubig, R.R., Larsen, S.D. “Design, synthesis and prostate cancer cell-based studies of analogs of the Rho/MKL1 transcriptional pathway inhibitor, CCG-1423”, Bioorg. Med. Chem. Lett 2010, 20, 665-72.
8. Chen Y-C, Brooks AF, Goodenough-Lashua DM, Kittendorf JD, Showalter HD, Garcia GA. Evolution of tRNA Guanine Transglycosylase: Insight Gained from the Heterocyclic Substrate Recognition by the Wild-type and Mutant Human and E. coli tRNA Guanine Transglycosylases. Nucleic Acids Research, 2011, 39:2834-2844.
9. Yep A, Sorenson RJ, Wilson MR, Showalter HDH, Larsen SD, Keller PR, Woodard RW. Enediol Mimics as Inhibitors of the D-arabinose 5-phosphate Isomerase (KdsD) from Francisella tularensis. Bioorg. Med. Chem. Lett., 2011, 21:2679-2682. PMID: 21236668.
10. Kapuria V, Peterson LF, Showalter HDH, Kirchhoff PD, Talpaz M, Donato NJ. Novel Protein Cross-linking Activity of a Ubiquitin-activating Enzyme Inhibitor. Biochem. Pharmacol., 2011, 82:341-349.
11. Okawada M, Koga H, Larsen SD, Showalter HD, Turbiak AJ, Jin X, Lucas PC, Lipka, E, Hillfinger J, Kim JS, Teitelbaum DH. Use of Enterally-delivered Angiotensin II Type Ia Receptor Antagonists to Reduce the Severity of Colitis. Dig. Dis. Sci., 2011, 56:2553-2565.
12. Jin Y, Gill SK, Kirchhoff PD, Wan B, Franzblau SG, Garcia GA, Showalter HDH. Synthesis and Structure-Activity Relationships of Novel Substituted 8-Amino, 8-Thio, and 1,8-Pyrazole Congeners of Antitubercular Rifamycin S and Rifampin. Bioorg. Med. Chem. Lett., 2011, 21:6094-6099.
13. Fribley AM, Cruz PG, Miller JR, Callaghan MU, Cai P, Narula N, Neubig RR, Showalter HD, Larsen SD, Kirchhoff PD, Larsen MJ, Burr DA, Schultz PJ, Jacobs RR, Tamayo-Castillo G, Ron D, Sherman DH, Kaufman RJ. Complementary Cell-Based High Throughput Screens Identify Novel Modulators of the Unfolded Protein Response. J Biomed. Screen., 2011, 16:825-835.
14. Kapuria V, Levitzki A, Bornmann WG, Maxwell D, Priebe W, Sorenson RJ, Showalter HD, Talpaz M, Donato NJ. A Novel Small Molecule Deubiquitinase Inhibitor Blocks Jak2 Signaling Through Jak2 Ubiquitination. Cell. Signal., 2011, 23:2076-2085.
15. Burkholder K, Perry J, Wobus C, Donato N, Showalter H, Kapuria V, O'Riordan M, A Small Molecule Deubiquitinase Inhibitor Increases Localization of Inducible Nitric Oxide Synthase to the Macrophage Phagosome and Enhances Bacterial Killing. Infect. Immun., 2011, 79:4850-4857.
16. Puliyappadamba T, Wu W, Polin L, Kilkuskie R, Finley R, Larsen SD, Levi E, Miller FR, Wali A, Rishi AK. Antagonists of Anaphase Promoting Complex (APC)-2-Cell Cycle and Apoptosis Regulatory Protein (CARP)-1 Interaction Are Novel Regulators of Cell Growth and Apoptosis. J. Biol. Chem., 2011, 286:38000-17.
17. Larsen SD, Wilson MW, Abe A, Shu L, George CH, Kirchhoff P, Showalter HD, Xiang J, Keep RF, Shayman JA. Property-Based Design of a Substrate-Based Glucosylceramide Synthase Inhibitor that Reduces Glucosylceramide Levels in the Central Nervous System. J. Lipid Res., 2012, 53:282-291.
