Login Register Cart 0
Generic placeholder image

Current Topics in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Next-generation Bruton’s Tyrosine Kinase (BTK) Inhibitors Potentially Targeting BTK C481S Mutation- Recent Developments and Perspectives

Author(s): Debasis Das*, Jingbing Wang and Jian Hong

Volume 22, Issue 20, 2022

Published on: 20 August, 2022

Page: [1674 - 1691] Pages: 18

DOI: 10.2174/1568026622666220801101706

Price: $65

Abstract

Bruton’s tyrosine kinase (BTK) plays a vital role in B-cell antigen receptor (BCR) signalling transduction pathway. Controlling BCR signalling by BTK inhibitors is a promising therapeutic approach for the treatment of inflammatory and autoimmune diseases. Since the approval of ibrutinib for the treatment of different haematological cancers in 2013, great efforts have been made to explore new BTK inhibitors. Despite the remarkable potency and efficacy of first and second generation irreversible BTK inhibitors against various lymphomas and leukaemia, there are also some clinical limitations, such as off-target toxicity and primary/acquired drug resistance. Acquired drug resistance due to the C481S mutation in BTK is the major challenging problem of irreversible inhibitors. After, the BTK C481S mutation, the irreversible covalent inhibitors cannot form covalent bond with BTK and drop activities. Hence, there is an urgent need to develop novel BTK inhibitors to overcome the mutation problem. In recent years, a few reversible BTK inhibitors have been developed and are under clinical evaluation stages. In addition, a few reversible BTK-PROTACs have been explored and under developments. A number of reversible non-covalent BTK inhibitors, including MK1026/ ARQ531, LOXO305, fenebrutinib are at different stages of clinical trials for autoimmune diseases. In this review, we summarized the discovery and development of nextgeneration BTK inhibitors, especially targeting BTK C481S mutation and their applications for the treatment of lymphomas and autoimmune diseases.

Keywords: Bruton’s tyrosine kinase, BCR signalling, Irreversible inhibitor, Reversible inhibitor, PROTAC, Xenografts, Anticancer.

« Previous Next »
Graphical Abstract

[1]
Davis, R.E.; Ngo, V.N.; Lenz, G.; Tolar, P.; Young, R.M.; Romesser, P.B.; Kohlhammer, H.; Lamy, L.; Zhao, H.; Yang, Y.; Xu, W.; Shaffer, A.L.; Wright, G.; Xiao, W.; Powell, J.; Jiang, J.K.; Thomas, C.J.; Rosenwald, A.; Ott, G.; Muller-Hermelink, H.K.; Gascoyne, R.D.; Connors, J.M.; Johnson, N.A.; Rimsza, L.M.; Campo, E.; Jaffe, E.S.; Wilson, W.H.; Delabie, J.; Smeland, E.B.; Fisher, R.I.; Braziel, R.M.; Tubbs, R.R.; Cook, J.R.; Weisenburger, D.D.; Chan, W.C.; Pierce, S.K.; Staudt, L.M. Chronic active B-cell-receptor signalling in diffuse large B-cell lymphoma. Nature, 2010, 463(7277), 88-92.
[http://dx.doi.org/10.1038/nature08638] [PMID: 20054396]
[2]
Kwak, K.; Akkaya, M.; Pierce, S.K. B cell signaling in context. Nat. Immunol., 2019, 20(8), 963-969.
[http://dx.doi.org/10.1038/s41590-019-0427-9] [PMID: 31285625]
[3]
Burger, J.A.; Wiestner, A.; Targeting, B. Targeting B cell receptor signalling in cancer: Preclinical and clinical advances. Nat. Rev. Cancer, 2018, 18(3), 148-167.
[http://dx.doi.org/10.1038/nrc.2017.121] [PMID: 29348577]
[4]
Hendriks, R.W.; Yuvaraj, S.; Kil, L.P. Targeting Bruton’s tyrosine kinase in B cell malignancies. Nat. Rev. Cancer, 2014, 14(4), 219-232.
[http://dx.doi.org/10.1038/nrc3702] [PMID: 24658273]
[5]
Weber, A.N.R.; Bittner, Z.; Liu, X.; Dang, T-M.; Radsak, M.P.; Brunner, C. Bruton’s tyrosine kinase: An emerging key player in innate immunity. Front. Immunol., 2017, 8, 1454.
[http://dx.doi.org/10.3389/fimmu.2017.01454] [PMID: 29167667]
[6]
Liang, C.; Tian, D.; Ren, X.; Ding, S.; Jia, M.; Xin, M.; Thareja, S. The development of Bruton’s tyrosine kinase (BTK) inhibitors from 2012 to 2017: A mini-review. Eur. J. Med. Chem., 2018, 151, 315-326.
[http://dx.doi.org/10.1016/j.ejmech.2018.03.062] [PMID: 29631132]
[7]
Seiler, T.; Dreyling, M. Bruton’s tyrosine kinase inhibitors in B-cell lymphoma: Current experience and future perspectives. Expert Opin. Investig. Drugs, 2017, 26(8), 909-915.
[http://dx.doi.org/10.1080/13543784.2017.1349097] [PMID: 28661188]
[8]
Davids, M.S.; Brown, J.R. Ibrutinib: A first in class covalent inhibitor of Bruton’s tyrosine kinase. Future Oncol., 2014, 10(6), 957-967.
[http://dx.doi.org/10.2217/fon.14.51] [PMID: 24941982]
[9]
Wang, M.L.; Rule, S.; Martin, P.; Goy, A.; Auer, R.; Kahl, B.S.; Jurczak, W.; Advani, R.H.; Romaguera, J.E.; Williams, M.E.; Barrientos, J.C.; Chmielowska, E.; Radford, J.; Stilgenbauer, S.; Dreyling, M.; Jedrzejczak, W.W.; Johnson, P.; Spurgeon, S.E.; Li, L.; Zhang, L.; Newberry, K.; Ou, Z.; Cheng, N.; Fang, B.; McGreivy, J.; Clow, F.; Buggy, J.J.; Chang, B.Y.; Beaupre, D.M.; Kunkel, L.A.; Blum, K.A. Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma. N. Engl. J. Med., 2013, 369(6), 507-516.
[http://dx.doi.org/10.1056/NEJMoa1306220] [PMID: 23782157]
[10]
Guha, M. Imbruvica--next big drug in B-cell cancer--approved by FDA. Nat. Biotechnol., 2014, 32(2), 113-115.
[http://dx.doi.org/10.1038/nbt0214-113] [PMID: 24509736]
[11]
Treon, S.P.; Tripsas, C.K.; Meid, K.; Warren, D.; Varma, G.; Green, R.; Argyropoulos, K.V.; Yang, G.; Cao, Y.; Xu, L.; Patterson, C.J.; Rodig, S.; Zehnder, J.L.; Aster, J.C.; Harris, N.L.; Kanan, S.; Ghobrial, I.; Castillo, J.J.; Laubach, J.P.; Hunter, Z.R.; Salman, Z.; Li, J.; Cheng, M.; Clow, F.; Graef, T.; Palomba, M.L.; Advani, R.H. Ibrutinib in previously treated Waldenström’s macroglobulinemia. N. Engl. J. Med., 2015, 372(15), 1430-1440.
[http://dx.doi.org/10.1056/NEJMoa1501548] [PMID: 25853747]
[12]
Rawstron, A.C.; Hillmen, P.; Maycock, S.; Webster, N.; Brock, K.; Boucher, R.H.; Yates, F.; Jarvis, R.; Dalal, S.; de Tute, R.M.; Moss, P.; Macdonald, D.; Patten, P.; Fegan, C.; Pettitt, A.; Fox, C.P.; Bloor, A.; Sheehy, O.; Hillmen, P. Ibrutinib and Obinutuzumab in CLL: MRD responses sustained for several years with deepest MRD depletion in patients with 1 year prior Ibrutinib exposure. Blood, 2020, 136(Suppl. 1), 27-28.
