{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T14:59:03Z","timestamp":1787237943202,"version":"build-2736575974"},"reference-count":62,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2020,4,8]],"date-time":"2020-04-08T00:00:00Z","timestamp":1586304000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,4,8]],"date-time":"2020-04-08T00:00:00Z","timestamp":1586304000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004281","name":"National Science Centre of Poland","doi-asserted-by":"publisher","award":["2014\/13\/N\/ST5\/01582"],"award-info":[{"award-number":["2014\/13\/N\/ST5\/01582"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005982","name":"Politechnika Wroc\u0142awska","doi-asserted-by":"publisher","award":["049U\/0096\/19"],"award-info":[{"award-number":["049U\/0096\/19"]}],"id":[{"id":"10.13039\/501100005982","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005982","name":"Politechnika Wroc\u0142awska","doi-asserted-by":"publisher","award":["049U\/0096\/19"],"award-info":[{"award-number":["049U\/0096\/19"]}],"id":[{"id":"10.13039\/501100005982","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005982","name":"Politechnika Wroc\u0142awska","doi-asserted-by":"publisher","award":["049U\/0096\/19"],"award-info":[{"award-number":["049U\/0096\/19"]}],"id":[{"id":"10.13039\/501100005982","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005982","name":"Politechnika Wroc\u0142awska","doi-asserted-by":"publisher","award":["049U\/0096\/19"],"award-info":[{"award-number":["049U\/0096\/19"]}],"id":[{"id":"10.13039\/501100005982","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Invest New Drugs"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:p>\n                    One of the strategies employed by novel anticancer therapies is to put the process of apoptosis back on track by blocking the interaction between inhibitor of apoptosis proteins (IAPs) and caspases. The activity of caspases is modulated by the caspases themselves in a caspase\/procaspase proteolytic cascade and by their interaction with IAPs. Caspases can be released from the inhibitory influence of IAPs by proapoptotic proteins such as secondary mitochondrial activator of caspases (Smac) that share an IAP binding motif (IBM). The main purpose of the present study was the design and synthesis of phosphorus-based peptidyl antagonists of IAPs that mimic the endogenous Smac protein, which blocks the interaction between IAPs and caspases. Based on the structure of the IAP antagonist and recently reported thiadiazole derivatives, we designed and evaluated the biochemical properties of a series of phosphonic peptides bearing the\n                    <jats:italic>N<\/jats:italic>\n                    -Me-Ala-Val\/Chg-Pro-OH motif (Chg: cyclohexylglycine). The ability of the obtained compounds to interact with the binding groove of the X-linked inhibitor of apoptosis protein baculovirus inhibitor of apoptosis protein repeat (XIAP BIR3) domain was examined by a fluorescence polarization assay, while their potential to induce autoubiquitination followed by proteasomal degradation of cellular IAP1 was examined using the MDA-MB-231 breast cancer cell line. The highest potency against BIR3 was observed among peptides containing C-terminal phosphonic phenylalanine analogs, which displayed nanomolar K\n                    <jats:sub>i<\/jats:sub>\n                    values. Their antiproliferative potential as well as their proapoptotic action, manifested by an increase in caspase-3 activity, was examined using various cell lines.