Abstract
Background: Breast cancer has always been a vicious disease that threatens female health. Although the existing surgery, radiotherapy, chemotherapy, and kinase-targeted drugs have achieved certain effects, there are still many shortcomings. Novel compounds used to treat breast cancer, particularly TNBC, are eagerly being discovered.
Methods: More than 100 novel compounds that show anti-breast cancer growth were compiled from public databases. The compound design strategies, structure-activity relationship research, and activity evaluation methods have also been reviewed.
Results: These novel anti-breast cancer compounds can be divided into mechanisms of action: kinase inhibitors, epigenetic inhibitors, dual inhibitors, degraders, metal complexes, etc. The design strategies mainly include conformational constraint, scaffold-hopping, merging key pharmacophores, etc. Structure-activity relationship studies of these new compounds mainly focus on increasing activity, improving selectivity, increasing membrane permeability, reducing toxicity, improving pharmacokinetic properties, etc.
Conclusion: Through the structural optimization of kinase inhibitors, microtubule-targeted drugs, and metal complexes, it is expected to obtain more advantageous breast cancer treatment drugs. It cannot be ignored that epigenetic inhibitors, dual inhibitors and degraders may bring new breast cancer treatment strategies.
Graphical Abstract
[http://dx.doi.org/10.3322/caac.21754] [PMID: 36190501]
[http://dx.doi.org/10.1038/s41573-022-00579-0] [PMID: 36344672]
[http://dx.doi.org/10.2174/1568009621666210901101851] [PMID: 34468298]
[http://dx.doi.org/10.1016/S0140-6736(20)32381-3] [PMID: 33812473]
[http://dx.doi.org/10.1101/cshperspect.a009076] [PMID: 24186067]
[http://dx.doi.org/10.3390/cancers8120107] [PMID: 27916840]
[http://dx.doi.org/10.1021/acs.jmedchem.2c01346] [PMID: 36358010]
[http://dx.doi.org/10.20892/j.issn.2095-3941.2017.0033] [PMID: 29372101]
[http://dx.doi.org/10.1053/j.seminoncol.2018.03.006] [PMID: 29935901]
[http://dx.doi.org/10.1016/j.bmcl.2019.126637] [PMID: 31477350]
[http://dx.doi.org/10.3390/molecules26154462] [PMID: 34361615]
[http://dx.doi.org/10.1021/acs.jmedchem.2c00947] [PMID: 36350721]
[http://dx.doi.org/10.2174/1568026620666200303123102] [PMID: 32124699]
[http://dx.doi.org/10.2174/1389557516666160321114917] [PMID: 26996617]
[http://dx.doi.org/10.1007/s10549-012-2289-9] [PMID: 23073759]
[http://dx.doi.org/10.3390/molecules26134065] [PMID: 34279406]
[http://dx.doi.org/10.1080/14737140.2018.1491795] [PMID: 29936878]
[http://dx.doi.org/10.1002/wdev.176] [PMID: 25772309]
[http://dx.doi.org/10.1158/1535-7163.MCT-16-0451] [PMID: 27811009]
[http://dx.doi.org/10.1177/1010428317705517] [PMID: 28618969]
[http://dx.doi.org/10.1016/j.ejmech.2020.112866] [PMID: 33039722]
[http://dx.doi.org/10.1021/acs.jmedchem.2c00255] [PMID: 35549181]
[http://dx.doi.org/10.1016/S1097-2765(02)00636-6] [PMID: 12408816]
[http://dx.doi.org/10.1126/science.1199498] [PMID: 21659604]
[http://dx.doi.org/10.2174/156800908786733513] [PMID: 19075588]
[http://dx.doi.org/10.1016/j.ejmech.2021.113424]
[http://dx.doi.org/10.1038/nrc3860] [PMID: 25533673]
[http://dx.doi.org/10.1038/nrm2882] [PMID: 20379207]
[http://dx.doi.org/10.1021/acs.jmedchem.2c01422] [PMID: 36455032]
[http://dx.doi.org/10.1038/onc.2014.451] [PMID: 25619835]
[http://dx.doi.org/10.1007/s00432-019-02994-0] [PMID: 31492983]
[http://dx.doi.org/10.1016/j.ejmech.2022.114424] [PMID: 35576702]
[http://dx.doi.org/10.1038/s41573-021-00252-y] [PMID: 34354255]