[http://dx.doi.org/10.1182/blood-2020-136990]
[13]
Barreca, M.; Spanò, V.; Raimondi, M.V.; Bivacqua, R.; Giuffrida, S.; Montalbano, A.; Cavalli, A.; Bertoni, F.; Barraja, P. GPCR inhibition in treating lymphoma. ACS Med. Chem. Lett., 2022, 13(3), 358-364.
[http://dx.doi.org/10.1021/acsmedchemlett.1c00600]
[14]
Arribas, A.; Napoli, S.; Cascione, L.; Gaudio, E.; Bordone-Pittau, R.; Barreca, M.; Sartori, G.; Chiara, T.; Spriano, F.; Rinaldi, A.; Stathis, A.; Stussi, G.; Rossi, D.; Emanuele, Z.; Bertoni, F. Secondary resistance to the PI3K inhibitor Copanlisib in marginal zone lymphoma. Eur. J. Cancer, 2020, 138, S40.
[http://dx.doi.org/10.1016/S0959-8049(20)31181-3]
[15]
Johnson, A.R.; Kohli, P.B.; Katewa, A.; Gogol, E.; Belmont, L.D.; Choy, R.; Penuel, E.; Burton, L.; Eigenbrot, C.; Yu, C.; Ortwine, D.F.; Bowman, K.; Franke, Y.; Tam, C.; Estevez, A.; Mortara, K.; Wu, J.; Li, H.; Lin, M.; Bergeron, P.; Crawford, J.J.; Young, W.B. Battling Btk mutants with noncovalent inhibitors that overcome cys481 and thr474 mutations. ACS Chem. Biol., 2016, 11(10), 2897-2907.
[http://dx.doi.org/10.1021/acschembio.6b00480] [PMID: 27571029]
[16]
Cheng, S.; Guo, A.; Lu, P.; Ma, J.; Coleman, M.; Wang, Y.L. Functional characterization of BTK(C481S) mutation that confers ibrutinib resistance: Exploration of alternative kinase inhibitors. Leukemia, 2015, 29(4), 895-900.
[http://dx.doi.org/10.1038/leu.2014.263] [PMID: 25189416]
[17]
Maddocks, K.J.; Ruppert, A.S.; Lozanski, G.; Heerema, N.A.; Zhao, W.; Abruzzo, L.; Lozanski, A.; Davis, M.; Gordon, A.; Smith, L.L.; Mantel, R.; Jones, J.A.; Flynn, J.M.; Jaglowski, S.M.; Andritsos, L.A.; Awan, F.; Blum, K.A.; Grever, M.R.; Johnson, A.J.; Byrd, J.C.; Woyach, J.A. Etiology of ibrutinib therapy discontinuation and outcomes in patients with chronic lymphocytic leukemia. JAMA Oncol., 2015, 1(1), 80-87.
[http://dx.doi.org/10.1001/jamaoncol.2014.218] [PMID: 26182309]
[18]
Woyach, J.A.; Ruppert, A.S.; Guinn, D.; Lehman, A.; Blachly, J.S.; Lozanski, A.; Heerema, N.A.; Zhao, W.; Coleman, J.; Jones, D.; Abruzzo, L.; Gordon, A.; Mantel, R.; Smith, L.L.; McWhorter, S.; Davis, M.; Doong, T-J.; Ny, F.; Lucas, M.; Chase, W.; Jones, J.A.; Flynn, J.M.; Maddocks, K.; Rogers, K.; Jaglowski, S.; Andritsos, L.A.; Awan, F.T.; Blum, K.A.; Grever, M.R.; Lozanski, G.; Johnson, A.J.; Byrd, J.C. BTKC481S-mediated resistance to ibrutinib in chronic lymphocytic leukemia. J. Clin. Oncol., 2017, 35(13), 1437-1443.
[http://dx.doi.org/10.1200/JCO.2016.70.2282] [PMID: 28418267]
[19]
Pal Singh, S.; Dammeijer, F.; Hendriks, R.W. Role of Bruton’s tyrosine kinase in B cells and malignancies. Mol. Cancer, 2018, 17(1), 57.
[http://dx.doi.org/10.1186/s12943-018-0779-z] [PMID: 29455639]
[20]
Zhang, Z.; Zhang, D.; Liu, Y.; Yang, D.; Ran, F.; Wang, M.L.; Zhao, G. Targeting Bruton’s tyrosine kinase for the treatment of B cell associated malignancies and autoimmune diseases: Preclinical and clinical developments of small molecule inhibitors. Arch. Pharm. (Weinheim), 2018, 351(7), e1700369.
[http://dx.doi.org/10.1002/ardp.201700369] [PMID: 29741794]
[21]
Buggy, J.J.; Elias, L. Bruton tyrosine kinase (BTK) and its role in B-cell malignancy. Int. Rev. Immunol., 2012, 31(2), 119-132.
[http://dx.doi.org/10.3109/08830185.2012.664797] [PMID: 22449073]
[22]
Wilson, W.H.; Young, R.M.; Schmitz, R.; Yang, Y.; Pittaluga, S.; Wright, G.; Lih, C-J.; Williams, P.M.; Shaffer, A.L.; Gerecitano, J.; de Vos, S.; Goy, A.; Kenkre, V.P.; Barr, P.M.; Blum, K.A.; Shustov, A.; Advani, R.; Fowler, N.H.; Vose, J.M.; Elstrom, R.L.; Habermann, T.M.; Barrientos, J.C.; McGreivy, J.; Fardis, M.; Chang, B.Y.; Clow, F.; Munneke, B.; Moussa, D.; Beaupre, D.M.; Staudt, L.M.; Targeting, B. Targeting B cell receptor signaling with ibrutinib in diffuse large B cell lymphoma. Nat. Med., 2015, 21(8), 922-926.
[http://dx.doi.org/10.1038/nm.3884] [PMID: 26193343]
[23]
Carnero Contentti, E.; Correale, J. Bruton’s tyrosine kinase inhibitors: A promising emerging treatment option for multiple sclerosis. Expert Opin. Emerg. Drugs, 2020, 25(4), 377-381.
[http://dx.doi.org/10.1080/14728214.2020.1822817] [PMID: 32910702]
[24]
Vetrie, D.; Vorechovský, I.; Sideras, P.; Holland, J.; Davies, A.; Flinter, F.; Hammarström, L.; Kinnon, C.; Levinsky, R.; Bobrow, M.; Smith, C.I.E.; Bentley, D.R. The gene involved in X-linked agammaglobulinaemia is a member of the src family of protein-tyrosine kinases. Nature, 1993, 361(6409), 226-233.
[http://dx.doi.org/10.1038/361226a0] [PMID: 8380905]
[25]
Yoon, Y. Small chemicals with inhibitory effects on PtdIns(3,4,5)] P3 binding of BtK PH domain. Bioorg. Med. Chem. Lett., 2014, 24(10), 2334-2339.
[http://dx.doi.org/10.1016/j.bmcl.2014.03.068] [PMID: 24731277]
[26]
Jiang, Z.; Liang, Z.; Shen, B.; Hu, G. Computational analysis of the binding specificities of PH domains. BioMed Res. Int., 2015, 2015, 792904.
[http://dx.doi.org/10.1155/2015/792904] [PMID: 26881206]
[27]
Mohamed, A.J.; Nore, B.F.; Christensson, B.; Smith, C.I. Signalling of Bruton’s Tyrosine Kinase, Btk. Scand. J. Immunol., 1999, 49(2), 113-118.
