BX795 is an inhibitor of 3-phosphoinositide-dependent protein kinase 1 (PDK1), with an IC50 value of 11nM. BX795 blocks the PDK1/Akt signaling pathway in tumor cells, inhibits the anchorage-dependent growth of various tumor cell lines in vitro, or induces their apoptosis. BX795 also inhibits TANK-binding kinase 1 (TBK1) and IκB kinase ε (IKKε), with the IC50 values of 6 and 41nM, respectively. BX795 potently inhibits diverse HSV-1 strains across transformed human cells, primary corneal cultures (human and animal), and murine ocular surface models. BX795 shows substantial promise as a broad-spectrum human antiviral[1][2][3].
In vitro, BX795 (0.1-10µM; 18h) dose-dependently inhibited the levels of phospho-Thr308-Akt and phospho-Thr389-S6K1 in PC-3 cells[1]. BX795 potently inhibited the growth of PC-3 cells in soft agar, displaying IC50 value of 0.25µM[1]. BX795 (1µM; 60min) blocks TBK1- and IKKε-mediated Activation of IRF3 and Production of IFN-β in HEK293-TLR3 cells[2]. BX795 (3.125-25μM; 24h) inhibited the replication of HSV-1 (HF) and HSV-2 (G) in HEC-1-A and Vero cells in a dose-dependent manner[3].
In vivo, BX795 (20mg/kg; i.p.; every other day for 8 doses) significantly reduced brain metastasis and prolonged survival in brain-metastatic mouse models[4]. BX795 (0.0473mg/kg; 10μL; twice a week for 8 weeks）alleviated cartilage degeneration, synovitis, and OA pain, and improved cartilage inflammation, senescence, and matrix metabolism in Destabilization of the Medial Meniscus (DMM)-induced mouse osteoarthritis models[5].
References:
[1] Feldman RI, Wu JM, Polokoff MA, et al. Novel small molecule inhibitors of 3-phosphoinositide-dependent kinase-1. J Biol Chem. 2005;280(20):19867-19874. doi:10.1074/jbc.M501367200.
[2] Clark K, Plater L, Peggie M, Cohen P. Use of the pharmacological inhibitor BX795 to study the regulation and physiological roles of TBK1 and IkappaB kinase epsilon: a distinct upstream kinase mediates Ser-172 phosphorylation and activation. J Biol Chem. 2009;284(21):14136-14146.
[3] Su AR, Qiu M, Li YL, et al. BX-795 inhibits HSV-1 and HSV-2 replication by blocking the JNK/p38 pathways without interfering with PDK1 activity in host cells. Acta Pharmacol Sin. 2017;38(3):402-414.
[4] Khan F, Petrosyan E, Liu Y, et al. Microglial TBK1 Signaling Promotes Breast Cancer Brain Metastasis. Cancer Res. 2026;86(1):12-21.
[5] Lu R, Qu Y, Wang Z, et al. TBK1 pharmacological inhibition mitigates osteoarthritis through attenuating inflammation and cellular senescence in chondrocytes. J Orthop Translat. 2024;47:207-222.