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| 250mg |
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Purity: ≥98%
Afatinib (formerly BIBW 2992; BIBW-2992; brand name: Gilotrif), is a potent, covalent/irreversible, and orally bioavailable dual (EGFR/ErbB) receptor tyrosine kinase (RTK) inhibitor with anticancer activity. Afatinib is an FDA-approved anticancer medication used to treat lung cancer that is not small cell (NSCLC). In the USA, Gilotrif is the brand name under which it is sold. It is 100 times more active against the Gefitinib-resistant L858R-T790M EGFR mutant. It irreversibly binds to and inhibits EGFR/HER2, including EGFR(wt), EGFR(L858R), EGFR(L858R/T790M), and HER2. In cell-free assays, its IC50 values are 0.5 nM, 0.4 nM, 10 nM, and 14 nM, respectively.
| Targets |
EGFRL858R (IC50 = 0.4 nM); EGFR (wt) (IC50 = 0.5 nM); ErbB4 (IC50 = 1 nM); EGFRL858R/T790M (IC50 = 10 nM); HER2 (IC50 = 14 nM)
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| ln Vitro |
BIBW2992 exhibits potent inhibition of EGFR and HER2 in both wild-type and mutant forms. It has comparable potency to gefitinib against L858R EGFR, but it is approximately 100 times more active against the L858R-T790M EGFR double mutant that is resistant to gefitinib. In vivo, BIBW2992 demonstrates strong effects on the phosphorylation of both EGFR and HER2. When compared to reference compounds (like Lapatinib et al.), it performs well in all tested cell types, including human epidermoid carcinoma cell line A431 that expresses EGFR, murine NIH-3T3 cells transfected with HER2, breast cancer cell line BT-474, and gastric cancer cell line NCI-N87 that express endogenous HER2.[1]
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| ln Vivo |
Afatinib (0-20 mg/kg, Orally, daily for 25 days) exhibits a significant decrease in tumor growth and phosphorylation of AKT, HER2, EGFR, and HER3.
Afatinib (15 mg/kg, Orally, in a schedule of 5 days on plus 2 days off, for two weeks) strongly inhibits the growth of HKESC-2 tumor. |
| Enzyme Assay |
The human EGFR wild type and EGFR L858R/T790M double mutant tyrosine kinase domains are fused to GST and extracted. Next, enzyme activity is measured with and without the inhibitor BIBW2992, which is serially diluted in 50% DMSO. Biotinylated pEY (bio-pEY) is added as a tracer substrate and a random polymer, pEY (4:1), is used as the substrate. Utilizing the baculovirus system, the HER2 kinase domain is cloned and extracted in a manner akin to that of EGFR kinase. Supplementary information contains specifics about the assays conducted for EGFR, HER2, SRC, BIRK, and VEGFR2 kinase activity.
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| Cell Assay |
For the EGFR phosphorylation test, 1 × 104 NSCLC cells are plated into each well of a 96-well plate and grown for an entire night in serum-free medium. The following day, the plates are incubated at 37 °C for one hour following the addition of BIBW2992. EGF stimulation is carried out at room temperature for 10 minutes using 100 ng/mL. Following an hour of shaking at room temperature and an extraction using 120 μL of HEPEX buffer per well, the cells are cleaned with ice-cold PBS. HER2 phosphorylation assay uses 2 × 104 cells per well in total. The c-erb2/HER2 oncoprotein Ab-5(Clone N24)-Biotin and anti-EGFR-Biotin are coated on streptavidin precoated plates at a 1:100 dilution in blocking buffer. Once in the antibody-coated wells, cell extracts are allowed to sit at room temperature for one hour. Measurement of extinction occurs at 450 nm.
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| Animal Protocol |
Athymic NMRI-nu/nu female mice
20 mg/kg Oral administration |
| References |
| Molecular Formula |
C24H25CLFN5O3
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|---|---|
| Molecular Weight |
485.94
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| Exact Mass |
485.16
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| Elemental Analysis |
C, 59.32; H, 5.19; Cl, 7.30; F, 3.91; N, 14.41; O, 9.88
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| CAS # |
850140-72-6
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| Related CAS # |
Afatinib dimaleate;850140-73-7;Afatinib-d6;1313874-96-2;Afatinib oxalate;1398312-64-5;(R)-Afatinib;439081-17-1;Afatinib-d4
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| Appearance |
White to light yellow solid powder
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| SMILES |
CN(C)C/C=C/C(=O)NC1=C(C=C2C(=C1)C(=NC=N2)NC3=CC(=C(C=C3)F)Cl)O[C@H]4CCOC4
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| InChi Key |
ULXXDDBFHOBEHA-CWDCEQMOSA-N
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| InChi Code |
InChI=1S/C24H25ClFN5O3/c1-31(2)8-3-4-23(32)30-21-11-17-20(12-22(21)34-16-7-9-33-13-16)27-14-28-24(17)29-15-5-6-19(26)18(25)10-15/h3-6,10-12,14,16H,7-9,13H2,1-2H3,(H,30,32)(H,27,28,29)/b4-3+/t16-/m0/s1
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| Chemical Name |
(E)-N-[4-(3-chloro-4-fluoroanilino)-7-[(3S)-oxolan-3-yl]oxyquinazolin-6-yl]-4-(dimethylamino)but-2-enamide
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| Synonyms |
BIBW2992; Afatinib free base; BIBW 2992; BIBW 2992; Afatinib; trade name: Gilotrif, Tomtovok and Tovok
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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 |
| 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 (5.14 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 (5.14 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.14 mM) (saturation unknown) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 2% DMSO+30% PEG 300+5% Tween 80+ddH2O: 10 mg/mL Solubility in Formulation 5: 5 mg/mL (10.29 mM) in 0.5% Methylcellulose/saline water (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0579 mL | 10.2893 mL | 20.5787 mL | |
| 5 mM | 0.4116 mL | 2.0579 mL | 4.1157 mL | |
| 10 mM | 0.2058 mL | 1.0289 mL | 2.0579 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT05154396 | Active Recruiting |
Drug: Afatinib | Chordoma | Leiden University Medical Center | June 21, 2018 | Phase 2 |
| NCT03827070 | Active Recruiting |
Drug: Afatinib Drug: Talcum powder |
Non Small Cell Lung Cancer | Center Trials & Treatment Europe | March 5, 2019 | Phase 1 |
| NCT04413201 | Active Recruiting |
Drug: Afatinib Drug: Osimertinib |
Non-squamous NSCLC | Michael Hopp | September 11, 2020 | Phase 4 |
| NCT05267288 | Recruiting | Drug: afatinib | PFS | Qingdao Central Hospital | February 1, 2021 | Phase 2 |
| NCT05519917 | Not yet recruiting | Drug: Afatinib | Chordoma of Clivus | Huashan Hospital | October 1, 2022 | Phase 2 |
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Afatinib covalently binds to cysteine number 797 of the epidermal growth factor receptor (EGFR) via a Michael addition (IC50 = 0.5 nM).Schubert-Zsilavecz, M, Wurglics, M,Neue Arzneimittel Frühjahr 2013.(in German) |
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