Michelle Arkin, PhD

Department Chair and Professor
Pharmaceutical Chemistry
+1 415 514-4313

Michelle’s lab develops innovative approaches to screen for chemical tools and drug leads, using biophysical approaches like fragment-based drug discovery and biological approaches including high-content imaging with primary cells and organisms. Our goal is to demonstrate ‘druggability’ of new target classes and to use our compounds to discover new targets for drug discovery. Areas of interest include protein-protein interactions, allosteric and scaffolding sites in enzymes, and orphan and neglected diseases. Michelle is co-Director of the Small Molecule Discovery Center, a collaborative research and core lab that includes a high-throughput screening facility and medicinal chemistry (smdc.ucsf.edu).

Publications: 

Abstract B004: ATR-CHK1-WEE1 pathway is a critical dependency in the context of DNA damage and replicative stress in osteosarcoma.

Clinical Cancer Research

Leanne C. Sayles, Henry Martell, Amanda Koehne, Kean-Hooi Ang, Chris Wilson, Michelle Arkin, E. Alejandro Sweet-Cordero

Adaptor-Specific Antibody Fragment Inhibitors for the Intracellular Modulation of p97 (VCP) Protein-Protein Interactions.

Journal of the American Chemical Society

Jiang Z, Kuo YH, Zhong M, Zhang J, Zhou XX, Xing L, Wells JA, Wang Y, Arkin MR

Caspase-6-cleaved tau is relevant in Alzheimer's disease and marginal in four-repeat tauopathies: diagnostic and therapeutic implications.

Neuropathology and applied neurobiology

Theofilas P, Piergies AMH, Oh I, Lee YB, Li SH, Pereira FL, Petersen C, Ehrenberg AJ, Eser RA, Ambrose AJ, Chin B, Yang T, Khan S, Ng R, Spina S, Seeley WW, Miller BL, Arkin MR, Grinberg LT

Phenotypic Screening Using High-Content Imaging to Identify Lysosomal pH Modulators in a Neuronal Cell Model.

ACS chemical neuroscience

Chin MY, Ang KH, Davies J, Alquezar C, Garda VG, Rooney B, Leng K, Kampmann M, Arkin MR, Kao AW

Inhibiting a dynamic viral protease by targeting a non-catalytic cysteine.

Cell chemical biology

Hulce KR, Jaishankar P, Lee GM, Bohn MF, Connelly EJ, Wucherer K, Ongpipattanakul C, Volk RF, Chuo SW, Arkin MR, Renslo AR, Craik CS

In Vivo Dopamine Neuron Imaging-Based Small Molecule Screen Identifies Novel Neuroprotective Compounds and Targets.

Frontiers in pharmacology

Kim GJ, Mo H, Liu H, Okorie M, Chen S, Zheng J, Li H, Arkin M, Huang B, Guo S

Caspase-6-cleaved tau is relevant in Alzheimer's disease but not in 4-repeat tauopathies: Diagnostic and therapeutic implications.

Alzheimer's & Dementia

Antonia M. H. Piergies, Panos Theofilas, Song Li, Cathrine Petersen, Alexander J. Ehrenberg, Rana April Eser, Brian Chin, Teddy Yang, Shireen Khan, Raymond Ng, Salvatore Spina, William W. Seeley, Bruce L. Miller, Michelle R. Arkin, Lea T. Grinberg

Caspase inhibition mitigates tau cleavage and neurotoxicity in iPSC-induced neurons with the V337M MAPT mutation.

Alzheimer's & Dementia

Panos Theofilas, Andrew J. Ambrose, David Butler, Chao Wang, Dulce O. Morales, Cathrine Petersen, Brian Chin, Teddy Yang, Shireen Khan, Raymond Ng, Rakez Kayed, Celeste M. Karch, Bruce L. Miller, Jason E. Gestwicki, Li Gan, Sally Temple, Michelle R. Arkin, Lea T. Grinberg

A zebrafish screen reveals Renin-angiotensin system inhibitors as neuroprotective via mitochondrial restoration in dopamine neurons.

eLife

Kim GJ, Mo H, Liu H, Wu Z, Chen S, Zheng J, Zhao X, Nucum D, Shortland J, Peng L, Elepano M, Tang B, Olson S, Paras N, Li H, Renslo AR, Arkin MR, Huang B, Lu B, Sirota M, Guo S

Genetically Encoded, pH-Sensitive mTFP1 Biosensor for Probing Lysosomal pH.

ACS sensors

Chin MY, Patwardhan AR, Ang KH, Wang AL, Alquezar C, Welch M, Nguyen PT, Grabe M, Molofsky AV, Arkin MR, Kao AW

Exploration of a 14-3-3 PPI Pocket by Covalent Fragments as Stabilizers.

ACS medicinal chemistry letters

Sijbesma E, Hallenbeck KK, Andrei SA, Rust RR, Adriaans JMC, Brunsveld L, Arkin MR, Ottmann C

An Integrated Approach to Identify New Anti-Filarial Leads to Treat River Blindness, a Neglected Tropical Disease.

Pathogens (Basel, Switzerland)

Tyagi R, Bulman CA, Cho-Ngwa F, Fischer C, Marcellino C, Arkin MR, McKerrow JH, McNamara CW, Mahoney M, Tricoche N, Jawahar S, Janetka JW, Lustigman S, Sakanari J, Mitreva M

A multi-dimensional, time-lapse, high content screening platform applied to schistosomiasis drug discovery.

Communications biology

Chen S, Suzuki BM, Dohrmann J, Singh R, Arkin MR, Caffrey CR

Caspase-6-mediated tau cleavage and pathology in Alzheimer’s disease and other tauopathies.

