230. Karatas H, Townsend EC, Bernard D, Dou Y, Wang S (2010) Analysis of the binding of mixed
lineage leukemia 1 (MLL1) and histone 3 peptides to WD repeat domain 5 (WDR5) for the
design of inhibitors of the MLL1-WDR5 interaction. J Med Chem 53(14):5179–5185. https://
doi.org/10.1021/jm100139b
231. Karatas H, Townsend EC, Cao F, Chen Y, Bernard D, Liu L, Lei M, Dou Y, Wang S (2013)
High-affinity, small-molecule peptidomimetic inhibitors of MLL1/WDR5 protein-protein
interaction. J Am Chem Soc 135(2):669–682. https://doi.org/10.1021/ja306028q
232. Karatas H, Li Y, Liu L, Ji J, Lee S, Chen Y, Yang J, Huang L, Bernard D, Xu J, Townsend EC,
Cao F, Ran X, Li X, Wen B, Sun D, Stuckey JA, Lei M, Dou Y, Wang S (2017) Discovery
of a highly potent, cell-permeable macrocyclic peptidomimetic (MM-589) targeting the
WD repeat domain 5 protein (WDR5)-mixed lineage leukemia (MLL) protein-protein interaction. J Med Chem 60(12):4818–4839. https://doi.org/10.1021/acs.jmedchem.6b01796
233. Senisterra G, Wu H, Allali-Hassani A, Wasney GA, Barsyte-Lovejoy D, Dombrovski L,
Dong A, Nguyen KT, Smil D, Bolshan Y, Hajian T, He H, Seitova A, Chau I, Li F,
Poda G, Couture JF, Brown PJ, Al-Awar R, Schapira M, Arrowsmith CH, Vedadi M (2013)
Small-molecule inhibition of MLL activity by disruption of its interaction with WDR5.
Biochem J 449(1):151–159. https://doi.org/10.1042/BJ20121280
234. Bolshan Y, Getlik M, Kuznetsova E, Wasney GA, Hajian T, Poda G, Nguyen KT, Wu H,
Dombrovski L, Dong A, Senisterra G, Schapira M, Arrowsmith CH, Brown PJ, Al-Awar R,
Vedadi M, Smil D (2013) Synthesis, optimization, and evaluation of novel small molecules as
antagonists of WDR5-MLL interaction. ACS Med Chem Lett 4(3):353–357. https://doi.org/
10.1021/ml300467n
235. Getlik M, Smil D, Zepeda-Velazquez C, Bolshan Y, Poda G, Wu H, Dong A, Kuznetsova E,
Marcellus R, Senisterra G, Dombrovski L, Hajian T, Kiyota T, Schapira M, Arrowsmith CH,
Brown PJ, Vedadi M, Al-Awar R (2016) Structure-based optimization of a small molecule
antagonist of the interaction between WD repeat-containing protein 5 (WDR5) and mixedlineage leukemia 1 (MLL1). J Med Chem 59(6):2478–2496. https://doi.org/10.1021/acs.
jmedchem.5b01630
236. Li DD, Chen WL, Wang ZH, Xie YY, Xu XL, Jiang ZY, Zhang XJ, You QD, Guo XK (2016)
High-affinity small molecular blockers of mixed lineage leukemia 1 (MLL1)-WDR5 interaction inhibit MLL1 complex H3K4 methyltransferase activity. Eur J Med Chem 124:480–489.
https://doi.org/10.1016/j.ejmech.2016.08.036
237. Li DD, Chen WL, Xu XL, Jiang F, Wang L, Xie YY, Zhang XJ, Guo XK, You QD, Sun HP
(2016) Structure-based design and synthesis of small molecular inhibitors disturbing the
interaction of MLL1-WDR5. Eur J Med Chem 118:1–8. https://doi.org/10.1016/j.ejmech.
