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Naquotinib

Names

[ CAS No. ]:
1448232-80-1

[ Name ]:
Naquotinib

[Synonym ]:
Naquotinib
6-Ethyl-3-{4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]anilino}-5-{[(3R)-1-(prop-2-enoyl)pyrrolidin-3-yl]oxy}pyrazine-2-carboxamide
UNII-47DD4548PB
2-Pyrazinecarboxamide, 6-ethyl-3-[[4-[4-(4-methyl-1-piperazinyl)-1-piperidinyl]phenyl]amino]-5-[[(3R)-1-(1-oxo-2-propen-1-yl)-3-pyrrolidinyl]oxy]-
ASP8273
5-{[(3R)-1-Acryloyl-3-pyrrolidinyl]oxy}-6-ethyl-3-({4-[4-(4-methyl-1-piperazinyl)-1-piperidinyl]phenyl}amino)-2-pyrazinecarboxamide
6-ethyl-3-({4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}amino)-5-{[(3R)-1-(1-oxoprop-2-en-1-yl)pyrrolidin-3-yl]oxy}pyrazine-2-carboxamide

Biological Activity

[Description]:

Naquotinib (ASP8273) is an orally available, mutant-selective and irreversible EGFR inhibitor; with IC50s of 8-33 nM toward EGFR mutants and 230 nM for EGFR.

[Related Catalog]:

Research Areas >> Cancer

[Target]

EGFR:230 nM (IC50)

EGFRT790M

EGFRL858R/T790M

EGFRL858R

EGFRExon 19 deletion/T790M


[In Vitro]

In assays using endogenously EGFR-dependent cells, Naquotinib inhibits the growth of PC-9(del ex19), HCC827(del ex19), NCI-H1975(del ex19/T790M) and PC-9ER(del ex19/T790M) with IC50s of 8-33 nM[1]. Naquotinib selectively inhibits phosphorylation of EGFR and its down-stream signal pathway, ERK and Akt from 10nM in HCC827 and NCI-H1975 while inhibitory effects are only detected at 1000nM in A431.In NCI-H1650 (del ex19), Naquotinib inhibits cell growth with an IC50 value of 70nM while other EGFR-TKIs are only partially effective[2].

[In Vivo]

Oral Naquotinib treatment dose dependently induces tumor regression in NCI-H1975 (L858R/T790M), HCC827 (del ex19) and PC-9 (del ex19) xenograft models. Dosing schedules does not affect the efficacy of Naquotinib. In an NCI-H1975 xenograft model, complete regression of tumor is achieved after 14-days of Naquotinib treatment. Complete regression is maintained in 50% of mice more than 85 days after cessation of Naquotinib treatment[2].

[References]

[1]. Sakagami H, et al. ASP8273, a novel mutant-selective irreversible EGFR inhibitor, inhibits growth of non-small cell lung cancer (NSCLC) cells with EGFR activating and T790M resistance mutations. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1728. doi:10.1158/1538-7445.AM2014-1728

[2]. Konagai S, et al. ASP8273 selectively inhibits mutant EGFR signal pathway and induces tumor shrinkage in EGFR mutated tumor models. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2586. doi:10.1158/1538-7445.AM2015-2586


[Related Small Molecules]

Osimertinib (AZD9291) | Tyrphostin B42 (AG-490) | Neratinib (HKI-272) | Genistein | (-)-Epigallocatechin gallate | AG-1478 | Dacomitinib (PF-00299804) | Irbinitinib | Poziotinib | Olmutinib | Sapitinib | AZD-3759 | Pyrotinib | Canertinib dihydrochloride | BMS-690514

Chemical & Physical Properties

[ Density]:
1.2±0.1 g/cm3

[ Boiling Point ]:
717.6±60.0 °C at 760 mmHg

[ Molecular Formula ]:
C30H42N8O3

[ Molecular Weight ]:
562.706

[ Flash Point ]:
387.8±32.9 °C

[ Exact Mass ]:
562.338013

[ LogP ]:
3.74

[ Vapour Pressure ]:
0.0±2.3 mmHg at 25°C

[ Index of Refraction ]:
1.624

[ Storage condition ]:
-20℃

Related Compounds