Alzheimer's & Dementia

Antonia MH Piergies, Panos Theofilas, Cathrine Petersen, Alexander J Ehrenberg, Song Li, Dulce Ovando Morales, Rana A Eser, Teddy Yang, Shireen Khan, Brian Chin, Raymond Ng, Michelle Arkin, Lea Tenenholz Grinberg

Multiparametric High-Content Assays to Measure Cell Health and Oxidative Damage as a Model for Drug-Induced Liver Injury.

Current protocols in chemical biology

Pohan G, Espinosa JA, Chen S, Ang KK, Arkin MR, Markossian S

Fluorescence Anisotropy-Based Tethering for Discovery of Protein-Protein Interaction Stabilizers.

ACS chemical biology

Sijbesma E, Somsen BA, Miley GP, Leijten-van de Gevel IA, Brunsveld L, Arkin MR, Ottmann C

Expression and Purification of Active Human Kinases Using Pichia pastoris as A General-Purpose Host.

Protein expression and purification

Abdel Aziz MH, Fan Y, Liu L, Moasser M, Fu H, Jura N, Arkin MR

Author Correction: Transcriptional profiling and therapeutic targeting of oxidative stress in neuroinflammation.

Nature immunology

Mendiola AS, Ryu JK, Bardehle S, Meyer-Franke A, Ang KK, Wilson C, Baeten KM, Hanspers K, Merlini M, Thomas S, Petersen MA, Williams A, Thomas R, Rafalski VA, Meza-Acevedo R, Tognatta R, Yan Z, Pfaff SJ, Machado MR, Bedard C, Coronado PER, Jiang X, Wang J, Pleiss MA, Green AJ, Zamvil SS, Pico AR, Bruneau BG, Arkin MR, Akassoglou K

High-Throughput Screening: today's biochemical and cell-based approaches.

Drug discovery today

Blay V, Tolani B, Ho SP, Arkin MR

Inhibition and Crystal Structure of the Human DHTKD1-Thiamin Diphosphate Complex.

ACS chemical biology

Leandro J, Khamrui S, Wang H, Suebsuwong C, Nemeria NS, Huynh K, Moustakim M, Secor C, Wang M, Dodatko T, Stauffer B, Wilson CG, Yu C, Arkin MR, Jordan F, Sanchez R, DeVita RJ, Lazarus MB, Houten SM

Fragment-based Differential Targeting of PPI Stabilizer Interfaces.

Journal of medicinal chemistry

Guillory X, Wolter M, Leysen S, Neves JF, Kuusk A, Genet S, Somsen B, Morrow J, Rivers E, van Beek L, Patel J, Goodnow R, Schoenherr H, Fuller N, Cao Q, Doveston RG, Brunsveld L, Arkin MR, Castaldi MP, Boyd H, Landrieu I, Chen H, Ottmann C

Transcriptional profiling and therapeutic targeting of oxidative stress in neuroinflammation.

Nature immunology

Mendiola AS, Ryu JK, Bardehle S, Meyer-Franke A, Ang KK, Wilson C, Baeten KM, Hanspers K, Merlini M, Thomas S, Petersen MA, Williams A, Thomas R, Rafalski VA, Meza-Acevedo R, Tognatta R, Yan Z, Pfaff SJ, Machado MR, Bedard C, Rios Coronado PE, Jiang X, Wang J, Pleiss MA, Green AJ, Zamvil SS, Pico AR, Bruneau BG, Arkin MR, Akassoglou K

Promoting tau secretion and propagation by hyperactive p300/CBP via autophagy-lysosomal pathway in tauopathy.

Molecular neurodegeneration

Chen X, Li Y, Wang C, Tang Y, Mok SA, Tsai RM, Rojas JC, Karydas A, Miller BL, Boxer AL, Gestwicki JE, Arkin M, Cuervo AM, Gan L

Identification of Plasmodium dipeptidyl aminopeptidase allosteric inhibitors by high throughput screening.

PloS one

Sanchez MI, de Vries LE, Lehmann C, Lee JT, Ang KK, Wilson C, Chen S, Arkin MR, Bogyo M, Deu E

A Cell-Based Renilla Luminescence Reporter Plasmid Assay for High-Throughput Screening to Identify Novel FDA-Approved Drug Inhibitors of HPV-16 Infection.

SLAS discovery : advancing life sciences R & D

Walhart T, Isaacson-Wechsler E, Ang KH, Arkin M, Tugizov S, Palefsky JM

Specificity for latent C termini links the E3 ubiquitin ligase CHIP to caspases.

Nature chemical biology

Ravalin M, Theofilas P, Basu K, Opoku-Nsiah KA, Assimon VA, Medina-Cleghorn D, Chen YF, Bohn MF, Arkin M, Grinberg LT, Craik CS, Gestwicki JE

TAU-MEDIATED CELL DEATH MECHANISMS IN MAPT V337M IPSC-DERIVED HUMAN NEURONS.

Alzheimer's & Dementia

Panos Theofilas, Mifrah Hayath, Chao Wang, David Butler, Salome McAllen, Michelle Arkin, Jason Gestwicki, Ana Maria Cuervo, Rakez Kayed, Celeste M. Karch, Sally Temple, Li Gan, Lea T. Grinberg

Modulating protein-protein interaction networks in protein homeostasis.

Current opinion in chemical biology

Zhong M, Lee GM, Sijbesma E, Ottmann C, Arkin MR

Site-Directed Fragment-based Screening for the Discovery of Protein-Protein Interaction Stabilizers.

