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Amidino-Rocaglates: A Potent Class of eIF4A Inhibitors.

Chu J, Zhang W, Cencic R, Devine WG, Beglov D, Henkel T, Brown LE, Vajda S, Porco JA Jr, Pelletier J.

Cell Chem Biol. 2019 Sep 9. pii: S2451-9456(19)30273-9. doi: 10.1016/j.chembiol.2019.08.008. [Epub ahead of print]


Gold(I)-Mediated Cycloisomerization/Cycloaddition Enables Bioinspired Syntheses of Neonectrolides B-E and Analogues.

Purgett TJ, Dyer MW, Bickel B, McNeely J, Porco JA Jr.

J Am Chem Soc. 2019 Sep 12. doi: 10.1021/jacs.9b06355. [Epub ahead of print]


Drug-induced Stress Granule Formation Protects Sensory Hair Cells in Mouse Cochlear Explants During Ototoxicity.

Gonçalves AC, Towers ER, Haq N, Porco JA Jr, Pelletier J, Dawson SJ, Gale JE.

Sci Rep. 2019 Aug 29;9(1):12501. doi: 10.1038/s41598-019-48393-w.


eIF4A inhibitors suppress cell cycle feedback response and acquired resistance to CDK4/6 inhibition in cancer.

Kong T, Xue Y, Cencic R, Zhu X, Monast A, Fu Z, Pilon V, Sangwan V, Guiot MC, Foulkes WD, Porco JA, Park M, Pelletier J, Huang S.

Mol Cancer Ther. 2019 Aug 8. pii: molcanther.0162.2019. doi: 10.1158/1535-7163.MCT-19-0162. [Epub ahead of print]


Intercepted Retro-Nazarov Reaction: Syntheses of Amidino-Rocaglate Derivatives and Their Biological Evaluation as eIF4A Inhibitors.

Zhang W, Chu J, Cyr AM, Yueh H, Brown LE, Wang TT, Pelletier J, Porco JA Jr.

J Am Chem Soc. 2019 Aug 14;141(32):12891-12900. doi: 10.1021/jacs.9b06446. Epub 2019 Jul 30.


Regiodivergent Photocyclization of Dearomatized Acylphloroglucinols: Asymmetric Syntheses of (-)-Nemorosone and (-)-6-epi-Garcimultiflorone A.

Wen S, Boyce JH, Kandappa SK, Sivaguru J, Porco JA Jr.

J Am Chem Soc. 2019 Jul 17;141(28):11315-11321. doi: 10.1021/jacs.9b05600. Epub 2019 Jul 2.


Targeting translation initiation by synthetic rocaglates for treating MYC-driven lymphomas.

Zhang X, Bi C, Lu T, Zhang W, Yue T, Wang C, Tian T, Zhang X, Huang Y, Lunning M, Hao X, Brown LE, Devine WG, Vose J, Porco JA Jr, Fu K.

Leukemia. 2019 Jun 6. doi: 10.1038/s41375-019-0503-z. [Epub ahead of print]


Tracing MYC Expression for Small Molecule Discovery.

Steinberger J, Robert F, Hallé M, Williams DE, Cencic R, Sawhney N, Pelletier D, Williams P, Igarashi Y, Porco JA Jr, Rodriguez AD, Kopp B, Bachmann B, Andersen RJ, Pelletier J.

Cell Chem Biol. 2019 May 16;26(5):699-710.e6. doi: 10.1016/j.chembiol.2019.02.007. Epub 2019 Mar 14.


Small Molecule Amyloid-β Protein Precursor Processing Modulators Lower Amyloid-β Peptide Levels via cKit Signaling.

Chen CD, Zeldich E, Khodr C, Camara K, Tung TY, Lauder EC, Mullen P, Polanco TJ, Liu YY, Zeldich D, Xia W, Van Nostrand WE, Brown LE, Porco JA, Abraham CR.

J Alzheimers Dis. 2019;67(3):1089-1106. doi: 10.3233/JAD-180923.


Oxo-aglaiastatin-Mediated Inhibition of Translation Initiation.

Itoua Maïga R, Cencic R, Chu J, Waller DD, Brown LE, Devine WG, Zhang W, Sebag M, Porco JA Jr, Pelletier J.

Sci Rep. 2019 Feb 4;9(1):1265. doi: 10.1038/s41598-018-37666-5.


