{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T01:25:41Z","timestamp":1790126741373,"version":"4.0.1"},"reference-count":47,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,7,14]],"date-time":"2021-07-14T00:00:00Z","timestamp":1626220800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["RO1DK114356"],"award-info":[{"award-number":["RO1DK114356"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["UM1HG006348"],"award-info":[{"award-number":["UM1HG006348"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007313","name":"University of Texas MD Anderson Cancer Center","doi-asserted-by":"publisher","award":["1S10OD012304-01"],"award-info":[{"award-number":["1S10OD012304-01"]}],"id":[{"id":"10.13039\/100007313","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004917","name":"Cancer Prevention and Research Institute of Texas","doi-asserted-by":"publisher","award":["RP130397"],"award-info":[{"award-number":["RP130397"]}],"id":[{"id":"10.13039\/100004917","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Biochemical Pharmacology"],"published-print":{"date-parts":[[2021,10]]},"DOI":"10.1016\/j.bcp.2021.114688","type":"journal-article","created":{"date-parts":[[2021,7,16]],"date-time":"2021-07-16T01:58:56Z","timestamp":1626400736000},"page":"114688","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":47,"special_numbering":"C","title":["TTI-101: A competitive inhibitor of STAT3 that spares oxidative phosphorylation and reverses mechanical allodynia in mouse models of neuropathic pain"],"prefix":"10.1016","volume":"192","author":[{"given":"Moses M.","family":"Kasembeli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pooja","family":"Singhmar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiacheng","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jules","family":"Edralin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongfu","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"Clydell","family":"Adams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cobi J.","family":"Heijnen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annemieke","family":"Kavelaars","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Tweardy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"2","key":"10.1016\/j.bcp.2021.114688_b0005","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1124\/pr.119.018440","article-title":"Targeting janus kinases and signal transducer and activator of transcription 3 to treat inflammation, fibrosis, and cancer: rationale, progress, and caution","volume":"72","author":"Bharadwaj","year":"2020","journal-title":"Pharmacol. Rev."},{"issue":"8","key":"10.1016\/j.bcp.2021.114688_b0010","doi-asserted-by":"crossref","first-page":"2299","DOI":"10.3390\/ijms19082299","article-title":"Contribution of STAT3 to inflammatory and fibrotic diseases and prospects for its targeting for treatment","volume":"19","author":"Kasembeli","year":"2018","journal-title":"Int. J. Mol. Sci."},{"issue":"8","key":"10.1016\/j.bcp.2021.114688_b0015","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1038\/nrc.2017.36","article-title":"Drugging the 'undruggable' cancer targets","volume":"17","author":"Dang","year":"2017","journal-title":"Nat. Rev. Cancer"},{"issue":"1","key":"10.1016\/j.bcp.2021.114688_b0020","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1007\/s00280-014-2480-2","article-title":"Phase 1, open-label, dose-escalation, and pharmacokinetic study of STAT3 inhibitor OPB-31121 in subjects with advanced solid tumors","volume":"74","author":"Bendell","year":"2014","journal-title":"Cancer Chemother. Pharmacol."