Journal of the American Chemical Society

Sijbesma E, Hallenbeck KK, Leysen S, de Vink P, Skora L, Jahnke W, Brunsveld L, Arkin MR, Ottmann C

Guidelines for DNA recombination and repair studies: Mechanistic assays of DNA repair processes.

Microbial cell (Graz, Austria)

Klein HL, Ang KKH, Arkin MR, Beckwitt EC, Chang YH, Fan J, Kwon Y, Morten MJ, Mukherjee S, Pambos OJ, El Sayyed H, Thrall ES, Vieira-da-Rocha JP, Wang Q, Wang S, Yeh HY, Biteen JS, Chi P, Heyer WD, Kapanidis AN, Loparo JJ, Strick TR, Sung P, Van Houten B, Niu H, Rothenberg E

Fibrin-targeting immunotherapy protects against neuroinflammation and neurodegeneration.

Nature immunology

Ryu JK, Rafalski VA, Meyer-Franke A, Adams RA, Poda SB, Rios Coronado PE, Pedersen LØ, Menon V, Baeten KM, Sikorski SL, Bedard C, Hanspers K, Bardehle S, Mendiola AS, Davalos D, Machado MR, Chan JP, Plastira I, Petersen MA, Pfaff SJ, Ang KK, Hallenbeck KK, Syme C, Hakozaki H, Ellisman MH, Swanson RA, Zamvil SS, Arkin MR, Zorn SH, Pico AR, Mucke L, Freedman SB, Stavenhagen JB, Nelson RB, Akassoglou K

Optimization of Phenyl Indole Inhibitors of the AAA+ ATPase p97.

ACS medicinal chemistry letters

LaPorte MG, Burnett JC, Colombo R, Bulfer SL, Alverez C, Chou TF, Neitz RJ, Green N, Moore WJ, Yue Z, Li S, Arkin MR, Wipf P, Huryn DM

A Genetic Interaction Map of Insulin Production Identifies Mfi as an Inhibitor of Mitochondrial Fission.

Endocrinology

Lee J, Pappalardo Z, Chopra DG, Hennings TG, Vaughn I, Lan C, Choe JJ, Ang K, Chen S, Arkin M, McManus MT, German MS, Ku GM

Assay Guidance Manual: Quantitative Biology and Pharmacology in Preclinical Drug Discovery.

Clinical and translational science

Coussens NP, Sittampalam GS, Guha R, Brimacombe K, Grossman A, Chung TDY, Weidner JR, Riss T, Trask OJ, Auld D, Dahlin JL, Devanaryan V, Foley TL, McGee J, Kahl SD, Kales SC, Arkin M, Baell J, Bejcek B, Gal-Edd N, Glicksman M, Haas JV, Iversen PW, Hoeppner M, Lathrop S, Sayers E, Liu H, Trawick B, McVey J, Lemmon VP, Li Z, McManus O, Minor L, Napper A, Wildey MJ, Pacifici R, Chin WW, Xia M, Xu X, Lal-Nag M, Hall MD, Michael S, Inglese J, Simeonov A, Austin CP

Small-Molecule Screening for Genetic Diseases.

Annual review of genomics and human genetics

Markossian S, Ang KK, Wilson CG, Arkin MR

EXTH-55. REPURPOSING THERAPEUTICS IN PATIENT-DERIVED GLIOMAS AND AN IDH1 MUTANT GLIOMA MODEL.

Neuro-Oncology

Christin Schmidt, Steven Chen, Shirin IIkhanizadeh, Hanna Sabelstrom, Edith Yuan, Andy Ding, William Weiss, Mitchel S Berger, Michelle Arkin, Anders Persson

USP7 small-molecule inhibitors interfere with ubiquitin binding.

Nature

Kategaya L, Di Lello P, Rougé L, Pastor R, Clark KR, Drummond J, Kleinheinz T, Lin E, Upton JP, Prakash S, Heideker J, McCleland M, Ritorto MS, Alessi DR, Trost M, Bainbridge TW, Kwok MCM, Ma TP, Stiffler Z, Brasher B, Tang Y, Jaishankar P, Hearn BR, Renslo AR, Arkin MR, Cohen F, Yu K, Peale F, Gnad F, Chang MT, Klijn C, Blackwood E, Martin SE, Forrest WF, Ernst JA, Ndubaku C, Wang X, Beresini MH, Tsui V, Schwerdtfeger C, Blake RA, Murray J, Maurer T, Wertz IE

A Liquid Chromatography/Mass Spectrometry Method for Screening Disulfide Tethering Fragments.

SLAS discovery : advancing life sciences R & D

Hallenbeck KK, Davies JL, Merron C, Ogden P, Sijbesma E, Ottmann C, Renslo AR, Wilson C, Arkin MR

Probing the correlation of neuronal loss, neurofibrillary tangles, and cell death markers across the Alzheimer's disease Braak stages: a quantitative study in humans.

Neurobiology of aging

Theofilas P, Ehrenberg AJ, Nguy A, Thackrey JM, Dunlop S, Mejia MB, Alho AT, Paraizo Leite RE, Rodriguez RD, Suemoto CK, Nascimento CF, Chin M, Medina-Cleghorn D, Cuervo AM, Arkin M, Seeley WW, Miller BL, Nitrini R, Pasqualucci CA, Filho WJ, Rueb U, Neuhaus J, Heinsen H, Grinberg LT

Applying Biophysical and Biochemical Methods to the Discovery of Allosteric Modulators of the AAA ATPase p97.

