T0070907 is a potent and selective peroxisome proliferator-activated receptor γ (PPARγ) antagonist with an IC50 value of 1nM[1]. T0070907 is an anti-microtubule drug that can reduce α and β tubulin in colon cancer cells[2]. T0070907 can inhibit adipogenesis and induce rapid apoptosis of immature adipocytes[3].
In vitro, T0070907 (0.1-20μM) treatment of breast cancer MB-231 cells for 48h inhibited cell migration and invasion in a dose-dependent manner[4]. T0070907 (50μM) treatment of liver cancer HepG2 and Hep3B cells for 48h prevented cell reattachment to extracellular matrix (ECM) proteins and induced cell anoikis[5].
In vivo, oral administration of T0070907 (1, 5mg/kg/day) for 4 weeks to mice bearing HT-29 cell xenografts significantly reduced the number of liver tumor metastases and the size of tumor tissue in mice[6].
References:
[1] Lee G, Elwood F, McNally J, et al. T0070907, a selective ligand for peroxisome proliferator-activated receptor γ, functions as an antagonist of biochemical and cellular activities[J]. Journal of Biological Chemistry, 2002, 277(22): 19649-19657.
[2] An Z, Yu J R, Park W Y. T0070907 inhibits repair of radiation-induced DNA damage by targeting RAD51[J]. Toxicology In Vitro, 2016, 37: 1-8.
[3] Kawahara A, Haraguchi N, Tsuchiya H, et al. Peroxisome proliferator-activated receptor γ (PPARγ)-independent specific cytotoxicity against immature adipocytes induced by PPARγ antagonist T0070907[J]. Biological and Pharmaceutical Bulletin, 2013, 36(9): 1428-1434.
[4] Zaytseva Y Y, Wallis N K, Southard R C, et al. The PPARγ antagonist T0070907 suppresses breast cancer cell proliferation and motility via both PPARγ-dependent and-independent mechanisms[J]. Anticancer research, 2011, 31(3): 813-823.
[5] Schaefer K L, Wada K, Takahashi H, et al. Peroxisome proliferator-activated receptor γ inhibition prevents adhesion to the extracellular matrix and induces anoikis in hepatocellular carcinoma cells[J]. Cancer Research, 2005, 65(6): 2251-2259.
[6] Schaefer K L, Takahashi H, Morales V M, et al. PPARγ inhibitors reduce tubulin protein levels by a PPARγ, PPARδ and proteasome‐independent mechanism, resulting in cell cycle arrest, apoptosis and reduced metastasis of colorectal carcinoma cells[J]. International journal of cancer, 2007, 120(3): 702-713.
T0070907是一种有效的选择性过氧化物酶体增殖物激活受体γ(PPARγ)拮抗剂,IC50值为1nM[1]。T0070907是一种抗微管药物,能够降低结肠癌细胞中的α和β微管蛋白[2]。T0070907能够抑制脂肪生成,诱导未成熟脂肪细胞快速凋[3]。
在体外,T0070907(0.1-20μM)处理乳腺癌MB-231细胞48h,以剂量依赖性方式抑制了细胞迁移和侵袭[4]。T0070907(50μM)处理肝癌HepG2和Hep3B细胞48h,阻止了细胞与细胞外基质(ECM)蛋白的再附着,诱导了细胞的失巢凋亡[5]。
在体内,T0070907(1, 5mg/kg/day)通过口服治疗HT-29细胞异种移植小鼠4周,显著减少了小鼠体内肝脏肿瘤转移灶的数量,减小了肿瘤组织的大小[6]。
