Isolation and Synthesis of Novel Meroterpenoids from Rhodomyrtus tomentosa: Investigation of a Reactive Enetrione Intermediate.

Qin XJ, Rauwolf TJ, Li PP, Liu H, McNeely J, Hua Y, Liu HY, Porco JA Jr.

Angew Chem Int Ed Engl. 2019 Mar 22;58(13):4291-4296. doi: 10.1002/anie.201814421. Epub 2019 Feb 20.


Structural basis for species-selective targeting of Hsp90 in a pathogenic fungus.

Whitesell L, Robbins N, Huang DS, McLellan CA, Shekhar-Guturja T, LeBlanc EV, Nation CS, Hui R, Hutchinson A, Collins C, Chatterjee S, Trilles R, Xie JL, Krysan DJ, Lindquist S, Porco JA Jr, Tatu U, Brown LE, Pizarro J, Cowen LE.

Nat Commun. 2019 Jan 24;10(1):402. doi: 10.1038/s41467-018-08248-w.


Discovery of Macrocyclic Inhibitors of Apurinic/Apyrimidinic Endonuclease 1.

Trilles R, Beglov D, Chen Q, He H, Wireman R, Reed A, Chennamadhavuni S, Panek JS, Brown LE, Vajda S, Porco JA Jr, Kelley MR, Georgiadis MM.

J Med Chem. 2019 Feb 28;62(4):1971-1988. doi: 10.1021/acs.jmedchem.8b01529. Epub 2019 Feb 6.


Canvass: A Crowd-Sourced, Natural-Product Screening Library for Exploring Biological Space.

Kearney SE, Zahoránszky-Kőhalmi G, Brimacombe KR, Henderson MJ, Lynch C, Zhao T, Wan KK, Itkin Z, Dillon C, Shen M, Cheff DM, Lee TD, Bougie D, Cheng K, Coussens NP, Dorjsuren D, Eastman RT, Huang R, Iannotti MJ, Karavadhi S, Klumpp-Thomas C, Roth JS, Sakamuru S, Sun W, Titus SA, Yasgar A, Zhang YQ, Zhao J, Andrade RB, Brown MK, Burns NZ, Cha JK, Mevers EE, Clardy J, Clement JA, Crooks PA, Cuny GD, Ganor J, Moreno J, Morrill LA, Picazo E, Susick RB, Garg NK, Goess BC, Grossman RB, Hughes CC, Johnston JN, Joullie MM, Kinghorn AD, Kingston DGI, Krische MJ, Kwon O, Maimone TJ, Majumdar S, Maloney KN, Mohamed E, Murphy BT, Nagorny P, Olson DE, Overman LE, Brown LE, Snyder JK, Porco JA Jr, Rivas F, Ross SA, Sarpong R, Sharma I, Shaw JT, Xu Z, Shen B, Shi W, Stephenson CRJ, Verano AL, Tan DS, Tang Y, Taylor RE, Thomson RJ, Vosburg DA, Wu J, Wuest WM, Zakarian A, Zhang Y, Ren T, Zuo Z, Inglese J, Michael S, Simeonov A, Zheng W, Shinn P, Jadhav A, Boxer MB, Hall MD, Xia M, Guha R, Rohde JM.

ACS Cent Sci. 2018 Dec 26;4(12):1727-1741. doi: 10.1021/acscentsci.8b00747. Epub 2018 Dec 5.


METTL13 Methylation of eEF1A Increases Translational Output to Promote Tumorigenesis.

Liu S, Hausmann S, Carlson SM, Fuentes ME, Francis JW, Pillai R, Lofgren SM, Hulea L, Tandoc K, Lu J, Li A, Nguyen ND, Caporicci M, Kim MP, Maitra A, Wang H, Wistuba II, Porco JA Jr, Bassik MC, Elias JE, Song J, Topisirovic I, Van Rechem C, Mazur PK, Gozani O.

Cell. 2019 Jan 24;176(3):491-504.e21. doi: 10.1016/j.cell.2018.11.038. Epub 2019 Jan 3.


Chemical Synthesis Enables Structural Reengineering of Aglaroxin C Leading to Inhibition Bias for Hepatitis C Viral Infection.

Zhang W, Liu S, Maiga RI, Pelletier J, Brown LE, Wang TT, Porco JA Jr.