Applied Biophysics for Drug Discovery

Stacie L. Bulfer, Michelle R. Arkin

Joining Forces: The Chemical Biology-Medicinal Chemistry Continuum.

Cell chemical biology

Plowright AT, Ottmann C, Arkin M, Auberson YP, Timmerman H, Waldmann H

High-Throughput Screening To Identify Potent and Specific Inhibitors of Microbial Sulfate Reduction.

Environmental science & technology

Carlson HK, Mullan MR, Mosqueda LA, Chen S, Arkin MR, Coates JD

A threonine turnstile defines a dynamic amphiphilic binding motif in the AAA ATPase p97 allosteric binding site.

Organic & biomolecular chemistry

Burnett JC, Lim C, Peyser BD, Samankumara LP, Kovaliov M, Colombo R, Bulfer SL, LaPorte MG, Hermone AR, McGrath CF, Arkin MR, Gussio R, Huryn DM, Wipf P

A Whole-Genome RNA Interference Screen Reveals a Role for Spry2 in Insulin Transcription and the Unfolded Protein Response.

Diabetes

Pappalardo Z, Gambhir Chopra D, Hennings TG, Richards H, Choe J, Yang K, Baeyens L, Ang K, Chen S, Arkin M, German MS, McManus MT, Ku GM

Targeting Non-Catalytic Cysteine Residues Through Structure-Guided Drug Discovery.

Current topics in medicinal chemistry

Hallenbeck KK, Turner DM, Renslo AR, Arkin MR

Identification of Inhibitors of the Association of ZAP-70 with the T Cell Receptor by High-Throughput Screen.

SLAS discovery : advancing life sciences R & D

Visperas PR, Wilson CG, Winger JA, Yan Q, Lin K, Arkin MR, Weiss A, Kuriyan J

A High-Content Larval Zebrafish Brain Imaging Method for Small Molecule Drug Discovery.

PloS one

Liu H, Chen S, Huang K, Kim J, Mo H, Iovine R, Gendre J, Pascal P, Li Q, Sun Y, Dong Z, Arkin M, Guo S, Huang B

Ceapins are a new class of unfolded protein response inhibitors, selectively targeting the ATF6a branch.

eLife

Gallagher CM, Garri C, Cain EL, Ang KK, Wilson CG, Chen S, Hearn BR, Jaishankar P, Aranda-Diaz A, Arkin MR, Renslo AR, Walter P

2.3 Å resolution cryo-EM structure of human p97 and mechanism of allosteric inhibition.

Science (New York, N.Y.)

Banerjee S, Bartesaghi A, Merk A, Rao P, Bulfer SL, Yan Y, Green N, Mroczkowski B, Neitz RJ, Wipf P, Falconieri V, Deshaies RJ, Milne JL, Huryn D, Arkin M, Subramaniam S

Making FBDD Work in Academia.

Fragment-based Drug Discovery Lessons and Outlook

Stacie L. Bulfer, Frantz L. Jean-Francois, Michelle R. Arkin

Allosteric Indole Amide Inhibitors of p97: Identification of a Novel Probe of the Ubiquitin Pathway.

ACS medicinal chemistry letters

Alverez C, Bulfer SL, Chakrasali R, Chimenti MS, Deshaies RJ, Green N, Kelly M, LaPorte MG, Lewis TS, Liang M, Moore WJ, Neitz RJ, Peshkov VA, Walters MA, Zhang F, Arkin MR, Wipf P, Huryn DM

A gene-expression screen identifies a non-toxic sumoylation inhibitor that mimics SUMO-less human LRH-1 in liver.

eLife

Suzawa M, Miranda DA, Ramos KA, Ang KK, Faivre EJ, Wilson CG, Caboni L, Arkin MR, Kim YS, Fletterick RJ, Diaz A, Schneekloth JS, Ingraham HA

Covalent targeting of acquired cysteines in cancer.

Current opinion in chemical biology

Visscher M, Arkin MR, Dansen TB

Structure-Activity Study of Bioisosteric Trifluoromethyl and Pentafluorosulfanyl Indole Inhibitors of the AAA ATPase p97.

ACS medicinal chemistry letters

Alverez C, Arkin MR, Bulfer SL, Colombo R, Kovaliov M, LaPorte MG, Lim C, Liang M, Moore WJ, Neitz RJ, Yan Y, Yue Z, Huryn DM, Wipf P

Tackling reproducibility in academic preclinical drug discovery.

Nature reviews. Drug discovery

Frye SV, Arkin MR, Arrowsmith CH, Conn PJ, Glicksman MA, Hull-Ryde EA, Slusher BS

Utilizing Chemical Genomics to Identify Cytochrome b as a Novel Drug Target for Chagas Disease.

PLoS pathogens

Khare S, Roach SL, Barnes SW, Hoepfner D, Walker JR, Chatterjee AK, Neitz RJ, Arkin MR, McNamara CW, Ballard J, Lai Y, Fu Y, Molteni V, Yeh V, McKerrow JH, Glynne RJ, Supek F

Machine Learning Models and Pathway Genome Data Base for Trypanosoma cruzi Drug Discovery.

PLoS neglected tropical diseases

Ekins S, de Siqueira-Neto JL, McCall LI, Sarker M, Yadav M, Ponder EL, Kallel EA, Kellar D, Chen S, Arkin M, Bunin BA, McKerrow JH, Talcott C

Tetrafluorophenoxymethyl ketone cruzain inhibitors with improved pharmacokinetic properties as therapeutic leads for Chagas' disease.