\n                  <\/jats:p>","DOI":"10.1007\/s10637-020-00923-4","type":"journal-article","created":{"date-parts":[[2020,4,8]],"date-time":"2020-04-08T09:03:17Z","timestamp":1586336597000},"page":"1350-1364","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Structure-based design, synthesis, and evaluation of the biological activity of novel phosphoroorganic small molecule IAP antagonists"],"prefix":"10.1007","volume":"38","author":[{"given":"Agnieszka","family":"\u0141upicka-S\u0142owik","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mateusz","family":"Psurski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata","family":"Grzywa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Cuprych","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaros\u0142aw","family":"Ciekot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waldemar","family":"Goldeman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"El\u017cbieta","family":"Wojaczy\u0144ska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacek","family":"Wojaczy\u0144ski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f3zef","family":"Oleksyszyn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5528-5264","authenticated-orcid":false,"given":"Marcin","family":"Sie\u0144czyk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,4,8]]},"reference":[{"key":"923_CR1","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1080\/01926230701320337","volume":"35","author":"S Elmore","year":"2007","unstructured":"Elmore S (2007) Apoptosis: a review of programmed cell death. Toxicol Pathol 35:495\u2013516. https:\/\/doi.org\/10.1080\/01926230701320337","journal-title":"Toxicol Pathol"},{"key":"923_CR2","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1186\/1756-9966-30-87","volume":"30","author":"RS Wong","year":"2011","unstructured":"Wong RS (2011) Apoptosis in cancer: from pathogenesis to treatment. J Exp Clin Cancer Res 30:87. https:\/\/doi.org\/10.1186\/1756-9966-30-87","journal-title":"J Exp Clin Cancer Res"},{"key":"923_CR3","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1038\/35040009","volume":"1","author":"MP Mattson","year":"2000","unstructured":"Mattson MP (2000) Apoptosis in neurodegenerative disorders. Nat Rev Mol Cell Biol 1:120\u2013129. https:\/\/doi.org\/10.1038\/35040009","journal-title":"Nat Rev Mol Cell Biol"},{"key":"923_CR4","doi-asserted-by":"publisher","first-page":"1387","DOI":"10.1007\/s10495-009-0419-6","volume":"14","author":"PA Krijnen","year":"2009","unstructured":"Krijnen PA, Simsek S, Niessen HW (2009) Apoptosis in diabetes. Apoptosis 14:1387\u20131388. https:\/\/doi.org\/10.1007\/s10495-009-0419-6","journal-title":"Apoptosis"},{"key":"923_CR5","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1128\/MMBR.64.4.821-846.2000","volume":"64","author":"HY Chang","year":"2000","unstructured":"Chang HY, Yang X (2000) Proteases for cell suicide: functions and regulation of caspases. Microbiol Mol Biol Rev 64:821\u2013846","journal-title":"Microbiol Mol Biol Rev"},{"key":"923_CR6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1042\/bj3260001","volume":"326","author":"GM Cohen","year":"1997","unstructured":"Cohen GM (1997) Caspases: the executioners of apoptosis. Biochem J 326:1\u201316","journal-title":"Biochem J"},{"key":"923_CR7","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1038\/nrm2312","volume":"9","author":"RC Taylor","year":"2008","unstructured":"Taylor RC, Cullen SP, Martin SJ (2008) Apoptosis: controlled demolition at the cellular level. Nat Rev Mol Cell Biol 9:231\u2013241. https:\/\/doi.org\/10.1038\/nrm2312","journal-title":"Nat Rev Mol Cell Biol"},{"key":"923_CR8","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1038\/nrc.2016.58","volume":"16","author":"G Ichim","year":"2016","unstructured":"Ichim G, Tait SW (2016) A fate worse than death: apoptosis as an oncogenic process. Nat Rev Cancer 