| Description: |
PQ401 is a cell-permeable phenylquinolinyl-urea compound that inhibits IGF-1R autophosphorylation. The mechanism of inhibition likely involves indirect blocking of ATP binding. PQ401 also decreases IGF-1R-dependent tumor cell growth in vitro.
For the detailed information about the solubility of PQ401 in water, the solubility of PQ401 in DMSO, the solubility of PQ401 in PBS buffer, the animal experiment（test） of PQ401,the in vivo,in vitro and clinical trial test of PQ401,the cell experiment（test） of PQ401,the IC50, EC50 and Affinity of PQ401, PQ401, a selective insulin-like growth factor-1 receptor blocker, is a novel diarylurea compound that inhibits IGF1R autophosphorylation with IC50 < 1 uM. |
| Target: |
IC50 Value: 12 uM (inhibited autophosphorylation of the IGF-IR in cultured human MCF-7 cells) [1]
Target: IGF1R |
| 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 |
| In 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]. |
| 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.
[4]. Youssif C, et al. Myeloid p38α signaling promotes intestinal IGF-1 production and inflammation-associated tumorigenesis. EMBO Mol Med. 2018 Jul;10(7). pii: e8403. |