J Am Chem Soc. 2019 Jan 23;141(3):1312-1323. doi: 10.1021/jacs.8b11477. Epub 2019 Jan 11.


Asymmetric Synthesis of Griffipavixanthone Employing a Chiral Phosphoric Acid-Catalyzed Cycloaddition.

Smith MJ, Reichl KD, Escobar RA, Heavey TJ, Coker DF, Schaus SE, Porco JA Jr.

J Am Chem Soc. 2019 Jan 9;141(1):148-153. doi: 10.1021/jacs.8b12520. Epub 2018 Dec 26.


Sensitization of renal carcinoma cells to TRAIL-induced apoptosis by rocaglamide and analogs.

Nalli AD, Brown LE, Thomas CL, Sayers TJ, Porco JA Jr, Henrich CJ.

Sci Rep. 2018 Nov 30;8(1):17519. doi: 10.1038/s41598-018-35908-0.


Diastereodivergent Synthesis of Chiral Tetrahydropyrrolodiazepinediones via a One-Pot Intramolecular aza-Michael/Lactamization Sequence.

Chennamadhavuni S, Panek JS, Porco JA Jr, Brown LE.

J Org Chem. 2018 Dec 21;83(24):15449-15462. doi: 10.1021/acs.joc.8b02724. Epub 2018 Dec 5.


Eucalyptusdimers A-C, Dimeric Phloroglucinol-Phellandrene Meroterpenoids from Eucalyptus robusta.

Qin XJ, Feng MY, Liu H, Ni W, Rauwolf T, Porco JA Jr, Yan H, He L, Liu HY.

Org Lett. 2018 Aug 17;20(16):5066-5070. doi: 10.1021/acs.orglett.8b02259. Epub 2018 Aug 8.


High-throughput Screening in Larval Zebrafish Identifies Novel Potent Sedative-hypnotics.

Yang X, Jounaidi Y, Dai JB, Marte-Oquendo F, Halpin ES, Brown LE, Trilles R, Xu W, Daigle R, Yu B, Schaus SE, Porco JA Jr, Forman SA.

Anesthesiology. 2018 Sep;129(3):459-476. doi: 10.1097/ALN.0000000000002281.


Asymmetric Synthesis of Gonytolide A: Strategic Use of an Aryl Halide Blocking Group for Oxidative Coupling.

Wu X, Iwata T, Scharf A, Qin T, Reichl KD, Porco JA Jr.

J Am Chem Soc. 2018 May 9;140(18):5969-5975. doi: 10.1021/jacs.8b02535. Epub 2018 Apr 25.


Rocaglates as dual-targeting agents for experimental cerebral malaria.

Langlais D, Cencic R, Moradin N, Kennedy JM, Ayi K, Brown LE, Crandall I, Tarry MJ, Schmeing M, Kain KC, Porco JA Jr, Pelletier J, Gros P.

Proc Natl Acad Sci U S A. 2018 Mar 6;115(10):E2366-E2375. doi: 10.1073/pnas.1713000115. Epub 2018 Feb 20.


Total Synthesis of Aurofusarin: Studies on the Atropisomeric Stability of Bis-Naphthoquinones.

Qi C, Wang W, Reichl KD, McNeely J, Porco JA Jr.

Angew Chem Int Ed Engl. 2018 Feb 19;57(8):2101-2104. doi: 10.1002/anie.201711535. Epub 2018 Jan 29.


Total Syntheses of the Isomeric Aglain Natural Products Foveoglin A and Perviridisin B: Selective Excited-State Intramolecular Proton-Transfer Photocycloaddition.

Wang W, Clay A, Krishnan R, Lajkiewicz NJ, Brown LE, Sivaguru J, Porco JA Jr.

Angew Chem Int Ed Engl. 2017 Nov 13;56(46):14479-14482. doi: 10.1002/anie.201707539. Epub 2017 Oct 13.


Biomimetic Total Synthesis of (±)-Griffipavixanthone via a Cationic Cycloaddition-Cyclization Cascade.

Reichl KD, Smith MJ, Song MK, Johnson RP, Porco JA Jr.

J Am Chem Soc. 2017 Oct 11;139(40):14053-14056. doi: 10.1021/jacs.7b09265. Epub 2017 Oct 2.


A photochemical flow reactor for large scale syntheses of aglain and rocaglate natural product analogues.

Yueh H, Gao Q, Porco JA Jr, Beeler AB.