[http://dx.doi.org/10.1046/j.1365-3083.1999.00504.x]
[28]
Liu, X-J. Xu-Liu; Pang, X.J.; -Ying Yuan, X.; Yu, G.X.; Li, Y.R.; Guan, Y.F.; Zhang, Y.B.; Song, J.; Zhang, Q.R.; Zhang, S.Y. Progress in the development of small molecular inhibitors of the Bruton’s tyrosine kinase (BTK) as a promising cancer therapy. Bioorg. Med. Chem., 2021, 47, 116358.
[http://dx.doi.org/10.1016/j.bmc.2021.116358] [PMID: 34479103]
[29]
Ismail, N.S.M.; Ali, E.M.H.; Ibrahim, D.A.; Serya, R.A.T.; Abou El Ella, D.A. Pyrazolo[3,4-d]pyrimidine based scaffold derivatives targeting kinases as anticancer agents. Future J. Pharmaceut. Sci., 2016, 2(1), 20-30.
[http://dx.doi.org/10.1016/j.fjps.2016.02.002]
[30]
FDA grants accelerated approval to acalabrutinib for mantle cell lymphoma. 2017. Available from: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-acalabrutinib-mantle-cell-lymphoma
[31]
Barf, T.; Covey, T.; Izumi, R.; van de Kar, B.; Gulrajani, M.; van Lith, B.; van Hoek, M.; de Zwart, E.; Mittag, D.; Demont, D.; Verkaik, S.; Krantz, F.; Pearson, P.G.; Ulrich, R.; Kaptein, A. Acalabrutinib (ACP-196): A covalent bruton tyrosine kinase inhibitor with a differentiated selectivity and in vivo potency profile. J. Pharmacol. Exp. Ther., 2017, 363(2), 240-252.
[http://dx.doi.org/10.1124/jpet.117.242909] [PMID: 28882879]
[32]
Hillmen, P.; Brown, J.R.; Kahl, B.S.; Ghia, P.; Robak, T.; Marimpietri, C.; Cohen, A.; Huang, J.; Tam, C.S.L. Phase 3 Zanubrutinib (BGB-3111) vs Bendamustine + Rituximab (BR) in Patients (Pts) with Treatment-Naïve (TN) Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL). J. Clin. Oncol., 2018, 36(15)(suppl.), TPS7581-TPS7581.
[http://dx.doi.org/10.1200/JCO.2018.36.15_suppl.TPS7581]
[33]
Dhillon, S. Tirabrutinib: First approval. Drugs, 2020, 80(8), 835-840.
[http://dx.doi.org/10.1007/s40265-020-01318-8] [PMID: 32382949]
[34]
Liclican, A.; Serafini, L.; Xing, W.; Czerwieniec, G.; Steiner, B.; Wang, T.; Brendza, K.M.; Lutz, J.D.; Keegan, K.S.; Ray, A.S.; Schultz, B.E.; Sakowicz, R.; Feng, J.Y. Biochemical characterization of tirabrutinib and other irreversible inhibitors of Bruton’s tyrosine kinase reveals differences in on - and off - target inhibition. Biochim. Biophys. Acta, Gen. Subj., 2020, 1864(4), 129531.
[http://dx.doi.org/10.1016/j.bbagen.2020.129531] [PMID: 31953125]
[35]
Dhillon, S. Orelabrutinib: First Approval. Drugs, 2021, 81(4), 503-507.
[http://dx.doi.org/10.1007/s40265-021-01482-5] [PMID: 33704654]
[36]
Das, D.; Hong, J. Irreversible kinase inhibitors targeting cysteine residues and their applications in cancer therapy. Mini Rev. Med. Chem., 2020, 20(17), 1732-1753.
[http://dx.doi.org/10.2174/1389557520666200513121524] [PMID: 32400331]
[37]
Potashman, M.H.; Duggan, M.E. Covalent modifiers: An orthogonal approach to drug design. J. Med. Chem., 2009, 52(5), 1231-1246.
[http://dx.doi.org/10.1021/jm8008597] [PMID: 19203292]
[38]
Pan, Z.; Scheerens, H.; Li, S-J.; Schultz, B.E.; Sprengeler, P.A.; Burrill, L.C.; Mendonca, R.V.; Sweeney, M.D.; Scott, K.C.K.; Grothaus, P.G.; Jeffery, D.A.; Spoerke, J.M.; Honigberg, L.A.; Young, P.R.; Dalrymple, S.A.; Palmer, J.T. Discovery of selective irreversible inhibitors for Bruton’s tyrosine kinase. ChemMedChem, 2007, 2(1), 58-61.
[http://dx.doi.org/10.1002/cmdc.200600221] [PMID: 17154430]
[39]
Honigberg, L.A.; Smith, A.M.; Sirisawad, M.; Verner, E.; Loury, D.; Chang, B.; Li, S.; Pan, Z.; Thamm, D.H.; Miller, R.A.; Buggy, J.J. The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in models of autoimmune disease and B-cell malignancy. Proc. Natl. Acad. Sci. USA, 2010, 107(29), 13075-13080.
[http://dx.doi.org/10.1073/pnas.1004594107] [PMID: 20615965]
[40]
Herman, S.E.M.; Gordon, A.L.; Hertlein, E.; Ramanunni, A.; Zhang, X.; Jaglowski, S.; Flynn, J.; Jones, J.; Blum, K.A.; Buggy, J.J.; Hamdy, A.; Johnson, A.J.; Byrd, J.C. Bruton tyrosine kinase represents a promising therapeutic target for treatment of chronic lymphocytic leukemia and is effectively targeted by PCI-32765. Blood, 2011, 117(23), 6287-6296.
[http://dx.doi.org/10.1182/blood-2011-01-328484] [PMID: 21422473]
[41]
Byrd, J.C.; Harrington, B.; O’Brien, S.; Jones, J.A.; Schuh, A.; Devereux, S.; Chaves, J.; Wierda, W.G.; Awan, F.T.; Brown, J.R.; Hillmen, P.; Stephens, D.M.; Ghia, P.; Barrientos, J.C.; Pagel, J.M.; Woyach, J.; Johnson, D.; Huang, J.; Wang, X.; Kaptein, A.; Lannutti, B.J.; Covey, T.; Fardis, M.; McGreivy, J.; Hamdy, A.; Rothbaum, W.; Izumi, R.; Diacovo, T.G.; Johnson, A.J.; Furman, R.R. Acalabrutinib (ACP-196) in relapsed chronic lymphocytic leukemia. N. Engl. J. Med., 2016, 374(4), 323-332.
[http://dx.doi.org/10.1056/NEJMoa1509981] [PMID: 26641137]
[42]
Golay, J.; Ubiali, G.; Introna, M. The specific Bruton tyrosine kinase inhibitor acalabrutinib (ACP-196) shows favorable in vitro activity against chronic lymphocytic leukemia B cells with CD20 antibodies. Haematologica, 2017, 102(10), e400-e403.
[http://dx.doi.org/10.3324/haematol.2017.169334] [PMID: 28642301]
[43]
Wu, J.; Zhang, M.; Liu, D. Acalabrutinib (ACP-196): A selective second-generation BTK inhibitor. J. Hematol. Oncol., 2016, 9(1), 21.