16:539\u2013548. https:\/\/doi.org\/10.1038\/nrc.2016.58","journal-title":"Nat Rev Cancer"},{"key":"923_CR9","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1038\/nrm3722","volume":"15","author":"PE Czabotar","year":"2014","unstructured":"Czabotar PE, Lessene G, Strasser A, Adams JM (2014) Control of apoptosis by the BCL-2 protein family: implications for physiology and therapy. Nat Rev Mol Cell Biol 15:49\u201363. https:\/\/doi.org\/10.1038\/nrm3722","journal-title":"Nat Rev Mol Cell Biol"},{"key":"923_CR10","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1038\/nrm2952","volume":"11","author":"SW Tait","year":"2010","unstructured":"Tait SW, Green DR (2010) Mitochondria and cell death: outer membrane permeabilization and beyond. Nat Rev Mol Cell Biol 11:621\u2013632. https:\/\/doi.org\/10.1038\/nrm2952","journal-title":"Nat Rev Mol Cell Biol"},{"key":"923_CR11","doi-asserted-by":"publisher","first-page":"a008656","DOI":"10.1101\/cshperspect.a008656","volume":"5","author":"DR McIlwain","year":"2013","unstructured":"McIlwain DR, Berger T, Mak TW (2013) Caspase functions in cell death and disease. Cold Spring Harb Perspect Biol 5:a008656. https:\/\/doi.org\/10.1101\/cshperspect.a008656","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"923_CR12","doi-asserted-by":"publisher","first-page":"a008730","DOI":"10.1101\/cshperspect.a008730","volume":"5","author":"J Silke","year":"2013","unstructured":"Silke J, Meier P (2013) Inhibitor of apoptosis (IAP) proteins-modulators of cell death and inflammation. Cold Spring Harb Perspect Biol 5:a008730. https:\/\/doi.org\/10.1101\/cshperspect.a008730","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"923_CR13","doi-asserted-by":"publisher","first-page":"reviews3009.1","DOI":"10.1186\/gb-2001-2-7-reviews3009","volume":"2","author":"AM Verhagen","year":"2001","unstructured":"Verhagen AM, Coulson EJ, Vaux DL (2001) Inhibitor of apoptosis proteins and their relatives: IAPs and other BIRPs. Genome Biol 2:reviews3009.1. https:\/\/doi.org\/10.1186\/gb-2001-2-7-reviews3009","journal-title":"Genome Biol"},{"key":"923_CR14","doi-asserted-by":"publisher","first-page":"5212","DOI":"10.1128\/MCB.14.8.5212","volume":"14","author":"RJ Clem","year":"1994","unstructured":"Clem RJ, Miller LK (1994) Control of programmed cell death by the baculovirus genes p35 and iap. Mol Cell Biol 14:5212\u20135222","journal-title":"Mol Cell Biol"},{"key":"923_CR15","doi-asserted-by":"publisher","first-page":"2168","DOI":"10.1128\/JVI.67.4.2168-2174.1993","volume":"67","author":"NE Crook","year":"1993","unstructured":"Crook NE, Clem RJ, Miller LK (1993) An apoptosis-inhibiting baculovirus gene with a zinc finger-like motif. J Virol 67:2168\u20132174","journal-title":"J Virol"},{"key":"923_CR16","doi-asserted-by":"publisher","first-page":"16182","DOI":"10.1073\/pnas.0502828102","volume":"102","author":"J Silke","year":"2005","unstructured":"Silke J, Kratina T, Chu D et al (2005) Determination of cell survival by RING-mediated regulation of inhibitor of apoptosis (IAP) protein abundance. PNAS 102:16182\u201316187. https:\/\/doi.org\/10.1073\/pnas.0502828102","journal-title":"PNAS"},{"key":"923_CR17","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1038\/nrd3627","volume":"11","author":"S Fulda","year":"2012","unstructured":"Fulda S, Vucic D (2012) Targeting IAP proteins for therapeutic intervention in cancer. Nat Rev Drug Discov 11:109\u2013124. https:\/\/doi.org\/10.1038\/nrd3627","journal-title":"Nat Rev Drug Discov"},{"key":"923_CR18","first-page":"200","volume":"34","author":"MC de Almagro","year":"2012","unstructured":"de Almagro MC, Vucic D (2012) The inhibitor of apoptosis (IAP) proteins are critical regulators of signaling pathways and targets