{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T20:04:13Z","timestamp":1778961853698,"version":"3.51.4"},"reference-count":117,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2018,1,26]],"date-time":"2018-01-26T00:00:00Z","timestamp":1516924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of General Medical Sciences of the National Institutes of Health","award":["SC3GM121178"],"award-info":[{"award-number":["SC3GM121178"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Plakins are a family of seven cytoskeletal cross-linker proteins (microtubule-actin crosslinking factor 1 (MACF), bullous pemphigoid antigen (BPAG1) desmoplakin, envoplakin, periplakin, plectin, epiplakin) that network the three major filaments that comprise the cytoskeleton. Plakins have been found to be involved in disorders and diseases of the skin, heart, nervous system, and cancer that are attributed to autoimmune responses and genetic alterations of these macromolecules. Despite their role and involvement across a spectrum of several diseases, there are no current drugs or pharmacological agents that specifically target the members of this protein family. On the contrary, microtubules have traditionally been targeted by microtubule inhibiting agents, used for the treatment of diseases such as cancer, in spite of the deleterious toxicities associated with their clinical utility. The Research Collaboratory for Structural Bioinformatics (RCSB) was used here to identify therapeutic drugs targeting the plakin proteins, particularly the spectraplakins MACF1 and BPAG1, which contain microtubule-binding domains. RCSB analysis revealed that plakin proteins had 329 ligands, of which more than 50% were MACF1 and BPAG1 ligands and 10 were documented, clinically or experimentally, to have several therapeutic applications as anticancer, anti-inflammatory, and antibiotic agents.<\/jats:p>","DOI":"10.3390\/ijms19020368","type":"journal-article","created":{"date-parts":[[2018,1,26]],"date-time":"2018-01-26T03:08:06Z","timestamp":1516936086000},"page":"368","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Microtubule-Actin Crosslinking Factor 1 and Plakins as Therapeutic Drug Targets"],"prefix":"10.3390","volume":"19","author":[{"given":"Quincy","family":"Quick","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, Tennessee State University, 3500 John A. Merritt Blvd, Nashville, TN 37209, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2018,1,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1006\/geno.1996.0587","article-title":"Cloning and characterization of mouse ACF7, a novel member of the dystonin subfamily of actin binding proteins","volume":"38","author":"Bernier","year":"1996","journal-title":"Genomics"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1016\/0888-7543(90)90261-R","article-title":"Bullous pemphigoid antigen (BPAG1): cDNA cloning and mapping of the gene to the short arm of human chromosome 6","volume":"8","author":"Sawamura","year":"1990","journal-title":"Genomics"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1111\/j.1432-0436.1982.tb01274.x","article-title":"Desmoplakins of epithelial and myocardial desmosomes are immunologically and biochemically related","volume":"23","author":"Franke","year":"1982","journal-title":"Differentiation"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1083\/jcb.134.3.715","article-title":"Envoplakin, a novel precursor of the cornified envelope that has homology to desmoplakin","volume":"134","author":"Ruhrberg","year":"1996","journal-title":"J. Cell Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1006\/geno.1997.5188","article-title":"cDNA cloning, mRNA expression, and chromosomal mapping of human and mouse periplakin genes","volume":"48","author":"Aho","year":"1998","journal-title":"Genomics"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1101\/SQB.1982.046.01.044","article-title":"Plectin: A high-molecular-weight cytoskeletal polypeptide component that copurifies with intermediate filaments of the vimentin type","volume":"46","author":"Wiche","year":"1982","journal-title":"Cold Spring Harb. Symp. Quant. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1111\/1523-1747.ep12340171","article-title":"Identification of a 450-kDa human epidermal autoantigen as a new member of the plectin family","volume":"106","author":"Fujiwara","year":"1996","journal-title":"J. Investig. Dermatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/S0962-8924(01)02180-8","article-title":"Plakins: A family of versatile cytolinker proteins","volume":"12","author":"Leung","year":"2002","journal-title":"Trends Cell Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1038\/jid.2013.498","article-title":"Plakins, a versatile family of cytolinkers: Roles in skin integrity and in human diseases","volume":"134","author":"Bouameur","year":"2014","journal-title":"J. Investig. Dermatol."