2016.04.032
238. Li DD, Wang ZH, Chen WL, Xie YY, You QD, Guo XK (2016) Structure-based design
of ester compounds to inhibit MLL complex catalytic activity by targeting mixed lineage
leukemia 1 (MLL1)-WDR5 interaction. Bioorg Med Chem 24(22):6109–6118. https://doi.org/
10.1016/j.bmc.2016.09.073
239. Lu J, Li X, Wang Q, Pei G (2017) Dopamine D2 receptor and beta-arrestin 2 mediate
Amyloid-beta elevation induced by anti-Parkinson’s disease drugs, levodopa and piribedil,
in neuronal cells. PLoS One 12(3):e0173240. https://doi.org/10.1371/journal.pone.0173240
240. Zhang X, Zheng X, Yang H, Yan J, Fu X, Wei R, Xu X, Zhang Z, Yu A, Zhou K, Ding J,
Geng M, Huang X (2018) Piribedil disrupts the MLL1-WDR5 interaction and sensitizes
MLL-rearranged acute myeloid leukemia (AML) to doxorubicin-induced apoptosis. Cancer
Lett 431:150–160. https://doi.org/10.1016/j.canlet.2018.05.034
241. Xie J, Wang C, Virostko J, Manning HC, Pham W, Bauer J, Gore JC (2013) A novel
reporter system for molecular imaging and high-throughput screening of anticancer drugs.
Chembiochem 14(12):1494–1503. https://doi.org/10.1002/cbic.201300142
242. Li L, Zhang H, Zhang M, Zhao M, Feng L, Luo X, Gao Z, Huang Y, Ardayfio O, Zhang JH,
Lin Y, Fan H, Mi Y, Li G, Liu L, Feng L, Luo F, Teng L, Qi W, Ottl J, Lingel A, Bussiere DE,
Yu Z, Atadja P, Lu C, Li E, Gu J, Zhao K (2017) Discovery and molecular basis of
a diverse set of polycomb repressive complex 2 inhibitors recognition by EED. PLoS One
12(1):e0169855. https://doi.org/10.1371/journal.pone.0169855
398
G. Sbardella
lineage leukemia 1 (MLL1) and histone 3 peptides to WD repeat domain 5 (WDR5) for the
design of inhibitors of the MLL1-WDR5 interaction. J Med Chem 53(14):5179–5185. https://
doi.org/10.1021/jm100139b
231. Karatas H, Townsend EC, Cao F, Chen Y, Bernard D, Liu L, Lei M, Dou Y, Wang S (2013)
High-affinity, small-molecule peptidomimetic inhibitors of MLL1/WDR5 protein-protein
interaction. J Am Chem Soc 135(2):669–682. https://doi.org/10.1021/ja306028q
232. Karatas H, Li Y, Liu L, Ji J, Lee S, Chen Y, Yang J, Huang L, Bernard D, Xu J, Townsend EC,
Cao F, Ran X, Li X, Wen B, Sun D, Stuckey JA, Lei M, Dou Y, Wang S (2017) Discovery
of a highly potent, cell-permeable macrocyclic peptidomimetic (MM-589) targeting the
WD repeat domain 5 protein (WDR5)-mixed lineage leukemia (MLL) protein-protein interaction. J Med Chem 60(12):4818–4839. https://doi.org/10.1021/acs.jmedchem.6b01796
233. Senisterra G, Wu H, Allali-Hassani A, Wasney GA, Barsyte-Lovejoy D, Dombrovski L,
Dong A, Nguyen KT, Smil D, Bolshan Y, Hajian T, He H, Seitova A, Chau I, Li F,
Poda G, Couture JF, Brown PJ, Al-Awar R, Schapira M, Arrowsmith CH, Vedadi M (2013)
Small-molecule inhibition of MLL activity by disruption of its interaction with WDR5.