[http://dx.doi.org/10.1186/s13045-016-0250-9] [PMID: 26957112]
[44]
Guo, Y.; Liu, Y.; Hu, N.; Yu, D.; Zhou, C.; Shi, G.; Zhang, B.; Wei, M.; Liu, J.; Luo, L.; Tang, Z.; Song, H.; Guo, Y.; Liu, X.; Su, D.; Zhang, S.; Song, X.; Zhou, X.; Hong, Y.; Chen, S.; Cheng, Z.; Young, S.; Wei, Q.; Wang, H.; Wang, Q.; Lv, L.; Wang, F.; Xu, H.; Sun, H.; Xing, H.; Li, N.; Zhang, W.; Wang, Z.; Liu, G.; Sun, Z.; Zhou, D.; Li, W.; Liu, L.; Wang, L.; Wang, Z. Discovery of zanubrutinib (BGB-3111), a novel, potent, and selective covalent inhibitor of bruton’s tyrosine kinase. J. Med. Chem., 2019, 62(17), 7923-7940.
[http://dx.doi.org/10.1021/acs.jmedchem.9b00687] [PMID: 31381333]
[45]
Bender, A.T.; Gardberg, A.; Pereira, A.; Johnson, T.; Wu, Y.; Grenningloh, R.; Head, J.; Morandi, F.; Haselmayer, P.; Liu-Bujalski, L. Ability of bruton’s tyrosine kinase inhibitors to sequester Y551 and prevent phosphorylation determines potency for inhibition of Fc receptor but not b-cell receptor signaling. Mol. Pharmacol., 2017, 91(3), 208-219.
[http://dx.doi.org/10.1124/mol.116.107037] [PMID: 28062735]
[46]
Chen, J.; Kinoshita, T.; Sukbuntherng, J.; Chang, B.Y.; Elias, L. Ibrutinib inhibits ERBB receptor tyrosine kinases and HER2-amplified breast cancer cell growth. Mol. Cancer Ther., 2016, 15(12), 2835-2844.
[http://dx.doi.org/10.1158/1535-7163.MCT-15-0923] [PMID: 27678331]
[47]
Evans, E.K.; Tester, R.; Aslanian, S.; Karp, R.; Sheets, M.; Labenski, M.T.; Witowski, S.R.; Lounsbury, H.; Chaturvedi, P.; Mazdiyasni, H.; Zhu, Z.; Nacht, M.; Freed, M.I.; Petter, R.C.; Dubrovskiy, A.; Singh, J.; Westlin, W.F. Inhibition of Btk with CC-292 provides early pharmacodynamic assessment of activity in mice and humans. J. Pharmacol. Exp. Ther., 2013, 346(2), 219-228.
[http://dx.doi.org/10.1124/jpet.113.203489] [PMID: 23709115]
[48]
Brown, J.R.; Harb, W.A.; Hill, B.T.; Gabrilove, J.; Sharman, J.P.; Schreeder, M.T.; Barr, P.M.; Foran, J.M.; Miller, T.P.; Burger, J.A.; Kelly, K.R.; Mahadevan, D.; Ma, S.; Barnett, E.; Marine, J.; Nava-Parada, P.; Azaryan, A.; Mei, J.; Kipps, T.J. Phase 1 study of single agent CC-292, a highly selective bruton’s tyrosine kinase (BTK) Inhibitor, in relapsed/refractory chronic lymphocytic leukemia (CLL). Blood, 2013, 122(21), 1630-1630.
[http://dx.doi.org/10.1182/blood.V122.21.1630.1630]
[49]
Caldwell, R.D.; Qiu, H.; Askew, B.C.; Bender, A.T.; Brugger, N.; Camps, M.; Dhanabal, M.; Dutt, V.; Eichhorn, T.; Gardberg, A.S.; Goutopoulos, A.; Grenningloh, R.; Head, J.; Healey, B.; Hodous, B.L.; Huck, B.R.; Johnson, T.L.; Jones, C.; Jones, R.C.; Mochalkin, I.; Morandi, F.; Nguyen, N.; Meyring, M.; Potnick, J.R.; Santos, D.C.; Schmidt, R.; Sherer, B.; Shutes, A.; Urbahns, K.; Follis, A.V.; Wegener, A.A.; Zimmerli, S.C.; Liu-Bujalski, L. Discovery of evobrutinib: An oral, potent, and highly selective, covalent Bruton’s tyrosine kinase (BTK) inhibitor for the treatment of immunological diseases. J. Med. Chem., 2019, 62(17), 7643-7655.
[http://dx.doi.org/10.1021/acs.jmedchem.9b00794] [PMID: 31368705]
[50]
Byun, J-Y.; Koh, Y.T.; Jang, S.Y.; Witcher, J.W.; Chan, J.R.; Pustilnik, A.; Daniels, M.J.; Kim, Y.H.; Suh, K.H.; Linnik, M.D.; Lee, Y-M. Target modulation and pharmacokinetics/pharmaco dynamics translation of the BTK inhibitor poseltinib for model-informed phase II dose selection. Sci. Rep., 2021, 11(1), 18671.
[http://dx.doi.org/10.1038/s41598-021-98255-7] [PMID: 34548595]
[51]
Park, J.K.; Byun, J-Y.; Park, J.A.; Kim, Y-Y.; Lee, Y.J.; Oh, J.I.; Jang, S.Y.; Kim, Y.H.; Song, Y.W.; Son, J.; Suh, K.H.; Lee, Y-M.; Lee, E.B. HM71224, a novel Bruton’s tyrosine kinase inhibitor, suppresses B cell and monocyte activation and ameliorates arthritis in a mouse model: A potential drug for rheumatoid arthritis. Arthritis Res. Ther., 2016, 18(1), 91.
[http://dx.doi.org/10.1186/s13075-016-0988-z] [PMID: 27090981]
[52]
Ghoshdastidar, K.; Patel, H.; Bhayani, H.; Patel, A.; Thakkar, K.; Patel, D.; Sharma, M.; Singh, J.; Mohapatra, J.; Chatterjee, A.; Patel, D.; Bahekar, R.; Sharma, R.; Gupta, L.; Patel, N.; Giri, P.; Srinivas, N.R.; Jain, M.; Bandyopadhyay, D.; Patel, P.R.; Desai, R.C. ZYBT1, a potent, irreversible Bruton’s Tyrosine Kinase (BTK) inhibitor that inhibits the C481S BTK with profound efficacy against arthritis and cancer. Pharmacol. Res. Perspect., 2020, 8(4), e00565.
[http://dx.doi.org/10.1002/prp2.565] [PMID: 32790160]
[53]
Watterson, S.H.; Liu, Q.; Beaudoin Bertrand, M.; Batt, D.G.; Li, L.; Pattoli, M.A.; Skala, S.; Cheng, L.; Obermeier, M.T.; Moore, R.; Yang, Z.; Vickery, R.; Elzinga, P.A.; Discenza, L.; D’Arienzo, C.; Gillooly, K.M.; Taylor, T.L.; Pulicicchio, C.; Zhang, Y.; Heimrich, E.; McIntyre, K.W.; Ruan, Q.; Westhouse, R.A.; Catlett, I.M.; Zheng, N.; Chaudhry, C.; Dai, J.; Galella, M.A.; Tebben, A.J.; Pokross, M.; Li, J.; Zhao, R.; Smith, D.; Rampulla, R.; Allentoff, A.; Wallace, M.A.; Mathur, A.; Salter-Cid, L.; Macor, J.E.; Carter, P.H.; Fura, A.; Burke, J.R.; Tino, J.A. Discovery of Branebrutinib (BMS-986195): A strategy for identifying a highly potent and selective covalent inhibitor providing rapid in vivo inactivation of Bruton’s Tyrosine Kinase (BTK). J. Med. Chem., 2019, 62(7), 3228-3250.