for anti-cancer therapy. Exp Oncol 34:200\u2013211","journal-title":"Exp Oncol"},{"key":"923_CR19","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1016\/j.canlet.2006.09.024","volume":"250","author":"B Liu","year":"2007","unstructured":"Liu B, Han M, Wen JK, Wang L (2007) Livin\/ML-IAP as a new target for cancer treatment. Cancer Lett 250:168\u2013176. https:\/\/doi.org\/10.1016\/j.canlet.2006.09.024","journal-title":"Cancer Lett"},{"key":"923_CR20","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1111\/febs.13554","volume":"283","author":"AJ Kocab","year":"2016","unstructured":"Kocab AJ, Duckett CS (2016) Inhibitor of apoptosis proteins as intracellular signalling intermediates. FEBS J 283:221\u2013231. https:\/\/doi.org\/10.1111\/febs.13554","journal-title":"FEBS J"},{"key":"923_CR21","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1016\/j.csbj.2019.01.009","volume":"17","author":"F Cossu","year":"2019","unstructured":"Cossu F, Milani M, Mastrangelo E, Lecis D (2019) Targeting the BIR Domains of Inhibitor of Apoptosis (IAP) Proteins in Cancer Treatment. Comput Struct Biotechnol J 17:142\u2013150. https:\/\/doi.org\/10.1016\/j.csbj.2019.01.009","journal-title":"Comput Struct Biotechnol J"},{"key":"923_CR22","first-page":"4914","volume":"9","author":"M Krajewska","year":"2003","unstructured":"Krajewska M, Krajewski S, Banares S et al (2003) Elevated expression of inhibitor of apoptosis proteins in prostate cancer. Clin Cancer Res 9:4914\u20134925","journal-title":"Clin Cancer Res"},{"key":"923_CR23","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1007\/s00432-002-0364-z","volume":"128","author":"HS Hofmann","year":"2002","unstructured":"Hofmann HS, Simm A, Hammer A, Silber RE, Bartling B (2002) Expression of inhibitors of apoptosis (IAP) proteins in non-small cell human lung cancer. J Cancer Res Clin Oncol 128:554\u2013560. https:\/\/doi.org\/10.1007\/s00432-002-0364-z","journal-title":"J Cancer Res Clin Oncol"},{"key":"923_CR24","doi-asserted-by":"publisher","first-page":"1449","DOI":"10.3892\/ijo_00000464","volume":"35","author":"E Krepela","year":"2009","unstructured":"Krepela E, Dankova P, Moravcikova E et al (2009) Increased expression of inhibitor of apoptosis proteins, survivin and XIAP, in non-small cell lung carcinoma. Int J Oncol 35:1449\u20131462","journal-title":"Int J Oncol"},{"key":"923_CR25","doi-asserted-by":"publisher","first-page":"4043","DOI":"10.1182\/blood-2004-08-3168","volume":"105","author":"BZ Carter","year":"2005","unstructured":"Carter BZ, Gronda M, Wang Z et al (2005) Small-molecule XIAP inhibitors derepress downstream effector caspases and induce apoptosis of acute myeloid leukemia cells. Blood 105:4043\u20134050. https:\/\/doi.org\/10.1182\/blood-2004-08-3168","journal-title":"Blood"},{"key":"923_CR26","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1002\/ajh.20285","volume":"78","author":"Y Nakagawa","year":"2005","unstructured":"Nakagawa Y, Hasegawa M, Kurata M et al (2005) Expression of IAP-family proteins in adult acute mixed lineage leukemia (AMLL). Am J Hematol 78:173\u2013180. https:\/\/doi.org\/10.1002\/ajh.20285","journal-title":"Am J Hematol"},{"key":"923_CR27","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1186\/s13014-015-0437-1","volume":"10","author":"L Flanagan","year":"2015","unstructured":"Flanagan L, Kehoe J, Fay J et al (2015) High levels of X-linked Inhibitor-of-Apoptosis Protein (XIAP) are indicative of radio chemotherapy resistance in rectal cancer. Radiat Oncol 10:131. https:\/\/doi.org\/10.1186\/s13014-015-0437-1","journal-title":"Radiat Oncol"},{"key":"923_CR28","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1016\/S1097-2765(03)00054-6","volume":"11","author":"EN