Apogossypolone (ApoG2) is a semi-synthesized derivative of gossypol which is a nonpeptidic small molecule inhibitor targeting Bcl-2 family proteins with K i values of 35, 25 and 660 nM for Bcl-2, Mcl-1 and Bcl-X L, respectively. Apogossypolone shows antitumor activities, induces cell apoptosis [1] and autophagy [2]. Apogossypolone also has antifungal activity [3].

Mcl-1:25 nM (Ki), Bcl-xL:660 nM (Ki), Bcl-2:35 nM (Ki)

Apogossypolone (ApoG2) shows better stability under stressed conditions [1]. Apogossypolone (0-1 μM, 72 or 96 h) inhibits WSU-DLCL 2 cells growth in a dose-dependent manner [1]. Apogossypolone (0-5 μM, 24 or 48 h) interferes with the formation of heterodimers between anti-apoptotic and pro-apoptotic Bcl-2 family members, and leads to cleavage of caspase-3, caspase-9 and PARP [1]. Apogossypolone (0-8 μM, 0-72 h) induces apoptotic WSU-DLCL 2 cell death in a time- and dose-dependent manner [1]. Apogossypolone (0-10 μM, 0-24 h) induces autophagy and promotes ROS generation in HCC cells [2]. Cell Proliferation Assay [1] Cell Line: WSU-DLCL 2 Concentration: 250, 350, 500 and 1000 nM Incubation Time: 96 h for cell counting, 72 h for MTT Result: Inhibited growth in a dose-dependent manner. The 50% growth inhibition concentration (IC 50 ) was approximately 350 nM. Western Blot Analysis [1] Cell Line: WSU-DLCL 2 Concentration: 0.35, 0.5, 1 and 5 μM Incubation Time: 24 or 48 h Result: Blocked the formation of heterodimers between Bcl-X L and Bim in a concentration-dependent manner. Resulted in the activation of cleavages of caspase-3, caspase-9 and PARP. Apoptosis Analysis [1] Cell Line: WSU-DLCL 2 Concentration: 0, 1, 2, 4 and 8 μM Incubation Time: 24, 48 and 72 h Result: Induced cell apoptosis in a time- and dose-dependent manner. Cell Autophagy Assay [2] Cell Line: HepG2 and Hep3B Concentration: 1.25, 2.5, 5 and 10 μM Incubation Time: 6, 12, 18 and 24 h Result: Induced LC3 (Light chain 3)-II conversion in a dose- and time-dependent manner.

Apogossypolone (ApoG2) (120 mg/kg; i.v. or p.o.; once a day for 5 days) can effectively inhibit growth of diffuse large cell lymphoma cells without toxicity [1]. Animal Model: Four-week-old female ICR-SCID mice, each mouse received 10 7 WSU-DLCL 2 cells (in serum-free RPMI 1640) subcutaneously (sc) in each flank area [1] Dosage: 120 mg/kg Administration: Intravenous or administration per day for five days Result: Inhibited the growth of WSU-DLCL 2 and significantly decreased the tumor weight. Animal Model: Non-tumor-bearing SCID mice [1] Dosage: 160 mg/kg Administration: Intravenous or administration per day for five days Result: Was well tolerated in mice up to 800 mg/kg. Displayed no gross signs of toxicity.