[http://dx.doi.org/10.1021/acs.jmedchem.9b00167] [PMID: 30893553]
[54]
Angst, D.; Gessier, F.; Janser, P.; Vulpetti, A.; Wälchli, R.; Beerli, C.; Littlewood-Evans, A.; Dawson, J.; Nuesslein-Hildesheim, B.; Wieczorek, G.; Gutmann, S.; Scheufler, C.; Hinniger, A.; Zimmerlin, A.; Funhoff, E.G.; Pulz, R.; Cenni, B. Discovery of LOU064 (remibrutinib), a potent and highly selective covalent inhibitor of bruton’s tyrosine kinase. J. Med. Chem., 2020, 63(10), 5102-5118.
[http://dx.doi.org/10.1021/acs.jmedchem.9b01916] [PMID: 32083858]
[55]
Gabizon, R.; London, N. A Fast and clean BTK inhibitor. J. Med. Chem., 2020, 63(10), 5100-5101.
[http://dx.doi.org/10.1021/acs.jmedchem.0c00597] [PMID: 32401033]
[56]
Bond, D.A.; Woyach, J.A. Targeting BTK in CLL: Beyond Ibrutinib. Curr. Hematol. Malig. Rep., 2019, 14(3), 197-205.
[http://dx.doi.org/10.1007/s11899-019-00512-0] [PMID: 31028669]
[57]
Woyach, J.A.; Furman, R.R.; Liu, T-M.; Ozer, H.G.; Zapatka, M.; Ruppert, A.S.; Xue, L.; Li, D.H-H.; Steggerda, S.M.; Versele, M.; Dave, S.S.; Zhang, J.; Yilmaz, A.S.; Jaglowski, S.M.; Blum, K.A.; Lozanski, A.; Lozanski, G.; James, D.F.; Barrientos, J.C.; Lichter, P.; Stilgenbauer, S.; Buggy, J.J.; Chang, B.Y.; Johnson, A.J.; Byrd, J.C. Resistance mechanisms for the Bruton’s tyrosine kinase inhibitor ibrutinib. N. Engl. J. Med., 2014, 370(24), 2286-2294.
[http://dx.doi.org/10.1056/NEJMoa1400029] [PMID: 24869598]
[58]
Lin, A.; Giuliano, C.J.; Palladino, A.; John, K.M.; Abramowicz, C.; Yuan, M.L.; Sausville, E.L.; Lukow, D.A.; Liu, L.; Chait, A.R.; Galluzzo, Z.C.; Tucker, C.; Sheltzer, J.M. Off-target toxicity is a common mechanism of action of cancer drugs undergoing clinical trials. Sci. Transl. Med., 2019, 11(509), eaaw8412.
[http://dx.doi.org/10.1126/scitranslmed.aaw8412] [PMID: 31511426]
[59]
Ran, F.; Liu, Y.; Wang, C.; Xu, Z.; Zhang, Y.; Liu, Y.; Zhao, G.; Ling, Y. Review of the development of BTK inhibitors in overcoming the clinical limitations of ibrutinib. Eur. J. Med. Chem., 2022, 229, 114009.
[http://dx.doi.org/10.1016/j.ejmech.2021.114009] [PMID: 34839996]
[60]
Feng, Y.; Duan, W.; Cu, X.; Liang, C.; Xin, M. Bruton’s tyrosine kinase (BTK) inhibitors in treating cancer: A patent review (2010-2018). Expert Opin. Ther. Pat., 2019, 29(4), 217-241.
[http://dx.doi.org/10.1080/13543776.2019.1594777] [PMID: 30888232]
[61]
Reiff, S.D.; Mantel, R.; Smith, L.L.; Greene, J.T.; Muhowski, E.M.; Fabian, C.A.; Goettl, V.M.; Tran, M.; Harrington, B.K.; Rogers, K.A.; Awan, F.T.; Maddocks, K.; Andritsos, L.; Lehman, A.M.; Sampath, D.; Lapalombella, R.; Eathiraj, S.; Abbadessa, G.; Schwartz, B.; Johnson, A.J.; Byrd, J.C.; Woyach, J.A. The BTK Inhibitor ARQ 531 Targets Ibrutinib-Resistant CLL and Richter Transformation. Cancer Discov., 2018, 8(10), 1300-1315.
[http://dx.doi.org/10.1158/2159-8290.CD-17-1409] [PMID: 30093506]
[62]
Eathiraj, S.; Savage, R.; Yu, Y.; Schwartz, B.; Woyach, J.; Johnson, A.; Reiff, S.; Abbadessa, G. Targeting ibrutinib-resistant BTK-C481S Mutation with ARQ 531, a reversible non-covalent inhibitor of BTK. Clin. Lymphoma Myeloma Leuk., 2016, 16, S47-S48.
[http://dx.doi.org/10.1016/j.clml.2016.07.068]
[63]
Gomez, E.B.; Isabel, L.; Rosendahal, M.S.; Rothenberg, S.M.; Andrews, S.W.; Brandhuber, B.J. Loxo-305, a highly selective and non-covalent next generation BTK inhibitor, inhibits diverse BTK C481 substitution mutations. Blood, 2019, 134(Suppl. 1), 4644-4644.
[http://dx.doi.org/10.1182/blood-2019-126114]
[64]
Crawford, J.J.; Johnson, A.R.; Misner, D.L.; Belmont, L.D.; Castanedo, G.; Choy, R.; Coraggio, M.; Dong, L.; Eigenbrot, C.; Erickson, R.; Ghilardi, N.; Hau, J.; Katewa, A.; Kohli, P.B.; Lee, W.; Lubach, J.W.; McKenzie, B.S.; Ortwine, D.F.; Schutt, L.; Tay, S.; Wei, B.; Reif, K.; Liu, L.; Wong, H.; Young, W.B. Discovery of GDC-0853: A potent, selective, and noncovalent bruton’s tyrosine kinase inhibitor in early clinical development. J. Med. Chem., 2018, 61(6), 2227-2245.
[http://dx.doi.org/10.1021/acs.jmedchem.7b01712] [PMID: 29457982]
[65]
Fabian, C.A.; Reiff, S.D.; Guinn, D.; Neuman, L.; Fox, J.A.; Wilson, W.; Byrd, J.C.; Woyach, J.A.; Johnson, A.J. SNS-062 demonstrates efficacy in chronic lymphocytic leukemia in vitro and inhibits c481s mutated bruton tyrosine kinase. Proc. Exper. Mol. Ther., 2017, 1207, 1207.
[66]
Di Paolo, J.A.; Huang, T.; Balazs, M.; Barbosa, J.; Barck, K.H.; Bravo, B.J.; Carano, R.A.D.; Darrow, J.; Davies, D.R.; DeForge, L.E.; Diehl, L.; Ferrando, R.; Gallion, S.L.; Giannetti, A.M.; Gribling, P.; Hurez, V.; Hymowitz, S.G.; Jones, R.; Kropf, J.E.; Lee, W.P.; Maciejewski, P.M.; Mitchell, S.A.; Rong, H.; Staker, B.L.; Whitney, J.A.; Yeh, S.; Young, W.B.; Yu, C.; Zhang, J.; Reif, K.; Currie, K.S. Specific Btk inhibition suppresses B cell- and myeloid cell-mediated arthritis. Nat. Chem. Biol., 2011, 7(1), 41-50.
[http://dx.doi.org/10.1038/nchembio.481] [PMID: 21113169]
[67]
Gui, F.; Jiang, J.; He, Z.; Li, L.; Li, Y.; Deng, Z.; Lu, Y.; Wu, X.; Chen, G.; Su, J.; Song, S.; Zhang, Y.M.; Yun, C.H.; Huang, X.; Weisberg, E.; Zhang, J.; Deng, X. A non-covalent inhibitor XMU-MP-3 overrides ibrutinib-resistant BtkC481S mutation in B-cell malignancies. Br. J. Pharmacol., 2019, 176(23), 4491-4509.