Shiozaki","year":"2003","unstructured":"Shiozaki EN, Chai J, Rigotti DJ et al (2003) Mechanism of XIAP-mediated inhibition of caspase-9. Mol Cell 11:519\u2013527","journal-title":"Mol Cell"},{"key":"923_CR29","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1038\/sj.emboj.7600544","volume":"24","author":"FL Scott","year":"2005","unstructured":"Scott FL, Denault J-B, Riedl SJ et al (2005) XIAP inhibits caspase-3 and \u2013 7 using two binding sites: evolutionarily conserved mechanism of IAPs. EMBO J 24:645\u2013655. https:\/\/doi.org\/10.1038\/sj.emboj.7600544","journal-title":"EMBO J"},{"key":"923_CR30","doi-asserted-by":"publisher","first-page":"1004","DOI":"10.1038\/35050006","volume":"408","author":"Z Liu","year":"2000","unstructured":"Liu Z, Sun C, Olejniczak ET et al (2000) Structural basis for binding of Smac\/DIABLO to the XIAP BIR3 domain. Nature 408:1004\u20131008. https:\/\/doi.org\/10.1038\/35050006","journal-title":"Nature"},{"key":"923_CR31","doi-asserted-by":"publisher","first-page":"1008","DOI":"10.1038\/35050012","volume":"408","author":"G Wu","year":"2000","unstructured":"Wu G, Chai J, Suber TL et al (2000) Structural basis of IAP recognition by Smac\/DIABLO. Nature 408:1008\u20131012. https:\/\/doi.org\/10.1038\/35050012","journal-title":"Nature"},{"key":"923_CR32","doi-asserted-by":"publisher","first-page":"898","DOI":"10.1007\/s10495-017-1375-1","volume":"22","author":"R Rathore","year":"2017","unstructured":"Rathore R, McCallum JE, Varghese E, Florea AM, Busselberg D (2017) Overcoming chemotherapy drug resistance by targeting inhibitors of apoptosis proteins (IAPs). Apoptosis 22:898\u2013919. https:\/\/doi.org\/10.1007\/s10495-017-1375-1","journal-title":"Apoptosis"},{"key":"923_CR33","doi-asserted-by":"publisher","first-page":"5750","DOI":"10.1021\/acs.jmedchem.8b01668","volume":"62","author":"H Cong","year":"2019","unstructured":"Cong H, Xu L, Wu Y et al (2019) Inhibitor of Apoptosis Protein (IAP) Antagonists in anticancer agent discovery: current status and perspectives. J Med Chem 62:5750\u20135772. https:\/\/doi.org\/10.1021\/acs.jmedchem.8b01668","journal-title":"J Med Chem"},{"key":"923_CR34","doi-asserted-by":"publisher","first-page":"1264","DOI":"10.1021\/ar8000553","volume":"41","author":"H Sun","year":"2008","unstructured":"Sun H, Nikolovska-Coleska Z, Yang CY et al (2008) Design of small-molecule peptidic and nonpeptidic Smac mimetics. Acc Chem Res 41:1264\u20131277. https:\/\/doi.org\/10.1021\/ar8000553","journal-title":"Acc Chem Res"},{"key":"923_CR35","doi-asserted-by":"publisher","first-page":"2714","DOI":"10.1021\/jm101505d","volume":"54","author":"Q Cai","year":"2011","unstructured":"Cai Q, Sun H, Peng Y et al (2011) A potent and orally active antagonist (SM-406\/AT-406) of multiple inhibitor of apoptosis proteins (IAPs) in clinical development for cancer treatment. J Med Chem 54:2714\u20132726. https:\/\/doi.org\/10.1021\/jm101505d","journal-title":"J Med Chem"},{"key":"923_CR36","doi-asserted-by":"publisher","first-page":"2565","DOI":"10.1007\/s13277-013-1338-2","volume":"35","author":"Q Qin","year":"2014","unstructured":"Qin Q, Zuo Y, Yang X et al (2014) Smac mimetic compound LCL161 sensitizes esophageal carcinoma cells to radiotherapy by inhibiting the expression of inhibitor of apoptosis protein. Tumour Biol 35:2565\u20132574. https:\/\/doi.org\/10.1007\/s13277-013-1338-2","journal-title":"Tumour Biol"},{"key":"923_CR37","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1186\/s13046-016-0435-7","volume":"35","author":"C Yang","year":"2016","unstructured":"Yang C, Wang H, Zhang B et al (2016) LCL161 increases paclitaxel-induced apoptosis by degrading cIAP1 and cIAP2 in NSCLC. J Exp Clin Cancer Res 35:158. https:\/\/doi.org\/10.1186\/s13046-016-0435-7","journal-title":"J