},{"issue":"7","key":"10.1016\/j.bcp.2021.114688_b0025","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1111\/cas.12683","article-title":"Phase I study of OPB-51602, an oral inhibitor of signal transducer and activator of transcription 3, in patients with relapsed\/refractory hematological malignancies","volume":"106","author":"Ogura","year":"2015","journal-title":"Cancer Sci."},{"issue":"25","key":"10.1016\/j.bcp.2021.114688_b0030","doi-asserted-by":"crossref","first-page":"E4924","DOI":"10.1073\/pnas.1615730114","article-title":"Mitochondrial dysfunction induced by a SH2 domain-targeting STAT3 inhibitor leads to metabolic synthetic lethality in cancer cells","volume":"114","author":"Genini","year":"2017","journal-title":"PNAS"},{"issue":"21","key":"10.1016\/j.bcp.2021.114688_b0035","doi-asserted-by":"crossref","first-page":"3646","DOI":"10.1128\/MCB.00541-15","article-title":"A Synthetic Lethal Interaction between Glutathione Synthesis and Mitochondrial Reactive Oxygen Species Provides a Tumor-Specific Vulnerability Dependent on STAT3","volume":"35","author":"Garama","year":"2015","journal-title":"Mol. Cell. Biol."},{"issue":"5","key":"10.1016\/j.bcp.2021.114688_b0040","doi-asserted-by":"crossref","first-page":"532","DOI":"10.7150\/ijbs.15153","article-title":"Mitochondrial Stat3, the Need for Design Thinking","volume":"12","author":"Yang","year":"2016","journal-title":"International journal of biological sciences"},{"issue":"18","key":"10.1016\/j.bcp.2021.114688_b0045","doi-asserted-by":"crossref","first-page":"26307","DOI":"10.18632\/oncotarget.8368","article-title":"Small-molecule inhibition of STAT3 in radioresistant head and neck squamous cell carcinoma","volume":"7","author":"Bharadwaj","year":"2016","journal-title":"Oncotarget"},{"key":"10.1016\/j.bcp.2021.114688_b0050","series-title":"STAT Inhibitors in Cancer","first-page":"95","article-title":"STAT3 Inhibitors in Cancer: A Comprehensive Update","author":"Bharadwaj","year":"2016"},{"key":"10.1016\/j.bcp.2021.114688_b0055","unstructured":"NCT03195699, Oral STAT3 Inhibitor, TTI-101, in Patients With Advanced Cancers, June 22, 2017. https:\/\/ClinicalTrials.gov\/show\/NCT03195699."},{"issue":"12","key":"10.1016\/j.bcp.2021.114688_b0060","doi-asserted-by":"crossref","first-page":"2301","DOI":"10.1038\/nprot.2016.136","article-title":"The MaxQuant computational platform for mass spectrometry-based shotgun proteomics","volume":"11","author":"Tyanova","year":"2016","journal-title":"Nat. Protoc."},{"key":"10.1016\/j.bcp.2021.114688_b0065","series-title":"Mass Spectrometry of Proteins: Methods and Protocols","first-page":"99","article-title":"Detection of Unknown Chemical Adduct Modifications on Proteins: From Wet to Dry Laboratory","author":"Antinori","year":"2019"},{"issue":"2","key":"10.1016\/j.bcp.2021.114688_b0070","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/0304-3959(83)90201-4","article-title":"Ethical guidelines for investigations of experimental pain in conscious animals","volume":"16","author":"Zimmermann","year":"1983","journal-title":"Pain"},{"issue":"6","key":"10.1016\/j.bcp.2021.114688_b0075","doi-asserted-by":"crossref","first-page":"e1000412","DOI":"10.1371\/journal.pbio.1000412","article-title":"Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research","volume":"8","author":"Kilkenny","year":"2010","journal-title":"PLoS Biol."