[http://dx.doi.org/10.1111/bph.14809] [PMID: 31364164]
[68]
Kawahata, W.; Asami, T.; Kiyoi, T.; Irie, T.; Kashimoto, S.; Furuichi, H.; Sawa, M. Discovery of AS-1763: A potent, selective, noncovalent, and orally available inhibitor of Bruton’s Tyrosine Kinase. J. Med. Chem., 2021, 64(19), 14129-14141.
[http://dx.doi.org/10.1021/acs.jmedchem.1c01279] [PMID: 34529443]
[69]
Eathiraj, S.; Yu, Y.; Savage, R.; Woyach, J.A.; Reiff, S.D.; Johnson, A.J.; Schwartz, B. ARQ 531, a potent reversible BTK inhibitor, exhibits potent antitumor activity in Ibrutinib-resistant diffuse large B-Cell lymphoma.Proc. Exper. Mol. Therapeut; , 2018, 1963, pp. 1963-1963.
[70]
Liu, J.; Ji, M.; Li, Z.; Xu, X.; Li, L.; Li, H.; Tian, Y.; Su, X. A rapid UHPLC-MS/MS method for the quantification of ARQ531 in rat plasma: Validation and its application to a pharmacokinetic study. Biomed. Chromatogr., 2020, 34(11), e4937.
[http://dx.doi.org/10.1002/bmc.4937] [PMID: 32614971]
[71]
Elgamal, O.A.; Mehmood, A.; Jeon, J.Y.; Carmichael, B.; Lehman, A.; Orwick, S.J.; Truxall, J.; Goettl, V.M.; Wasmuth, R.; Tran, M.; Mitchell, S.; Lapalombella, R.; Eathiraj, S.; Schwartz, B.; Stegmaier, K.; Baker, S.D.; Hertlein, E.; Byrd, J.C. Preclinical efficacy for a novel tyrosine kinase inhibitor, ArQule 531 against acute myeloid leukemia. J. Hematol. Oncol., 2020, 13(1), 8.
[http://dx.doi.org/10.1186/s13045-019-0821-7] [PMID: 31992353]
[72]
Brandhuber, B.; Gomez, E.; Smith, S.; Eary, T.; Spencer, S.; Rothenberg, S.M.; Andrews, S. LOXO-305, A next generation reversible BTK inhibitor, for overcoming acquired resistance to irreversible BTK inhibitors. Clin. Lymphoma Myeloma Leuk., 2018, 18, S216.
[http://dx.doi.org/10.1016/j.clml.2018.07.081]
[73]
Wang, M.; Shah, N.N.; Alencar, A.J.; Gerson, J.N.; Patel, M.R.; Fakhri, B.; Jurczak, W.; Tan, X.N.; Lewis, K.L.; Fenske, T.S.; Coombs, C.C.; Flinn, I.W.; Lewis, D.J.; Le Gouill, S.; Palomba, M.L.; Woyach, J.A.; Pagel, J.M.; Lamanna, N.; Cohen, J.B.; Barve, M.; Ghia, P.; Eyre, T.A.; Yin, M.; Nair, B.; Tsai, D.; Ku, N.C.; Mato, A.; Cheah, C.Y. LOXO-305, a next generation, highly selective, non-covalent btk inhibitor in previously treated mantle cell lymphoma, Waldenström’s macroglobulinemia, and other non-hodgkin lymphomas: Results from the phase 1/2 BRUIN Study. Blood, 2020, 136, 8-10.
[http://dx.doi.org/10.1182/blood-2020-137237]
[74]
Jebaraj, B.M.C.; Müller, A.; Dheenadayalan, R.P.; Endres, S.; Roessner, P.M.; Seyfried, F.; Walliser, C.; Wist, M.; Qi, J.; Tausch, E.; Mertens, D.; Fox, J.A.; Debatin, K-M.; Meyer, L.H.; Taverna, P.; Seiffert, M.; Gierschik, P.; Stilgenbauer, S. Evaluation of vecabrutinib as a model for non-covalent BTK/ITK inhibition for treatment of chronic lymphocytic leukemia. Blood, 2002, 139(6), 859-875.
[75]
Sodhi, J.K.; Wong, S.; Kirkpatrick, D.S.; Liu, L.; Khojasteh, S.C.; Hop, C.E.C.A.; Barr, J.T.; Jones, J.P.; Halladay, J.S. A novel reaction mediated by human aldehyde oxidase: Amide hydrolysis of GDC-0834. Drug Metab. Dispos., 2015, 43(6), 908-915.
[http://dx.doi.org/10.1124/dmd.114.061804] [PMID: 25845827]
[76]
Crawford, J.J.; Zhang, H. Discovery and development of non-covalent, reversible bruton’s tyrosine kinase inhibitor fenebrutinib (GDC-0853). ACS Sympos. Ser., 2019, 1332, 239-266.
[http://dx.doi.org/10.1021/bk-2019-1332.ch009]
[77]
Lou, Y.; Han, X.; Kuglstatter, A.; Kondru, R.K.; Sweeney, Z.K.; Soth, M.; McIntosh, J.; Litman, R.; Suh, J.; Kocer, B.; Davis, D.; Park, J.; Frauchiger, S.; Dewdney, N.; Zecic, H.; Taygerly, J.P.; Sarma, K.; Hong, J.; Hill, R.J.; Gabriel, T.; Goldstein, D.M.; Owens, T.D. Structure-based drug design of RN486, a potent and selective Bruton’s tyrosine kinase (BTK) inhibitor, for the treatment of rheumatoid arthritis. J. Med. Chem., 2015, 58(1), 512-516.
[http://dx.doi.org/10.1021/jm500305p] [PMID: 24712864]
[78]
Xu, D.; Kim, Y.; Postelnek, J.; Vu, M.D.; Hu, D-Q.; Liao, C.; Bradshaw, M.; Hsu, J.; Zhang, J.; Pashine, A.; Srinivasan, D.; Woods, J.; Levin, A.; O’Mahony, A.; Owens, T.D.; Lou, Y.; Hill, R.J.; Narula, S.; DeMartino, J.; Fine, J.S. RN486, a selective Bruton’s tyrosine kinase inhibitor, abrogates immune hypersensitivity responses and arthritis in rodents. J. Pharmacol. Exp. Ther., 2012, 341(1), 90-103.
[http://dx.doi.org/10.1124/jpet.111.187740] [PMID: 22228807]
[79]
Das, D.; Xie, L.; Wang, J.; Xu, X.; Zhang, Z.; Shi, J.; Le, X.; Hong, J. Discovery of new quinazoline derivatives as irreversible dual EGFR/HER2 inhibitors and their anticancer activities - Part 1. Bioorg. Med. Chem. Lett., 2019, 29(4), 591-596.
[http://dx.doi.org/10.1016/j.bmcl.2018.12.056] [PMID: 30600209]
[80]
Das, D.; Xie, L.; Wang, J.; Shi, J.; Hong, J. In vivo efficacy studies of novel quinazoline derivatives as irreversible dual EGFR/HER2 inhibitors, in lung cancer xenografts (NCI-H1975) mice models. Bioorg. Chem., 2020, 99, 103790.
[http://dx.doi.org/10.1016/j.bioorg.2020.103790] [PMID: 32279037]
[81]
Das, D.; Wang, J.; Li, Y.; Shi, J.; Hong, J. Design, synthesis of orally bioavailable novel anaplastic lymphoma kinase (ALK) inhibitor diphenylaminopyrimidine analogs and efficacy study on NCI-H2228 xenografts mice model. Bioorg. Med. Chem. Lett., 2019, 29(12), 1514-1517.
[http://dx.doi.org/10.1016/j.bmcl.2019.04.012] [PMID: 31005443]
[82]
Hong, J.; Xu, X.; Le, X. Pyrazolopyrimidine derivative, manufacturing method, pharmaceutical composition and use thereof., Patent WO 2016 154998, 2016.
