{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T06:42:55Z","timestamp":1790318575805,"version":"4.1.0"},"reference-count":37,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2020,1,13]],"date-time":"2020-01-13T00:00:00Z","timestamp":1578873600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2020,1,13]],"date-time":"2020-01-13T00:00:00Z","timestamp":1578873600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Chem Biol"],"published-print":{"date-parts":[[2020,2]]},"DOI":"10.1038\/s41589-019-0447-7","type":"journal-article","created":{"date-parts":[[2020,1,13]],"date-time":"2020-01-13T17:02:48Z","timestamp":1578934968000},"page":"206-213","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["Lipid droplets can promote drug accumulation and activation"],"prefix":"10.1038","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0687-5831","authenticated-orcid":false,"given":"Ramin","family":"Dubey","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig E.","family":"Stivala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huy Quoc","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1680-1569","authenticated-orcid":false,"given":"Young-Hwa","family":"Goo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoni","family":"Paul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5187-8070","authenticated-orcid":false,"given":"Jan E.","family":"Carette","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7369-9121","authenticated-orcid":false,"given":"Barry M.","family":"Trost","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7609-8858","authenticated-orcid":false,"given":"Rajat","family":"Rohatgi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,1,13]]},"reference":[{"key":"447_CR1","doi-asserted-by":"publisher","first-page":"6015","DOI":"10.1021\/ja00092a081","volume":"116","author":"PA Horton","year":"1994","unstructured":"Horton, P. A., Koehn, F. E., Longley, R. E. & McConnell, O. J. Lasonolide A, a new cytotoxic macrolide from the marine sponge Forcepia sp. J. Am. Chem. Soc. 116, 6015\u20136016 (1994).","journal-title":"J. Am. Chem. Soc."},{"key":"447_CR2","doi-asserted-by":"publisher","first-page":"1351","DOI":"10.1021\/np040028e","volume":"67","author":"AE Wright","year":"2004","unstructured":"Wright, A. E. et al. Lasonolides C\u2013G, five new lasonolide compounds from the sponge Forcepia sp. J. Nat. Prod. 67, 1351\u20131355 (2004).","journal-title":"J. Nat. Prod."},{"key":"447_CR3","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1124\/jpet.109.155531","volume":"331","author":"RA Isbrucker","year":"2009","unstructured":"Isbrucker, R. A., Guzman, E. A., Pitts, T. P. & Wright, A. E. Early effects of lasonolide A on pancreatic cancer cells. J. Pharmacol. Exp. Ther. 331, 733\u2013739 (2009).","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"447_CR4","doi-asserted-by":"publisher","first-page":"4424","DOI":"10.4161\/cc.22768","volume":"11","author":"YW Zhang","year":"2012","unstructured":"Zhang, Y. W., Ghosh, A. K. & Pommier, Y. Lasonolide A, a potent and reversible inducer of chromosome condensation. Cell Cycle 11, 4424\u20134435 (2012).","journal-title":"Cell Cycle"},{"key":"447_CR5","doi-asserted-by":"publisher","first-page":"3625","DOI":"10.3390\/md13063625","volume":"13","author":"R Josse","year":"2015","unstructured":"Josse, R. et al. Activation of RAF1 (c-RAF) by the marine alkaloid lasonolide A induces rapid premature chromosome condensation. Mar. Drugs 13, 3625\u20133639 (2015).","journal-title":"Mar. Drugs"},{"key":"447_CR6","doi-asserted-by":"publisher","first-page":"11690","DOI":"10.1021\/jacs.6b05127","volume":"138","author":"BM Trost","year":"2016","unstructured":"Trost, B. M. et al. Total synthesis of (\u2212)-lasonolide A. J. Am. Chem. Soc. 138, 11690\u201311701 (2016).","journal-title":"J. Am. Chem. Soc."