},{"issue":"1","key":"10.1016\/j.bcp.2021.114688_b0080","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0165-0270(94)90144-9","article-title":"Quantitative assessment of tactile allodynia in the rat paw","volume":"53","author":"Chaplan","year":"1994","journal-title":"J. Neurosci. Methods"},{"issue":"6","key":"10.1016\/j.bcp.2021.114688_b0085","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1097\/j.pain.0000000000000893","article-title":"HDAC6 inhibition effectively reverses chemotherapy-induced peripheral neuropathy","volume":"158","author":"Krukowski","year":"2017","journal-title":"Pain"},{"issue":"6","key":"10.1016\/j.bcp.2021.114688_b0090","doi-asserted-by":"crossref","first-page":"e100701","DOI":"10.1371\/journal.pone.0100701","article-title":"The anti-diabetic drug metformin protects against chemotherapy-induced peripheral neuropathy in a mouse model","volume":"9","author":"Mao-Ying","year":"2014","journal-title":"PLoS ONE"},{"issue":"10","key":"10.1016\/j.bcp.2021.114688_b0095","doi-asserted-by":"crossref","first-page":"5463","DOI":"10.1073\/pnas.1913444117","article-title":"The fibroblast-derived protein PI16 controls neuropathic pain","volume":"117","author":"Singhmar","year":"2020","journal-title":"PNAS"},{"issue":"85","key":"10.1016\/j.bcp.2021.114688_b0100","doi-asserted-by":"crossref","first-page":"35581","DOI":"10.18632\/oncotarget.26272","article-title":"Nasal administration of mesenchymal stem cells restores cisplatin-induced cognitive impairment and brain damage in mice","volume":"9","author":"Chiu","year":"2018","journal-title":"Oncotarget"},{"issue":"12","key":"10.1016\/j.bcp.2021.114688_b0105","doi-asserted-by":"crossref","first-page":"2877","DOI":"10.1097\/j.pain.0000000000001667","article-title":"Cell-specific role of histone deacetylase 6 in chemotherapy-induced mechanical allodynia and loss of intraepidermal nerve fibers","volume":"160","author":"Ma","year":"2019","journal-title":"Pain"},{"issue":"17-18","key":"10.1016\/j.bcp.2021.114688_b0110","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1016\/j.drudis.2007.07.013","article-title":"The significance of mitochondrial toxicity testing in drug development","volume":"12","author":"Dykens","year":"2007","journal-title":"Drug Discovery Today"},{"issue":"38","key":"10.1016\/j.bcp.2021.114688_b0115","doi-asserted-by":"crossref","first-page":"15731","DOI":"10.1074\/jbc.M117.791863","article-title":"The unintended mitochondrial uncoupling effects of the FDA-approved anti-helminth drug nitazoxanide mitigates experimental parkinsonism in mice","volume":"292","author":"Amireddy","year":"2017","journal-title":"J. Biol. Chem."},{"issue":"2","key":"10.1016\/j.bcp.2021.114688_b0120","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1042\/BJ20110162","article-title":"Assessing mitochondrial dysfunction in cells","volume":"435","author":"Brand","year":"2011","journal-title":"Biochem. J."},{"issue":"3","key":"10.1016\/j.bcp.2021.114688_b0125","doi-asserted-by":"crossref","first-page":"e4783","DOI":"10.1371\/journal.pone.0004783","article-title":"Chemical probes that competitively and selectively inhibit Stat3 activation","volume":"4","author":"Xu","year":"2009","journal-title":"PLoS ONE"},{"key":"10.1016\/j.bcp.2021.114688_b0130","doi-asserted-by":"crossref","DOI":"10.1021\/acs.jmedchem.0c00144","article-title":"Re-evaluating the mechanism of action of alpha, beta-unsaturated carbonyl DUB inhibitors b-AP15 and VLX1570: A paradigmatic example of unspecific protein cross-linking with michael acceptor motif-containing drugs","author":"Ward","year":"2020","journal-title":"J. Med. Chem."},{"issue":"11","key":"10.1016\/j.bcp.2021.114688_b0135","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1016\/j.chembiol.2006.11.001","article-title":"A new small-molecule Stat3 inhibitor","volume":"13","author":"McMurray","year":"2006","journal-title":"Chem. Biol."},{"issue":"15","key":"10.1016\/j.bcp.2021.114688_b0140","doi-asserted-by":"crossref","first-page":"20669","DOI":"10.18632\/oncotarget.7838","article-title":"Signal transducer and activator of transcription 3 (STAT3) inhibitor, S3I\u2013201, acts as a potent and non-selective alkylating agent","volume":"7","author":"Ball","year":"2016","journal-title":"Oncotarget"},{"key":"10.1016\/j.bcp.2021.114688_b0145","doi-asserted-by":"crossref","first-page":"108","DOI":"10.3389\/fnmol.2017.00108","article-title":"Inhibition of mitochondrial p53 accumulation by PFT-\u03bc prevents cisplatin-induced peripheral neuropathy","volume":"10","author":"Maj","year":"2017","journal-title":"Front. Mol. Neurosci."