for the development of functional modulators of pseudokinases that have been
linked to the development of many diseases but which have not been targeted
so far. Efficient development of allosteric inhibitors would require an even better
understanding of the molecular mechanisms of kinase regulation and the dynamic
properties of these enzymes. The fraction of the kinome that has been successfully
targeted is still quite small despite the large number of disease associations that
have been identified for kinases that have not been extensively studied as targets
for the development of drugs [8]. It is therefore likely that many new kinases will
be explored for the development of new medicines in the future.
Compliance with Ethical Standards
Conflict of interest: The authors have no conflict of interest.
Funding: The authors are grateful for support by the SGC, a registered charity (number 1097737)
that receives funds from AbbVie, Bayer Pharma AG, Boehringer Ingelheim, Canada Foundation for
Innovation, Eshelman Institute for Innovation, Genome Canada, Innovative Medicines Initiative
(EU/EFPIA), Janssen, Merck KGaA Darmstadt Germany, MSD, Novartis Pharma AG, Ontario
Ministry of Economic Development and Innovation, Pfizer, São Paulo Research FoundationFAPESP, Takeda, and Wellcome [106169/ZZ14/Z].
Ethical Approval: This manuscript is a review of previously published accounts, as such no animal
or human studies were performed.
References
1. Manning G et al (2002) The protein kinase complement of the human genome. Science
298(5600):1912–1934
2. Ishikawa HO et al (2012) The Raine syndrome protein FAM20C is a Golgi kinase that
phosphorylates bio-mineralization proteins. PLoS One 7(8):e42988
3. Cui J et al (2015) A secretory kinase complex regulates extracellular protein phosphorylation.
elife 4:e06120
4. Zhang H et al (2018) Structure and evolution of the Fam20 kinases. Nat Commun 9(1):1218
5. Taylor SS et al (2013) Pseudokinases from a structural perspective. Biochem Soc Trans
41(4):981–986
6. Boudeau J et al (2006) Emerging roles of pseudokinases. Trends Cell Biol 16(9):443–452
7. Knapp S, Sundstrom M (2014) Recently targeted kinases and their inhibitors-the path to
clinical trials. Curr Opin Pharmacol 17:58–63
8. Fedorov O, Muller S, Knapp S (2010) The (un)targeted cancer kinome. Nat Chem Biol
6(3):166–169
9. van Linden OP et al (2014) KLIFS: a knowledge-based structural database to navigate
kinase-ligand interaction space. J Med Chem 57(2):249–277
10. Liu Q et al (2013) Developing irreversible inhibitors of the protein kinase cysteinome.
Chem Biol 20(2):146–159
11. Chaikuad A et al (2018) The Cysteinome of protein kinases as a target in drug development.
Angew Chem Int Ed Engl 57(16):4372–4385
12. Mobitz H, Jahnke W, Cowan-Jacob SW (2017) Expanding the opportunities for modulating
kinase targets with allosteric approaches. Curr Top Med Chem 17(1):59–70
13. Cowan-Jacob SW, Jahnke W, Knapp S (2014) Novel approaches for targeting kinases:
allosteric inhibition, allosteric activation and pseudokinases. Future Med Chem 6(5):541–561
18
S. Röhm et al.
linked to the development of many diseases but which have not been targeted
so far. Efficient development of allosteric inhibitors would require an even better
understanding of the molecular mechanisms of kinase regulation and the dynamic
properties of these enzymes. The fraction of the kinome that has been successfully
targeted is still quite small despite the large number of disease associations that
have been identified for kinases that have not been extensively studied as targets
for the development of drugs [8]. It is therefore likely that many new kinases will
be explored for the development of new medicines in the future.
Compliance with Ethical Standards
Conflict of interest: The authors have no conflict of interest.
Funding: The authors are grateful for support by the SGC, a registered charity (number 1097737)
that receives funds from AbbVie, Bayer Pharma AG, Boehringer Ingelheim, Canada Foundation for
Innovation, Eshelman Institute for Innovation, Genome Canada, Innovative Medicines Initiative
(EU/EFPIA), Janssen, Merck KGaA Darmstadt Germany, MSD, Novartis Pharma AG, Ontario
Ministry of Economic Development and Innovation, Pfizer, São Paulo Research FoundationFAPESP, Takeda, and Wellcome [106169/ZZ14/Z].
Ethical Approval: This manuscript is a review of previously published accounts, as such no animal
or human studies were performed.
References
1. Manning G et al (2002) The protein kinase complement of the human genome. Science
298(5600):1912–1934
2. Ishikawa HO et al (2012) The Raine syndrome protein FAM20C is a Golgi kinase that
phosphorylates bio-mineralization proteins. PLoS One 7(8):e42988
3. Cui J et al (2015) A secretory kinase complex regulates extracellular protein phosphorylation.
elife 4:e06120
4. Zhang H et al (2018) Structure and evolution of the Fam20 kinases. Nat Commun 9(1):1218
5. Taylor SS et al (2013) Pseudokinases from a structural perspective. Biochem Soc Trans
41(4):981–986
6. Boudeau J et al (2006) Emerging roles of pseudokinases. Trends Cell Biol 16(9):443–452
7. Knapp S, Sundstrom M (2014) Recently targeted kinases and their inhibitors-the path to
clinical trials. Curr Opin Pharmacol 17:58–63
8. Fedorov O, Muller S, Knapp S (2010) The (un)targeted cancer kinome. Nat Chem Biol
6(3):166–169
9. van Linden OP et al (2014) KLIFS: a knowledge-based structural database to navigate
kinase-ligand interaction space. J Med Chem 57(2):249–277
10. Liu Q et al (2013) Developing irreversible inhibitors of the protein kinase cysteinome.
Chem Biol 20(2):146–159
11. Chaikuad A et al (2018) The Cysteinome of protein kinases as a target in drug development.
Angew Chem Int Ed Engl 57(16):4372–4385
12. Mobitz H, Jahnke W, Cowan-Jacob SW (2017) Expanding the opportunities for modulating
kinase targets with allosteric approaches. Curr Top Med Chem 17(1):59–70
13. Cowan-Jacob SW, Jahnke W, Knapp S (2014) Novel approaches for targeting kinases:
allosteric inhibition, allosteric activation and pseudokinases. Future Med Chem 6(5):541–561
18
S. Röhm et al.