[83]
Das, D.; Xie, L.; Wang, J.; Qiao, D.; Hong, J. Design, synthesis of new pyrazolo[3,4-d]pyrimidine derivatives and in vitro evaluation of antiproliferative activity against leukemia cell lines. Russ. J. Bioorg. Chem., 2022, 48(1), 153-162.
[http://dx.doi.org/10.1134/S1068162022010046]
[84]
Xie, L.; Qiao, D.; Das, D. Small molecule inhibitors of BTK and/or mutant C481S of BTK. CN112574200A, 2021.
[85]
Brullo, C.; Villa, C.; Tasso, B.; Russo, E.; Spallarossa, A. Btk inhibitors: A medicinal chemistry and drug delivery perspective. Int. J. Mol. Sci., 2021, 22(14), 7641.
[http://dx.doi.org/10.3390/ijms22147641] [PMID: 34299259]
[86]
Liu, J.; Chen, C.; Wang, D.; Zhang, J.; Zhang, T. Emerging small-molecule inhibitors of the Bruton’s tyrosine kinase (BTK): Current development. Eur. J. Med. Chem., 2021, 217, 113329.
[http://dx.doi.org/10.1016/j.ejmech.2021.113329] [PMID: 33740548]
[87]
Tasso, B.; Spallarossa, A.; Russo, E.; Brullo, C. The development of BTK inhibitors: A five-year update. Molecules, 2021, 26(23), 7411.
[http://dx.doi.org/10.3390/molecules26237411] [PMID: 34885993]
[88]
Zhang, D.; Gong, H.; Meng, F. Recent advances in BTK inhibitors for the treatment of inflammatory and autoimmune diseases. Molecules, 2021, 26(16), 4907.
[http://dx.doi.org/10.3390/molecules26164907] [PMID: 34443496]
[89]
Burger, J.A.; Barr, P.M.; Robak, T.; Owen, C.; Ghia, P.; Tedeschi, A.; Bairey, O.; Hillmen, P.; Coutre, S.E.; Devereux, S.; Grosicki, S.; McCarthy, H.; Simpson, D.; Offner, F.; Moreno, C.; Dai, S.; Lal, I.; Dean, J.P.; Kipps, T.J. Long-term efficacy and safety of first-line ibrutinib treatment for patients with CLL/SLL: 5 years of follow-up from the phase 3 RESONATE-2 study. Leukemia, 2020, 34(3), 787-798.
[http://dx.doi.org/10.1038/s41375-019-0602-x] [PMID: 31628428]
[90]
Zhou, H.; Hu, P.; Yan, X.; Zhang, Y.; Shi, W. Ibrutinib in chronic lymphocytic leukemia: Clinical applications, drug resistance, and prospects. OncoTargets Ther., 2020, 13, 4877-4892.
[http://dx.doi.org/10.2147/OTT.S249586] [PMID: 32581549]
[91]
Gu, D.; Tang, H.; Wu, J.; Li, J.; Miao, Y. Targeting Bruton tyrosine kinase using non-covalent inhibitors in B cell malignancies. J. Hematol. Oncol., 2021, 14(1), 40.
[http://dx.doi.org/10.1186/s13045-021-01049-7] [PMID: 33676527]
[92]
Estupiñán, H.Y.; Berglöf, A.; Zain, R.; Smith, C.I.E. Comparative analysis of BTK inhibitors and mechanisms underlying adverse effects. Front. Cell Dev. Biol., 2021, 9, 630942.
[http://dx.doi.org/10.3389/fcell.2021.630942] [PMID: 33777941]
[93]
Woyach, J.; Stephens, D.M.; Flinn, I.W.; Bhat, S.A.; Savage, R.E.; Chai, F.; Eathiraj, S.; Granlund, L.; Szuszkiewicz, L.A.; Schwartz, B.; Byrd, J.C. Final results of phase 1, dose escalation study evaluating ARQ 531 in patients with relapsed or refractory B-cell lymphoid malignancies. Blood, 2019, 134(Suppl. 1), 4298-4298.
[http://dx.doi.org/10.1182/blood-2019-127260]
[94]
Reiff, S.D.; Muhowski, E.M.; Guinn, D.; Lehman, A.; Fabian, C.A.; Cheney, C.; Mantel, R.; Smith, L.; Johnson, A.J.; Young, W.B.; Johnson, A.R.; Liu, L.; Byrd, J.C.; Woyach, J.A. Noncovalent inhibition of C481S Bruton tyrosine kinase by GDC-0853: A new treatment strategy for ibrutinib-resistant CLL. Blood, 2018, 132(10), 1039-1049.
[http://dx.doi.org/10.1182/blood-2017-10-809020] [PMID: 30018078]
[95]
Herman, A.E.; Chinn, L.W.; Kotwal, S.G.; Murray, E.R.; Zhao, R.; Florero, M.; Lin, A.; Moein, A.; Wang, R.; Bremer, M.; Kokubu, S.; Serone, A.P.; Hanze, E.L.; Viberg, A.; Morimoto, A.M.; Winter, H.R.; Katsumoto, T.R. Safety, pharmacokinetics, and pharmacodynamics in healthy volunteers treated with GDC-0853, a selective reversible bruton’s tyrosine kinase inhibitor. Clin. Pharmacol. Ther., 2018, 103(6), 1020-1028.
[http://dx.doi.org/10.1002/cpt.1056] [PMID: 29484638]
[96]
Byrd, J.C.; Smith, S.; Wagner-Johnston, N.; Sharman, J.; Chen, A.I.; Advani, R.; Augustson, B.; Marlton, P.; Renee Commerford, S.; Okrah, K.; Liu, L.; Murray, E.; Penuel, E.; Ward, A.F.; Flinn, I.W. First-in-human phase 1 study of the BTK inhibitor GDC-0853 in relapsed or refractory B-cell NHL and CLL. Oncotarget, 2018, 9(16), 13023-13035.
[http://dx.doi.org/10.18632/oncotarget.24310] [PMID: 29560128]
[97]
Gillooly, K.M.; Pulicicchio, C.; Pattoli, M.A.; Cheng, L.; Skala, S.; Heimrich, E.M.; McIntyre, K.W.; Taylor, T.L.; Kukral, D.W.; Dudhgaonkar, S.; Nagar, J.; Banas, D.; Watterson, S.H.; Tino, J.A.; Fura, A.; Burke, J.R. Bruton’s tyrosine kinase inhibitor BMS-986142 in experimental models of rheumatoid arthritis enhances efficacy of agents representing clinical standard-of-care. PLoS One, 2017, 12(7), e0181782.
[http://dx.doi.org/10.1371/journal.pone.0181782] [PMID: 28742141]
[98]
Smith, P.F.; Krishnarajah, J.; Nunn, P.A.; Hill, R.J.; Karr, D.; Tam, D.; Masjedizadeh, M.; Funk, J.O.; Gourlay, S.G. A phase I trial of PRN1008, a novel reversible covalent inhibitor of Bruton’s tyrosine kinase, in healthy volunteers. Br. J. Clin. Pharmacol., 2017, 83(11), 2367-2376.
[http://dx.doi.org/10.1111/bcp.13351] [PMID: 28636208]
[99]
Luh, L.M.; Scheib, U.; Juenemann, K.; Wortmann, L.; Brands, M.; Cromm, P.M. Prey for the proteasome: Targeted protein degradation-a medicinal chemist’s perspective. Angew. Chem. Int. Ed. Engl., 2020, 59(36), 15448-15466.