},{"key":"447_CR7","doi-asserted-by":"publisher","first-page":"1231","DOI":"10.1126\/science.1178955","volume":"326","author":"JE Carette","year":"2009","unstructured":"Carette, J. E. et al. Haploid genetic screens in human cells identify host factors used by pathogens. Science 326, 1231\u20131235 (2009).","journal-title":"Science"},{"key":"447_CR8","doi-asserted-by":"publisher","first-page":"542","DOI":"10.1038\/nbt.1857","volume":"29","author":"JE Carette","year":"2011","unstructured":"Carette, J. E. et al. Global gene disruption in human cells to assign genes to phenotypes by deep sequencing. Nat. Biotechnol. 29, 542\u2013546 (2011).","journal-title":"Nat. Biotechnol."},{"key":"447_CR9","doi-asserted-by":"publisher","first-page":"5810","DOI":"10.1158\/0008-5472.CAN-16-0716","volume":"76","author":"R Dubey","year":"2016","unstructured":"Dubey, R. et al. Chromatin-remodeling complex SWI\/SNF controls multidrug resistance by transcriptionally regulating the drug efflux pump ABCB1. Cancer Res. 76, 5810\u20135821 (2016).","journal-title":"Cancer Res."},{"key":"447_CR10","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1038\/nature10348","volume":"477","author":"JE Carette","year":"2011","unstructured":"Carette, J. E. et al. Ebola virus entry requires the cholesterol transporter Niemann\u2013Pick C1. Nature 477, 340\u2013343 (2011).","journal-title":"Nature"},{"key":"447_CR11","doi-asserted-by":"publisher","first-page":"11051","DOI":"10.1074\/jbc.R109.097600","volume":"285","author":"GM Simon","year":"2010","unstructured":"Simon, G. M. & Cravatt, B. F. Activity-based proteomics of enzyme superfamilies: serine hydrolases as a case study. J. Biol. Chem. 285, 11051\u201311055 (2010).","journal-title":"J. Biol. Chem."},{"key":"447_CR12","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1038\/nrd3620","volume":"11","author":"DA Bachovchin","year":"2012","unstructured":"Bachovchin, D. A. & Cravatt, B. F. The pharmacological landscape and therapeutic potential of serine hydrolases. Nat. Rev. Drug Discov. 11, 52\u201368 (2012).","journal-title":"Nat. Rev. Drug Discov."},{"key":"447_CR13","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1038\/msb.2011.28","volume":"7","author":"D Hebenstreit","year":"2011","unstructured":"Hebenstreit, D. et al. RNA sequencing reveals two major classes of gene expression levels in metazoan cells. Mol. Syst. Biol. 7, 497\u2013497 (2011).","journal-title":"Mol. Syst. Biol."},{"key":"447_CR14","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1161\/ATVBAHA.113.302448","volume":"34","author":"YH Goo","year":"2014","unstructured":"Goo, Y. H., Son, S. H., Kreienberg, P. B. & Paul, A. Novel lipid droplet-associated serine hydrolase regulates macrophage cholesterol mobilization. Arterioscler. Thromb. Vasc. Biol. 34, 386\u2013396 (2014).","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"447_CR15","doi-asserted-by":"publisher","first-page":"2198","DOI":"10.1242\/jcs.120493","volume":"126","author":"K Thiel","year":"2013","unstructured":"Thiel, K. et al. The evolutionarily conserved protein CG9186 is associated with lipid droplets, required for their positioning and for fat storage. J. Cell Sci. 126, 2198\u20132212 (2013).","journal-title":"J. Cell Sci."},{"key":"447_CR16","doi-asserted-by":"publisher","first-page":"D222","DOI":"10.1093\/nar\/gku1221","volume":"43","author":"A Marchler-Bauer","year":"2015","unstructured":"Marchler-Bauer, A. et al. CDD: NCBI\u2019s conserved domain database. Nucleic Acids Res. 43, D222\u2013D226 (2015).","journal-title":"Nucleic Acids Res."},{"key":"447_CR17","doi-asserted-by":"publisher","first-page":"4194","DOI":"10.1093\/hmg\/ddy310","volume":"27","author":"BB Currall","year":"2018","unstructured":"Currall, B. B. et al. Loss of LDAH associated with prostate cancer and hearing loss. Hum. Mol. Genet. 27, 4194\u20134203 (2018).","journal-title":"Hum. Mol. Genet."},{"key":"447_CR18","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1194\/jlr.M072538","volume":"58","author":"N Kory","year":"2017","unstructured":"Kory, N. et al. Mice lacking lipid droplet-associated hydrolase, a gene linked to human prostate cancer, have normal cholesterol ester metabolism. J. Lipid Res. 58, 226\u2013235 (2017).","journal-title":"J. Lipid Res."