[http://dx.doi.org/10.1186/s13045-020-00977-0] [PMID: 33109256]
[http://dx.doi.org/10.1016/j.phrs.2022.106552] [PMID: 36403719]
[http://dx.doi.org/10.1038/s41580-022-00483-w] [PMID: 35562425]
[http://dx.doi.org/10.1016/j.ejmech.2019.06.072] [PMID: 31276898]
[http://dx.doi.org/10.1021/jm200903z] [PMID: 21780790]
[http://dx.doi.org/10.1016/j.bioorg.2017.04.005] [PMID: 28460359]
[http://dx.doi.org/10.1074/jbc.M404298200] [PMID: 15173171]
[http://dx.doi.org/10.2174/1568026618666180518091144] [PMID: 29773061]
[http://dx.doi.org/10.1084/jem.20092506] [PMID: 20142433]
[http://dx.doi.org/10.1038/nature08617] [PMID: 19935646]
[http://dx.doi.org/10.1021/ml400036z] [PMID: 23795241]
[http://dx.doi.org/10.1021/jm500660f] [PMID: 25271760]
[http://dx.doi.org/10.1038/s41573-020-00108-x] [PMID: 33469207]
[http://dx.doi.org/10.1002/ijc.33375] [PMID: 33128779]
[http://dx.doi.org/10.1016/j.phrs.2020.105335] [PMID: 33285227]
[http://dx.doi.org/10.2174/1574892816666210728125224] [PMID: 34323202]
[http://dx.doi.org/10.1016/j.ejmech.2022.114410] [PMID: 35525212]
[http://dx.doi.org/10.1038/s41580-019-0155-x] [PMID: 31350521]
[http://dx.doi.org/10.1021/acs.chemrev.6b00801] [PMID: 28338320]
[http://dx.doi.org/10.1080/14728222.2018.1474203] [PMID: 29781349]
[http://dx.doi.org/10.2174/1389203721666200124143145] [PMID: 31976831]
[http://dx.doi.org/10.1021/acschembio.5b00839] [PMID: 26598975]
[http://dx.doi.org/10.1038/s41589-022-01024-4] [PMID: 35578032]
[http://dx.doi.org/10.1016/j.ejmech.2022.115032] [PMID: 36566712]
[http://dx.doi.org/10.1021/jm501061a] [PMID: 25364867]
[http://dx.doi.org/10.1016/j.abb.2021.108811] [PMID: 33600786]
[http://dx.doi.org/10.1021/acs.jmedchem.2c00013] [PMID: 35786929]
[http://dx.doi.org/10.1007/s12272-019-01126-z] [PMID: 30806885]
[http://dx.doi.org/10.1038/s41580-019-0143-1] [PMID: 31270442]
[http://dx.doi.org/10.1038/s41591-019-0376-8] [PMID: 30842676]
[http://dx.doi.org/10.1080/17460441.2021.1877656] [PMID: 33530771]
[http://dx.doi.org/10.1021/jm801449a] [PMID: 19243174]
[http://dx.doi.org/10.1038/nrc3256] [PMID: 22722403]
[http://dx.doi.org/10.1056/NEJMc1211175] [PMID: 23113498]
[http://dx.doi.org/10.1158/2159-8290.CD-17-0605] [PMID: 29263030]
[PMID: 28078999]
[http://dx.doi.org/10.2174/1381612827666210917143953] [PMID: 34533439]
[http://dx.doi.org/10.1038/ncomms15482] [PMID: 28516956]
[http://dx.doi.org/10.1021/acs.jmedchem.2c01191] [PMID: 36622852]
[http://dx.doi.org/10.1016/j.apsb.2020.06.003] [PMID: 33532187]
[http://dx.doi.org/10.1016/j.molcel.2020.04.027] [PMID: 32416067]
[http://dx.doi.org/10.1038/s41467-020-17503-y] [PMID: 32796829]
[http://dx.doi.org/10.1042/BJ20040776] [PMID: 15456408]
[http://dx.doi.org/10.2174/1389557522666220321150700] [PMID: 35319364]
[http://dx.doi.org/10.1021/acs.jmedchem.2c00135] [PMID: 35442700]
[http://dx.doi.org/10.1038/nm.4036] [PMID: 26845405]
[http://dx.doi.org/10.1016/j.phrs.2022.106159] [PMID: 35259482]
[http://dx.doi.org/10.1038/nature09784] [PMID: 21248841]
[http://dx.doi.org/10.1016/j.cell.2018.08.058] [PMID: 30220457]
[http://dx.doi.org/10.1021/acs.jmedchem.2c01607] [PMID: 36774555]
[http://dx.doi.org/10.1021/acs.jmedchem.2c00673] [PMID: 36153841]
[http://dx.doi.org/10.1023/A:1020299707510] [PMID: 12408373]
[http://dx.doi.org/10.1186/bcr3206] [PMID: 22691381]
[http://dx.doi.org/10.1021/acs.jmedchem.1c01646] [PMID: 35286086]
[http://dx.doi.org/10.1021/jm400467w] [PMID: 23786452]
[http://dx.doi.org/10.1016/S1470-2045(19)30164-0] [PMID: 31036468]
[http://dx.doi.org/10.1038/bjc.2011.156] [PMID: 21559012]
[http://dx.doi.org/10.1016/j.ejmech.2021.113870] [PMID: 34610548]
