ACBI2 is a highly potent and orally active VHL PROTAC SMARCA2 degrader (EC50: 7 nM), which selectively degrades SMARCA2 with a DC50 value of 1 nM in RKO cells. ACBI2 can be used in the research of lung cancer.
ACBI2 degrades SMARCA2 and SMARCA4 in RKO cells, with DC50s of 1 nM and 32 nM respectively[1].ACBI2 (0.1 nM-1 μM, 4-18 h) rapidly and completely degrades SMARCA2 in two sensitive cell lines (A549 and NCI-H1568)[1].ACBI2 (1 nM-1 μM, 18 h) significantly degrades SMARCA2 with clear selectivity over SMARCA4[1].ACBI2 (0-1 μM; 18 h) dose-dependently degrades SMARCA2 in human whole blood[1].
ACBI2 (80 mg/kg, p.o., once daily) significantly inhibits tumor growth in an A549 xenograft mice model[1].ACBI2 (5-100 mg/kg, p.o., tumors collected 24 or 48 h after treatment) dose-dependently degrades tumor SMARCA2 in A549 engrafted tumor bearing mice (IHC staining)[1].ACBI2 (30 mg/kg, p.o., mice) shows oral bioavailability of 22%[1].
References:
[1]. Kofink C, et al. A selective and orally bioavailable VHL-recruiting PROTAC achieves SMARCA2 degradation in vivo. Nat Commun. 2022 Oct 10;13(1):5969.