"目录号: HY-13686
Protein Tyrosine Kinase/RTK-
PQ401是IGF1R阻断剂，能抑制IGF1R自磷酸化，IC50 < 1 uM。
IGF-1R
相关产品
LDK378-Linsitinib-BMS-754807-NVP-AEW541-AXL1717-BMS-536924-AG1024-AZD-3463-GSK1838705A-XL228-NVP-ADW742-GSK1904529A-
生物活性
Description
PQ401, a selective insulin-like growth factor-1 receptor blocker, is a novel diarylurea compound that inhibits IGF1R autophosphorylation with IC50 < 1 uM.IC50 Value: 12 uM (inhibited autophosphorylation of the IGF-IR in cultured human MCF-7 cells) [1]Target: IGF1Rin vitro: PQ401 inhibited autophosphorylation of the IGF-IR in cultured human MCF-7 cells with an IC50 of 12 micromol/L and autophosphorylation of the isolated kinase domain of the IGF-IR with an IC50 <1 micromol/L. In addition,PQ401 inhibited the growth of cultured breast cancer cells in serum at 10 micromol/L. PQ401 was even more effective at inhibiting IGF-I-stimulated growth of MCF-7 cells (IC50, 6 micromol/L) [1]. Twenty-four hours of treatment with 15 micromol/L PQ401 induced caspase-mediated apoptosis. Pretreatment with PQ401 before IGF-1 (10 ng in 0.5 μl), both administered to the POA 30 min apart, showed significant attenuation of the IGF-1-induced increase in core body temperature (p < 0.05). A similar attenuated hyperthermic response to IGF-1 by PQ401 pretreatment is observed when the temperature of the BAT is measured [3].in vivo: IGF1R inhibition by PQ401 exerted no significant effects on diabetic kidney disease parameters, arguing against a role for IGF-I in the pathogenesis of diabetic kidney disease. However, PQ401 affects normal kidneys, inducing renal hypertrophy as well as collagen and fat accumulation, with increased renal IGF-I mRNA, suggestive of a damage-regeneration process [2].Clinical trial: No Development Reported
References
[1].Gable KL, Maddux BA, Penaranda C, Diarylureas are small-molecule inhibitors of insulin-like growth factor I receptor signaling and breast cancer cell growth. Mol Cancer Ther. 2006 Apr;5(4):1079-86.
[2].Troib A, Landau D, Youngren JF, The effects of type 1 IGF receptor inhibition in a mouse model of diabetic kidney disease. Growth Horm IGF Res. 2011 Oct;21(5):285-91.
[3].Sanchez-Alavez M, Osborn O, Tabarean IV, Insulin-like growth factor 1-mediated hyperthermia involves anterior hypothalamic insulin receptors. J Biol Chem. 2011 Apr 29;286(17):14983-90.