},{"key":"447_CR19","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1038\/s41580-018-0085-z","volume":"20","author":"JA Olzmann","year":"2019","unstructured":"Olzmann, J. A. & Carvalho, P. Dynamics and functions of lipid droplets. Nat. Rev. Mol. Cell Biol. 20, 137\u2013155 (2019).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"447_CR20","doi-asserted-by":"publisher","first-page":"3.15.1","DOI":"10.1002\/cpcb.10","volume":"72","author":"DL Brasaemle","year":"2016","unstructured":"Brasaemle, D. L. & Wolins, N. E. Isolation of lipid droplets from cells by density gradient centrifugation. Curr. Protoc. Cell Biol. 72, 3.15.1\u20133.15.13 (2016).","journal-title":"Curr. Protoc. Cell Biol."},{"key":"447_CR21","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1038\/nrm.2017.7","volume":"18","author":"SF Banani","year":"2017","unstructured":"Banani, S. F., Lee, H. O., Hyman, A. A. & Rosen, M. K. Biomolecular condensates: organizers of cellular biochemistry. Nat. Rev. Mol. Cell Biol. 18, 285\u2013298 (2017).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"447_CR22","doi-asserted-by":"publisher","first-page":"1279","DOI":"10.1126\/science.aat9689","volume":"364","author":"DJ Greenwood","year":"2019","unstructured":"Greenwood, D. J. et al. Subcellular antibiotic visualization reveals a dynamic drug reservoir in infected macrophages. Science 364, 1279\u20131282 (2019).","journal-title":"Science"},{"key":"447_CR23","doi-asserted-by":"publisher","first-page":"1619","DOI":"10.1021\/mp200092v","volume":"8","author":"N Zheng","year":"2011","unstructured":"Zheng, N., Tsai, H. N., Zhang, X. & Rosania, G. R. The subcellular distribution of small molecules: from pharmacokinetics to synthetic biology. Mol. Pharm. 8, 1619\u20131628 (2011).","journal-title":"Mol. Pharm."},{"key":"447_CR24","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1016\/j.it.2018.01.012","volume":"39","author":"MH den Brok","year":"2018","unstructured":"den Brok, M. H., Raaijmakers, T. K., Collado-Camps, E. & Adema, G. J. Lipid droplets as immune modulators in myeloid cells. Trends Immunol. 39, 380\u2013392 (2018).","journal-title":"Trends Immunol."},{"key":"447_CR25","first-page":"372","volume":"41","author":"S Fowler","year":"1979","unstructured":"Fowler, S., Shio, H. & Haley, N. J. Characterization of lipid-laden aortic cells from cholesterol-fed rabbits. IV. Investigation of macrophage-like properties of aortic cell populations. Lab. Investig. 41, 372\u2013378 (1979).","journal-title":"Lab. Investig."},{"key":"447_CR26","doi-asserted-by":"publisher","first-page":"750","DOI":"10.1016\/j.bbalip.2010.05.004","volume":"1801","author":"P Foley","year":"2010","unstructured":"Foley, P. Lipids in Alzheimer\u2019s disease: a century-old story. Biochim. Biophys. Acta 1801, 750\u2013753 (2010).","journal-title":"Biochim. Biophys. Acta"},{"key":"447_CR27","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1002\/nbm.1661","volume":"24","author":"EJ Delikatny","year":"2011","unstructured":"Delikatny, E. J., Chawla, S., Leung, D.-J. & Poptani, H. MR-visible lipids and the tumor microenvironment. NMR Biomedicine 24, 592\u2013611 (2011).","journal-title":"NMR Biomedicine"},{"key":"447_CR28","doi-asserted-by":"publisher","first-page":"1941","DOI":"10.3390\/molecules23081941","volume":"23","author":"T Petan","year":"2018","unstructured":"Petan, T., Jarc, E. & Jusovi\u0107, M. Lipid droplets in cancer: guardians of fat in a stressful world. Molecules 23, 1941 (2018).","journal-title":"Molecules"},{"key":"447_CR29","doi-asserted-by":"publisher","first-page":"e48694","DOI":"10.1371\/journal.pone.0048694","volume":"7","author":"JP Sundelin","year":"2012","unstructured":"Sundelin, J. P. et al. Increased expression of the very low-density lipoprotein