دورية أكاديمية
A selective BCL-X L PROTAC degrader achieves safe and potent antitumor activity.
العنوان: | A selective BCL-X |
---|---|
المؤلفون: | Khan S; Department of Pharmacodynamics, University of Florida, Gainesville, FL, USA., Zhang X; Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, FL, USA., Lv D; Department of Pharmacodynamics, University of Florida, Gainesville, FL, USA., Zhang Q; Department of Leukemia, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA., He Y; Department of Pharmacodynamics, University of Florida, Gainesville, FL, USA., Zhang P; Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, FL, USA., Liu X; Department of Pharmacodynamics, University of Florida, Gainesville, FL, USA., Thummuri D; Department of Pharmacodynamics, University of Florida, Gainesville, FL, USA., Yuan Y; Department of Pharmacodynamics, University of Florida, Gainesville, FL, USA., Wiegand JS; Department of Pharmacodynamics, University of Florida, Gainesville, FL, USA., Pei J; Department of Pharmacodynamics, University of Florida, Gainesville, FL, USA., Zhang W; Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL, USA., Sharma A; Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL, USA., McCurdy CR; Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, FL, USA., Kuruvilla VM; Department of Leukemia, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA., Baran N; Department of Leukemia, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA., Ferrando AA; Department of Pediatrics, Pathology, Cell Biology and Systems of Biology and Institute for Cancer Genetics, Columbia University, New York, NY, USA., Kim YM; Department of Pediatrics, Children's Hospital Los Angeles, Los Angeles, CA, USA., Rogojina A; Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA., Houghton PJ; Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA., Huang G; Department of Medicine, the Long School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA., Hromas R; Department of Medicine, the Long School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA., Konopleva M; Department of Leukemia, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA., Zheng G; Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, FL, USA. zhengg@cop.ufl.edu., Zhou D; Department of Pharmacodynamics, University of Florida, Gainesville, FL, USA. zhoudaohong@cop.ufl.edu. |
المصدر: | Nature medicine [Nat Med] 2019 Dec; Vol. 25 (12), pp. 1938-1947. Date of Electronic Publication: 2019 Dec 02. |
نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. |
اللغة: | English |
بيانات الدورية: | Publisher: Nature Publishing Company Country of Publication: United States NLM ID: 9502015 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1546-170X (Electronic) Linking ISSN: 10788956 NLM ISO Abbreviation: Nat Med Subsets: MEDLINE |
أسماء مطبوعة: | Publication: New York Ny : Nature Publishing Company Original Publication: New York, NY : Nature Pub. Co., [1995- |
مواضيع طبية MeSH: | Aniline Compounds/*pharmacology , Sulfonamides/*pharmacology , Thrombocytopenia/*drug therapy , Von Hippel-Lindau Tumor Suppressor Protein/*genetics , bcl-X Protein/*genetics, Aniline Compounds/chemistry ; Animals ; Antineoplastic Agents/pharmacology ; Blood Platelets/drug effects ; Blood Platelets/metabolism ; Gene Expression Regulation, Neoplastic/drug effects ; Heterografts ; Humans ; Mice ; Proteolysis ; Sulfonamides/chemistry ; Thrombocytopenia/genetics ; Thrombocytopenia/pathology ; bcl-X Protein/antagonists & inhibitors |