},{"key":"ref_10","first-page":"5525","article-title":"MACF1 Controls Migration and Positioning of Cortical GABAergic Interneurons in Mice","volume":"27","author":"Ka","year":"2017","journal-title":"Cereb. Cortex"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.ydbio.2014.09.009","article-title":"MACF1 regulates the migration of pyramidal neurons via microtubule dynamics and GSK-3 signaling","volume":"395","author":"Ka","year":"2014","journal-title":"Dev. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"9143","DOI":"10.1523\/JNEUROSCI.0416-12.2012","article-title":"Spectraplakins promote microtubule-mediated axonal growth by functioning as structural microtubule-associated proteins and EB1-dependent +TIPs (tip interacting proteins)","volume":"32","author":"Beaven","year":"2012","journal-title":"J. Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/0092-8674(95)90333-X","article-title":"Gene targeting of BPAG1: Abnormalities in mechanical strength and cell migration in stratified epithelia and neurologic degeneration","volume":"81","author":"Guo","year":"1995","journal-title":"Cell"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1006\/mcne.1997.0660","article-title":"Dystonin Is Essential for Maintaining Neuronal Cytoskeleton Organization","volume":"10","author":"Leclerc","year":"1998","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.1083\/jcb.139.7.1835","article-title":"Periplakin, a novel component of cornified envelopes and desmosomes that belongs to the plakin family and forms complexes with envoplakin","volume":"139","author":"Ruhrberg","year":"1997","journal-title":"J. Cell Biol."},{"key":"ref_16","first-page":"62","article-title":"Rearrangement of intercellular junctions and cytoskeletal proteins during rabbit myocardium development","volume":"68","author":"Schaart","year":"1995","journal-title":"Eur. J. Cell Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1161\/01.RES.80.1.88","article-title":"Dissociated spatial patterning of gap junctions and cell adhesion junctions during postnatal differentiation of ventricular myocardium","volume":"80","author":"Angst","year":"1997","journal-title":"Circ. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1083\/jcb.200609109","article-title":"Desmoplakin: An unexpected regulator of microtubule organization in the epidermis","volume":"176","author":"Lechler","year":"2007","journal-title":"J. Cell Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1292\/jvms.64.123","article-title":"Expression of desmosomal proteins in rat keratinocytes during in vitro differentiation","volume":"64","author":"Mochizuki","year":"2002","journal-title":"J. Vet. Med. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1006\/excr.1994.1011","article-title":"Thapsigargin raises intracellular free calcium levels in human keratinocytes and inhibits the coordinated expression of differentiation markers","volume":"210","author":"Jones","year":"1994","journal-title":"Exp. Cell Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1159\/000050828","article-title":"Disappearance of desmosomal components in rat corneal epithelium during wound healing","volume":"215","author":"Okada","year":"2001","journal-title":"Ophthalmologica"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.cell.2010.12.033","article-title":"Skin stem cells orchestrate directional migration by regulating microtubule-ACF7 connections through GSK3\u03b2","volume":"144","author":"Wu","year":"2011","journal-title":"Cell"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1933","DOI":"10.1101\/gad.1411206","article-title":"The role of microtubule actin cross-linking factor 1 (MACF1) in the Wnt signaling pathway","volume":"20","author":"Chen","year":"2006","journal-title":"Genes Dev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2954","DOI":"10.1091\/mbc.e09-01-0051","article-title":"BPAG1e maintains keratinocyte polarity through beta4 integrin-mediated modulation of Rac1 and cofilin activities","volume":"20","author":"Hamill","year":"2009","journal-title":"Mol. Biol. Cell"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"18701","DOI":"10.1074\/jbc.M312382200","article-title":"Plectin-RACK1 (receptor for activated C kinase 1) scaffolding: A novel mechanism to regulate protein kinase C activity","volume":"279","author":"Wiche","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1016\/j.jprot.2011.12.018","article-title":"Plectin promotes migration and invasion of cancer cells and is a novel prognostic marker for head and neck squamous cell carcinoma","volume":"75","author":"Katada","year":"2012","journal-title":"J. Proteom."