Bioorg Med Chem. 2017 Dec 1;25(23):6197-6202. doi: 10.1016/j.bmc.2017.06.010. Epub 2017 Jun 11.


Inhibiting the oncogenic translation program is an effective therapeutic strategy in multiple myeloma.

Manier S, Huynh D, Shen YJ, Zhou J, Yusufzai T, Salem KZ, Ebright RY, Shi J, Park J, Glavey SV, Devine WG, Liu CJ, Leleu X, Quesnel B, Roche-Lestienne C, Snyder JK, Brown LE, Gray N, Bradner J, Whitesell L, Porco JA Jr, Ghobrial IM.

Sci Transl Med. 2017 May 10;9(389). pii: eaal2668. doi: 10.1126/scitranslmed.aal2668.


Asymmetric Dearomatization/Cyclization Enables Access to Polycyclic Chemotypes.

Hayashi M, Brown LE, Porco JA Jr.

European J Org Chem. 2016 Oct;2016(28):4800-4804. doi: 10.1002/ejoc.201601003.


Development of a Potent and Selective HDAC8 Inhibitor.

Ingham OJ, Paranal RM, Smith WB, Escobar RA, Yueh H, Snyder T, Porco JA Jr, Bradner JE, Beeler AB.

ACS Med Chem Lett. 2016 Sep 1;7(10):929-932. eCollection 2016 Oct 13.


Synthesis of Aza-Rocaglates via ESIPT-Mediated (3+2) Photocycloaddition.

Wang W, Cencic R, Whitesell L, Pelletier J, Porco JA Jr.

Chemistry. 2016 Aug 16;22(34):12006-10. doi: 10.1002/chem.201602953. Epub 2016 Jul 15.


CRISPR-Mediated Drug-Target Validation Reveals Selective Pharmacological Inhibition of the RNA Helicase, eIF4A.

Chu J, Galicia-Vázquez G, Cencic R, Mills JR, Katigbak A, Porco JA Jr, Pelletier J.

Cell Rep. 2016 Jun 14;15(11):2340-7. doi: 10.1016/j.celrep.2016.05.005. Epub 2016 May 26.


Photochemical Approaches to Complex Chemotypes: Applications in Natural Product Synthesis.

Kärkäs MD, Porco JA Jr, Stephenson CR.

Chem Rev. 2016 Sep 14;116(17):9683-747. doi: 10.1021/acs.chemrev.5b00760. Epub 2016 Apr 27. Review.


Fine-tuning of macrophage activation using synthetic rocaglate derivatives.

Bhattacharya B, Chatterjee S, Devine WG, Kobzik L, Beeler AB, Porco JA Jr, Kramnik I.

Sci Rep. 2016 Apr 18;6:24409. doi: 10.1038/srep24409.


nanoCAGE reveals 5' UTR features that define specific modes of translation of functionally related MTOR-sensitive mRNAs.

Gandin V, Masvidal L, Hulea L, Gravel SP, Cargnello M, McLaughlan S, Cai Y, Balanathan P, Morita M, Rajakumar A, Furic L, Pollak M, Porco JA Jr, St-Pierre J, Pelletier J, Larsson O, Topisirovic I.

Genome Res. 2016 May;26(5):636-48. doi: 10.1101/gr.197566.115. Epub 2016 Mar 16.


A Novel Class of Small Molecule Compounds that Inhibit Hepatitis C Virus Infection by Targeting the Prohibitin-CRaf Pathway.

Liu S, Wang W, Brown LE, Qiu C, Lajkiewicz N, Zhao T, Zhou J, Porco JA Jr, Wang TT.

EBioMedicine. 2015 Sep 14;2(11):1600-6. doi: 10.1016/j.ebiom.2015.09.018. eCollection 2015 Nov.


Asymmetric Syntheses of the Flavonoid Diels-Alder Natural Products Sanggenons C and O.

Qi C, Xiong Y, Eschenbrenner-Lux V, Cong H, Porco JA Jr.

J Am Chem Soc. 2016 Jan 27;138(3):798-801. doi: 10.1021/jacs.5b12778. Epub 2016 Jan 19.


Translation Inhibition by Rocaglates Is Independent of eIF4E Phosphorylation Status.

Chu J, Cencic R, Wang W, Porco JA Jr, Pelletier J.