مستخلص: | B-cell lymphoma extra large (BCL-X |
References: | Hanahan, D. & Weinberg, R. A. Hallmarks of cancer: the next generation. Cell. 144, 646–674 (2011). (PMID: 2137623010.1016/j.cell.2011.02.01321376230) Singh, R., Letai, A. & Sarosiek, K. Regulation of apoptosis in health and disease: the balancing act of BCL-2 family proteins. Nat. Rev. Mol. Cell Biol. 20, 175–193 (2019). (PMID: 3065560910.1038/s41580-018-0089-830655609) Igney, F. H. & Krammer, P. H. Death and anti-death: tumour resistance to apoptosis. Nat. Rev. Cancer 2, 277–288 (2002). (PMID: 1200198910.1038/nrc77612001989) Ashkenazi, A., Fairbrother, W. J., Leverson, J. D. & Souers, A. J. From basic apoptosis discoveries to advanced selective BCL-2 family inhibitors. Nat. Rev. Drug Discov. 16, 273–284 (2017). (PMID: 2820999210.1038/nrd.2016.25328209992) Adams, J. M. & Cory, S. The Bcl-2 apoptotic switch in cancer development and therapy. Oncogene 26, 1324–1337 (2007). (PMID: 17322918293098110.1038/sj.onc.1210220) Reed, J. C. Bcl-2-family proteins and hematologic malignancies: history and future prospects. Blood 111, 3322–3330 (2008). (PMID: 18362212227500210.1182/blood-2007-09-078162) Thomas, S. et al. Targeting the Bcl-2 family for cancer therapy. Expert Opin. Ther. Targets 17, 61–75 (2013). (PMID: 2317384210.1517/14728222.2013.73300123173842) Opfermann, J. T. Attacking cancer’s Achilles heel: antagonism of antiapoptotic BCL-2 family members. FEBS J. 283, 2661–2675 (2016). (PMID: 10.1111/febs.13472) Garner, T. P., Lopez, A., Reyna, D. E., Spitz, A. Z. & Gavathiotis, E. Progress in targeting the BCL-2 family of proteins. Curr. Opin. Chem. Biol. 39, 133–142 (2017). (PMID: 28735187566754510.1016/j.cbpa.2017.06.014) Delbridge, A. R., Grabow, S., Strasser, A. & Vaux, D. L. Thirty years of BCL-2: translating cell death discoveries into novel cancer therapies. Nat. Rev. Cancer 16, 99–109 (2016). (PMID: 2682257710.1038/nrc.2015.1726822577) Delbridge, A. R. & Strasser, A. The BCL-2 protein family, BH3-mimetics and cancer therapy. Cell Death Differ. 22, 1071–1080 (2015). (PMID: 25952548457287210.1038/cdd.2015.50) Oltersdorf, T. et al. An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Nature 435, 677–681 (2005). (PMID: 10.1038/nature035791590220815902208) Tse, C. et al. ABT-263: a potent and orally bioavailable Bcl-2 family inhibitor. Cancer Res. 68, 3421–3428 (2008). (PMID: 184511701845117010.1158/0008-5472.CAN-07-5836) Souers, A. J. et al. ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. Nat. Med. 19, 202–208 (2013). (PMID: 232916302329163010.1038/nm.3048) Tao, Z. F. et al. Discovery of a potent and selective BCL-XL inhibitor with in vivo activity. ACS Med. Chem. Lett. 5, 1088–1093 (2014). (PMID: 25313317419063910.1021/ml5001867) Kotschy, A. et al. The MCL1 inhibitor S63845 is tolerable and effective in diverse cancer models. Nature 538, 477–482 (2016). (PMID: 277601112776011110.1038/nature19830) Deeks, E. D. Venetoclax: first global approval. Drugs 76, 979–987 (2016). (PMID: 2726033510.1007/s40265-016-0596-x27260335) Roberts, A. W. et al. Targeting BCL2 with venetoclax in relapsed chronic lymphocytic leukemia. N. Engl. J. Med. 374, 311–322 (2016). (PMID: 266393482663934810.1056/NEJMoa1513257) Mason, K. D. et al. Programmed anuclear cell death delimits platelet life span. Cell. 128, 1173–1186 (2007). (PMID: 1738288510.1016/j.cell.2007.01.03717382885) Schoenwaelder, S. M. et al. Bcl-xL-inhibitory BH3 mimetics can induce a transient thrombocytopathy that undermines the hemostatic function of platelets. Blood 118, 1663–1674 (2011). (PMID: 2167334410.1182/blood-2011-04-34784921673344) Kaefer, A. et al. Mechanism-based pharmacokinetic/pharmacodynamic meta-analysis of navitoclax (ABT-263) induced thrombocytopenia. Cancer Chemother. Pharmacol. 74, 593–602 (2014). (PMID: 2505338910.1007/s00280-014-2530-925053389) Itchaki, G. & Brown, J. R. The potential of venetoclax (ABT-199) in chronic lymphocytic leukemia. Adv. Hematol. 7, 270–287 (2016). (PMID: 10.1177/2040620716655350) Perini, G. F., Ribeiro, G. N., Neto, J. V. P., Campos, L. T. & Hamerschlak, N. BCL-2 as therapeutic target for hematological malignancies. J. Hematol. Oncol. 11, 65 (2018). (PMID: 29747654594644510.1186/s13045-018-0608-2) Leverson, J. D. et al. Exploiting selective BCL-2 family inhibitors to dissect cell survival dependencies and define improved strategies for cancer therapy. Sci. Transl. Med. 7, 279ra40 (2015). (PMID: 257877662578776610.1126/scitranslmed.aaa4642) Amundson, S. A. et al. An informatics approach identifying markers of chemosensitivity in human cancer cell lines. Cancer Res. 60, 6101–6110 (2000). (PMID: 1108553411085534) Vogler, M. Targeting BCL2-proteins for the treatment of solid tumours. J. Adv Med. 2014, 943648 (2014). Lai, A. C. & Crews, C. M. Induced protein degradation: an emerging drug discovery paradigm. Nat. Rev. Drug Discov. 16, 101–114 (2017). (PMID: 2788528310.1038/nrd.2016.21127885283) Runcie, A. C., Chan, K. H., Zengerle, M. & Ciulli, A. Chemical genetics approaches for selective intervention in epigenetics. Curr. Opin. Chem. Biol. 33, 186–194 (2016). (PMID: 27423045506155810.1016/j.cbpa.2016.06.031) Deshaies, R. J. Protein degradation: prime time for PROTACs. Nat. Chem. Biol. 11, 634–635 (2015). (PMID: 2628466810.1038/nchembio.188726284668) Churcher, I. Protac-induced protein degradation in drug discovery: breaking the rules or just making new ones? J. Med. Chem. 61, 444–452 (2018). (PMID: 2914473910.1021/acs.jmedchem.7b0127229144739) Ohoka, N., Shibata, N., Hattori, T. & Naito, M. Protein knockdown technology: application of ubiquitin ligase to cancer therapy. Curr. Cancer Drug Targets 16, 136–146 (2016). (PMID: 2656011810.2174/156800961666615111212250226560118) Lu, J. et al. Hijacking the E3 ubiquitin ligase cereblon to efficiently target BRD4. Chem. Biol. 22, 755–763 (2015). (PMID: 26051217447545210.1016/j.chembiol.2015.05.009) Bondeson, D. P. et al. Catalytic in vivo protein knockdown by small-molecule PROTACs. Nat. Chem. Biol. 11, 611–617 (2015). (PMID: 26075522462985210.1038/nchembio.1858) Lai, A. C. et al. Modular PROTAC design for the degradation of oncogenic BCR-ABL. Angew. Chem. Int. Ed. 55, 807–810 (2016). (PMID: 10.1002/anie.201507634) Raina, K. et al. PROTAC-induced BET protein degradation as a therapy for castration-resistant prostate cancer. Proc. Natl Acad. Sci. USA 113, 7124–7129 (2016). (PMID: 2727405210.1073/pnas.1521738113) Saenz, D. T. et al. Novel BET protein proteolysis-targeting chimera exerts superior