},{"key":"10.1016\/j.bcp.2021.114688_b0150","doi-asserted-by":"crossref","unstructured":"H. Song, R. Wang, S. Wang, J. Lin, A low-molecular-weight compound discovered through virtual database screening inhibits Stat3 function in breast cancer cells, Proceedings of the National Academy of Sciences of the United States of America 102(13) (2005) 4700.","DOI":"10.1073\/pnas.0409894102"},{"issue":"6","key":"10.1016\/j.bcp.2021.114688_b0155","first-page":"326","article-title":"Mitotoxicity in distal symmetrical sensory peripheral neuropathies. Nature reviews","volume":"10","author":"Bennett","year":"2014","journal-title":"Neurology"},{"issue":"Suppl 1","key":"10.1016\/j.bcp.2021.114688_b0160","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1097\/j.pain.0000000000001540","article-title":"Chemotherapy-induced peripheral neuropathy: where are we now?","volume":"160 Suppl 1","author":"Colvin","year":"2019","journal-title":"Pain"},{"issue":"11","key":"10.1016\/j.bcp.2021.114688_b0165","doi-asserted-by":"crossref","first-page":"2289","DOI":"10.1002\/cncr.31248","article-title":"Beyond symptomatic relief for chemotherapy-induced peripheral neuropathy: Targeting the source","volume":"124","author":"Ma","year":"2018","journal-title":"Cancer"},{"issue":"5","key":"10.1016\/j.bcp.2021.114688_b0170","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1097\/ALN.0000000000000850","article-title":"Spinal IL-33\/ST2 Signaling Contributes to Neuropathic Pain via Neuronal CaMKII-CREB and Astroglial JAK2-STAT3 Cascades in Mice","volume":"123","author":"Liu","year":"2015","journal-title":"Anesthesiology"},{"issue":"1","key":"10.1016\/j.bcp.2021.114688_b0175","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1111\/j.1471-4159.2008.05566.x","article-title":"JAK\/STAT3 pathway is activated in spinal cord microglia after peripheral nerve injury and contributes to neuropathic pain development in rat","volume":"107","author":"Dominguez","year":"2008","journal-title":"J. Neurochem."},{"issue":"Pt 4","key":"10.1016\/j.bcp.2021.114688_b0180","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1093\/brain\/awr025","article-title":"JAK-STAT3 pathway regulates spinal astrocyte proliferation and neuropathic pain maintenance in rats","volume":"134","author":"Tsuda","year":"2011","journal-title":"Brain"},{"key":"10.1016\/j.bcp.2021.114688_b0185","doi-asserted-by":"crossref","first-page":"14306","DOI":"10.1038\/srep14306","article-title":"A new minimally-invasive method for microinjection into the mouse spinal dorsal horn","volume":"5","author":"Kohro","year":"2015","journal-title":"Sci. Rep."},{"key":"10.1016\/j.bcp.2021.114688_b0190","doi-asserted-by":"crossref","unstructured":"Y.Y. Li, H. Li, Z.L. Liu, Q. Li, H.W. Qiu, L.J. Zeng, W. Yang, X.Z. Zhang, Z.Y. Li, Activation of STAT3-mediated CXCL12 up-regulation in the dorsal root ganglion contributes to oxaliplatin-induced chronic pain, Molecular pain 13 (2017) 1744806917747425.","DOI":"10.1177\/1744806917747425"},{"issue":"4","key":"10.1016\/j.bcp.2021.114688_b0195","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1097\/j.pain.0000000000000805","article-title":"Epigenetic upregulation of CXCL12 expression mediates antitubulin chemotherapeutics-induced neuropathic pain","volume":"158","author":"Xu","year":"2017","journal-title":"Pain"},{"issue":"3","key":"10.1016\/j.bcp.2021.114688_b0200","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1038\/sj.onc.1206122","article-title":"Stat3 activation regulates the expression of vascular