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117. Wu P, Clausen MH, Nielsen TE (2015) Allosteric small-molecule kinase inhibitors.
Pharmacol Ther 156:59–68
118. Hashemzadeh S, Ramezani F, Rafii-Tabar H (2018) Study of molecular mechanism of the
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119. Roskoski Jr R (2017) Allosteric MEK1/2 inhibitors including cobimetanib and trametinib
in the treatment of cutaneous melanomas. Pharmacol Res 117:20–31
120. Shang J et al (2016) Allosteric modulators of MEK1: drug design and discovery. Chem Biol
Drug Des 88(4):485–497
121. Iverson C et al (2009) RDEA119/BAY 869766: a potent, selective, allosteric inhibitor
of MEK1/2 for the treatment of cancer. Cancer Res 69(17):6839–6847
122. Bagal SK et al (2018) Discovery of allosteric, potent, subtype selective, and peripherally
restricted TrkA kinase inhibitors. J Med Chem 62(1):247–265
123. Furuya N et al (2017) The juxtamembrane region of TrkA kinase is critical for inhibitor
selectivity. Bioorg Med Chem Lett 27(5):1233–1236
124. Freeman SN, Mainwaring WI, Furr BJ (1989) A possible explanation for the peripheral
selectivity of a novel non-steroidal pure antiandrogen, Casodex (ICI 176,334). Br J Cancer
60(5):664–668
125. Lamba V, Ghosh I (2012) New directions in targeting protein kinases: focusing upon true
allosteric and bivalent inhibitors. Curr Pharm Des 18(20):2936–2945
126. Zhang J et al (2010) Targeting Bcr-Abl by combining allosteric with ATP-binding-site
inhibitors. Nature 463(7280):501–506
127. Nagar B et al (2003) Structural basis for the autoinhibition of c-Abl tyrosine kinase. Cell
112(6):859–871
128. Pendergast AM, Witte ON (1987) Role of the ABL oncogene tyrosine kinase activity in
human leukaemia. Baillieres Clin Haematol 1(4):1001–1020
129. Adrian FJ et al (2006) Allosteric inhibitors of Bcr-abl-dependent cell proliferation. Nat Chem
Biol 2(2):95–102
130. Schneider R et al (2012) Direct binding assay for the detection of type IV allosteric inhibitors
of Abl. J Am Chem Soc 134(22):9138–9141
131. Nagar B et al (2006) Organization of the SH3-SH2 unit in active and inactive forms of
the c-Abl tyrosine kinase. Mol Cell 21(6):787–798
132. Fang Z, Grutter C, Rauh D (2013) Strategies for the selective regulation of kinases with
allosteric modulators: exploiting exclusive structural features. ACS Chem Biol 8(1):58–70
133. Eadie LN et al (2018) The new allosteric inhibitor asciminib is susceptible to resistance
mediated by ABCB1 and ABCG2 overexpression in vitro. Oncotarget 9(17):13423–13437
134. Schoepfer J et al (2018) Discovery of Asciminib (ABL001), an allosteric inhibitor of
the tyrosine kinase activity of BCR-ABL1. J Med Chem 61(18):8120–8135
135. Converso A et al (2009) Development of thioquinazolinones, allosteric Chk1 kinase inhibitors.
Bioorg Med Chem Lett 19(4):1240–1244
136. Vanderpool D et al (2009) Characterization of the CHK1 allosteric inhibitor binding site.
Biochemistry 48(41):9823–9830
137. Rettenmaier TJ et al (2014) A small-molecule mimic of a peptide docking motif inhibits
the protein kinase PDK1. Proc Natl Acad Sci U S A 111(52):18590–18595
138. Hartnett JC et al (2008) Optimization of 2,3,5-trisubstituted pyridine derivatives as potent
allosteric Akt1 and Akt2 inhibitors. Bioorg Med Chem Lett 18(6):2194–2197
Function, Structure and Topology of Protein Kinases
23
of metastatic non-small cell lung cancers Harboring BRAF V600E mutations. Oncologist
23(6):740–745
115. Garnock-Jones KP (2015) Cobimetinib: First Global Approval. Drugs 75(15):1823–1830
116. Martin-Liberal J (2018) Encorafenib plus binimetinib: an embarrassment of riches. Lancet
Oncol 19(10):1263–1264
117. Wu P, Clausen MH, Nielsen TE (2015) Allosteric small-molecule kinase inhibitors.
Pharmacol Ther 156:59–68
118. Hashemzadeh S, Ramezani F, Rafii-Tabar H (2018) Study of molecular mechanism of the
interaction between MEK1/2 and Trametinib with docking and molecular dynamic simulation.
