A3397-1g | Erlotinib [183321-74-6] Clinisciences

Background

Erlotinib (also known as NSC 718781 or CP 358,774) is a potent and orally-bioavailable inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase that selectively and reversibly inhibits EGFR-associated intracellular autophosphorylation of tyrosine kinase. Erlotinib inhibits purified EGFR tyrosine kinase and EGFR autophosphorylation intact cells with 50% inhibition concentration IC₅₀ values of 2 nmol/L and 20 nmol/L respectively. Erlotinib competes for the ATP-binding sits on the intracellular domain of EGFR resulting in the inhibition of downstream signaling pathway involved in angiogenesis, cell propagation and cell survival. Erlotinib concentration-dependently inhibits EGFR-mediated propagation signals transduction, displays prominent anti-tumor activity against neoplasms harboring EGFR expression and exhibits a tolerable toxicologic profile.

Reference

Janine Smith. Erlotinib: small-molecule targeted therapy in the treatment of non-small-cell lung cancer. Clinical Therapeutics 2005; 27(10): 1513-1534

Product Citation

1. Min P, Zhao S, et al. "MICAL-L2 potentiates Cdc42-dependent EGFR stability and promotes gastric cancer cell migration." J Cell Mol Med. 2019 Jun;23(6):4475-4488. PMID:31034158
2. Shen M, Jiang YZ, et al. "Tinagl1 Suppresses Triple-Negative Breast Cancer Progression and Metastasis by Simultaneously Inhibiting Integrin/FAK and EGFR Signaling." Cancer Cell. 2019 Jan 14;35(1):64-80.e7. PMID:30612941
3. Zheng J, Duan B, et al."Folliculin Interacts with Rab35 to Regulate EGF-Induced EGFR Degradation." Front Pharmacol. 2017 Sep 26;8:688. PMID:29018350
4. Wang Y, Deng W, et al. "MICAL2 Promotes Breast Cancer Cell Migration by Maintaining EGFR Stability and EGFR/P38 Signaling Activation." Acta Physiol (Oxf). 2017 Jul 18. PMID:28719045
5. Lee HS, Park SB, et al. "A novel HDAC inhibitor, CG200745, inhibits pancreatic cancer cell growth and overcomes gemcitabine resistance." Sci Rep. 2017 Jan 30;7:41615. PMID:28134290

Chemical Properties

Physical Appearance	A solid
Storage	Store at -20°C
M.Wt	393.44
Cas No.	183321-74-6
Formula	C₂₂H₂₃N₃O₄
Synonyms	NSC 718781;OSI-744;R-1415;OSI744;OSI 744;R1415;R 1415
Solubility	insoluble in H2O; ≥19.65 mg/mL in DMSO; ≥30.27 mg/mL in EtOH with gentle warming
Chemical Name	N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)quinazolin-4-amine
SDF	Download SDF
Canonical SMILES	COCCOC1=C(C=C2C(=C1)C(=NC=N2)NC3=CC=CC(=C3)C#C)OCCOC
Shipping Condition	Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice.
General tips	We do not recommend long-term storage for the solution, please use it up soon.

Protocol

Kinase experiment [1]:
Binding assays	The kinase reaction was performed in50 μl of 50 mM HEPES(pH 7.3), containing 125 mM NaCl, 24 mM MgCl2, 0.1 mM sodium orthovanadate, 20 μM ATP, 1.6 μg/ml EGF, and 15 ng of EGFR. The compound in DMSO was added to give a final DMSO concentration of 2.5%. Phosphorylation was initiated by addition of ATP and proceeded for 8 min at room temperature with constant shaking. The kinase reaction was terminated by aspiration of the reaction mixture and was washed 4 times with wash buffer. Phosphorylated POT was measured by 25 min of incubation with 50 μl per well HRP-conjugated PY54 antiphosphotyrosine antibody, diluted to 0.2 μg/mI in blocking buffer (3% BSA and 0.05% Tween 20 in PBS). Removed antibody by aspiration and washed the plate 4 times with wash buffer. The colonmetric signal was developed by addition of TMB Microwell Peroxidase Substrate, 50 μl per well, and stopped by the addition of 0.09 M sulfuric acid, 50 μ1 per well. Phosphotyrosine is estimated by measurement of absorbance at 450 nm.
Cell experiment [1-3]:
Cell lines	Human NSCLC cell lines H322, A549, H1650, and H1975 cells.
Preparation method	The solubility of this compound in DMSO is >19.7mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.
Reacting condition	2 μmol/L, 24h
Applications	Erlotinib alone induced G1-phase arrest in ~80% H322 cells. Erlotinib (2 μM) significantly inhibited growth of AsPC-1 and BxPC-3 pancreatic cells. Erlotinib potently inhibited EGFR activation in HNS human head and neck tumor cells, DiFi human colon cancer cells and MDA MB-468 human breast cancer cells. Erlotinib (1 μM) induced apoptosis in DiFi human colon cancer cells.
Animal experiment [4]:
Animal models	H460a and A549 tumor models
Dosage form	100 mg/kg
Application	Erlotinib (100 mg/kg) exhibited antitumor activity at the MTD in both the H460a and A549 tumor models.
Other notes	Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.
References: [1]. Moyer J D, Barbacci E G, Iwata K K, et al. Induction of apoptosis and cell cycle arrest by CP-358,774, an inhibitor of epidermal growth factor receptor tyrosine kinase[J]. Cancer research, 1997, 57(21): 4838-4848. [2]. Li T, Ling Y H, Goldman I D, et al. Schedule-dependent cytotoxic synergism of pemetrexed and erlotinib in human non–small cell lung cancer cells[J]. Clinical Cancer Research, 2007, 13(11): 3413-3422. [3]. Ali S, Banerjee S, Ahmad A, et al. Apoptosis-inducing effect of erlotinib is potentiated by 3, 3′-diindolylmethane in vitro and in vivo using an orthotopic model of pancreatic cancer[J]. Molecular cancer therapeutics, 2008, 7(6): 1708-1719. [4]. Higgins B, Kolinsky K, Smith M, et al. Antitumor activity of erlotinib (OSI-774, Tarceva) alone or in combination in human non-small cell lung cancer tumor xenograft models[J]. Anti-cancer drugs, 2004, 15(5): 503-512.