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OSI-420

OSI-420 is an active metabolite of Erlotinib which is an orally active EGFR inhibitor for inhibition of human EGFR and EGFR autophosphorylation with IC50 of 2 nM and 20 nM, respectively.

Catalog No.S2205

1 Reviews 3 Product Citations

: Tel: +1-832-582-8158[email protected]

OSI-420 Chemical Structure
Molecular Weight: 415.87

Validation & Quality Control

Product Citations(3)

Submitted in partial fulfillment of the requirements, ,

Carcinogenesis, 2010, 31(11), 1948-1955

Sci Pharm, 2012, 80(3):633-46

Customer Reviews(1) in vivo invitation

Mean plasma concentration vs. time after single-dose oral administration of CCB and ERT in six Wistar rats.

Sci Pharm, 2012, 80(3), 633-646 . OSI-420 purchased from Selleck

Quality Control & MSDS

Related Compound Libraries

OSI-420 is available in the following compound libraries:

Chemical Library (96-well) Chemotherapeutic Agent Library (96-well) FDA Approved Drug Library (96-well) Inhibitor Library (96-well) Kinase Inhibitor Library (96-well) Tyrosine Kinase Inhibitor Library (96-Well)

Product Information

Compare EGFR Inhibitors

Research Area
Research Area
Dr. Antonino Maria Sparta demonstrates a breakthrough in leukemia research by utilizing two inhibitors produced by Selleck Chemicals.

Cat.No.	Product Name	Solubility (25°C)
S1023	Erlotinib HCl	<1 mg/mL	3 mg/mL	<1 mg/mL
S1025	Gefitinib (Iressa)	<1 mg/mL	89 mg/mL	4 mg/mL
S1028	Lapatinib Ditosylate (Tykerb)	<1 mg/mL	185 mg/mL	<1 mg/mL
S1011	Afatinib (BIBW2992)	<1 mg/mL	97 mg/mL	15 mg/mL
S1143	AG-490	<1 mg/mL	59 mg/mL	6 mg/mL
S2111	Lapatinib	<1 mg/mL	100 mg/mL	<1 mg/mL
S1167	CP-724714	<1 mg/mL	94 mg/mL	94 mg/mL
S2727	Dacomitinib (PF299804,PF-00299804)	<1 mg/mL	19 mg/mL	<1 mg/mL
S2728	AG-1478 (Tyrphostin AG-1478)	<1 mg/mL	25 mg/mL	13 mg/mL
S1019	CI-1033 (Canertinib)	<1 mg/mL	2 mg/mL	9 mg/mL
S1194	CUDC-101	<1 mg/mL	20 mg/mL	<1 mg/mL
S2150	Neratinib (HKI-272)	<1 mg/mL	2 mg/mL	<1 mg/mL
S1173	WZ4002	<1 mg/mL	13 mg/mL	<1 mg/mL
S1392	Pelitinib (EKB-569)	<1 mg/mL	13 mg/mL	<1 mg/mL
S2192	AZD8931	<1 mg/mL	40 mg/mL	<1 mg/mL
S2185	AST-1306	<1 mg/mL	124 mg/mL	<1 mg/mL
S2752	Arry-380	<1 mg/mL	114 mg/mL	<1 mg/mL
S1079	PD153035 HCl	<1 mg/mL	0.5 mg/mL	<1 mg/mL
S2755	ARRY334543	<1 mg/mL	6 mg/mL	<1 mg/mL
S2867	WHI-P154	<1 mg/mL	75 mg/mL	<1 mg/mL
S1179	WZ8040	<1 mg/mL	96 mg/mL	3 mg/mL
S2205	OSI-420	2 mg/mL	83 mg/mL	<1 mg/mL
S1056	BMS-599626 (AC480)	<1 mg/mL	113 mg/mL	20 mg/mL
S1486	AEE788 (NVP-AEE788)	<1 mg/mL	88 mg/mL	<1 mg/mL
S2784	TAK-285	<1 mg/mL	110 mg/mL	54 mg/mL
S2826	Desmethyl Erlotinib (CP-473420)	<1 mg/mL	11 mg/mL	5 mg/mL
S8009	AG 18 (Tyrphostin 23)	<1 mg/mL	37 mg/mL	37 mg/mL
S1170	WZ3146	<1 mg/mL	93 mg/mL	<1 mg/mL
S2895	Tyrphostin 9 (SF 6847)	<1 mg/mL	56 mg/mL	56 mg/mL
S2922	Icotinib	<1 mg/mL	78 mg/mL	7 mg/mL
S7039	PD168393	<1 mg/mL	74 mg/mL	<1 mg/mL