receptor mediates lipid accumulation in clear-cell renal cell carcinoma. PLoS ONE 7, e48694 (2012).","journal-title":"PLoS ONE"},{"key":"447_CR30","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1097\/01.mco.0000232896.66791.62","volume":"9","author":"MH Hager","year":"2006","unstructured":"Hager, M. H., Solomon, K. R. & Freeman, M. R. The role of cholesterol in prostate cancer. Curr. Opin. Clin. Nutr. Metab. Care 9, 379\u2013385 (2006).","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"447_CR31","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1002\/1097-0142(196304)16:4<521::AID-CNCR2820160414>3.0.CO;2-B","volume":"16","author":"MH Aboumrad","year":"1963","unstructured":"Aboumrad, M. H., Horn, R. C. Jr. & Fine, G. Lipid-secreting mammary carcinoma. Report of a case associated with Paget\u2019s disease of the nipple. Cancer 16, 521\u2013525 (1963).","journal-title":"Cancer"},{"key":"447_CR32","doi-asserted-by":"publisher","first-page":"812","DOI":"10.1002\/1097-0142(197403)33:3<812::AID-CNCR2820330328>3.0.CO;2-4","volume":"33","author":"CV Ramos","year":"1974","unstructured":"Ramos, C. V. & Taylor, H. B. Lipid-rich carcinoma of the breast. A clinicopathologic analysis of 13 examples. Cancer 33, 812\u2013819 (1974).","journal-title":"Cancer"},{"key":"447_CR33","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1038\/nrd.2018.46","volume":"17","author":"J Rautio","year":"2018","unstructured":"Rautio, J., Meanwell, N. A., Di, L. & Hageman, M. J. The expanding role of prodrugs in contemporary drug design and development. Nat. Rev. Drug Discov. 17, 559\u2013587 (2018).","journal-title":"Nat. Rev. Drug Discov."},{"key":"447_CR34","doi-asserted-by":"publisher","first-page":"2281","DOI":"10.1038\/nprot.2013.143","volume":"8","author":"FA Ran","year":"2013","unstructured":"Ran, F. A. et al. Genome engineering using the CRISPR-Cas9 system. Nat. Protoc. 8, 2281\u20132308 (2013).","journal-title":"Nat. Protoc."},{"key":"447_CR35","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1038\/nmeth.3047","volume":"11","author":"NE Sanjana","year":"2014","unstructured":"Sanjana, N. E., Shalem, O. & Zhang, F. Improved vectors and genome-wide libraries for CRISPR screening. Nat. Methods 11, 783\u2013784 (2014).","journal-title":"Nat. Methods"},{"key":"447_CR36","doi-asserted-by":"publisher","first-page":"e6529","DOI":"10.1371\/journal.pone.0006529","volume":"4","author":"E Campeau","year":"2009","unstructured":"Campeau, E. et al. A versatile viral system for expression and depletion of proteins in mammalian cells. PLoS ONE 4, e6529 (2009).","journal-title":"PLoS ONE"},{"key":"447_CR37","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1021\/ja411270d","volume":"136","author":"BM Trost","year":"2014","unstructured":"Trost, B. M. et al. A concise synthesis of (\u2212)-lasonolide A. J. Am. Chem. Soc. 136, 88\u201391 (2014).","journal-title":"J. Am. Chem. Soc."}],"container-title":["Nature Chemical Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/s41589-019-0447-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s41589-019-0447-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s41589-019-0447-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,25]],"date-time":"2023-09-25T01:25:00Z","timestamp":1695605100000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41589-019-0447-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,13]]},"references-count":37,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2020,2]]}},"alternative-id":["447"],"URL":"https:\/\/doi.org\/10.1038\/s41589-019-0447-7","relation":{},"ISSN":["1552-4450","1552-4469"],"issn-type":[{"value":"1552-4450","type":"print"},{"value":"1552-4469","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,13]]},"assertion":[{"value":"13 February 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 December 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 January 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}