Bioorganic & medicinal chemistry letters

Neitz RJ, Bryant C, Chen S, Gut J, Hugo Caselli E, Ponce S, Chowdhury S, Xu H, Arkin MR, Ellman JA, Renslo AR

Altered cofactor regulation with disease-associated p97/VCP mutations.

Proceedings of the National Academy of Sciences of the United States of America

Zhang X, Gui L, Zhang X, Bulfer SL, Sanghez V, Wong DE, Lee Y, Lehmann L, Lee JS, Shih PY, Lin HJ, Iacovino M, Weihl CC, Arkin MR, Wang Y, Chou TF

Tethering in RNA: an RNA-binding fragment discovery tool.

Molecules (Basel, Switzerland)

Tran K, Arkin MR, Beal PA

Repurposing auranofin as a lead candidate for treatment of lymphatic filariasis and onchocerciasis.

PLoS neglected tropical diseases

Bulman CA, Bidlow CM, Lustigman S, Cho-Ngwa F, Williams D, Rascón AA, Tricoche N, Samje M, Bell A, Suzuki B, Lim KC, Supakorndej N, Supakorndej P, Wolfe AR, Knudsen GM, Chen S, Wilson C, Ang KH, Arkin M, Gut J, Franklin C, Marcellino C, McKerrow JH, Debnath A, Sakanari JA

A Fragment-Based Ligand Screen Against Part of a Large Protein Machine: The ND1 Domains of the AAA+ ATPase p97/VCP.

Journal of biomolecular screening

Chimenti MS, Bulfer SL, Neitz RJ, Renslo AR, Jacobson MP, James TL, Arkin MR, Kelly MJ

Biophysical methods for identifying fragment-based inhibitors of protein-protein interactions.

Methods in molecular biology (Clifton, N.J.)

Pfaff SJ, Chimenti MS, Kelly MJ, Arkin MR

Modification by covalent reaction or oxidation of cysteine residues in the tandem-SH2 domains of ZAP-70 and Syk can block phosphopeptide binding.

The Biochemical journal

Visperas PR, Winger JA, Horton TM, Shah NH, Aum DJ, Tao A, Barros T, Yan Q, Wilson CG, Arkin MR, Weiss A, Kuriyan J

A small-molecule mimic of a peptide docking motif inhibits the protein kinase PDK1.

Proceedings of the National Academy of Sciences of the United States of America

Rettenmaier TJ, Sadowsky JD, Thomsen ND, Chen SC, Doak AK, Arkin MR, Wells JA

Lead identification to clinical candidate selection: drugs for Chagas disease.

Journal of biomolecular screening

Neitz RJ, Chen S, Supek F, Yeh V, Kellar D, Gut J, Bryant C, Gallardo-Godoy A, Molteni V, Roach SL, Khare S, Stinson M, Chatterjee AK, Robertson S, Renslo AR, Arkin M, Glynne R, McKerrow J, Siqueira-Neto JL

Screening for noise in gene expression identifies drug synergies.

Science (New York, N.Y.)

Dar RD, Hosmane NN, Arkin MR, Siliciano RF, Weinberger LS

Specific inhibition of p97/VCP ATPase and kinetic analysis demonstrate interaction between D1 and D2 ATPase domains.

Journal of molecular biology

Chou TF, Bulfer SL, Weihl CC, Li K, Lis LG, Walters MA, Schoenen FJ, Lin HJ, Deshaies RJ, Arkin MR

UCSF Small Molecule Discovery Center: innovation, collaboration and chemical biology in the Bay Area.

Combinatorial chemistry & high throughput screening

Arkin MR, Ang KK, Chen S, Davies J, Merron C, Tang Y, Wilson CG, Renslo AR

Inhibiting caspase-6 activation and catalytic activity for neurodegenerative diseases.

Current topics in medicinal chemistry

Flygare JA, Arkin MR

Inside Cover: Tailoring Small Molecules for an Allosteric Site on Procaspase-6 (ChemMedChem 1/2014).

ChemMedChem

Jeremy Murray, Anthony M. Giannetti, Micah Steffek, Paul Gibbons, Brian R. Hearn, Frederick Cohen, Christine Tam, Christine Pozniak, Brandon Bravo, Joe Lewcock, Priyadarshini Jaishankar, Cuong Q. Ly, Xianrui Zhao, Yinyan Tang, Preeti Chugha, Michelle R. Arkin, John Flygare, Adam R. Renslo

Probing structural adaptivity at PPI interfaces with small molecules.

Drug discovery today. Technologies

Wilson CG, Arkin MR

Tailoring small molecules for an allosteric site on procaspase-6.

ChemMedChem

Murray J, Giannetti AM, Steffek M, Gibbons P, Hearn BR, Cohen F, Tam C, Pozniak C, Bravo B, Lewcock J, Jaishankar P, Ly CQ, Zhao X, Tang Y, Chugha P, Arkin MR, Flygare J, Renslo AR

Bringing together the academic drug discovery community.

Nature reviews. Drug discovery

Slusher BS, Conn PJ, Frye S, Glicksman M, Arkin M

Imaging-based chemical screening reveals activity-dependent neural differentiation of pluripotent stem cells.

eLife

Sun Y, Dong Z, Jin T, Ang KH, Huang M, Haston KM, Peng J, Zhong TP, Finkbeiner S, Weiss WA, Arkin MR, Jan LY, Guo S

A high-throughput functional screen identifies small molecule regulators of temperature- and mechano-sensitive K2P channels.