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3143","DOI":"10.1101\/gad.11.23.3143","article-title":"Targeted inactivation of plectin reveals essential function in maintaining the integrity of skin, muscle, and heart cytoarchitecture","volume":"11","author":"Lassmann","year":"1997","journal-title":"Genes Dev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2009","DOI":"10.1083\/jcb.143.7.2009","article-title":"Desmoplakin is required early in development for assembly of desmosomes and cytoskeletal linkage","volume":"143","author":"Gallicano","year":"1998","journal-title":"J. Cell Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"5180","DOI":"10.1038\/srep05180","article-title":"Duplication in the microtubule-actin cross-linking factor 1 gene causes a novel neuromuscular condition","volume":"4","author":"Mosbech","year":"2014","journal-title":"Sci. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2878","DOI":"10.1007\/s12035-016-9861-y","article-title":"Genetic Variants of Microtubule Actin Cross-linking Factor 1 (MACF1) Confer Risk for Parkinson\u2019s Disease","volume":"54","author":"Wang","year":"2017","journal-title":"Mol. Neurobiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1128\/MCB.00709-10","article-title":"Global profiling and molecular characterization of alternative splicing events misregulated in lung cancer","volume":"31","author":"Cheng","year":"2011","journal-title":"Mol. Cell Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1097\/SLA.0b013e31824a9a8b","article-title":"An integrated proteomics and metabolomics approach for defining oncofetal biomarkers in the colorectal cancer","volume":"255","author":"Ma","year":"2012","journal-title":"Ann. Surg."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.1002\/ijc.28768","article-title":"Multilayer-omics analysis of renal cell carcinoma, including the whole exome, methylome and transcriptome","volume":"135","author":"Arai","year":"2014","journal-title":"Int. J. Cancer"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1778","DOI":"10.3892\/ijo.2017.3919","article-title":"Identification of novel mutations in endometrial cancer patients by whole-exome sequencing","volume":"50","author":"Chang","year":"2017","journal-title":"Int. J. Oncol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"310","DOI":"10.3892\/ijo.2016.3798","article-title":"Microtubule actin cross-linking factor 1, a novel target in glioblastoma","volume":"50","author":"Afghani","year":"2017","journal-title":"Int. J. Oncol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1007\/s00403-017-1736-1","article-title":"Prognostic factors for mortality in patients with bullous pemphigoid: A meta-analysis","volume":"309","author":"Liu","year":"2017","journal-title":"Arch. Dermatol. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1111\/j.1365-2133.2005.06987.x","article-title":"Antidesmoplakin antibodies in pemphigus vulgaris","volume":"154","author":"Cozzani","year":"2006","journal-title":"Br. J. Dermatol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1111\/j.1468-3083.1998.tb00774.x","article-title":"Antibodies to desmoplakin in a patient with pemphigus foliaceous","volume":"11","author":"Jiao","year":"1998","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_39","first-page":"238","article-title":"Detection of autoantibodies to desmoplakin in a patient with oral erythema multiforme","volume":"17","author":"Fukiwake","year":"2007","journal-title":"Eur. J. Dermatol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1111\/j.1365-2133.2004.06338.x","article-title":"Bullous pemphigoid antigen 1 isoforms: Potential new target autoantigens in multiple sclerosis?","volume":"152","author":"Laffitte","year":"2005","journal-title":"Br. J. Dermatol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1038\/ng0795-301","article-title":"The mouse dystonia musculorum gene is a neural isoform of bullous pemphigoid antigen 1","volume":"10","author":"Brown","year":"1995","journal-title":"Nat. Genet."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2694","DOI":"10.1093\/hmg\/ddt663","article-title":"Transgenic expression of neuronal dystonin isoform 2 partially rescues the disease phenotype of the dystonia musculorum mouse model of hereditary sensory autonomic neuropathy VI","volume":"23","author":"Ferrier","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1086\/344208","article-title":"Mutation in human desmoplakin domain binding to plakoglobin causes a dominant form of arrhythmogenic right ventricular cardiomyopathy","volume":"71","author":"Rampazzo","year":"2002","journal-title":"Am. J. Hum. Genet."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/S0735-1097(03)00628-4","article-title":"A recessive mutation in desmoplakin causes arrhythmogenic right ventricular dysplasia, skin disorder, and woolly hair","volume":"42","author":"Alcalai","year":"2003","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e5","DOI":"10.1136\/jmg.2005.032904","article-title":"Loss of desmoplakin isoform I causes early onset cardiomyopathy and heart failure in a Naxos-like syndrome","volume":"43","author":"Uzumcu","year":"2006","journal-title":"J. Med. Genet."