SB-02024

SB-02024 is an inhibitor of vacuolar protein sorting 34 (VPS34; IC₅₀ = 5 nM).¹ It selectively binds to VPS34 (K_d = 0.0011 ?M) over eight other PI3K kinases (K_ds = 1.2693->30 ?M), mTOR (K_d = 1.0199 ?M), a panel of 468 kinases at 1 ?M, and an additional panel of 97 kinases at 1 ?M.² SB-02024 (0.7 ?M) inhibits autophagic flux in H1299 cells. In vivo, SB-02024 (20 mg/kg) enhances increases in survival when used in combination with an antibody targeting programmed cell death protein 1 (PD-1) or PD-1 ligand (PD-L1) in B16/F10 murine melanoma and CT26 murine colorectal cancer models.³ SB-02024 (20 mg/kg) also enhances increases in survival and decreases in tumor volume when used in combination with the STING agonist ADU-S100 in a B16/F10 murine melanoma model.¹

References:
[1]. Yu, Y., Bogdan, M., Noman, M.Z., et al.Combining VPS34 inhibitors with STING agonists enhances type I interferon signaling and anti-tumor efficacyMol. Oncol.18(8)1904-1922(2024).
[2]. Dyczynski, M., Yu, Y., Otrocka, M., et al.Targeting autophagy by small molecule inhibitors of vacuolar protein sorting 34 (Vps34) improves the sensitivity of breast cancer cells to SunitinibCancer Lett.43532-43(2018).
[3]. Noman, M.Z., Parpal, S., Van More, K., et al.Inhibition of Vps34 reprograms cold into hot inflamed tumors and improves anti-PD-1/PD-L1 immunotherapySci. Adv.6(18)eaax7881(2020).