Product Description

Biological Activity Protocol Chemical Information Customer Reviews Product Citations Tech Support & FAQs

Biological Activity

Description	OSI-420 is an active metabolite of Erlotinib which is an orally active EGFR inhibitor for inhibition of human EGFR and EGFR autophosphorylation with IC50 of 2 nM and 20 nM, respectively.
Targets	EGFR
IC50	2 nM ^[1]
In vitro	OSI-420 is the major metabolite of Erlotinib in human plasma. Erlotinib disappearance from plasma after a short IV infusion is biexponential with a mean terminal half-life of 5.2 h and a mean clearance of 128 ml/min per m(2). OSI-420 exposure (AUC) in plasma is 30% (range 12-59%) of erlotinib, and OSI-420 clearance is more than 5-fold higher than erlotinib. Erlotinib and OSI-420 are equipotent, and the combined concentrations of erlotinib + OSI-420 achieved in the CSF exceeded the IC50 (7.9 ng/ml or 20 nM) for the EGFR tyrosine kinase inhibition in intact tumor cells. ^[1] Erlotinib potently inhibits EGFR activation in intact cells including HNS human head and neck tumor cells (IC50 20nM), DiFi humancolon cancer cells andMDA MB-468 human breast cancer cells. Erlotinib (1 μM) induces apoptosis in DiFi humancolon cancer cells. ^[2] Erlotinib growth of a panel of NSCLC cell lines including A549, H322, H3255, H358 H661, H1650, H1975, H1299, H596 with IC50 ranging from 29 nM to >20 μM. ^[3] Erlotinib(2 μM) significantly inhibits growth of AsPC-1 and BxPC-3 pancreatic cells. ^[4] The effects of Erlotinib HCl in combination with gemcitabine are considered additive in KRAS-mutated pancreatic cancer cells. Ten micromolar of Erlotinib inhibits EGFR phospho-rylation at the Y845 (Src-dependent phosphorylation) and Y1068 (auto-phosphorylation) sites. ^[5] Combination with Erlotinib could down-modulate rapamycin-stimulated Akt activity and produces a synergistic effect on cell growth inhibition. ^[6]
In vivo	At doses of 100 mg/kg, Erlotinib completely prevents EGF-induced autophosphorylation of EGFR in human HN5 tumors growing as xenografts in athymic mice and of the hepatic EGFR of the treated mice. ^[1] Erlotinib reduces the growth of xenografted human AML cells. ^[4]
Clinical Trials	Erlotinib has entered in a phase II clinical trial in the treatment of primary sclerosing cholangitis, cholangiocarcinoma and chemoprevention.
Features	OSI 420 is a major active metabolite of Erlotinib.

Protocol(Only for Reference)

Kinase Assay: ^[1]

Kinase Assays	96-well plates are coated by incubation overnight at 37 °C with 100 μL per well of 0.25 mg/mL PGT in PBS. Excess PGT is removed by aspiration, and the plate is washed 3 times with washing buffer (0.1% Tween 20 in PBS). The kinase reaction is performed in 50 μL of 50 mM HEPES (pH 7.3), containing 125 mM sodium chloride, 24 mM magnesium chloride, 0.1 mM sodium orthovanadate, 20 μM ATP, 1.6 μg/mL EGF, and 15 ng of EGFR, affinity purified from A431 cell membranes. Erlotinib HCl in DMSO is added to give a final DMSO concentration of 2.5%. Phosphorylation is initiated by addition of ATP and proceeded for 8 minutes at room temperature, with constant shaking. The kinase reaction is terminated by aspiration of the reaction mixture and is washed 4 times with washing buffer. Phosphorylated PGT is measured by 25 minutes of incubation with 50 μL per well HRP-conjugated PY54 antiphosphotyrosine antibody, diluted to 0.2 μg/mL in blocking buffer (3% BSA and 0.05% Tween 20 in PBS). Antibody is removed by aspiration, and the plate is washed 4 times with washing buffer. The colonmetric signal is developed by addition of TMB Microwell Peroxidase Substrate, 50μL per well, and stopped by the addition of 0.09 M sulfuric acid, 50 μL per well. Phosphotyrosine is estimated by measurement of absorbance at 450 nm. The signal for controls is typically 0.6-1.2 absorbance units, with essentially no back ground in wells without AlP, EGFR, or PGT and is proportional to the time of incubation for 10 minutes.