Exp Clin Cancer Res"},{"key":"923_CR38","doi-asserted-by":"publisher","first-page":"4101","DOI":"10.1021\/jm300060k","volume":"55","author":"JA Flygare","year":"2012","unstructured":"Flygare JA, Beresini M, Budha N et al (2012) The discovery of a potent small-molecule antagonist of inhibitor of apoptosis (IAP) proteins and clinical candidate for the treatment of cancer (GDC-0152). J Med Chem 55:4101\u20134113. https:\/\/doi.org\/10.1021\/jm300060k","journal-title":"J Med Chem"},{"key":"923_CR39","doi-asserted-by":"publisher","first-page":"e2325","DOI":"10.1038\/cddis.2016.214","volume":"7","author":"A Tchoghandjian","year":"2016","unstructured":"Tchoghandjian A, Soub\u00e9ran A, Tabouret E et al (2016) Inhibitor of apoptosis protein expression in glioblastomas and their in vitro and in vivo targeting by SMAC mimetic GDC-0152. Cell Death Dis 7:e2325. https:\/\/doi.org\/10.1038\/cddis.2016.214","journal-title":"Cell Death Dis"},{"key":"923_CR40","doi-asserted-by":"publisher","first-page":"2104","DOI":"10.1124\/dmd.113.053926","volume":"41","author":"H Wong","year":"2013","unstructured":"Wong H, Gould SE, Budha N et al (2013) Learning and confirming with preclinical studies: modeling and simulation in the discovery of GDC-0917, an inhibitor of apoptosis proteins antagonist. Drug Metab Dispos 41:2104\u20132113. https:\/\/doi.org\/10.1124\/dmd.113.053926","journal-title":"Drug Metab Dispos"},{"key":"923_CR41","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1517\/13543776.2015.1041922","volume":"25","author":"AW Hird","year":"2015","unstructured":"Hird AW, Aquila BM, Hennessy EJ, Vasbinder MM, Yang B (2015) Small molecule inhibitor of apoptosis proteins antagonists: a patent review. Expert Opin Ther Pat 25:755\u2013774. https:\/\/doi.org\/10.1517\/13543776.2015.1041922","journal-title":"Expert Opin Ther Pat"},{"key":"923_CR42","doi-asserted-by":"publisher","first-page":"3103","DOI":"10.1200\/JCO.2013.52.3993","volume":"32","author":"JR Infante","year":"2014","unstructured":"Infante JR, Dees EC, Olszanski AJ et al (2014) Phase I dose-escalation study of LCL161, an oral inhibitor of apoptosis proteins inhibitor, in patients with advanced solid tumors. J Clin Oncol 32:3103\u20133110. https:\/\/doi.org\/10.1200\/JCO.2013.52.3993","journal-title":"J Clin Oncol"},{"key":"923_CR43","doi-asserted-by":"publisher","first-page":"1723","DOI":"10.1021\/jm801450c","volume":"52","author":"F Cohen","year":"2009","unstructured":"Cohen F, Alicke B, Elliott LO et al (2009) Orally bioavailable antagonists of inhibitor of apoptosis proteins based on an azabicyclooctane scaffold. J Med Chem 52:1723\u20131730. https:\/\/doi.org\/10.1021\/jm801450c","journal-title":"J Med Chem"},{"key":"923_CR44","doi-asserted-by":"publisher","first-page":"8223","DOI":"10.1021\/bi034227t","volume":"42","author":"MC Franklin","year":"2003","unstructured":"Franklin MC, Kadkhodayan S, Ackerly H et al (2003) Structure and function analysis of peptide antagonists of melanoma inhibitor of apoptosis (ML-IAP). Biochemistry 42:8223\u20138231. https:\/\/doi.org\/10.1021\/bi034227t","journal-title":"Biochemistry"},{"key":"923_CR45","doi-asserted-by":"publisher","unstructured":"Deshayes K, Murray J, Vucic D (2012) The development of small-molecule IAP antagonists for the treatment of cancer. In: Wendt M (ed) Protein-protein interactions. Topics in medicinal chemistry. Springer, Berlin. https:\/\/doi.org\/10.1007\/978-3-642-28965-1_3","DOI":"10.1007\/978-3-642-28965-1_3"},{"key":"923_CR46","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.fjps.2015.05.005","volume":"1","author":"NMY Elsayed","year":"2015","unstructured":"Elsayed NMY, Abou El Ella DA, Serya RAT, Abouzid KAM (2015) Targeting