IG-105

IG-105 is a potent tubulin inhibitor, with an IC₅₀ of 0.6 μM for competitive inhibition of [³H] colchicine binding to tubulin, and an IC₅₀ of 3 μM for inhibition of tubulin polymerization. IG-105 inhibits microtubule polymerization by binding to the colchicine pocket of tubulin, induces cell cycle arrest at the G2-M phase, and subsequently activates the caspase cascade through Bcl-2 inactivation and p53 upregulation to induce apoptosis. As a non-Pgp substrate, IG-105 effectively overcomes multidrug resistance. IG-105 can be used in the research of leukemia, breast cancer, liver cancer, prostate cancer, lung cancer, melanoma, pancreatic cancer and colon cancer^[1]. In Vitro:IG-105 (up to 1 μM; 72 h) exerts significant inhibitory effects on cell growth and viability in CEM, Molt-3, DND-1, MIA PaCa-2, MCF-7, Bel-7402, SW620, LoVo, DU-145, NCI-H23, SMMC-7721, MCF-7/Dox/Pgp and HUVEC cells, with IC₅₀ values ranging from 0.012 to 0.298 μM; in contrast, its inhibitory activity against non-malignant HUVEC cells is much weaker (IC₅₀ = 2.52 μM)^[1].
IG-105 (2 μM) does not stimulate P-glycoprotein (Pgp) ATPase activity in a cell-free system^[1].
IG-105 (0.16-6 μM; 30 min) potently inhibits tubulin polymerization in a cell-free system with an IC₅₀ of 3 μM. It also competitively inhibits [³H]colchicine binding with an IC₅₀ of 0.6 μM, and does not interact with the vinca alkaloid binding pocket^[1].
IG-105 (0.35 μM; 12 h) disrupts the cellular microtubule network and induces microtubule depolymerization in human hepatocellular carcinoma Bel-7402 cells^[1].
IG-105 (0.35 μM; 3-36 h) induces G₂-M phase arrest in human hepatocellular carcinoma cell line Bel-7402, upregulates cyclin B1 protein expression and downregulates cyclin D1 protein expression in a time-dependent manner, induces Bcl-2 phosphorylation, promotes caspase-3 cleavage, and upregulates the expressions of p53 and p21^[1].
IG-105 (0.086-0.346 μM for 48 h and 0.35 μM for 12-48 h) induces apoptotic DNA fragmentation in human hepatocellular carcinoma Bel-7402 cells^[1].
IG-105 (0.35 μM; 6-24 h) significantly enhances the activities of caspase-9, caspase-8, and caspase-3 in human hepatocellular carcinoma Bel-7402 cells^[1]. In Vivo:IG-105 (100-275 mg/kg; i.p.; once every two days; starting on day 11 post tumor implantation) significantly and completely inhibits tumor growth in a subcutaneous xenograft model of human hepatocellular carcinoma^[1].
IG-105 (100-200 mg/kg; i.p.; once every two days; starting on day 14 after tumor inoculation) significantly inhibits tumor growth in a subcutaneous xenograft model of human breast cancer^[1].
IG-105 (175 mg/kg; i.p.; once every two days; starting on day 11 post tumor implantation) converts subcurative doses of drugs into a synergistic complete control of tumor growth when combined with Oxaliplatin (HY-17371) or Doxorubicin (HY-15142) in a human hepatocellular carcinoma subcutaneous xenograft model^[1].
IG-105 (400-1000 mg/kg; i.p.; single administration; observation for 15 days) exhibits favorable safety in the acute toxicity model of healthy mice, with no lethal or significant pathological toxicity observed^[1].