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1002\/humu.21064","article-title":"A genetic variants database for arrhythmogenic right ventricular dysplasia\/cardiomyopathy","volume":"30","author":"Jongbloed","year":"2009","journal-title":"Hum. Mutat."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1016\/j.jmb.2011.06.047","article-title":"The nonlinear structure of the desmoplakin plakin domain and the effects of cardiomyopathy-linked mutations","volume":"411","author":"Knowles","year":"2011","journal-title":"J. Mol. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/S0169-5002(01)00486-X","article-title":"Differential expression and biodistribution of cytokeratin 18 and desmoplakins in non-small cell lung carcinoma subtypes","volume":"36","author":"Young","year":"2002","journal-title":"Lung Cancer"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"649731","DOI":"10.1155\/2010\/649731","article-title":"Desmosomal component expression in normal, dysplastic, and oral squamous cell carcinoma","volume":"2010","author":"Narayana","year":"2010","journal-title":"Dermatol. Res. Pract."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1016\/j.humpath.2009.02.002","article-title":"Altered desmoplakin expression at transcriptional and protein levels provides prognostic information in human oropharyngeal cancer","volume":"40","author":"Papagerakis","year":"2009","journal-title":"Hum. Pathol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2336","DOI":"10.1016\/j.yexcr.2007.01.010","article-title":"Increased keratinocyte proliferation initiated through downregulation of desmoplakin by RNA interference","volume":"313","author":"Wan","year":"2007","journal-title":"Exp. Cell Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1863","DOI":"10.1093\/carcin\/bgs226","article-title":"Desmoplakin acts as a tumor suppressor by inhibition of the Wnt\/\u03b2-catenin signaling pathway in human lung cancer","volume":"33","author":"Yang","year":"2012","journal-title":"Carcinogenesis"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.cca.2013.11.020","article-title":"Detection of autoantibodies to periplakin and envoplakin in paraneoplastic pemphigus but not idiopathic pulmonary fibrosis using full-length recombinant proteins","volume":"429","author":"Muro","year":"2014","journal-title":"Clin. Chim. Acta"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1007\/s00403-008-0901-y","article-title":"Detection of anti-envoplakin and anti-periplakin autoantibodies by ELISA in patients with paraneoplastic pemphigus","volume":"301","author":"Huang","year":"2009","journal-title":"Arch. Dermatol. Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/j.biopha.2016.12.103","article-title":"Loss of periplakin expression is associated with the tumorigenesis of colorectal carcinoma","volume":"87","author":"Li","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1002\/cam4.369","article-title":"Aberrant DNA hypermethylation reduces the expression of the desmosome-related molecule periplakin in esophageal squamous cell carcinoma","volume":"4","author":"Otsubo","year":"2015","journal-title":"Cancer Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.jdermsci.2014.11.005","article-title":"Plectin-related skin diseases","volume":"77","author":"Natsuga","year":"2015","journal-title":"J. Dermatol. Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1158\/1078-0432.CCR-10-0999","article-title":"Plectin-1 as a novel biomarker for pancreatic cancer","volume":"17","author":"Bausch","year":"2011","journal-title":"Clin. Cancer Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/00005792-195302000-00001","article-title":"Pemphigus","volume":"32","author":"Lever","year":"1953","journal-title":"Medicine"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1111\/j.1365-2230.2005.01736.x","article-title":"Molecular abnormalities of the desmosomal protein desmoplakin in human disease","volume":"30","author":"Wessagowit","year":"2005","journal-title":"Clin. Exp. Dermatol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"86","DOI":"10.15420\/AER.2015.04.02.86","article-title":"Arrhythmogenic Right Ventricular Cardiomyopathy\u2014Antiarrhythmic Therapy","volume":"4","author":"Ermakov","year":"2015","journal-title":"Arrhythm. Electrophysiol. Rev."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.2174\/1871520615666150716105425","article-title":"Paraneoplastic Pemphigus: Autoimmune-Cancer Nexus in the Skin","volume":"15","author":"Sinha","year":"2015","journal-title":"Anticancer Agents Med. Chem."},{"key":"ref_63","first-page":"1076","article-title":"Mucocutaneous paraneoplastic syndromes associated with hematologic malignancies","volume":"25","author":"Steele","year":"2011","journal-title":"Oncology"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1111\/1346-8138.13079","article-title":"Malignancies in bullous pemphigoid: A controversial association","volume":"43","author":"Balestri","year":"2016","journal-title":"J. Dermatol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1001\/archinte.1980.00330220077028","article-title":"Bullous pemphigoid as a manifestation of chronic lymphocytic leukemia","volume":"140","author":"Goodnough","year":"1980","journal-title":"Arch. Intern. Med."