apoptotic machinery as approach for anticancer therapy: Smac mimetics as anticancer agents. Future J Pharm Sci 1:16\u201321. https:\/\/doi.org\/10.1016\/j.fjps.2015.05.005","journal-title":"Future J Pharm Sci"},{"key":"923_CR47","doi-asserted-by":"publisher","first-page":"1331","DOI":"10.1021\/ar8000603","volume":"41","author":"J Chatterjee","year":"2008","unstructured":"Chatterjee J, Gilon C, Hoffman A, Kessler H (2008) N-methylation of peptides: a new perspective in medicinal chemistry. Acc Chem Res 41:1331\u20131342. https:\/\/doi.org\/10.1021\/ar8000603","journal-title":"Acc Chem Res"},{"key":"923_CR48","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1034\/j.1399-3011.2002.21018.x","volume":"60","author":"D Li","year":"2002","unstructured":"Li D, Elbert DL (2002) The kinetics of the removal of the N-methyltrityl (Mtt) group during the synthesis of branched peptides. J Pept Res 60:300\u2013303","journal-title":"J Pept Res"},{"key":"923_CR49","doi-asserted-by":"crossref","unstructured":"Oleksyszyn J (1981) Synthesis of N-Acylated 1-Aminoalkyl-Diphenylphosphine oxides by amidoalkylation of diphenylchlorophosphine. Synthesis-Stuttgart 444\u2013445","DOI":"10.1055\/s-1981-29475"},{"key":"923_CR50","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1021\/cb600276q","volume":"1","author":"K Zobel","year":"2006","unstructured":"Zobel K, Wang L, Varfolomeev E et al (2006) Design, synthesis, and biological activity of a potent Smac mimetic that sensitizes cancer cells to apoptosis by antagonizing IAPs. ACS Chem Biol 1:525\u2013533. https:\/\/doi.org\/10.1021\/cb600276q","journal-title":"ACS Chem Biol"},{"key":"923_CR51","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1098\/rsta.2009.0210","volume":"368","author":"NT Ross","year":"2010","unstructured":"Ross NT, Katt WP, Hamilton AD (2010) Synthetic mimetics of protein secondary structure domains. Phil Trans A Math Phys Eng Sci 368:989\u20131008. https:\/\/doi.org\/10.1098\/rsta.2009.0210","journal-title":"Phil Trans A Math Phys Eng Sci"},{"key":"923_CR52","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1158\/1535-7163.MCT-13-0153","volume":"13","author":"D Finlay","year":"2014","unstructured":"Finlay D, Vamos M, Gonz\u00e1lez-L\u00f3pez M et al (2014) Small-molecule IAP antagonists sensitize cancer cells to TRAIL-induced apoptosis: roles of XIAP and cIAPs. Mol Cancer Ther 13:5\u201315. https:\/\/doi.org\/10.1158\/1535-7163.MCT-13-0153","journal-title":"Mol Cancer Ther"},{"key":"923_CR53","doi-asserted-by":"publisher","first-page":"935","DOI":"10.1007\/s10822-010-9385-x","volume":"24","author":"T ten Brink","year":"2010","unstructured":"ten Brink T, Exner TE (2010) pK(a) based protonation states and microspecies for protein-ligand docking. J Comput Aided Mol Des 24:935\u2013942. https:\/\/doi.org\/10.1007\/s10822-010-9385-x","journal-title":"J Comput Aided Mol Des"},{"key":"923_CR54","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1007\/s11721-007-0006-9","volume":"1","author":"O Korb","year":"2007","unstructured":"Korb O, St\u00fctzle T, Exner TE (2007) An ant colony optimization approach to flexible protein\u2013ligand docking. Swarm Intell 1:115\u2013134. https:\/\/doi.org\/10.1007\/s11721-007-0006-9","journal-title":"Swarm Intell"},{"key":"923_CR55","unstructured":"Soroka M, Iwa\u0144czyk D (2001) Method of obtaining triallylmethylamines. PL 339713 (A1) Patent"},{"key":"923_CR56","doi-asserted-by":"publisher","first-page":"6541","DOI":"10.1021\/jm300599x","volume":"55","author":"L Winiarski","year":"2012","unstructured":"Winiarski L, Oleksyszyn J, Sienczyk M (2012) Human neutrophil elastase phosphonic inhibitors with improved potency of action. J Med Chem 55:6541\u20136553. https:\/\/doi.org\/10.1021\/jm300599x","journal-title":"J