lethal activity than bromodomain inhibitor (BETi) against post-myeloproliferative neoplasm secondary (s) AML cells. Leukemia 31, 1951–1961 (2017). (PMID: 28042144553705510.1038/leu.2016.393) Winter, G. E. et al. Drug development. Phthalimide conjugation as a strategy for in vivo target protein degradation. Science 348, 1376–1381 (2015). (PMID: 25999370493779010.1126/science.aab1433) Huang, H. T. et al. A chemoproteomic approach to query the degradable kinome using a multi-kinase degrader. Cell Chem. Biol. 25, 88–99.e6 (2018). (PMID: 2912971710.1016/j.chembiol.2017.10.00529129717) Bray, P. F. et al. The complex transcriptional landscape of the anucleate human platelet. BMC Genomics 14, 1 (2013). (PMID: 23323973372212610.1186/1471-2164-14-1) Kissopoulou, A., Jonasson, J., Lindahl, T. L. & Osman, A. Next generation sequencing analysis of human platelet PolyA + mRNAs and rRNA-depleted total RNA. PLoS One 8, e81809 (2013). (PMID: 24349131385954510.1371/journal.pone.0081809) Cerami, E. et al. The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov. 2, 401–404 (2012). (PMID: 2258887710.1158/2159-8290.CD-12-009522588877) Gao, J. et al. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci. Signal. 6, pl1 (2013). (PMID: 23550210416030710.1126/scisignal.2004088) Vogler, M. et al. BCL2/BCL-X(L) inhibition induces apoptosis, disrupts cellular calcium homeostasis, and prevents platelet activation. Blood. 117, 7145–7154 (2011). (PMID: 2156204710.1182/blood-2011-03-34481221562047) Gadd, M. S. et al. Structural basis of PROTAC cooperative recognition for selective protein degradation. Nat. Chem. Biol. 13, 514–521 (2017). (PMID: 28288108539235610.1038/nchembio.2329) Nowak, R. P. et al. Plasticity in binding confers selectivity in ligand-induced protein degradation. Nat. Chem. Biol. 14, 706–714 (2018). (PMID: 29892083620224610.1038/s41589-018-0055-y) Riching, K. M. et al. Quantitative live-cell kinetic degradation and mechanistic profiling of PROTAC mode of action. ACS Chem. Biol. 13, 2758–2770 (2018). (PMID: 3013796210.1021/acschembio.8b0069230137962) Farmer, T., O’Neill, K. L., Naslavsky, N., Luo, X. & Caplan, S. Retromer facilitates the localization of Bcl-xL to the mitochondrial outer membrane. Mol. Biol. Cell 30, 1138–1146 (2019). (PMID: 30840537672452410.1091/mbc.E19-01-0044) Smith, B. E. et al. Differential PROTAC substrate specificity dictated by orientation of recruited E3 ligase. Nat. Commun. 10, 131 (2019). (PMID: 30631068632858710.1038/s41467-018-08027-7) Morowski, M. et al. Only severe thrombocytopenia results in bleeding and defective thrombus formation in mice. Blood 121, 4938–4947 (2013). (PMID: 2358488010.1182/blood-2012-10-46145923584880) Rinder, H. M. et al. Correlation of thrombosis with increased platelet turnover in thrombocytosis. Blood 91, 1288–1294 (1998). (PMID: 945475910.1182/blood.V91.4.12889454759) Koch, R. et al. Biomarker-driven strategy for MCL1 inhibition in T-cell lymphomas. Blood 133, 566–575 (2018). (PMID: 3049806410.1182/blood-2018-07-86552730498064) Berger, S. et al. Computationally designed high specificity inhibitors delineate the roles of BCL2 family proteins in cancer. eLife. 