Mol Cancer Ther. 2016 Jan;15(1):136-41. doi: 10.1158/1535-7163.MCT-15-0409. Epub 2015 Nov 19.


Syntheses of Dimeric Tetrahydroxanthones with Varied Linkages: Investigation of "Shapeshifting" Properties.

Qin T, Iwata T, Ransom TT, Beutler JA, Porco JA Jr.

J Am Chem Soc. 2015 Dec 9;137(48):15225-33. doi: 10.1021/jacs.5b09825. Epub 2015 Nov 25.


Divergent Total Syntheses of Rhodomyrtosones A and B.

Gervais A, Lazarski KE, Porco JA Jr.

J Org Chem. 2015 Oct 2;80(19):9584-91. doi: 10.1021/acs.joc.5b01570.


Inhibition of Oncogenic Transcription Factor REL by the Natural Product Derivative Calafianin Monomer 101 Induces Proliferation Arrest and Apoptosis in Human B-Lymphoma Cell Lines.

Yeo AT, Chennamadhavuni S, Whitty A, Porco JA Jr, Gilmore TD.

Molecules. 2015 Apr 23;20(5):7474-94. doi: 10.3390/molecules20057474.


Atropselective syntheses of (-) and (+) rugulotrosin A utilizing point-to-axial chirality transfer.

Qin T, Skraba-Joiner SL, Khalil ZG, Johnson RP, Capon RJ, Porco JA Jr.

Nat Chem. 2015 Mar;7(3):234-40. doi: 10.1038/nchem.2173. Epub 2015 Feb 2.


Biomimetic kinetic resolution: highly enantio- and diastereoselective transfer hydrogenation of aglain ketones to access flavagline natural products.

Stone SD, Lajkiewicz NJ, Whitesell L, Hilmy A, Porco JA Jr.

J Am Chem Soc. 2015 Jan 14;137(1):525-30. doi: 10.1021/ja511728b. Epub 2014 Dec 29.


Thiourea-catalyzed enantioselective addition of indoles to pyrones: alkaloid cores with quaternary carbons.

Yeung CS, Ziegler RE, Porco JA Jr, Jacobsen EN.

J Am Chem Soc. 2014 Oct 1;136(39):13614-7. doi: 10.1021/ja508523g. Epub 2014 Sep 17.


Translation initiation factor eIF4F modifies the dexamethasone response in multiple myeloma.

Robert F, Roman W, Bramoullé A, Fellmann C, Roulston A, Shustik C, Porco JA Jr, Shore GC, Sebag M, Pelletier J.

Proc Natl Acad Sci U S A. 2014 Sep 16;111(37):13421-6. doi: 10.1073/pnas.1402650111. Epub 2014 Sep 2.


Identification of a novel polyprenylated acylphloroglucinol‑derived SIRT1 inhibitor with cancer‑specific anti-proliferative and invasion-suppressing activities.

Zhu L, Qi J, Chiao CY, Zhang Q, Porco JA Jr, Faller DV, Dai Y.

Int J Oncol. 2014 Nov;45(5):2128-36. doi: 10.3892/ijo.2014.2639. Epub 2014 Sep 3.


RNA G-quadruplexes cause eIF4A-dependent oncogene translation in cancer.

Wolfe AL, Singh K, Zhong Y, Drewe P, Rajasekhar VK, Sanghvi VR, Mavrakis KJ, Jiang M, Roderick JE, Van der Meulen J, Schatz JH, Rodrigo CM, Zhao C, Rondou P, de Stanchina E, Teruya-Feldstein J, Kelliher MA, Speleman F, Porco JA Jr, Pelletier J, Rätsch G, Wendel HG.

Nature. 2014 Sep 4;513(7516):65-70. doi: 10.1038/nature13485. Epub 2014 Jul 27.


Rapid synthesis of polyprenylated acylphloroglucinol analogs via dearomative conjunctive allylic annulation.

Grenning AJ, Boyce JH, Porco JA Jr.

J Am Chem Soc. 2014 Aug 20;136(33):11799-804. doi: 10.1021/ja5060302. Epub 2014 Aug 7.


How proteins bind macrocycles.

Villar EA, Beglov D, Chennamadhavuni S, Porco JA Jr, Kozakov D, Vajda S, Whitty A.

Nat Chem Biol. 2014 Sep;10(9):723-31. doi: 10.1038/nchembio.1584. Epub 2014 Jul 20.

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