errors are shown. The trendline (black, partly obscured by the line of unity), equation, and R2 were calculated based on all the data combined, showing almost linear slope and very little offset.
Source: Reproduced with permission. Copyright© 2020, American Chemical Society [130].
Figure 2.6 Structures of initial hit and lead compound [130].
2.4 Conclusion and Future Outlook
For the many researchers who have dedicated decades of their professional lives to the invention, development, and improvement of computational methods to aid drug discovery, it is deeply gratifying to now routinely see reports of these methods accelerating the discovery of novel and more effective drug therapies. These computational methods enable discovery teams to more comprehensively vet protein targets under consideration for project tractability and rapidly discover novel hits as was demonstrated for ACC and KRAS, and also accelerate hit‐to‐lead and lead optimization, as was shown for PDE2A and TYK2. Yet, despite these successes, there is clearly a great deal of work yet to do. We anticipate a major focus of future work to include the development of mixed experimental/computational approaches such as machine learning enhanced DNA‐encoded library screening and FEP‐guided fragment linking. We would also highlight that the development of predictive ADMET methods, especially related to rate of clearance, is an area clearly in need of improvement. We are excited though by the progress that has been made and look forward to what will be accomplished in the future.
References
1 1 Fortune (1981). The next industrial revolution: designing drugs by computer at Merck. https://www.backissues.com/issue/Fortune‐October‐05‐1981 (accessed 29 August 2020).
2 2 Seddon, G., Lounnas, V., McGuire, R. et al. (2012). Drug design for ever, from hype to hope. J. Comput. Aided Mol. Des. 26: 137.
3 3 Atlas Venture (2013). The Nimbus experiment: structure‐based drug deals. https://lifescivc.com/2013/06/the‐nimbus‐experiment‐structure‐based‐drug‐deals (accessed 29 August 2020).
4 4 Atlas Venture (2016). Nimbus delivers its Apollo Mission: a $1.2B Gilead partnership. https://lifescivc.com/2016/04/nimbus‐delivers‐apollo‐mission‐1‐2b‐gilead‐partnership (accessed 29 August 2020)
5 5 Al Idrus, A. (2020). BIO: Nimbus CEO Keiper: “We're not just a one‐hit wonder”. https://www.fiercebiotech.com/biotech/bio‐nimbus‐ceo‐we‐re‐not‐just‐a‐one‐hit‐wonder (accessed 29 August 2020).
6 6 Nimbus Therapeutics (2020). Pipeline & Targets. https://www.nimbustx.com/pipeline‐targets (accessed 30 August 2020).
7 7 BioSpace (2019). Schrödinger expands drug discovery partnership with Morphic Therapeutic. https://www.biospace.com/article/schrodinger‐expands‐drug‐discovery‐partnership‐with‐morphic‐therapeutic (accessed 29 August 2020).
8 8 Morphic Therapeutic (2020). Morphic announces corporate highlights and second quarter 2020 financial results. https://investor.morphictx.com/news‐releases/news‐release‐details/morphic‐announces‐corporate‐highlights‐and‐second‐quarter‐2020 (accessed 29 August 2020).
9 9 Morphic Therapeutic (2020). Integrins in human disease. https://morphictx.com/pipeline (accessed 30 August 2020).
10 10 Bhat, S., Dahlgren, M.K., Giordanetto, F. et al. (2020). Pyrazolo[3,4‐b]pyrazine derivatives as shp2 phosphatase inhibitors. https://uspto.report/patent/app/20200253969 (accessed 29 August 2020).
11 11 Bhat, S., Dahlgren, M.K., DiPietro, L.V. et al. (2020). Pyrazolo[3,4‐b]pyrazine derivatives as shp2 phosphatase inhibitors. https://uspto.report/patent/app/20200172546 (accessed 29 August 2020).
12 12 Bhat, S., Dahlgren, M.K., DiPietro, L.V. et al. (2020). shp2 phosphatase inhibitors and methods of use thereof https://uspto.report/patent/app/20200062760 (accessed 29 August 2020).
13 13 Murcko, M. (2018).Workshop on free energy, kinetics, and Markov state models. https://www.youtube.com/watch?v=T4zEx‐l10BQ (accessed 29 August 2020).
14 14 Relay Therapeutics (2020).Our focus on protein motion is creating new possibilities in drug discovery. https://relaytx.com/pipeline (accessed 30 August 2020).
15 15 Business WIre (2020).Schrödinger and Bayer collaborate to co‐develop de novo design technology to accelerate drug discovery. https://www.businesswire.com/news/home/20200108005059/en/Schr%C3%B6dinger‐Bayer‐Collaborate‐Co‐Develop‐de‐novo‐Design (accessed 29 August 2020).
16 16 Business WIre (2019).Schrödinger announces collaboration with AstraZeneca to deploy advanced computing technology for drug discovery. https://www.businesswire.com/news/home/20190904005166/en/Schr%C3%B6dinger‐Announces‐Collaboration‐AstraZeneca‐Deploy‐Advanced‐Computing (accessed 29 August 2020).
17 17 Business WIre (2020).Schrödinger announces expanded collaboration with AstraZeneca to extend computational modeling solutions to biologics. https://www.businesswire.com/news/home/20200323005050/en/Schr%C3%B6dinger‐Announces‐Expanded‐Collaboration‐AstraZeneca‐Extend‐Computational (accessed 29 August 2020).
18 18 Rees, V. (2020).Discovering and designing drugs with artificial intelligence. https://www.drugtargetreview.com/article/56366/discovering‐and‐designing‐drugs‐with‐artificial‐intelligence (accessed 30 August 2020).
19 19 Bell, J.A., Cao, Y., Gunn, J.R. et al. (2012). PrimeX and the Schrödinger computational chemistry suite of programs. In: International. Tables for Crystallography, 534–538. Wiley