endothelial growth factor and human pancreatic cancer angiogenesis and metastasis","volume":"22","author":"Wei","year":"2003","journal-title":"Oncogene"},{"issue":"13","key":"10.1016\/j.bcp.2021.114688_b0205","doi-asserted-by":"crossref","first-page":"2000","DOI":"10.1038\/sj.onc.1205260","article-title":"Constitutive Stat3 activity up-regulates VEGF expression and tumor angiogenesis","volume":"21","author":"Niu","year":"2002","journal-title":"Oncogene"},{"key":"10.1016\/j.bcp.2021.114688_b0210","doi-asserted-by":"crossref","unstructured":"Y. Sun, M. Ju, Z. Lin, T.W. Fredrick, L.P. Evans, K.T. Tian, N.J. Saba, P.C. Morss, W.T. Pu, J. Chen, A. Stahl, J.S. Joyal, L.E. Smith, SOCS3 in retinal neurons and glial cells suppresses VEGF signaling to prevent pathological neovascular growth, Science signaling 8(395) (2015) ra94.","DOI":"10.1126\/scisignal.aaa8695"},{"issue":"6","key":"10.1016\/j.bcp.2021.114688_b0215","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1016\/j.ccell.2015.04.017","article-title":"A functional role for VEGFR1 expressed in peripheral sensory neurons in cancer pain","volume":"27","author":"Selvaraj","year":"2015","journal-title":"Cancer Cell"},{"key":"10.1016\/j.bcp.2021.114688_b0220","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.neuropharm.2017.12.020","article-title":"Adipose-derived stem cells decrease pain in a rat model of oxaliplatin-induced neuropathy: Role of VEGF-A modulation","volume":"131","author":"Di Cesare Mannelli","year":"2018","journal-title":"Neuropharmacology"},{"issue":"12","key":"10.1016\/j.bcp.2021.114688_b0225","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1200\/JCO.2006.09.6305","article-title":"Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200","volume":"25","author":"Giantonio","year":"2007","journal-title":"J. Clin. Oncol."},{"issue":"Pt 9","key":"10.1016\/j.bcp.2021.114688_b0230","doi-asserted-by":"crossref","first-page":"2629","DOI":"10.1093\/brain\/aws145","article-title":"Systemic anti-vascular endothelial growth factor therapies induce a painful sensory neuropathy","volume":"135","author":"Verheyen","year":"2012","journal-title":"Brain"},{"issue":"8","key":"10.1016\/j.bcp.2021.114688_b0235","doi-asserted-by":"crossref","first-page":"S193","DOI":"10.1074\/mcp.TIR118.001209","article-title":"Interactive peptide spectral annotator: A versatile web-based tool for proteomic applications","volume":"18","author":"Brademan","year":"2019","journal-title":"Mol. Cell. Proteom. MCP"}],"updated-by":[{"DOI":"10.1016\/j.bcp.2021.114860","type":"erratum","label":"Erratum","source":"publisher","updated":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000}}],"container-title":["Biochemical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0006295221003014?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0006295221003014?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:25:41Z","timestamp":1778631941000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0006295221003014"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10]]},"references-count":47,"alternative-id":["S0006295221003014"],"URL":"https:\/\/doi.org\/10.1016\/j.bcp.2021.114688","relation":{},"ISSN":["0006-2952"],"issn-type":[{"value":"0006-2952","type":"print"}],"subject":[],"published":{"date-parts":[[2021,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"TTI-101: A competitive inhibitor of STAT3 that spares oxidative phosphorylation and reverses mechanical allodynia in mouse models of neuropathic pain","name":"articletitle","label":"Article Title"},{"value":"Biochemical Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bcp.2021.114688","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 The Author(s). Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"114688"}}