ACS chemical biology

Bagriantsev SN, Ang KH, Gallardo-Godoy A, Clark KA, Arkin MR, Renslo AR, Minor DL

Pharmacological brake-release of mRNA translation enhances cognitive memory.

eLife

Sidrauski C, Acosta-Alvear D, Khoutorsky A, Vedantham P, Hearn BR, Li H, Gamache K, Gallagher CM, Ang KK, Wilson C, Okreglak V, Ashkenazi A, Hann B, Nader K, Arkin MR, Renslo AR, Sonenberg N, Walter P

Chemical-biological characterization of a cruzain inhibitor reveals a second target and a mammalian off-target.

Beilstein journal of organic chemistry

Choy JW, Bryant C, Calvet CM, Doyle PS, Gunatilleke SS, Leung SS, Ang KK, Chen S, Gut J, Oses-Prieto JA, Johnston JB, Arkin MR, Burlingame AL, Taunton J, Jacobson MP, McKerrow JM, Podust LM, Renslo AR

P2X Receptors for ATP: Molecular Properties and Functional Roles.

Richard J. Evans, Ivano Bertini, Giacomo Parigi, Noel Wyn Davies, Victor J. Morris, Marc Willem van der Kamp, Kuniaki Nagayama, Rumiana Koynova, Boris Tenchov, Marc Willem van der Kamp, Abhinav Nath, Elizabeth Rhoades, Marc Willem van der Kamp, Julie S. Biteen, Ranieri Bizzarri, Kuo-Hsiang Tang, Robert E. Blankenship, Ingo Grotjohann, Petra Fromme, Iain L. McConnell, Gary W. Brudvig, Xiaojing Yang, Jacqueline M. Matthews, Derek Marsh, Alison Rodger, Benyamin Rahmani, Hossein Ghanbari, Spyridon Tzamtzis, Gaetano Burriesci, Alexander M. Seifalian, Matt J. Kipper, Stephen E. Harding, Terry Jones, Vivien Jane Coulson-Thomas, Tarsis F. Gesteira, Yvette May Coulson-Thomas, Helena B. Nader, Eija Lehtomaki, Joel P. Mackay, Simon Bernèche, Shi-Bing Yang, Lily Y. Jan, Sami Yunus, Alain M. Jonas, Boris Lakard, Roland Winter, Roland Winter, Assaf Friedler, Chen Katz, Lee Whitmore, Robert W. Janes, Jonathan Hirst, Jacqueline M. Matthews, Alison Rodger, Mikael Akke, Patrik Lundström, Gianfranco Gilardi, Andrew L. Lee, Jamie L. Kear, Gail E. Fanucci, Marc Willem van der Kamp, David R. Skoff, Martin T. Zanni, Robert H. Callender, R. Brian Dyer, Vijay Pande, Clare-Louise Towse, Valerie Daggett, Marc Willem van der Kamp, Gordon C. K. Roberts, Fuyuhiko Inagaki, Jonathan J. Ellis, Boštjan Kobe, Edda Kloppmann, Peter Hoenigschmid, Burkhard Rost, Ertan Eryilmaz, Dongsheng Liu, David Cowburn, Jon I. Mujika, Xabier Lopez, Anna Tramontano, Michael I. Sadowski, Daniel Barry Roche, Maria Teresa Buenavista, Liam James McGuffin, Michael I. Sadowski, Marina V. Rodnina, Jeffrey W. Peng, Marc R. Wilkins, Kleitos Sokratous, José P. Afonso, Preeti Chugha, Michelle Arkin, Gideon Schreiber, Arthur M. Lesk, Barbara Mulloy, Jeffrey J. Warren, James M. Mayer, Inés García-Rubio, Inés García-Rubio, Kandala V. R. Chary, Atul K. Srivastava, Chad Schwartz, Hui Zhang, Peixuan Guo, Russ Hille

Protein–Protein Interactions – Inhibition.

Encyclopedia of Biophysics

Preeti Chugha, Michelle Arkin

Mechanistic and structural understanding of uncompetitive inhibitors of caspase-6.

PloS one

Heise CE, Murray J, Augustyn KE, Bravo B, Chugha P, Cohen F, Giannetti AM, Gibbons P, Hannoush RN, Hearn BR, Jaishankar P, Ly CQ, Shah K, Stanger K, Steffek M, Tang Y, Zhao X, Lewcock JW, Renslo AR, Flygare J, Arkin MR

Small molecule inhibitors of Smoothened ciliary localization and ciliogenesis.

Proceedings of the National Academy of Sciences of the United States of America

Wu VM, Chen SC, Arkin MR, Reiter JF

Diverse inhibitor chemotypes targeting Trypanosoma cruzi CYP51.

PLoS neglected tropical diseases

Gunatilleke SS, Calvet CM, Johnston JB, Chen CK, Erenburg G, Gut J, Engel JC, Ang KK, Mulvaney J, Chen S, Arkin MR, McKerrow JH, Podust LM

Analysis of high-throughput screening assays using cluster enrichment.

Statistics in medicine

Pu M, Hayashi T, Cottam H, Mulvaney J, Arkin M, Corr M, Carson D, Messer K

Novel cruzain inhibitors for the treatment of Chagas' disease.

Chemical biology & drug design

Rogers KE, Keränen H, Durrant JD, Ratnam J, Doak A, Arkin MR, McCammon JA

A high-throughput drug screen for Entamoeba histolytica identifies a new lead and target.

Nature medicine

Debnath A, Parsonage D, Andrade RM, He C, Cobo ER, Hirata K, Chen S, García-Rivera G, Orozco E, Martínez MB, Gunatilleke SS, Barrios AM, Arkin MR, Poole LB, McKerrow JH, Reed SL

Discovery and Development of Potent LFA-1/ICAM-1 Antagonist SAR 1118 as an Ophthalmic Solution for Treating Dry Eye.

