Erlotinib HCl (OSI-744)

Catalog No.S1023

Erlotinib HCl (OSI-744) is an EGFR inhibitor with IC50 of 2 nM in cell-free assays, >1000-fold more sensitive for EGFR than human c-Src or v-Abl.

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Erlotinib HCl (OSI-744) Chemical Structure

Erlotinib HCl (OSI-744) Chemical Structure
Molecular Weight: 429.90

Validation & Quality Control

Cited by 72 publications:

15 customer reviews :

Quality Control & MSDS

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Product Information

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  • Research Area
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    Combination Therapy

Product Description

Biological Activity

Description Erlotinib HCl (OSI-744) is an EGFR inhibitor with IC50 of 2 nM in cell-free assays, >1000-fold more sensitive for EGFR than human c-Src or v-Abl.
Targets HER1/EGFR [1]
(Cell-free assay)
IC50 2 nM
In vitro Erlotinib HCl 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 HCl (1 μM) induces apoptosis in DiFi humancolon cancer cells. [1] Erlotinib inhibits 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. [2] Erlotinib HCl(2 μM) significantly inhibits growth of AsPC-1 and BxPC-3 pancreatic cells. [3] The effects of Erlotinib HCl in combination with gemcitabine are considered additive in KRAS-mutated pancreatic cancer cells. Ten micromolar of Erlotinib HCl inhibits EGFR phospho-rylation at the Y845 (Src-dependent phosphorylation) and Y1068 (auto-phosphorylation) sites. [4] Combination with Erlotinib HCl could down-modulate rapamycin-stimulated Akt activity and produces a synergistic effect on cell growth inhibition. [5]
In vivo At doses of 100 mg/kg, Erlotinib HCl 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 HCl (100 mg/Kg) inhibits H460a and A549 tumor models with 71 and 93% inhibition rate. [5]
Features

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.

Cell Assay: [2]

Cell lines A549, H322, H3255, H358 H661, H1650, H1975, H1299, H596 cells
Concentrations 30 nM-20 μM
Incubation Time 72 hours
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: [6]

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

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDog
Weight (kg)0.020.151.80.40.0810
Body Surface Area (m2)0.0070.0250.150.050.020.5
Km factor36128520
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

References

[1] Moyer JD, et al. Cancer Res. 1997, 57(21), 4838-4848.

[2] Li T, et al. Clin Cancer Res, 2007, 13(11), 3413-3422.

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Clinical Trial Information( data from http://clinicaltrials.gov, updated on 2016-07-23)

NCT Number Recruitment Conditions Sponsor
/Collaborators
Start Date Phases
NCT02795884 Not yet recruiting NSCLC Yonsei University June 2016 Phase 3
NCT02770014 Not yet recruiting Epidermal Growth Factor Receptor|Non-Small Cell Lung Cancer Dana-Farber Cancer Institute|Astellas Pharma Inc June 2016 Phase 2
NCT02689336 Not yet recruiting Glioma|Rhabdomyosarcoma|Osteosarcoma|Medulloblastoma|Neuroectodermal Tumor|Ependymoma|Ewings Sarcoma|Wilms Tumor Washington University School of Medicine May 2016 Phase 2
NCT02775006 Not yet recruiting Carcinoma, Non-small Cell Lung The Netherlands Cancer Institute|Dutch Society of Physici  ...more The Netherlands Cancer Institute|Dutch Society of Physicians for Pulmonology and Tuberculosis May 2016 Phase 3
NCT02759614 Not yet recruiting NSCLC Guangdong Association of Clinical Trials April 2016 Phase 3

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Chemical Information

Download Erlotinib HCl (OSI-744) SDF
Molecular Weight (MW) 429.90
Formula

C22H23N3O4.HCl

CAS No. 183319-69-9
Storage 3 years -20℃powder
6 months-80℃in solvent
Synonyms (CP358774, NSC 718781) HCl
Solubility (25°C) * In vitro DMSO 3 mg/mL (6.97 mM)
Water <1 mg/mL (<1 mM)
Ethanol <1 mg/mL (<1 mM)
In vivo 15% Captisol 16 mg/mL warmed
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
Chemical Name N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)quinazolin-4-amine hydrochloride

