Development of isoform selective PI3-kinase inhibitors as pharmacological tools for elucidating the PI3K pathway
journal contribution
posted on 2023-06-08, 19:29authored byIan Bruce, Mohammed Akhlaq, Graham C Bloomfield, Emma Budd, Brian Cox, Bernard Cuenoud, Peter Finan, Peter Gedeck, Julia Hatto, Judy F Hayler, Denise Head, Thomas Keller, Louise Kirman, Catherine Leblanc, Darren Le Grand, Clive McCarthy, Desmond O'Connor, Charles Owen, Mrinalini S Oza, Gaynor Pilgrim, Nicola E Press, Lilya Sviridenko, Lewis Whitehead
Using a parallel synthesis approach to target a non-conserved region of the PI3K catalytic domain a pan-PI3K inhibitor 1 was elaborated to provide alpha, delta and gamma isoform selective Class I PI3K inhibitors 21, 24, 26 and 27. The compounds had good cellular activity and were selective against protein kinases and other members of the PI3K superfamily including mTOR and DNA-PK.