18. Grembecka J, He S, Shi A, Purohit T, Muntean AG, Sorenson RJ, Showalter HD, Murai M, Belcher A, Hartley T, Hess JL, Cierpicki T. Menin-MLL Inhibitors Reverse Oncogenic Activity of MLL Fusion Proteins in Leukemia. Nat. Chem. Biol., 2012, 8:277-284.
19. Clifford-Nunn B, Showalter HDH, Andrews PC. Cyclic Diamines as Mass Spectrometry Cleavable Crosslinkers for Protein Interactions. J. Am. Soc. Mass Spectr., 2012, 23:201-212.
20. Sun H, Xu Y, Sitkiewicz I, Ma Y, Wang X, Yestrepsky BD, Huang Y, Lapadatscu MC, Larsen MJ, Larsen SD, Musser JM, Ginsburg D. Inhibitor of Streptokinase Gene Expression Improves Survival After Group A Streptococcus Infection in Mice. Proc. Nat. Acad. Sci., 2012, 109:3469-74.
21. Sindac JS, Yestrepsky BD, Barraza SJ, Bolduc KL, Blakely PK, Keep RF, Irani DN, Miller DJ, Larsen SD. Novel Inhibitors of Neurotropic Alphavirus Replication That Improve Host Survival in a Mouse Model of Acute Viral Encephalitis. J. Med. Chem., 2012, 55, 3535-45.
22. Shen D, Wang X, Li X, Zhang X, Yao Z, Dibble S, Dong X-P, Yu T, Lieberman A, Showalter HD, Xu H. Lipid Storage Disorders Block Lysosomal Trafficking by Inhibiting TRP Channel and Calcium Release. Nat. Commun., 2012, 3:1735/1.
23. Gill SK, Xu H, Kirchhoff PD, Cierpicki T, Turbiak AJ, Wan B, Zhang N, Peng K-W, Franzblau SG, Garcia GA, Showalter HDH. Structure-based Design of Novel Benzoxazinorifamycins with Potent Binding Affinity to Wild-type and Rifampin-resistant Mutant Mycobacterium Tuberculosis RNA Polymerases. J. Med. Chem., 2012, 55: 3814-3826. Wang Y, Cesena TI, Ohnishi Y, Burger-Caplan R, Lam V, Kirchhoff PD, Larsen SD, Larsen MJ, Nestler EJ, Rudenko G. Small Molecule Screening Identifies Regulators of the Transcription Factor deltaFosB. ACS Chem. Neuroscience, 2012, 3, 546-56.
24. Jacob RT, Larsen MJ, Larsen SD, Kirchhoff PD, Sherman DH, Neubig RR. MScreen: An Integrated Compound Management and High Throughput Screening (HTS) Data Storage and Analysis System. J. Biomol. Screening, 2012, 17, 1080-87.
25. Lall MS, Hoge G, Tran T, Kissel W, Murphy ST, Taylor C, Hutchings K, Samas B, Ellsworth E, Curran T, Showalter HDH. Stereoselective Synthesis of (S)-3-(Methylamino)-3-((R)-pyrrolidin-3-yl)propanenitrile. J. Org. Chem., 2012, 77: 4732-4739.
26. Asangani IA, Ateeq B, Cao Q, Dodson L, Pandhi M, Kandarpa M, Townsend E, Kunju LP, Mehra R, Lonigro RJ, Siddiqui J, Palanisamy N, Wu Y-M, Cao X, Kim JH, Zhao M, Qin ZS, Iyer MK, Maher CA, Barker PL, Larsen SD, Dou Y, Lauring J, Kuehl MW, Kuman-Sinha C, Varambally S, Chinnaiyan AM. Characterization of the EZH2-MMSET Histone Methyltransferase Regluatory Axis in Cancer. Cell, submitted.
27. Perry JW, Ahmed M, Chang K-O, Donato NJ, Showalter HD, Wobus CE. Antiviral Activity of a Small Molecule Deubiquitinase Inhibitor Occurs via Induction of the Unfolded Protein Response. Plos. Pathog., 2012, 8: e1002783. Brooks AF, Velez-Martinez CS, Showalter HDH, Garcia GA. Investigating the Prevalence of Queuine in Escherichia coli RNA via Incorporation of the Tritium Labeled Precursor, PreQ1. Biochem. Bioph. Res. Com., 2012, 425:83-88. Bolduc KL, Larsen SD, Sherman DH. Efficient, Divergent Synthesis of Cryptophycin Unit A Analogues. JCS Chem. Comm., 2012, 17, 1080-87.
