560TiP A phase I/IIa study to evaluate the safety and efficacy of CCS1477, a first in clinic inhibitor of p300/CBP, as monotherapy in patients with selected molecular alterations

CCS1477 is a potent, selective, orally bioavailable inhibitor of the bromodomains of p300 and CBP, two closely related histone acetyl transferases with oncogenic roles in cancer. In vitro and in vivo models demonstrate molecular alterations that increase sensitivity to p300/CBP inhibition with CCS1477. Tumours with loss of function mutations in either p300 or CBP become dependent on the corresponding non-mutated paralogue (twin) protein. When the non-mutated twin is inhibited, this drives synthetic lethality leading to apoptosis/cell death.