ACS medicinal chemistry letters

Zhong M, Gadek TR, Bui M, Shen W, Burnier J, Barr KJ, Hanan EJ, Oslob JD, Yu CH, Zhu J, Arkin MR, Evanchik MJ, Flanagan WM, Hoch U, Hyde J, Prabhu S, Silverman JA, Wright J

Quantification and clustering of phenotypic screening data using time-series analysis for chemotherapy of schistosomiasis.

BMC genomics

Lee H, Moody-Davis A, Saha U, Suzuki BM, Asarnow D, Chen S, Arkin M, Caffrey CR, Singh R

Structural and enzymatic insights into caspase-2 protein substrate recognition and catalysis.

The Journal of biological chemistry

Tang Y, Wells JA, Arkin MR

A screen against Leishmania intracellular amastigotes: comparison to a promastigote screen and identification of a host cell-specific hit.

PLoS neglected tropical diseases

De Muylder G, Ang KK, Chen S, Arkin MR, Engel JC, McKerrow JH

Mining a cathepsin inhibitor library for new antiparasitic drug leads.

PLoS neglected tropical diseases

Ang KK, Ratnam J, Gut J, Legac J, Hansell E, Mackey ZB, Skrzypczynska KM, Debnath A, Engel JC, Rosenthal PJ, McKerrow JH, Arkin MR, Renslo AR

Screening technologies for unusual and challenging targets.

The FASEB Journal

Michelle R. Arkin, Steven Chen, Brian Suzuki, Vlad Popescu, Adam Renslo, Jim A Wells, Rahul Singh, Conor R. Caffrey

A high-throughput turbidometric assay for screening inhibitors of Leishmania major protein disulfide isomerase.

Journal of biomolecular screening

Ben Khalaf N, De Muylder G, Ratnam J, Kean-Hooi Ang K, Arkin M, McKerrow J, Chenik M

An image-based assay for high throughput screening of Giardia lamblia.

Journal of microbiological methods

Gut J, Ang KK, Legac J, Arkin MR, Rosenthal PJ, McKerrow JH

Small-molecule inhibitors of IL-2/IL-2R: lessons learned and applied.

Current topics in microbiology and immunology

Wilson CG, Arkin MR

Structure-activity relationship (SAR) of the a-amino acid residue of potent tetrahydroisoquinoline (THIQ)-derived LFA-1/ICAM-1 antagonists.

Bioorganic & medicinal chemistry letters

Zhong M, Hanan EJ, Shen W, Bui M, Arkin MR, Barr KJ, Evanchik MJ, Hoch U, Hyde J, Martell JR, Oslob JD, Paulvannan K, Prabhu S, Silverman JA, Wright J, Yu CH, Zhu J, Flanagan WM

Discovery of tetrahydroisoquinoline (THIQ) derivatives as potent and orally bioavailable LFA-1/ICAM-1 antagonists.

Bioorganic & medicinal chemistry letters

Zhong M, Shen W, Barr KJ, Arbitrario JP, Arkin MR, Bui M, Chen T, Cunningham BC, Evanchik MJ, Hanan EJ, Hoch U, Huen K, Hyde J, Kumer JL, Lac T, Lawrence CE, Martell JR, Oslob JD, Paulvannan K, Prabhu S, Silverman JA, Wright J, Yu CH, Zhu J, Flanagan WM

Image-based high-throughput drug screening targeting the intracellular stage of Trypanosoma cruzi, the agent of Chagas' disease.

Antimicrobial agents and chemotherapy

Engel JC, Ang KK, Chen S, Arkin MR, McKerrow JH, Doyle PS

Voreloxin is an anticancer quinolone derivative that intercalates DNA and poisons topoisomerase II.

PloS one

Hawtin RE, Stockett DE, Byl JA, McDowell RS, Nguyen T, Arkin MR, Conroy A, Yang W, Osheroff N, Fox JA

Identification and optimization of inhibitors of Trypanosomal cysteine proteases: cruzain, rhodesain, and TbCatB.

Journal of medicinal chemistry

Mott BT, Ferreira RS, Simeonov A, Jadhav A, Ang KK, Leister W, Shen M, Silveira JT, Doyle PS, Arkin MR, McKerrow JH, Inglese J, Austin CP, Thomas CJ, Shoichet BK, Maloney DJ

Novel non-peptidic vinylsulfones targeting the S2 and S3 subsites of parasite cysteine proteases.

Bioorganic & medicinal chemistry letters

Bryant C, Kerr ID, Debnath M, Ang KK, Ratnam J, Ferreira RS, Jaishankar P, Zhao D, Arkin MR, McKerrow JH, Brinen LS, Renslo AR

Two approaches to discovering and developing new drugs for Chagas disease.

Memorias do Instituto Oswaldo Cruz

McKerrow JH, Doyle PS, Engel JC, Podust LM, Robertson SA, Ferreira R, Saxton T, Arkin M, Kerr ID, Brinen LS, Craik CS

The marine sponge Diacarnus bismarckensis as a source of peroxiterpene inhibitors of Trypanosoma brucei, the causative agent of sleeping sickness.

Journal of natural products

Rubio BK, Tenney K, Ang KH, Abdulla M, Arkin M, McKerrow JH, Crews P

SNS-032 is a potent and selective CDK 2, 7 and 9 inhibitor that drives target modulation in patient samples.