[http://dx.doi.org/10.1002/anie.202004310] [PMID: 32428344]
[100]
Martín-Acosta, P.; Xiao, X. PROTACs to address the challenges facing small molecule inhibitors. Eur. J. Med. Chem., 2021, 210, 112993.
[http://dx.doi.org/10.1016/j.ejmech.2020.112993] [PMID: 33189436]
[101]
Sakamoto, K.M.; Kim, K.B.; Kumagai, A.; Mercurio, F.; Crews, C.M.; Deshaies, R.J. Protacs: Chimeric molecules that target proteins to the Skp1-Cullin-F box complex for ubiquitination and degradation. Proc. Natl. Acad. Sci. USA, 2001, 98(15), 8554-8559.
[http://dx.doi.org/10.1073/pnas.141230798] [PMID: 11438690]
[102]
Troup, R.I.; Fallan, C.; Baud, M.G.J. Current strategies for the design of PROTAC linkers: A critical review. Explor. Target. Anti-tumor Ther., 2020, 1, 273-312.
[103]
Yin, L.; Hu, Q. Chimera induced protein degradation: PROTACs and beyond. Eur. J. Med. Chem., 2020, 206, 112494.
[http://dx.doi.org/10.1016/j.ejmech.2020.112494] [PMID: 32890974]
[104]
Zhou, X.; Dong, R.; Zhang, J-Y.; Zheng, X.; Sun, L-P. PROTAC: A promising technology for cancer treatment. Eur. J. Med. Chem., 2020, 203, 112539.
[http://dx.doi.org/10.1016/j.ejmech.2020.112539] [PMID: 32698111]
[105]
Yu, F.; Cai, M.; Shao, L.; Zhang, J. Targeting protein kinases degradation by PROTACs. Front Chem., 2021, 9, 679120.
[http://dx.doi.org/10.3389/fchem.2021.679120] [PMID: 34277564]
[106]
Churcher, I. Protac-induced protein degradation in drug discovery: Breaking the rules or just making new ones? J. Med. Chem., 2018, 61(2), 444-452.
[http://dx.doi.org/10.1021/acs.jmedchem.7b01272] [PMID: 29144739]
[107]
Burslem, G.M.; Smith, B.E.; Lai, A.C.; Jaime-Figueroa, S.; McQuaid, D.C.; Bondeson, D.P.; Toure, M.; Dong, H.; Qian, Y.; Wang, J.; Crew, A.P.; Hines, J.; Crews, C.M. The advantages of targeted protein degradation over inhibition: An RTK case study. Cell Chem. Biol., 2018, 25(1), 67-77.e3.
[http://dx.doi.org/10.1016/j.chembiol.2017.09.009] [PMID: 29129716]
[108]
Qi, S-M.; Dong, J.; Xu, Z-Y.; Cheng, X-D.; Zhang, W-D.; Qin, J-J. PROTAC: An effective targeted protein degradation strategy for cancer therapy. Front. Pharmacol., 2021, 12, 692574.
[http://dx.doi.org/10.3389/fphar.2021.692574] [PMID: 34025443]
[109]
Tinworth, C.P.; Lithgow, H.; Dittus, L.; Bassi, Z.I.; Hughes, S.E.; Muelbaier, M.; Dai, H.; Smith, I.E.D.; Kerr, W.J.; Burley, G.A.; Bantscheff, M.; Harling, J.D. PROTAC-mediated degradation of bruton’s tyrosine kinase is inhibited by covalent binding. ACS Chem. Biol., 2019, 14(3), 342-347.
[http://dx.doi.org/10.1021/acschembio.8b01094] [PMID: 30807093]
[110]
Zhao, Y.; Shu, Y.; Lin, J.; Chen, Z.; Xie, Q.; Bao, Y.; Lu, L.; Sun, N.; Wang, Y. Discovery of novel BTK PROTACs for B-Cell lymphomas. Eur. J. Med. Chem., 2021, 225, 113820.
[http://dx.doi.org/10.1016/j.ejmech.2021.113820] [PMID: 34509879]
[111]
Gabizon, R.; Shraga, A.; Gehrtz, P.; Livnah, E.; Shorer, Y.; Gurwicz, N.; Avram, L.; Unger, T.; Aharoni, H.; Albeck, S.; Brandis, A.; Shulman, Z.; Katz, B-Z.; Herishanu, Y.; London, N. Efficient targeted degradation via reversible and irreversible covalent PROTACs. J. Am. Chem. Soc., 2020, 142(27), 11734-11742.
[http://dx.doi.org/10.1021/jacs.9b13907] [PMID: 32369353]
[112]
Dobrovolsky, D.; Wang, E.S.; Morrow, S.; Leahy, C.; Faust, T.; Nowak, R.P.; Donovan, K.A.; Yang, G.; Li, Z.; Fischer, E.S.; Treon, S.P.; Weinstock, D.M.; Gray, N.S. Bruton tyrosine kinase degradation as a therapeutic strategy for cancer. Blood, 2019, 133(9), 952-961.
[http://dx.doi.org/10.1182/blood-2018-07-862953] [PMID: 30545835]
[113]
Buhimschi, A.D.; Armstrong, H.A.; Toure, M.; Jaime-Figueroa, S.; Chen, T.L.; Lehman, A.M.; Woyach, J.A.; Johnson, A.J.; Byrd, J.C.; Crews, C.M. Targeting the C481S Ibrutinib-Resistance Mutation in Bruton’s Tyrosine Kinase Using PROTAC-Mediated Degradation. Biochemistry, 2018, 57(26), 3564-3575.
[http://dx.doi.org/10.1021/acs.biochem.8b00391] [PMID: 29851337]
[114]
Jaime-Figueroa, S.; Buhimschi, A.D.; Toure, M.; Hines, J.; Crews, C.M. Design, synthesis and biological evaluation of Proteolysis Targeting Chimeras (PROTACs) as a BTK degraders with improved pharmacokinetic properties. Bioorg. Med. Chem. Lett., 2020, 30(3), 126877.
[http://dx.doi.org/10.1016/j.bmcl.2019.126877] [PMID: 31879210]
[115]
Sun, Y.; Zhao, X.; Ding, N.; Gao, H.; Wu, Y.; Yang, Y.; Zhao, M.; Hwang, J.; Song, Y.; Liu, W.; Rao, Y. PROTAC-induced BTK degradation as a novel therapy for mutated BTK C481S induced ibrutinib-resistant B-cell malignancies. Cell Res., 2018, 28(7), 779-781.
[http://dx.doi.org/10.1038/s41422-018-0055-1] [PMID: 29875397]
[116]
Robbins, D.W.; Kelly, A.; Tan, M.; McIntosh, J.; Wu, J.; Konst, Z.; Kato, D.; Peng, G.; Mihalic, J.; Weiss, D.; Perez, L.; Tung, J.; Kolobova, A.; Borodovsky, S.; Rountree, R.; Tenn-McClellan, A.; Noviski, M.; Ye, J.; Basham, S.; Ingallinera, T.; McKinnell, J.; Karr, D.E.; Powers, J.; Guiducci, C.; Sands, A. Nx-2127, a Degrader of BTK and IMiD Neosubstrates, for the Treatment of B-Cell Malignancies. Blood, 2020, 136(Suppl. 1), 34-34.
[http://dx.doi.org/10.1182/blood-2020-141461]
[117]
Qian, M.; Ye, F.; Zhang, C.; Wang, J.; Zhang, Y.; Cui, Y.; Li, L.; Gou, X.; Ni, J. Abstract 3761: HSK26784: An oral PROTACBTK degrader for multiple B Lymphocyte derived malignancies.Proc. Immunol; , 2020, pp. 3761-3761.

Rights & Permissions Print Cite
Article Metrics
116
2
Wayfinder Image
© 2024 Bentham Science Publishers | Privacy Policy