Kinase Assays

96-well plates are coated by incubation overnight at 37 °C with 100 μL per well of 0.25 mg/mL PGT in PBS. Excess PGT is removed by aspiration, and the plate is washed 3 times with washing buffer (0.1% Tween 20 in PBS). The kinase reaction is performed in 50 μL of 50 mM HEPES (pH 7.3), containing 125 mM sodium chloride, 24 mM magnesium chloride, 0.1 mM sodium orthovanadate, 20 μM ATP, 1.6 μg/mL EGF, and 15 ng of EGFR, affinity purified from A431 cell membranes. Erlotinib HCl in DMSO is added to give a final DMSO concentration of 2.5%. Phosphorylation is initiated by addition of ATP and proceeded for 8 minutes at room temperature, with constant shaking. The kinase reaction is terminated by aspiration of the reaction mixture and is washed 4 times with washing buffer. Phosphorylated PGT is measured by 25 minutes of incubation with 50 μL per well HRP-conjugated PY54 antiphosphotyrosine antibody, diluted to 0.2 μg/mL in blocking buffer (3% BSA and 0.05% Tween 20 in PBS). Antibody is removed by aspiration, and the plate is washed 4 times with washing buffer. The colonmetric signal is developed by addition of TMB Microwell Peroxidase Substrate, 50μL per well, and stopped by the addition of 0.09 M sulfuric acid, 50 μL per well. Phosphotyrosine is estimated by measurement of absorbance at 450 nm. The signal for controls is typically 0.6-1.2 absorbance units, with essentially no back ground in wells without AlP, EGFR, or PGT and is proportional to the time of incubation for 10 minutes.

Cell Assay: ^[3]

Cell lines	A549, H322, H3255, H358 H661, H1650, H1975, H1299, H596 cells
Concentrations	30 nM-20 μM
Incubation Time	72 hour
Method	Exponentially growing cells are seeded in 96-well plastic plates and exposed to serial dilutions of erlotinib, pemetrexed, or the combination at a constant concentration ratio of 4:1 in triplicates for 72 h. Cell viability is assayed by cell count and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Growth inhibition is expressed as the percentage of surviving cells in drug-treated versus PBS-treated control cells (which is considered as 100% viability). The IC50 value is the concentration resulting in 50% cell growth inhibition by a 72-h exposure to drug(s) compared with untreated control cells and is calculated by the CalcuSyn software.

Animal Study: ^[7]

Animal Models	Male 5-week-old BALB-nu/nu with HPAC
Formulation	6% Captisol
Dosages	50 mg/kg
Administration	Oral administration

References

Chemical Information

Download OSI-420 SDF

Molecular Weight (MW)	415.87
Formula	C₂₁H₂₁N₃O₄.HCl
CAS No.	183320-51-6
Synonyms	N/A

Solubility (25°C) DMSO 83 mg/mL Water 2 mg/mL Ethanol <1 mg/mL
Storage	2 years -20°CPowder
	2 weeks4°Cin DMSO
	6 months-80°Cin DMSO

Chemical Name	2-(4-(3-ethynylphenylamino)-7-(2-methoxyethoxy)quinazolin-6-yloxy)ethanol hydrochloride

Molarity Calculator Dilution Calculator Molecular Weight Calculator

Research Area

Customer Reviews (1)

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Source

Sci Pharm, 2012, 80(3), 633-646 . OSI-420 purchased from Selleck

Method

LC-MS/MS analysis

Cell Lines

Wistar rats

Concentrations

1.5-1150 ng/mL

Incubation Time

24 h, 12h

Results

An LC-MS/MS bioanalytical method for the simultaneous determination of three analytes, CCB, ERT, and OSI-420, was developed and validated in rat plasma. The method was good enough to detect the low concentration of 1.5 ng/mL for all analytes in 50 µL rat plasma, and can further be improved by increasing the plasma volume.

Product Citations (3)

Study of molecular mechanisms of sensitivity and resistance to EGFR-targeted therapy in lung cancer. [Zhang Z. Submitted in partial fulfillment of the requirements ;]
Secretory phospholipase A2-IIa is involved in prostate cancer progression and may potentially serve as a biomarker for prostate cancer. [Dong Z, et al. Carcinogenesis 2010;31(11), 1948-1955]
PubMed: 20837598
Simultaneous Determination of Celecoxib, Erlotinib, and its Metabolite Desmethyl-Erlotinib (OSI-420) in Rat Plasma by Liquid chromatography/Tandem Mass Spectrometry with Positive/Negative Ion-Switching Electrospray Ionisation. [Thappali SR, et al. Sci Pharm 2012;80(3):633-46]
PubMed: 23008811

Tech Support & FAQs

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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