Cancer chemotherapy and pharmacology

Conroy A, Stockett DE, Walker D, Arkin MR, Hoch U, Fox JA, Hawtin RE

HER-2-directed, small-molecule antagonists.

Current opinion in investigational drugs (London, England : 2000)

Arkin M, Moasser MM

A diaminocyclohexyl analog of SNS-032 with improved permeability and bioavailability properties.

Bioorganic & medicinal chemistry letters

Choong IC, Serafimova I, Fan J, Stockett D, Chan E, Cheeti S, Lu Y, Fahr B, Pham P, Arkin MR, Walker DH, Hoch U

Identification of Nonpeptidic Small-Molecule Inhibitors of Interleukin-2.

ChemInform

Nathan D. Waal, Wenjin Yang, Johan D. Oslob, Michelle R. Arkin, Jennifer Hyde, Wanli Lu, Robert S. McDowell, Chul H. Yu, Brian C. Raimundo

Identification of nonpeptidic small-molecule inhibitors of interleukin-2.

Bioorganic & medicinal chemistry letters

Waal ND, Yang W, Oslob JD, Arkin MR, Hyde J, Lu W, McDowell RS, Yu CH, Raimundo BC

Integrating fragment assembly and biophysical methods in the chemical advancement of small-molecule antagonists of IL-2: an approach for inhibiting protein-protein interactions.

Journal of medicinal chemistry

Raimundo BC, Oslob JD, Braisted AC, Hyde J, McDowell RS, Randal M, Waal ND, Wilkinson J, Yu CH, Arkin MR

Discovery of a potent small molecule IL-2 inhibitor through fragment assembly.

Journal of the American Chemical Society

Braisted AC, Oslob JD, Delano WL, Hyde J, McDowell RS, Waal N, Yu C, Arkin MR, Raimundo BC

Binding of small molecules to an adaptive protein-protein interface.

Proceedings of the National Academy of Sciences of the United States of America

Arkin MR, Randal M, DeLano WL, Hyde J, Luong TN, Oslob JD, Raphael DR, Taylor L, Wang J, McDowell RS, Wells JA, Braisted AC

Drug discovery at signaling interfaces.

Ernst Schering Research Foundation workshop

Wells J, Arkin M, Braisted A, DeLano W, McDowell B, Oslob J, Raimundo B, Randal M

In Vitro Mutagenesis.

Brenner\u0027s Encyclopedia of Genetics

M. Arkin

In vitro Mutagenesis.

Encyclopedia of Genetics

M. Arkin

Mutational Analysis.

Encyclopedia of Genetics

M. Arkin

First Observation of the Key Intermediate in the “Light-Switch” Mechanism of [Ru(phen) 2 dppz] 2+.

Journal of the American Chemical Society

E. J. C. Olson, D. Hu, A. Hörmann, A. M. Jonkman, M. R. Arkin, E. D. A. Stemp, J. K. Barton, P. F. Barbara

Long-range oxidation of guanine by Ru(III) in duplex DNA.

Chemistry & biology

Arkin MR, Stemp ED, Pulver SC, Barton JK

Oxidation of Guanine in DNA by Ru(phen) 2 (dppz) 3+ Using the Flash-Quench Technique.

Journal of the American Chemical Society

E. D. A. Stemp, M. R. Arkin, J. K. Barton

Rates of DNA-mediated electron transfer between metallointercalators.

Science (New York, N.Y.)

Arkin MR, Stemp ED, Holmlin RE, Barton JK, Hörmann A, Olson EJ, Barbara PF

Metallointercalators as Probes of the DNA p-way.

Michelle R. Arkin, Yonchu Jenkins, Catherine J. Murphy, Nicholas J. Turro, Jacqueline K. Barton

Luminescence Quenching in Supramolecular Systems:  A Comparison of DNA- and SDS Micelle-Mediated Photoinduced Electron Transfer between Metal Complexes.

Journal of the American Chemical Society

M. R. Arkin, E. D. A. Stemp, C. Turro, N. J. Turro, J. K. Barton

Time Resolved Electron Transfer Studies Between Metallointercalators in DNA.

A. Hörmann, E. J. C. Olson, P. F. Barbara, M. R. Arkin, E. D. A. Stemp, R. E. Holmlin, J. K. Barton

DNA-mediated electron transfer.

Journal of Inorganic Biochemistry

Jacqueline K. Barton, Michelle R. Arkin, Eric D.A. Stemp, R.Erik Holmlin, Yonchu Jenkins

Rates of electron transfer reactions between metallointercalators.

Journal of Inorganic Biochemistry

Michelle R. Arkin, Eric D.A. Stemp, R.Erik Holmin, Aldo Hoermann, Eric Olson, Paul F. Barbara, Jacqueline K. Barton

Electron transfer between metallointercalators bound to DNA: Spectral identification of the transient intermediate.

Journal of the American Chemical Society

Eric D. A. Stemp, Michelle R. Arkin, Jacqueline K. Barton

Fast photoinduced electron transfer through DNA intercalation.

Proceedings of the National Academy of Sciences of the United States of America

Murphy CJ, Arkin MR, Ghatlia ND, Bossmann S, Turro NJ, Barton JK

Long-range photoinduced electron transfer through a DNA helix.

Science (New York, N.Y.)

Murphy CJ, Arkin MR, Jenkins Y, Ghatlia ND, Bossmann SH, Turro NJ, Barton JK

Evidence for photoelectron transfer through DNA intercalation.

Journal of Inorganic Biochemistry

M. Arkin, C.J. Murphy, Y.C. Jenkins, N.J. Turro, J.K. Barton