28. Ma, Y.; Xu, Y.; Yestrepsky, B.D.; Sorenson, R.J.; Chen, M.; Larsen, S.D.; Sun, H. “Novel inhibitors of Staphylococcus aureus virulence gene expression and biofilm formation”, PLoS ONE 2012, 7, e47225.
29. Yestrepsky, B.D.; Xu, Y.; Sorenson, R.J.; Wilson, M.W.; Ryu, J.; Rajaswaran, W.; Breen, M.E.; Tsume, Y.; Zhang, W.; Li, X.; Sun, D.; Sun, H.; Larsen, S.D. “Novel Inhibitors of Bacterial Virulence: Development of 5,6-Dihydrobenzo[h]quinazoline-4(3H)-ones for the Inhibition of Group A Streptococcal Streptokinase Expression”, Bioorg. Med. Chem. 2013, 21, 1880-97.
30. Xu H, Sabit H, Amidon GL, Showalter HDH. An Improved Synthesis of a Fluorophosphonate –polyethyleneglycol-biotin Probe and its Use against Competitive Substrates. Beilstein J. Org. Chem., 2013, 9: 89-96.
31. Showalter HDH. Progress in the Synthesis of Canthine Alkaloids and Ring-Truncated Congeners. J. Nat. Prod., 2013; 76: 455 – 467
32. Arthur, J.R.; Wilson, M.W.; Larsen, S.D.; Shayman, J.A.; Seyfried, T.N. “Ethylenedioxy-PIP2 oxalate reduces ganglioside storage in brain and liver of mice with Sandhoff disease”, Neurochem. Res. 2013, 38, 866-75.
33. Bell, J.L.; Haak, A.J.; Wade, S.M.; Sun, Y.; Neubig, R.R.; Larsen, S.D. “Design and synthesis of tag-free photoprobes for the identification of the molecular target for CCG-1423, a novel inhibitor of the Rho/MKL1/SRF signaling pathway”, Beilstein J. Org. Chem. 2013, 9, 966-73.
34. Titchenell PM, Showalter HDH, Pons J-F, Barber AJ, Jin Y, Antonetti DA. Synthesis and Structure-activity Relationships of 2-Amino-3-carboxy-4-phenylthiophenes as Novel Atypical Protein Kinase C Inhibitors. Bioorg. Med. Chem. Lett., 2013, 23:3034-3038.
35. Bell, J.L.; Haak, A.J.; Wade, S.M., Kirchhoff, P.D.; Neubig, R.R.; Larsen, S.D. “Optimization of Novel Nipecotic Bis(amide) Inhibitors of the Rho/MKL1/SRF Transcriptional Pathway as Potential Anti-metastasis Agents”, Bioorg. Med. Chem. Lett. 2013, 23, 3826-32.
36. Molodtsov V, Nawarathne IN, Scharf NT, Kirchhoff PD, Showalter HDH, Garcia GA, Murakami KS. X-ray Crystal Structures of the Escherichia coli RNA Polymerase in Complex with Benzoxazinorifamycins. J. Med. Chem., 2013, 56: 4758-4763.
37. Sindac, J.A.; Barraza, S.J.; Dobry, C.J.; Xiang, J.; Blakely, P.K.; Irani, D.N.; Keep, R.F.; Miller, D.J.; Larsen, S.D. “Optimization of Novel Indole-2-carboxamide Inhibitors of Neurotropic Alphavirus Replication”, J. Med. Chem. 2013, 56, 9222-41.
38. Zeller J, Turbiak AJ, Powelson IA, Lee S, Sun D, Showalter HDH, Fearon ER. Investigation of 3-Aryl-pyrimid[5,4-e][1,2,4]triazine-5,7-diones as Small Molecule Antagonists of β-catenin/TCF Transcription. Bioorg. Med. Chem. Lett., 2013, 23:5814-5820.
39. Johnson, L.A.; Rodansky, E.; Haak, A.; Larsen, S.D.; Neubig, R.R.; Higgins, P.D.R. “Novel Rho/MRTF-A Inhibitors Block Matrix-stiffness and TGF-Induced Fibrogenesis in Human Colonic Myofibroblasts”, Inflamm. Bowel Dis. 2014, 20, 154-65.