[http://dx.doi.org/10.1038/s41580-020-0236-x] [PMID: 32313204]
[http://dx.doi.org/10.3892/ijo.2019.4796] [PMID: 31059004]
[http://dx.doi.org/10.1093/nar/gkz835] [PMID: 31584090]
[http://dx.doi.org/10.1021/acs.jmedchem.2c01058] [PMID: 36053318]
[http://dx.doi.org/10.1186/s13058-015-0659-z] [PMID: 26728598]
[http://dx.doi.org/10.1038/onc.2014.170] [PMID: 24931162]
[http://dx.doi.org/10.1007/s40265-020-01461-2] [PMID: 33369721]
[http://dx.doi.org/10.1016/j.ccell.2020.03.010] [PMID: 32289274]
[http://dx.doi.org/10.1021/acs.jmedchem.2c00063] [PMID: 35447031]
[http://dx.doi.org/10.1021/acs.jmedchem.2c00866] [PMID: 36097406]
[http://dx.doi.org/10.1081/JAS-120018783] [PMID: 12870839]
[http://dx.doi.org/10.2174/0929867325666180607094856] [PMID: 29874992]
[http://dx.doi.org/10.1158/0008-5472.CAN-07-2661] [PMID: 18339872]
[http://dx.doi.org/10.1021/acs.jmedchem.6b00608] [PMID: 27379978]
[http://dx.doi.org/10.1021/acs.jmedchem.2c01682] [PMID: 36695404]
[http://dx.doi.org/10.1021/acs.jmedchem.2c00384] [PMID: 35938508]
[http://dx.doi.org/10.1038/s41589-019-0421-4] [PMID: 31819273]
[http://dx.doi.org/10.1016/j.ejmech.2022.114462] [PMID: 35623249]
[http://dx.doi.org/10.1074/jbc.R800007200] [PMID: 18442971]
[http://dx.doi.org/10.1016/j.ejmech.2021.114013] [PMID: 34864330]
[http://dx.doi.org/10.1038/nrc3645] [PMID: 24505617]
[http://dx.doi.org/10.1007/s10555-008-9168-1] [PMID: 19165420]
[http://dx.doi.org/10.1021/acs.jmedchem.2c00756] [PMID: 36416208]
[http://dx.doi.org/10.1016/j.cell.2019.06.026] [PMID: 31353221]
[http://dx.doi.org/10.2147/DDDT.S380925] [PMID: 36081610]
[http://dx.doi.org/10.3390/ijms22157812] [PMID: 34360578]
[http://dx.doi.org/10.1021/acs.jmedchem.7b01682] [PMID: 29562737]
[http://dx.doi.org/10.1021/acs.jmedchem.2c00008] [PMID: 35357160]
[http://dx.doi.org/10.1039/D2CS00200K] [PMID: 35587208]
[http://dx.doi.org/10.1038/s41573-021-00371-6] [PMID: 35042991]
[http://dx.doi.org/10.2174/1389557521666210226150740] [PMID: 33634757]
[http://dx.doi.org/10.1016/j.jinorgbio.2009.07.003] [PMID: 19664824]
[http://dx.doi.org/10.1021/acs.jmedchem.2c01660] [PMID: 36715603]
[http://dx.doi.org/10.1021/acs.jmedchem.2c01224] [PMID: 36353870]
[http://dx.doi.org/10.1021/acs.jmedchem.2c01895] [PMID: 36891739]
[http://dx.doi.org/10.1016/j.ejmech.2018.08.054] [PMID: 30282320]
[http://dx.doi.org/10.1021/acs.jmedchem.2c00580] [PMID: 35895090]
[http://dx.doi.org/10.3390/ijms24010203] [PMID: 36613647]
[http://dx.doi.org/10.2174/1871520622666220331085144] [PMID: 35362388]
[http://dx.doi.org/10.1016/j.bioorg.2019.102925] [PMID: 31003078]
[http://dx.doi.org/10.1091/mbc.E17-11-0677] [PMID: 29535173]
[http://dx.doi.org/10.1016/j.ejmech.2019.03.025] [PMID: 30953881]
[http://dx.doi.org/10.1016/j.ejmech.2019.111728]
[http://dx.doi.org/10.1021/acs.jmedchem.2c01208] [PMID: 36511661]
[http://dx.doi.org/10.1021/acs.jmedchem.2c02115] [PMID: 36802449]
[http://dx.doi.org/10.1016/j.ejmech.2022.114300] [PMID: 35339100]
[http://dx.doi.org/10.1016/j.bioorg.2023.106660] [PMID: 37320914]
[http://dx.doi.org/10.3390/molecules26164899] [PMID: 34443487]
[PMID: 34249261]
[http://dx.doi.org/10.1016/j.ejmech.2022.115013] [PMID: 36566714]
[http://dx.doi.org/10.1021/acs.jmedchem.2c01115] [PMID: 36786551]
[http://dx.doi.org/10.1016/j.ejmech.2023.115192] [PMID: 36801517]
[http://dx.doi.org/10.1016/j.ejmech.2023.115181] [PMID: 36764122]
[http://dx.doi.org/10.1021/acs.jmedchem.2c01370] [PMID: 36692394]
[http://dx.doi.org/10.1016/j.ejmech.2023.115457] [PMID: 37207533]
[http://dx.doi.org/10.1021/acs.jmedchem.3c00505] [PMID: 37279162]
[http://dx.doi.org/10.1021/acs.jmedchem.2c02032] [PMID: 37161783]