},{"key":"ref_66","first-page":"233","article-title":"Paraneoplastic pemphigus associated with non-Hodgkin B-cell lymphoma and good response to prednisone","volume":"85","author":"Iranzo","year":"2005","journal-title":"Acta Derm. Venereol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1002\/pmic.200500262","article-title":"Proteomic analysis of primary esophageal squamous cell carcinoma reveals downregulation of a cell adhesion protein, periplakin","volume":"6","author":"Nishimori","year":"2006","journal-title":"Proteomics"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"201","DOI":"10.2220\/biomedres.35.201","article-title":"Loss of periplakin expression is associated with pathological stage and cancer-specific survival in patients with urothelial carcinoma of the urinary bladder","volume":"35","author":"Matsumoto","year":"2014","journal-title":"Biomed. Res."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Shimbo, T., Tanemura, A., Yamazaki, T., Tamai, K., Katayama, I., and Kaneda, Y. (2010). Serum anti-BPAG1 auto antibody is a novel marker for human melanoma. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0010566"},{"key":"ref_70","first-page":"309","article-title":"Tubulin and microtubules as targets for anticancer drugs","volume":"5","author":"Hadfield","year":"2003","journal-title":"Prog. Cell Cycle Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1023\/A:1025513106330","article-title":"Microtubules, microtubule-interfering agents and apoptosis","volume":"8","author":"Mollinedo","year":"2003","journal-title":"Apoptosis"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1081\/CNV-200055970","article-title":"Review: Tubulin function, action of antitubulin drugs, and new drug development","volume":"23","author":"Pellegrini","year":"2005","journal-title":"Cancer Investig."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2523","DOI":"10.2174\/1568026617666170104145640","article-title":"Microtubule Targeting Agents as Cancer Chemotherapeutics: An Overview of Molecular Hybrids as Stabilizing and Destabilizing Agents","volume":"17","author":"Tangutur","year":"2017","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1021\/np800568j","article-title":"Tubulin-interactive natural products as anticancer agents","volume":"72","author":"Kingston","year":"2009","journal-title":"J. Nat. Prod."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1016\/S0305-7372(05)80002-7","article-title":"How to maximize the efficacy of taxanes in breast cancer","volume":"31","year":"2005","journal-title":"Cancer Treat. Rev."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1980","DOI":"10.1200\/JCO.2007.10.8399","article-title":"Taxanes alone or in combination with anthracyclines as first-line therapy of patients with metastatic breast cancer","volume":"26","author":"Burzykowski","year":"2008","journal-title":"J. Clin. Oncol."},{"key":"ref_77","first-page":"43","article-title":"Paclitaxel in the treatment of advanced urothelial cancer","volume":"14","author":"Bajorin","year":"2000","journal-title":"Oncology"},{"key":"ref_78","first-page":"CD011773","article-title":"Procarbazine, lomustine and vincristine for recurrent high-grade glioma","volume":"7","author":"Parasramka","year":"2017","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"4665","DOI":"10.1200\/JCO.2002.12.111","article-title":"Cisplatin and etoposide regimen is superior to cyclophosphamide, epirubicin, and vincristine regimen in small-cell lung cancer: Results from a randomized phase III trial with 5 years\u2019 follow-up","volume":"20","author":"Bremnes","year":"2002","journal-title":"J. Clin. Oncol."},{"key":"ref_80","first-page":"393","article-title":"Improving outcomes for patients with diffuse large B-cell lymphoma","volume":"60","author":"Flowers","year":"2010","journal-title":"CA Cancer J. Clin."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1016\/j.ctrv.2015.10.006","article-title":"Vinca alkaloids in the therapeutic management of malignant pleural mesothelioma","volume":"41","author":"Ceresoli","year":"2015","journal-title":"Cancer Treat. Rev."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/PL00007853","article-title":"Chemotherapy-induced peripheral neuropathy","volume":"249","author":"Quasthoff","year":"2002","journal-title":"J. Neurol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1146\/annurev.med.48.1.353","article-title":"The development and clinical utility of the taxane class of antimicrotubule chemotherapy agents","volume":"48","author":"Rowinsky","year":"1997","journal-title":"Annu. Rev. Med."