40. Winters T, Sercel A, Suto C, Elliott W, Leopold W, Leopold J, Showalter H. Design and Synthesis of 2-Nitroimidazoles with Variable Alkylating and Acylating Functionality. Chem. Pharm. Bull., 2014, 62:301-303.
41. Lundquist, M.R.; Storaska, A.; Liu, T.-C.; Larsen, S.D.; Evans, T.; Neubig, R.R.; Jaffrey, S.R. “Redox modification of nuclear actin by MICAL-2 regulates SRF signaling”, Cell 2014, 156, 563-76.
42. Homan, K.T.; Wu, E.; Wilson, M.W.; Singh, P.; Larsen, S.D.; Tesmer, J.J.G. “Structural and Functional Analysis of G Protein-Coupled Receptor Kinase Inhibition by Paroxetine and a Rationally Designed Analog”, Mol. Pharmacol. 2014, 85, 237-48.
43. Peng Z, Maxwell D, Sun D, Pal A, Ying Y, Han D, Gao L, Wang S, Kapuria V, Talpaz M, Young M, Showalter HD, Donato NJ, Bornmann W. Tyrphostin-like Compounds with Deubiquitinase Inhibitory Activity as Possible Therapeutic Agents for Multiple Myeloma (II). Bioorg. Med. Chem., 2014, 22:1450–1458.
44. Yestrepsky, B.D.; Kretz, C.; Xu, Y.; Holmes, A.; Sun, H.; Ginsburg, D.; Larsen, S.D. “Development of tag-free photoprobes for studies aimed at identifying the target of novel Group A Streptococcus antivirulence agents”, Bioorg. Med. Chem. Lett. 2014, 24, 1538-44.
45. Larsen, M.J.; Larsen, S.D.; Fribley, A.; Grembecka, J.; Haak, A; Homan, K.; Mapp, A.; Nikolovska-Coleska, Z.; Stuckey, J.A.; Sun, D.; Sherman, D.H. “The Role of HTS in Drug Discovery at University of Michigan”, Combi. Chem. & High Throughput Screening 2014, 17, 210-30.
46. Baez-Santos, Y.M.; Barraza, S.J.; Wilson, M.W.; Agius, M.P.; Mielech, A.; Davis, N.M.; Baker, S.C.; Larsen, S.D.; Mesecar, A.D. “X-Ray Structural and Biological Evaluation of a Series of Potent and Highly Selective Inhibitors of Human Coronavirus Papain Like-Proteases”, J. Med. Chem., 2014, 57, 2393-2412.
47. Haak, A.; Tsou, P.-S.; Amin, M.A.; Ruth, J.H.; Campbell, P.; Fox, D.A.; Khanna, D.; Larsen, S.D.; Neubig, R.R. “Targeting the myofibroblast genetic switch: inhibitors of MRTF/SRF-regulated gene transcription prevent fibrosis in a murine model of skin injury”, J. Pharmacol. Exp. Ther. 2014, 349, 480-86.
48. Shayman, J.A.; Larsen, S.D. “The Development and Use of Small Molecule Inhibitors of Glycosphingolipid Metabolism for the Treatment of Lysosomal Storage Disease”, J. Lipid Res. 2014, 55, 1215-25.
49. Lenhart JS, Brandes ER, Schroeder JW, Sorenson RJ, Showalter HD, Simmons LA. RecO and RecR are Necessary for RecA Loading in Response to DNA Damage and Replication Fork Stress in Bacillus Subtilis. J. Bacteriology, 2014, 196:2851-2860.
50. Abulwerdi FA, Liao C, Mady AS, Shen C, DiBernardo J, Gavin J, Cierpicki T, Stuckey JA, Showalter HDH, Nikolovska-Coleska Z. Structure-Based Design and Synthesis of 3-Substituted-N-(4-Hydroxynaphthalen-1-yl)arylsulfonamides as Potent, Selective Inhibitors of the Anti-apoptotic Protein Mcl-1. J. Med. Chem., 2014, 57:4111-4133.
