OTUB2-IN-1

OTUB2-IN-1, a specific inhibitor of OTUB2 (KD: ~12 μM), reduces PD-L1 protein expression in tumor cells and inhibits tumor growth by promoting robust intra-tumor infiltration of cytotoxic T lymphocytes (CTL) .

OTUB2-IN-1 (0-40 μM) reduces PD-L1 levels in tumor cells (NCI-H358, SK-MES-1, and NCI-H226) in a dose-dependent manner, but it is unable to affect OTUB2 stability^[1].
OTUB2-IN-1 (0-50 μM; 1 h) does not interfere with protein interactions between OTUB2 and PD-L1^[1].
OTUB2-IN-1 (10 μM; 0-4 d) can’t inhibit the viability of B16-F10 tumor cells^[1].

OTUB2-IN-1 (20 mg/kg; i.p.; daily for five days) suggests the potential to enhance immune recognition and immune response of tumor cells in mice implanted with B16-F10 cells^[1].
OTUB2-IN-1 （20 mg/kg; i.p.; daily for five days）reduces the expression of YAP and phosphorylated p65 in mice implanted with LL/2 cells; reduces phosphorylated Akt expression in mice implanted with B16-F10 cells and it reduces phosphorylated p65 expression in mice implanted with KLN205 cells^[1].

References:
[1]. Ren W et al. Pharmaceutical targeting of OTUB2 sensitizes tumors to cytotoxic T cells via degradation of PD-L1. Nat Commun. 2024 Jan 2;15(1):9.