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1242\/jcs.114.1.161","article-title":"Characterization of the microtubule binding domain of microtubule actin crosslinking factor (MACF): Identification of a novel group of microtubule associated proteins","volume":"114","author":"Sun","year":"2001","journal-title":"J. Cell Sci."},{"key":"ref_85","first-page":"887","article-title":"The microtubule inhibiting agent epothilone B antagonizes glioma cell motility associated with reorganization of the actin-binding protein \u03b1-actinin 4","volume":"25","author":"Henry","year":"2011","journal-title":"Oncol. Rep."},{"key":"ref_86","unstructured":"National Center for Health Statistics (2017, November 07). Health, United States, 2016: With Chartbook on Long-term Trends in Health, Available online: www.cdc.gov\/nchs\/fastats\/leading-causes-of-death.htm."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1093\/nar\/28.1.235","article-title":"The Protein Data Bank","volume":"28","author":"Berman","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"694","DOI":"10.12998\/wjcc.v3.i8.694","article-title":"Targeting chronic lymphocytic leukemia cells in the tumor microenviroment: A review of the in vitro and clinical trials to date","volume":"3","author":"Crassini","year":"2015","journal-title":"World J. Clin. Cases"},{"key":"ref_89","first-page":"1","article-title":"Management of patients with chronic lymphocytic leukemia at high risk of relapse on ibrutinib therapy","volume":"8","author":"Ayed","year":"2017","journal-title":"Leuk. Lymphoma"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.1007\/s00277-017-3061-3","article-title":"Ibrutinib versus previous standard of care: An adjusted comparison in patients with relapsed\/refractory chronic lymphocytic leukaemia","volume":"96","author":"Hansson","year":"2017","journal-title":"Ann. Hematol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11899-012-0147-9","article-title":"Ibrutinib (PCI-32765), the first BTK (Bruton\u2019s tyrosine kinase) inhibitor in clinical trials","volume":"8","author":"Brown","year":"2013","journal-title":"Curr. Hematol. Malig. Rep."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1177\/1078155214561281","article-title":"A review of a novel, Bruton\u2019s tyrosine kinase inhibitor, ibrutinib","volume":"22","author":"Lee","year":"2016","journal-title":"J. Oncol. Pharm. Pract."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1629","DOI":"10.3324\/haematol.2017.164103","article-title":"Incidence and management of toxicity associated with ibrutinib and idelalisib: A practical approach","volume":"102","author":"Koopmans","year":"2017","journal-title":"Haematologica"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1846","DOI":"10.4049\/jimmunol.154.4.1846","article-title":"The complex of FK506-binding protein 12 and FK506 inhibits calcineurin phosphatase activity and IgE activation-induced cytokine transcripts, but not exocytosis, in mouse mast cells","volume":"154","author":"Fruman","year":"1995","journal-title":"J. Immunol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"19610","DOI":"10.1016\/S0021-9258(17)32213-5","article-title":"Regulation of calcineurin phosphatase activity and interaction with the FK-506.FK-506 binding protein complex","volume":"269","author":"Parsons","year":"1994","journal-title":"J. Biol. Chem."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/S0168-8278(05)80209-0","article-title":"FK 506 pre-treatment is associated with reduced levels of tumor necrosis factor and interleukin 6 following hepatic ischemia\/reperfusion","volume":"17","author":"Sakr","year":"1993","journal-title":"J. Hepatol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/0022-4804(92)90035-X","article-title":"FK-506 inhibits proliferation and IL-4 messenger RNA production by a T-helper 2 cell line","volume":"53","author":"Wang","year":"1992","journal-title":"J. Surg. Res."},{"key":"ref_98","first-page":"1597","article-title":"FK506, an immunosuppressant, partially inhibits interleukin 6 production by adherent rheumatoid synovial cells","volume":"21","author":"Sugiyama","year":"1994","journal-title":"J. Rheumatol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"8582","DOI":"10.1016\/S0021-9258(17)37234-4","article-title":"The interleukin-8 AP-1 and kappa B-like sites are genetic end targets of FK506-sensitive pathway accompanied by calcium mobilization","volume":"269","author":"Okamoto","year":"1994","journal-title":"J. Biol. Chem."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1097\/00007890-199310000-00038","article-title":"A dual mechanism of immunosuppression by FK-506. Differential suppression of IL-4 and IL-10 levels in T helper 2 cells","volume":"56","author":"Wang","year":"1993","journal-title":"Transplantation"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1097\/00007890-199801150-00005","article-title":"A tacrolimus-related immunosuppressant with reduced toxicity","volume":"65","author":"Dumont","year":"1998","journal-title":"Transplantation"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2191","DOI":"10.1007\/s00415-017-8616-7","article-title":"Efficacy and safety of tacrolimus for myasthenia gravis: A systematic review and meta-analysis","volume":"264","author":"Wang","year":"2017","journal-title":"J. Neurol."