JET-209 (JET209) is a potent, selective PROTAC degrader of CBP/p300 based on GNE-207 with DC50 of 0.05 nM for CBP and 0.2 nM for p300, Dmax >95% for both proteins in the RS4;11 leukemia cell line.
JET-209 is extremely potent and effective in the inhibition of cell growth in the RS4;11 cell line with IC50 = 0.1 nM and Imax ≥ 94%.
JET-209 is also effective in the induction of cell cycle arrest in the RS4;11 cell line.
JET-209 is at least 1000 times more potent than CCS1477 and A-485 in inducing G1 cell cycle arrest in the RS4;11 cell line.
JET-209 is also a very potent inhibitor of cell growth in the MV4;11, HL-60, and MOLM-13 acute leukemia cell lines, achieving IC50 values of 0.04, 0.54, and 2.3 nM, respectively.
JET-209 potently and effectively suppresses the expression of MYC and MYB genes in the RS4;11 cell line.
JET-209 effectively depletes CBP/p300 proteins in RS4;11 xenograft tumors in mice, JET-209 (1 mg/kg twice a week or 3 mg/kg weekly for 2 weeks, IP injection) effectively inhibits tumor growth in xenograft tumor models.