51. Delekta, P.C.; Dobry, C.J.; Sindac, J.A.; Barraza, S.J.; Blakely, P.K.; Xiang, J.; Kirchhoff, P.D.; Keep, R.F.; Irani, D.N.; Larsen, S.D.; Miller, D.J. “Novel indole-2-carboxamide compounds are potent broad spectrum antivirals active against western equine encephalitis virus in vivo”, J. Virology 2014, 88, 11199-11214.
52. Gonzalez-Hernandez MJ, Gyan KE, Charbonneau M-E, Showalter HD, Donato NJ, O’Riordan M, Wobus CE. Chemical Derivatives of a Small Molecule Deubiquitinase Inhibitor have Antiviral Activity against Several RNA Viruses. Plos One, 2014, 9:e94491
53. Deng, X.; Agnihothram, S.; Mielech, A.M.; Nichols, D.B.; St. John, S.; Wilson, M.W.; Larsen, S.D.; Mesecar, A.D.; Lenschow, D.J.; Baric, R.; Baker, S.C. “A Chimeric Virus-Mouse Model System for Evaluating the Function and Inhibition of Papain-like Proteases of Emerging Coronaviruses”, J. Virology 2014, 88, 11825-33.
54. Charbonneau M-E, Gonzalez-Hernandez MJ, Showalter HD, Donato NJ, Wobus CE, O’Riordan MXD. Small Molecule Deubiquitinase Inhibitors Promote Macrophage Anti-infective Capacity. Plos One, 2014, 9:e104096.
55. Gibbons GS, Showalter HD, Nikolovska-Coleska Z. Novel Carboxaldehyde Mediated Synthetic Pathway for 5’-Amino Adenosine Analogues. Nucleosides, Nucleotides and Nucleic Acids, 2015, 34:348-360
56. Barraza, S.J.; Delekta, P.C.; Sindac, J.A.; Dobry, C.J.; Xiang, J.; Keep, R.F.; Miller, D.J.; Larsen,S.D. “Discovery of Anthranilamides as a Novel Class of Inhibitors of Neurotropic Alphavirus Replication”, Bioorg. Med. Chem 2015, 23, 1569-87.
57. Sisson, T.H.; Ajayi, I.O.; Subbotina, N.; Dodi, A.E.; Rodansky, E.S.; Chibucos, L.N.; Kim, K.K.; Keshamouni, V.G.; White, E.S.; Zhou, Y.; Higgins, P.D.R.; Larsen, S.D.; Neubig, R.R.; Horowitz, J.C. “Inhibition of MRTF/SRF Signaling Decreases Lung Fibrosis and Promotes Mesenchymal Cell Apoptosis”, Am. J. Pathology, 2015, 185, 969-86.
58. Peterson LF, Sun H, Liu Y, Potu H, Kandarpa M, Ermann M, Courtney SM, Young MA, Showalter HD, Sun D, Jakubowiak AJ, Malek SN, Talpaz M, Donato NJ. Targeting Deubiquitinase Activity with a Novel Small Molecule Inhibitor as Therapy for B-cell Malignancies, Blood, DOI: http://dx.doi.org/10.1182/blood-2014-10-605584.
59. Min, K.A.; Rajeswaran, W.G.; Oldenbourg, R.; Harris, G.; Keswani, R.K.; Chiang, M.; Hafeez, M.; Horobin, R.W.; Larsen, S.D.; Stringer, K.A.; Rosania, G.R. “Macrophages Preferentially Accumulate Chiral Phenazine Compounds as Ordered Molecular Aggregates within an Optically Anisotropic Cytoplasmic Phase”, Advanced Science 2015, in press.
60. Homan, K.T.; Waldschmidt, H; Glukhova, A.; Cannavo, A.; Koch, W.J.; Larsen, S.D.; Tesmer, J.J.G. “Crystal Structure of G Protein-Coupled Receptor Kinase 5 in Complex with a Rationally Designed Inhibitor “, J. Biol. Chem. 2015 in press.
61. Xu H, Majmudar JD, Ghanakota P, Davda D, Kim KH, Carlson HA, Showalter HD, Martin BR, Amidon GL. Substrate-competitive Activity-based Profiling of Ester Prodrug Activating Enzymes. Molecular Pharmaceutics, 2015. in press.

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Tuesday, September 3, 2013
Tuesday, September 3, 2013