},{"key":"ref_103","first-page":"2053","article-title":"Antitumor effect and potentiation of cytotoxic drugs activity in human cancer cells by ZD-1839 (Iressa), an epidermal growth factor receptor-selective tyrosine kinase inhibitor","volume":"6","author":"Ciardiello","year":"2000","journal-title":"Clin. Cancer Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/S0014-827X(01)01026-6","article-title":"The 4-anilinoquinazoline class of inhibitors of the erbB family of receptor tyrosine kinases","volume":"56","author":"Denny","year":"2001","journal-title":"Farmaco"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1586\/14737140.3.3.269","article-title":"Erlotinib (Tarceva): A promising drug targeting epidermal growth factor receptor tyrosine kinase","volume":"3","author":"Bulgaru","year":"2003","journal-title":"Expert Rev. Anticancer Ther."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1021\/jm00168a029","article-title":"Synthesis and biological evaluation of 2-styrylquinazolin-4(3H)-ones, a new class of antimitotic anticancer agents which inhibit tubulin polymerization","volume":"33","author":"Jiang","year":"1990","journal-title":"J. Med. Chem."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1038\/nchembio.117","article-title":"Targeted polypharmacology: Discovery of dual inhibitors of tyrosine and phosphoinositide kinases","volume":"4","author":"Apsel","year":"2008","journal-title":"Nat. Chem. Biol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.bbrc.2015.07.147","article-title":"The anti-esophageal cancer cell activity by a novel tyrosine\/phosphoinositide kinase inhibitor PP121","volume":"465","author":"Peng","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"8659","DOI":"10.1007\/s13277-014-2118-3","article-title":"PP121, a dual inhibitor of tyrosine and phosphoinositide kinases, inhibits anaplastic thyroid carcinoma cell proliferation and migration","volume":"35","author":"Che","year":"2014","journal-title":"Tumor Biol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"27720","DOI":"10.1038\/srep27720","article-title":"Amicoumacin A induces cancer cell death by targeting the eukaryotic ribosome","volume":"6","author":"Prokhorova","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Guha, G., Lu, W., Li, S., Liang, X., Kulesz-Martin, M.F., Mahmud, T., Indra, A.K., and Ganguli-Indra, G. (2015). Novel Pactamycin Analogs Induce p53 Dependent Cell-Cycle Arrest at S-Phase in Human Head and Neck Squamous Cell Carcinoma (HNSCC) Cells. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0125322"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1007\/BF00173646","article-title":"In vivo antitumor activity of sparsomycin and its analogues in eight murine tumor models","volume":"6","author":"Zylicz","year":"1988","journal-title":"Investig. New Drugs"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1007\/BF01637073","article-title":"In vitro and in vivo anticancer activity of mitozolomide and sparsomycin in human tumor xenografts, murine tumors and human bone marrow","volume":"116","author":"Fiebig","year":"1990","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1080\/14740338.2016.1207760","article-title":"A safety evaluation of omacetaxine mepesuccinate for the treatment of chronic myeloid leukemia","volume":"15","author":"Damlaj","year":"2016","journal-title":"Expert Opin. Drug Saf."},{"key":"ref_115","first-page":"3","article-title":"Integrating current treatment options for TKI-resistant chronic myeloid leukemia","volume":"12","author":"Radich","year":"2014","journal-title":"Clin. Adv. Hematol. Oncol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"2381","DOI":"10.1517\/14656566.2011.613378","article-title":"Omacetaxine mepesuccinate for the treatment of leukemia","volume":"12","author":"Kim","year":"2011","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1002\/cncr.29240","article-title":"Final analysis of the efficacy and safety of omacetaxine mepesuccinate in patients with chronic-or accelerated-phase chronic myeloid leukemia: Results with 24 months of follow-up","volume":"121","author":"Cortes","year":"2015","journal-title":"Cancer"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/2\/368\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T14:52:37Z","timestamp":1760194357000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/2\/368"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,1,26]]},"references-count":117,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2018,2]]}},"alternative-id":["ijms19020368"],"URL":"https:\/\/doi.org\/10.3390\/ijms19020368","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,1,26]]}}}