5, e20352 (2016). (PMID: 27805565512764110.7554/eLife.20352) Hikita, H. et al. Mcl-1 and Bcl-xL cooperatively maintain integrity of hepatocytes in developing and adult murine liver. Hepatology 50, 1217–1226. (PMID: 19676108356085210.1002/hep.23126) Chen, J. et al. The Bcl-2/Bcl-X(L)/Bcl-w inhibitor, navitoclax, enhances the activity of chemotherapeutic agents in vitro and in vivo. Mol. Cancer Ther. 10, 2340–2349 (2011). (PMID: 2191485310.1158/1535-7163.MCT-11-041521914853) Ackler, S. et al. The Bcl-2 inhibitor ABT-263 enhances the response of multiple chemotherapeutic regimens in hematologic tumors in vivo. Cancer Chemother. Pharmacol. 66, 869–880 (2010). (PMID: 2009906410.1007/s00280-009-1232-120099064) Pompili, L., Porru, M., Caruso, C., Biroccio, A. & Leonetti, C. Patient-derived xenografts: a relevant preclinical model for drug development. J. Exp. Clin. Cancer Res. 35, 189 (2016). (PMID: 27919280513901810.1186/s13046-016-0462-4) Zengerle, M., Chan, K. H. & Ciulli, A. Selective small molecule induced degradation of the BET bromodomain protein BRD4. ACS Chem. Biol. 10, 1770–1777 (2015). (PMID: 26035625454825610.1021/acschembio.5b00216) Bondeson, D. P. et al. Lessons in PROTAC design from selective degradation with a promiscuous warhead. Cell Chem Biol. 25, 78–87.e5 (2018). (PMID: 2912971810.1016/j.chembiol.2017.09.01029129718) Lv, D.-W., Zhang, K. & Li, R. Interferon regulatory factor 8 regulates aspase-1 expression to facilitate Epstein–Barr virus reactivation in response to B cell receptor stimulation and chemical induction. PLoS Pathog. 14, e1006868 (2018). (PMID: 29357389579419210.1371/journal.ppat.1006868) Wiśniewski, J. R. et al. Universal sample preparation method for proteome analysis. Nat. Methods 6, 359–362 (2009). (PMID: 10.1038/nmeth.1322) Nesvizhskii, A. I., Keller, A., Kolker, E. & Aebersold, R. A statistical model for identifying proteins by tandem mass spectrometry. Anal. Chem. 75, 4646–4658 (2003). (PMID: 1463207610.1021/ac034126114632076) Tyanova, S. et al. The Perseus computational platform for comprehensive analysis of (prote) omics data. Nat. Methods 13, 731–740 (2016). (PMID: 2734871210.1038/nmeth.390127348712) Vizcaíno, J. A. et al. The PRoteomics IDEntifications (PRIDE) database and associated tools: status in 2013. Nucleic Acids Res. 41, D1063–D1069 (2013). (PMID: 2320388210.1093/nar/gks126223203882) US Food and Drug Administration. Bioanalytical Method Validation, Guidance for Industry (US Department of Health and Human Services Food and Drug Administration, 2018). |
معلومات مُعتمدة: | R35 CA210065 United States CA NCI NIH HHS; R01 GM109645 United States GM NIGMS NIH HHS; R01 CA211963 United States CA NCI NIH HHS; R01 CA219836 United States CA NCI NIH HHS; R01 CA200673 United States CA NCI NIH HHS; R21 CA223371 United States CA NCI NIH HHS; R01 CA203834 United States CA NCI NIH HHS; R01 CA205224 United States CA NCI NIH HHS; R01 CA242003 United States CA NCI NIH HHS |
المشرفين على المادة: | 0 (Aniline Compounds) 0 (Antineoplastic Agents) 0 (BCL2L1 protein, human) 0 (Sulfonamides) 0 (bcl-X Protein) EC 2.3.2.27 (Von Hippel-Lindau Tumor Suppressor Protein) EC 6.3.2.- (VHL protein, human) XKJ5VVK2WD (navitoclax) |
تواريخ الأحداث: | Date Created: 20191204 Date Completed: 20200127 Latest Revision: 20220420 |
رمز التحديث: | 20240628 |
مُعرف محوري في PubMed: | PMC6898785 |
DOI: | 10.1038/s41591-019-0668-z |
PMID: | 31792461 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1546-170X |
---|---|
DOI: | 10.1038/s41591-019-0668-z |