PQ 401

Names

[ CAS No. ]:
196868-63-0

[ Name ]:
PQ 401

[Synonym ]:
1-(5-Chloro-2-methoxyphenyl)-3-(2-methyl-4-quinolinyl)urea
IGF-1R Inhibitor II
UNII-2N3LV83S8J
1-(5-Chloro-2-methoxyphenyl)-3-(2-methylquinolin-4-yl)urea
TCMDC-125497
N-(5-chloro-2-methoxyphenyl)-N'-(2-methyl-4-quinolinyl)
Urea, N-(5-chloro-2-methoxyphenyl)-N'-(2-methyl-4-quinolinyl)-
PQ 401
PQ401

Biological Activity

[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

[Related Catalog]:

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> IGF-1R

Research Areas >> Cancer

[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.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.4±0.1 g/cm3

[ Boiling Point ]:
426.1±45.0 °C at 760 mmHg

[ Melting Point ]:
190 °C(dec.)

[ Molecular Formula ]:
C₁₈H₁₆ClN₃O₂

[ Molecular Weight ]:
341.792

[ Flash Point ]:
211.5±28.7 °C

[ Exact Mass ]:
341.093109

[ PSA ]:
63.25000

[ LogP ]:
5.35

[ Appearance of Characters ]:
white

[ Vapour Pressure ]:
0.0±1.0 mmHg at 25°C

[ Index of Refraction ]:
1.709

[ Storage condition ]:
2-8°C

[ Water Solubility ]:
DMSO: >10mg/mL

MSDS

Click to get detail MSDS

Safety Information

[ Symbol ]:

GHS06

[ Signal Word ]:
Danger

[ Hazard Statements ]:
H301

[ Precautionary Statements ]:
P301 + P310

[ Personal Protective Equipment ]:
Eyeshields;Faceshields;Gloves;type P2 (EN 143) respirator cartridges

[ Hazard Codes ]:
T: Toxic;

[ Risk Phrases ]:
R25

[ Safety Phrases ]:
S45

[ RIDADR ]:
UN 2811 6.1/PG 3

[ HS Code ]:
2933499090

Customs

[ HS Code ]: 2933499090

[ Summary ]:
2933499090. other compounds containing in the structure a quinoline or isoquinoline ring-system (whether or not hydrogenated), not further fused. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

Articles

Identification of Novel IGF1R Kinase Inhibitors by Molecular Modeling and High-Throughput Screening.

Acta Naturae 5(2) , 90-9, (2013)

The aim of this study was to identify small molecule compounds that inhibit the kinase activity of the IGF1 receptor and represent novel chemical scaffolds, which can be potentially exploited to devel...

IGFBP-2 directly stimulates osteoblast differentiation.

J. Bone Miner Res. 29(11) , 2427-38, (2014)

Insulin-like growth factor binding protein 2 (IGFBP-2) is important for acquisition of normal bone mass in mice; however, the mechanism by which IGFBP-2 functions is not defined. These studies investi...

Diarylureas are small-molecule inhibitors of insulin-like growth factor I receptor signaling and breast cancer cell growth.

Mol. Cancer Ther. 5 , 1079-1086, (2006)

In breast and certain other cancers, receptor tyrosine kinases, including the insulin-like growth factor I receptor (IGF-IR), play an important role in promoting the oncogenic process. The IGF-IR is t...