Interdiscip Sci 11(1):115–124
119. Roskoski Jr R (2017) Allosteric MEK1/2 inhibitors including cobimetanib and trametinib
in the treatment of cutaneous melanomas. Pharmacol Res 117:20–31
120. Shang J et al (2016) Allosteric modulators of MEK1: drug design and discovery. Chem Biol
Drug Des 88(4):485–497
121. Iverson C et al (2009) RDEA119/BAY 869766: a potent, selective, allosteric inhibitor
of MEK1/2 for the treatment of cancer. Cancer Res 69(17):6839–6847
122. Bagal SK et al (2018) Discovery of allosteric, potent, subtype selective, and peripherally
restricted TrkA kinase inhibitors. J Med Chem 62(1):247–265
123. Furuya N et al (2017) The juxtamembrane region of TrkA kinase is critical for inhibitor
selectivity. Bioorg Med Chem Lett 27(5):1233–1236
124. Freeman SN, Mainwaring WI, Furr BJ (1989) A possible explanation for the peripheral
selectivity of a novel non-steroidal pure antiandrogen, Casodex (ICI 176,334). Br J Cancer
60(5):664–668
125. Lamba V, Ghosh I (2012) New directions in targeting protein kinases: focusing upon true
allosteric and bivalent inhibitors. Curr Pharm Des 18(20):2936–2945
126. Zhang J et al (2010) Targeting Bcr-Abl by combining allosteric with ATP-binding-site
inhibitors. Nature 463(7280):501–506
127. Nagar B et al (2003) Structural basis for the autoinhibition of c-Abl tyrosine kinase. Cell
112(6):859–871
128. Pendergast AM, Witte ON (1987) Role of the ABL oncogene tyrosine kinase activity in
human leukaemia. Baillieres Clin Haematol 1(4):1001–1020
129. Adrian FJ et al (2006) Allosteric inhibitors of Bcr-abl-dependent cell proliferation. Nat Chem
Biol 2(2):95–102
130. Schneider R et al (2012) Direct binding assay for the detection of type IV allosteric inhibitors
of Abl. J Am Chem Soc 134(22):9138–9141
131. Nagar B et al (2006) Organization of the SH3-SH2 unit in active and inactive forms of
the c-Abl tyrosine kinase. Mol Cell 21(6):787–798
132. Fang Z, Grutter C, Rauh D (2013) Strategies for the selective regulation of kinases with
allosteric modulators: exploiting exclusive structural features. ACS Chem Biol 8(1):58–70
133. Eadie LN et al (2018) The new allosteric inhibitor asciminib is susceptible to resistance
mediated by ABCB1 and ABCG2 overexpression in vitro. Oncotarget 9(17):13423–13437
134. Schoepfer J et al (2018) Discovery of Asciminib (ABL001), an allosteric inhibitor of
the tyrosine kinase activity of BCR-ABL1. J Med Chem 61(18):8120–8135
135. Converso A et al (2009) Development of thioquinazolinones, allosteric Chk1 kinase inhibitors.
Bioorg Med Chem Lett 19(4):1240–1244
136. Vanderpool D et al (2009) Characterization of the CHK1 allosteric inhibitor binding site.
Biochemistry 48(41):9823–9830
137. Rettenmaier TJ et al (2014) A small-molecule mimic of a peptide docking motif inhibits
the protein kinase PDK1. Proc Natl Acad Sci U S A 111(52):18590–18595
138. Hartnett JC et al (2008) Optimization of 2,3,5-trisubstituted pyridine derivatives as potent
allosteric Akt1 and Akt2 inhibitors. Bioorg Med Chem Lett 18(6):2194–2197
Function, Structure and Topology of Protein Kinases
23