Customer Product Validation(15)


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Rating
Source Nat Genet 2012 44(8):852-60. Erlotinib HCl (OSI-744) purchased from Selleck
Method Western blot
Cell Lines HHCC827 ER1 and ER2 cells
Concentrations 0.1 uM
Incubation Time 48 h
Results It sought to validate genetic findings using pharmacologic inhibitors of AXL. As expected, erlotinib decreased pEGFR, pERK, pAKT, pRelA and increased the levels of cleaved Parp in parental HCC827 cells irrespective of concurrent treatment with MP-470. In contrast, these effects of erlotinib treatment were observed only upon concurrent treatment with MP-470 in the HCC827 ER1 and ER2 cells.

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Source J Clin Invest 2012 122, 3197-210. Erlotinib HCl (OSI-744) purchased from Selleck
Method Relative growth assay
Cell Lines HME1 cell
Concentrations 0-0.4 μM
Incubation Time 7 d
Results FAM83B-expressing cells had sustained ERK1/2 phosphorylation and enhanced proliferation in the pres ence of EGFR-TKIs (AG1478, erlotinib, and CL387785) compared with control cells. In addition, FAM83B-expressing cells also grew significantly better than control cells after growth factor withdrawal.

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Source Cancer Res 2014 4(1):253-62. Erlotinib HCl (OSI-744) purchased from Selleck
Method IP
Cell Lines HCC827/ER cells
Concentrations 0.5 uM
Incubation Time 48 h
Results It reported recently that increased activation of AXL led to EGFR-TKI resistance in HCC827/ER cells. Consistent with what was observed for HCC827/ER cells, combined NPS-1034 and erlotinib treatment overcame erlotinib resistance via the complete inhibition of signaling downstream(p-Akt, p-Erk) from EGFR.

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Source Oncogene 2010 30, 2547-2557. Erlotinib HCl (OSI-744) purchased from Selleck
Method Western blot
Cell Lines MCF7-HER2 cells
Concentrations 500 nM
Incubation Time 24 h
Results we assessed whet her erlotinib, a TKI with selectivity for EGFR, could prevent the BEZ 235-induced increase of P-ERK. At 500 nM, erlotinib markedly reduced P-EGFR without affecting BEZ235-dependent P-ERK activation.

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Source Carcinogenesis 2010 31, 1948–1955. Erlotinib HCl (OSI-744) purchased from Selleck
Method Luciferase assay
Cell Lines LNCaP-AI cells, LNCaP cells
Concentrations 20 μM
Incubation Time 24 h
Results EGF significantly stimulates the promoter activity of sPLA2-IIa gene in both LNCaP and LNCaP-AI cells (shown in LNCaP-AI cells), whereas Erlotinib and other inhibitors tested all downregulated the promoter activity both at the basal level (shown in LNCaP cells) and in response to EGF stimulation (shown in LNCaP-AI cells)

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Source Carcinogenesis 2010 31, 1948–1955. Erlotinib HCl (OSI-744) purchased from Selleck
Method ELISA
Cell Lines LNCaP-AI cells
Concentrations 20 μM
Incubation Time 24 h
Results Lapatinib, LY294002 and Bortezomib significantly inhibited sPLA2-IIa secretion, whereas Erlotinib, Gefitinib and CI-1033 had a moderate effect in LNCaP-AI cells .

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Source J Immunother 2011 34, 372-81. Erlotinib HCl (OSI-744) purchased from Selleck
Method Cytotoxicity assay
Cell Lines NK-92 cells/ lung cancer cells
Concentrations 10 μM
Incubation Time 24 h
Results Susceptibility of lung cancer cells to cytolytic activity of NK cells was significantly increased by treatment with EGFR inhibitors (erlotinib/gefitinib) and was reversed by blocking step using mAb against NKG2D before the assay in all lung cancer cells.