Med Chem"},{"key":"923_CR57","doi-asserted-by":"crossref","unstructured":"Oleksyszyn J, Subotkowska L, Mastalerz P (1979) Diphenyl 1-aminoalkanephosphonates. Synthesis 985\u2013986","DOI":"10.1055\/s-1979-28903"},{"key":"923_CR58","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1177\/108705719900400206","volume":"4","author":"JH Zhang","year":"1999","unstructured":"Zhang JH, Chung TD, Oldenburg KR (1999) A simple statistical parameter for use in evaluation and validation of high throughput screening assays. J Biomol Screen 4:67\u201373. https:\/\/doi.org\/10.1177\/108705719900400206","journal-title":"J Biomol Screen"},{"key":"923_CR59","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1016\/j.ab.2004.05.055","volume":"332","author":"Z Nikolovska-Coleska","year":"2004","unstructured":"Nikolovska-Coleska Z, Wang R, Fang X et al (2004) Development and optimization of a binding assay for the XIAP BIR3 domain using fluorescence polarization. Anal Biochem 332:261\u2013273. https:\/\/doi.org\/10.1016\/j.ab.2004.05.055","journal-title":"Anal Biochem"},{"key":"923_CR60","doi-asserted-by":"publisher","first-page":"1107","DOI":"10.1093\/jnci\/82.13.1107","volume":"82","author":"P Skehan","year":"1990","unstructured":"Skehan P, Storeng R, Scudiero D et al (1990) New colorimetric cytotoxicity assay for anticancer-drug screening. J Natl Cancer Inst 82:1107\u20131112. https:\/\/doi.org\/10.1093\/jnci\/82.13.1107","journal-title":"J Natl Cancer Inst"},{"key":"923_CR61","doi-asserted-by":"publisher","first-page":"e106186","DOI":"10.1371\/journal.pone.0106186","volume":"9","author":"D Nevozhay","year":"2014","unstructured":"Nevozhay D (2014) Cheburator software for automatically calculating drug inhibitory concentration from in vitro screening assays. PLoS One 9:e106186. https:\/\/doi.org\/10.1371\/journal.pone.0106186","journal-title":"PLoS One"},{"key":"923_CR62","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.ejmech.2017.03.028","volume":"132","author":"M Psurski","year":"2017","unstructured":"Psurski M, Janczewski \u0141, \u015awitalska M et al (2017) Novel phosphonate analogs of sulforaphane: Synthesis, in vitro and in vivo anticancer activity. Eur J Med Chem 132:63\u201380. https:\/\/doi.org\/10.1016\/j.ejmech.2017.03.028","journal-title":"Eur J Med Chem"}],"container-title":["Investigational New Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10637-020-00923-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10637-020-00923-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10637-020-00923-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,10]],"date-time":"2023-03-10T23:47:59Z","timestamp":1678492079000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10637-020-00923-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,8]]},"references-count":62,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2020,10]]}},"alternative-id":["923"],"URL":"https:\/\/doi.org\/10.1007\/s10637-020-00923-4","relation":{},"ISSN":["0167-6997","1573-0646"],"issn-type":[{"value":"0167-6997","type":"print"},{"value":"1573-0646","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,8]]},"assertion":[{"value":"29 January 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 March 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 April 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"All authors declare no conflicts of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"This article does not contain any studies with human participants or animals performed by any of the authors.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"For this type of study, formal consent is not required.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}