Biochem J 449(1):151–159. https://doi.org/10.1042/BJ20121280
234. Bolshan Y, Getlik M, Kuznetsova E, Wasney GA, Hajian T, Poda G, Nguyen KT, Wu H,
Dombrovski L, Dong A, Senisterra G, Schapira M, Arrowsmith CH, Brown PJ, Al-Awar R,
Vedadi M, Smil D (2013) Synthesis, optimization, and evaluation of novel small molecules as
antagonists of WDR5-MLL interaction. ACS Med Chem Lett 4(3):353–357. https://doi.org/
10.1021/ml300467n
235. Getlik M, Smil D, Zepeda-Velazquez C, Bolshan Y, Poda G, Wu H, Dong A, Kuznetsova E,
Marcellus R, Senisterra G, Dombrovski L, Hajian T, Kiyota T, Schapira M, Arrowsmith CH,
Brown PJ, Vedadi M, Al-Awar R (2016) Structure-based optimization of a small molecule
antagonist of the interaction between WD repeat-containing protein 5 (WDR5) and mixedlineage leukemia 1 (MLL1). J Med Chem 59(6):2478–2496. https://doi.org/10.1021/acs.
jmedchem.5b01630
236. Li DD, Chen WL, Wang ZH, Xie YY, Xu XL, Jiang ZY, Zhang XJ, You QD, Guo XK (2016)
High-affinity small molecular blockers of mixed lineage leukemia 1 (MLL1)-WDR5 interaction inhibit MLL1 complex H3K4 methyltransferase activity. Eur J Med Chem 124:480–489.
https://doi.org/10.1016/j.ejmech.2016.08.036
237. Li DD, Chen WL, Xu XL, Jiang F, Wang L, Xie YY, Zhang XJ, Guo XK, You QD, Sun HP
(2016) Structure-based design and synthesis of small molecular inhibitors disturbing the
interaction of MLL1-WDR5. Eur J Med Chem 118:1–8. https://doi.org/10.1016/j.ejmech.
2016.04.032
238. Li DD, Wang ZH, Chen WL, Xie YY, You QD, Guo XK (2016) Structure-based design
of ester compounds to inhibit MLL complex catalytic activity by targeting mixed lineage
leukemia 1 (MLL1)-WDR5 interaction. Bioorg Med Chem 24(22):6109–6118. https://doi.org/
10.1016/j.bmc.2016.09.073
239. Lu J, Li X, Wang Q, Pei G (2017) Dopamine D2 receptor and beta-arrestin 2 mediate
Amyloid-beta elevation induced by anti-Parkinson’s disease drugs, levodopa and piribedil,
in neuronal cells. PLoS One 12(3):e0173240. https://doi.org/10.1371/journal.pone.0173240
240. Zhang X, Zheng X, Yang H, Yan J, Fu X, Wei R, Xu X, Zhang Z, Yu A, Zhou K, Ding J,
Geng M, Huang X (2018) Piribedil disrupts the MLL1-WDR5 interaction and sensitizes
MLL-rearranged acute myeloid leukemia (AML) to doxorubicin-induced apoptosis. Cancer
Lett 431:150–160. https://doi.org/10.1016/j.canlet.2018.05.034
241. Xie J, Wang C, Virostko J, Manning HC, Pham W, Bauer J, Gore JC (2013) A novel
reporter system for molecular imaging and high-throughput screening of anticancer drugs.
Chembiochem 14(12):1494–1503. https://doi.org/10.1002/cbic.201300142
242. Li L, Zhang H, Zhang M, Zhao M, Feng L, Luo X, Gao Z, Huang Y, Ardayfio O, Zhang JH,
Lin Y, Fan H, Mi Y, Li G, Liu L, Feng L, Luo F, Teng L, Qi W, Ottl J, Lingel A, Bussiere DE,
Yu Z, Atadja P, Lu C, Li E, Gu J, Zhao K (2017) Discovery and molecular basis of
a diverse set of polycomb repressive complex 2 inhibitors recognition by EED. PLoS One
12(1):e0169855. https://doi.org/10.1371/journal.pone.0169855
398
G. Sbardella