The insulin-like growth factor receptor (IGF-IR) is a transmembrane protein, signaling via the tyrosine kinase domain of which is important for normal cell growth and differentiation. In addition, the IGF-IR stimulates mitogenesis and suppresses apoptosis of cancer cells. PQ401 is a potent inhibitor of IGF-IR signaling which inhibits autophosphorylation of IGF-IR with an IC50 less than 1 μM. PQ401 significantly reduced the proliferation of MCF-7 cells grown in serum with an IC50 of 8 μM. PQ401 also inhibited the growth of MCNeuA cells with an IC50 of 15 μM. PQ401 (15 μM; 24 h) induced caspase-mediated apoptosis. In vivo, PQ401 (50 or 100 mg/kg; i.p.; three times per week) resulted in a significant dose-dependent reduction in tumor growth in female mice model bearing MCNeuA tumor cells[3].
PQ401 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Cal27 cells
5 μM
48 hours
Evaluate the growth inhibitory effect of PQ401 on Cal27 cells, showing that PQ401 alone inhibits cell growth and acts synergistically with gefitinib
Mol Cancer Ther. 2011 Nov;10(11):2124-34.
SCC-25 cells
5 μM
48 hours
Evaluate the growth inhibitory effect of PQ401 on SCC-25 cells, showing that PQ401 alone inhibits cell growth and acts synergistically with gefitinib
Mol Cancer Ther. 2011 Nov;10(11):2124-34.
Enterococcus faecium
4 μg/ml
PQ401 exhibited antimicrobial activity against E. faecium
mBio. 2020 Jun 30;11(3):e01140-20.
Vancomycin-resistant S. aureus (VRSA)
4 μg/ml
PQ401 exhibited bactericidal activity against VRSA
PQ401 exhibited bactericidal activity against MRSA, completely killing bacteria within 4 hours
mBio. 2020 Jun 30;11(3):e01140-20.
Antler chondrocytes
10 μM
24 hours
PQ401 pretreatment significantly attenuated the rIGF1-induced expression of IHH
Cell Cycle. 2017 Mar 19;16(6):522-532.
PQ401 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Caenorhabditis elegans
MRSA infection model
Liquid medium
5 μg/ml
5 days
PQ401 at 5 μg/ml completely prevented C. elegans death caused by MRSA infection
mBio. 2020 Jun 30;11(3):e01140-20.
Mice
C57BL/6J mice and NIRKO mice
POA injection
10 ng
Single injection, monitored for 6 hours
To investigate the inhibitory effect of PQ401 on IGF-1-induced hyperthermia. Results showed that pretreatment with PQ401 significantly attenuated the IGF-1-induced increase in core body temperature and BAT temperature.
J Biol Chem. 2011 Apr 29;286(17):14983-90
Non-obese diabetic (NOD) female mice
Type 1 diabetic mouse model
Intraperitoneal injection
50 mg/kg
Three times a week for 3 weeks
To investigate the effects of PQ401 on diabetic kidney disease parameters, results showed PQ401 had no significant effects on diabetic state (hyperglycemia, weight loss) or renal disease parameters (hypertrophy, hyperfiltration and albuminuria)
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