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Purity: ≥98%
OSI-420 HCl (also known as CP-473420; OSI420; Desmethyl Erlotinib), the demethylated and active metabolite of erlotinib, is a potent, selective, orally bioavailable and ATP competitive inhibitor of tyrosine kinase EGFR with potential antineoplastic activity.
| ln Vitro |
OSI-420 is the main Erlotinib metabolite found in human plasma. Following a brief IV infusion, erlotinib disappears from plasma biexponentially, with a mean clearance of 128 ml/min per m(2) and a mean terminal half-life of 5.2 h. The OSI-420 clearance is more than five times higher than the erlotinib clearance, and the OSI-420 exposure (AUC) in plasma is 30% (range 12-59%) of erlotinib. The combined concentrations of erlotinib + OSI-420 obtained in the CSF surpassed the IC50 (7.9 ng/ml or 20 nM) for the EGFR tyrosine kinase inhibition in intact tumor cells. Erlotinib and OSI-420 are equipotent.[1] Erlotinib has the ability to significantly suppress EGFR activation in intact cells, such as MDA MB-468 human breast cancer cells, DiFi human colon cancer cells, and HNS human head and neck tumor cells (IC50 20nM). In DiFi human colon cancer cells, erlotinib (1 μM) causes apoptosis. A panel of NSCLC cell lines, including A549, H322, H3255, H358 H661, H1650, H1975, H1299, and H596, are inhibited in growth by erlotinib, with IC50 values ranging from 29 nM to >20 μM.[3] AsPC-1 and BxPC-3 pancreatic cell growth is markedly inhibited by erlotinib (2 μM).[4] In KRAS-mutant pancreatic cancer cells, the effects of erlotinib HCl plus gemcitabine are thought to be additive. Phosphorylation of EGFR at the Src-dependent phosphorylation site (Y845) and the auto-phosphorylation site (Y1068) is inhibited by ten micromolar of erlotinib.[5] The synergistic effect of combination with erlotinib on cell growth inhibition may be achieved by down-regulating rapamycin-stimulated Akt activity.[6]
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| ln Vivo |
Erlotinib totally inhibits EGF-induced autophosphorylation of EGFR in human HN5 tumors growing as xenografts in athymic mice, as well as of the treated mice's hepatic EGFR, at doses of 100 mg/kg. Erlotinib inhibits the proliferation of human AML cells grown in xenografts.[4]
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| Enzyme Assay |
The process of coating 96-well plates involves incubating 100 μL of 0.25 mg/mL PGT in PBS per well for an entire night at 37 °C. Aspiration is used to remove excess PGT, and three washing buffer washes (0.1% Tween 20 in PBS) are performed on the plate. 50 μL of 50 mM HEPES (pH 7.3) containing 0.1 mM sodium orthovanadate, 125 mM sodium chloride, 24 mM magnesium chloride, 20 μM ATP, 1.6 μg/mL EGF, and 15 ng of affinity-purified EGFR from A431 cell membranes is used for the kinase reaction. A final DMSO concentration of 2.5% is achieved by adding erlotinib HCl in DMSO. When ATP is added, phosphorylation begins and continues for eight minutes at room temperature while being constantly shaken. Aspirating the reaction mixture stops the kinase reaction, and washing buffer is used four times to wash the mixture. To measure phosphorylated PGT, 50 μL of HRP-conjugated PY54 antiphosphotyrosine antibody per well is incubated for 25 minutes in blocking buffer (3% BSA and 0.05% Tween 20 in PBS), diluted to 0.2 μg/mL. By aspirating out the antibody, the plate is cleaned four times using washing buffer. TMB Microwell Peroxidase Substrate, 50μL per well, is added to develop the colonmetric signal.0.09 M sulfuric acid, 50μL per well, is added to stop the signal. The absorbance at 450 nm is used to estimate phosphotyrosine. The signal for controls is proportional to the incubation time for 10 minutes and usually ranges from 0.6 to 1.2 absorbance units. In wells devoid of AlP, EGFR, or PGT, the signal is negligible.
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| Cell Assay |
In triplicate, exponentially growing cells (A549, H322, H3255, H358 H661, H1650, H1975, H1299, and H596) are seeded in 96-well plastic plates and exposed to erlotinib, pemetrexed, or a constant concentration ratio of 4:1 for 72 hours. Cell viability is measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay in addition to cell count. The proportion of drug-treated control cells that survive compared to PBS-treated control cells (which is regarded as 100% viability) is known as growth inhibition. The CalcuSyn program determines the IC50 value, which is the concentration at which a 72-hour exposure to drug(s) results in a 50% inhibition of cell growth when compared to untreated control cells.
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| Animal Protocol |
Male 5-week-old BALB-nu/nu mice with HPAC
50 mg/kg Oral administration |
| References |
| Molecular Formula |
C21H21N3O4.HCL
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| Molecular Weight |
415.87
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| Exact Mass |
379.15
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| Elemental Analysis |
C, 66.48; H, 5.58; N, 11.08; O, 16.87
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| CAS # |
183320-51-6
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| Related CAS # |
Desmethyl Erlotinib;183321-86-0
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| Appearance |
Solid powder
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| SMILES |
COCCOC1=C(C=C2C(=C1)N=CN=C2NC3=CC=CC(=C3)C#C)OCCO.Cl
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| InChi Key |
BUOXOWNQZVIETJ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H21N3O4.ClH/c1-3-15-5-4-6-16(11-15)24-21-17-12-19(27-8-7-25)20(28-10-9-26-2)13-18(17)22-14-23-21;/h1,4-6,11-14,25H,7-10H2,2H3,(H,22,23,24);1H
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| Chemical Name |
2-[4-(3-ethynylanilino)-7-(2-methoxyethoxy)quinazolin-6-yl]oxyethanol;hydrochloride
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.01 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.01 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4046 mL | 12.0230 mL | 24.0460 mL | |
| 5 mM | 0.4809 mL | 2.4046 mL | 4.8092 mL | |
| 10 mM | 0.2405 mL | 1.2023 mL | 2.4046 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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