CAS 196868-63-0|PQ 401

Introduction：Basic information about CAS 196868-63-0|PQ 401, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Table of Contents

1. Names
2. PQ 401 BiologicalActivity
3. Chemical & Physical Properties
4. Safety Information
5. Customs
6. Articles6
7. Synonyms

Common Name	PQ 401
CAS Number	196868-63-0	Molecular Weight	341.792
Density	1.4±0.1 g/cm3	Boiling Point	426.1±45.0 °C at 760 mmHg
Molecular Formula	C₁₈H₁₆ClN₃O₂	Melting Point	190 °C(dec.)
MSDS	ChineseUSA	Flash Point	211.5±28.7 °C
Symbol	GHS06	Signal Word	Danger

Names

Name	1-(5-chloro-2-methoxyphenyl)-3-(2-methylquinolin-4-yl)urea
Synonym	More Synonyms

PQ 401 BiologicalActivity

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-1RResearch 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.

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-1RResearch 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.

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
InChIKey	YBLWOZUPHDKFOT-UHFFFAOYSA-N
SMILES	COc1ccc(Cl)cc1NC(=O)Nc1cc(C)nc2ccccc12
Storage condition	2-8°C
Water Solubility	DMSO: >10mg/mL

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%

Articles6

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...

Synonyms

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

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