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Source Transl Oncol 2011 4, 92-100. Erlotinib HCl (OSI-744) purchased from Selleck
Method Western Blot
Cell Lines Hs683 cells
Concentrations 10 μM
Incubation Time 4 d
Results Figure 4 shows that AZD0530 prevented TMZ-induced soluble caveolin-1 expression but did not change basal levels of soluble caveolin-1 in Hs683 GBM cells. In contrast, erlotinib increased soluble caveolin-1 expression to a similar degree as TMZ in these Hs683 GBM cells.

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Source Microvasc Res 2010 81, 135-142. Erlotinib HCl (OSI-744) purchased from Selleck
Method Myogenic tone of mice coronary arterioles
Cell Lines Coronary arterioles
Concentrations 1 μM
Incubation Time
Results In freshly isolated and mounted coronary arterioles in arteriograph, stepwise-increased intraluminal pressure induced myogenic tone development, which was significantly inhibited when the coronary arterioles we repretreated with EGFR tyrosine kinase inhibitor (AG1478, 1 μ M). Similar results were obtained using another EGFR tyrosine kinase inhibitor (Erlotininb, 1 μM)

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Source Tuberc Respir Dis 2013 75(1), 9-17. Erlotinib HCl (OSI-744) purchased from Selleck
Method Microscope imaging
Cell Lines NCI-H1299 cells
Concentrations 50 nM
Incubation Time 48 h
Results Growth inhibition induced by rapamycin or erlotinib is enhanced by combination treatment with monensin in NCI-H1299 cells.

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Source Head Neck 2013 35, 86-93. Erlotinib HCl (OSI-744) purchased from Selleck
Method MTT assays
Cell Lines MET1 cells/MET1 cells/MET4 cells/SCC12 cells/SCC13 cells
Concentrations 0-2000 nM
Incubation Time 48 h
Results Both erlotinib (Figure A) and PPP (Figure B) demonstrated dose-dependent decreases in cellproliferation with increasing concentrations. Next, all cell lines were cultured for 48 hours with varying concentrations of both erlotinib and PPP in combination (Figures C-F). In all cases, both erlotinib and PPP showed dose-dependent decreases in cell proliferation.

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Source Int J Proteomics 2011 2011, Article ID 215496. Erlotinib HCl (OSI-744) purchased from Selleck
Method Nikon inverted-phase microscope
Cell Lines lung tumor cell lines
Concentrations 0.1-1 μM
Incubation Time
Results Erlotinib, which inhibited the growth of HCC827 cells cultured in anchorage-dependent cell culture plates, was also able to reduce the size of the cell colonies grown in agar plates in an anchorage-independent fashion. Similarly, reduction of cell colony size for mation was also observed by the treatment with the irreversible HER1/2 inhibitor BIBW-2992 in H1975 and H1650 cells as seen when these cell s were grown in an anchorage-dependent manner.

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Rating
Source 2010 Dr. Balazs Halmos of Columbia University. Erlotinib HCl (OSI-744) purchased from Selleck
Method Western blot
Cell Lines HCC827 cells, H1975 cells, H441 cells
Concentrations 1 μM
Incubation Time
Results

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Rating
Source 2010 Dr. Balazs Halmos of Columbia University. Erlotinib HCl (OSI-744) purchased from Selleck
Method Real-time PCR analysis
Cell Lines HCC827 cells, PC9 cells
Concentrations
Incubation Time 0-12 h
Results

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Rating
Source 2010 Dr. Zhang of Tianjin Medical University. Erlotinib HCl (OSI-744) purchased from Selleck
Method Western blot
Cell Lines Breast cancer cells
Concentrations 0-5 nM
Incubation Time 24 h
Results

Tech Support

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