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Afatinib(BIBW2992)

Catalog No.GC13296

EGFR/HER2의 선택적 이중 억제제

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Afatinib(BIBW2992) Chemical Structure

Cas No.: 439081-18-2

Size 가격 재고 수량
10mM (in 1mL DMSO)
US$56.00
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10mg
US$50.00
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50mg
US$133.00
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100mg
US$173.00
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200mg
US$238.00
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Sample solution is provided at 25 µL, 10mM.

Product Documents

Quality Control & SDS

View current batch:

Protocol

Cell experiment: [1]

Cell lines

NCI-H1975 and BT474 cells

Preparation method

The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months.

Reaction Conditions

EC50: 92 nM for NCI-H1975 cells, 54 nM for BT474 cells; 96 hours

Applications

The effect of the inhibitor on cellular proliferation was tested in various assay formats including anchorage-dependent (BT474 cells grown on plastic; two-dimensional assays) and anchorage-independent (NCI-H1975 cells grown in soft agar; three-dimensional assays) assays. Afatinib dose-dependently inhibited cell proliferation and showed nanomolar activity. The EC50 values for NCI-H1975 and BT474 cells were 92 nM and 54 nM, respectively.

Animal experiment: [2]

Animal models

Transgenic mice expressing the delE748-A752 version of mouse Egfr and the L858R version of human EGFR

Dosage form

Oral administration, 5 mg/kg, once daily, 5 days per week

Applications

The transgenic mice received the oral administration of the drug until toxicity or death. All mice in the control group died, with a median survival time of 119 days. Afatinib treatment significantly enhanced the survival of transgenic mice with a median survival time of 456 days. No toxic death was observed in any mice. Four weeks after the initiation of treatment, body weight in the control group was significantly lower than in the afatinib group.

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] Solca F, Dahl G, Zoephel A, et al. Target binding properties and cellular activity of afatinib (BIBW 2992), an irreversible ErbB family blocker. Journal of Pharmacology and Experimental Therapeutics, 2012, 343(2): 342-350.

[2] Ninomiya T, Takigawa N, Ichihara E, et al. Afatinib prolongs survival compared with gefitinib in an epidermal growth factor receptor-driven lung cancer model. Molecular cancer therapeutics, 2013, 12(5): 589-597.

Background

아파티닙 (BIBW2992)은 ErbB 패밀리 티로신 키나제의 불가역적 억제제로, 표피 성장 인자 수용체 (EGFR)/인간 표피 성장 인자 수용체 2 (HER2)의 키나제 도메인에 각각 IC50 값이 0.5nM 및 14nM으로 결합하여 ErbB 신호를 하향 조절합니다. ErbB 수용체 티로신 키나제 패밀리는 네 개의 세포 막 수용체(ErbB1/EGFR/HER1, ErbB2/HER2, ErbB3/HER3 및 ErbB4/HER4)로 구성됩니다. EGFR과 HER2는 일부 공격적인 종류의 암 및 염증 관련 질환 발생과 진행에서 중요한 역할을 한다는 것이 입증되었습니다. 아파티닙은 A431, NIH-3T3-HER2, NCI-N87 및 BT-474와 같은 다양한 EGFR 과발현 및 HER2 발현세포주에서 EGF 유도 인자화와 세포 증식을 억제하는 것으로 나타났습니다[1]. 이 구성 요소는 또한 EGFR / HER2의 역할을 연구하기 위해 다양한 동물 모델에서 광범위하게 사용되었습니다. 아파티닙의 경구 투여는 이식종 및 전이성 폐암 모델에서 암 세포 성장과 생존을 억제하고 종양 회귀를 억제하는 것으로 나타났습니다[2]. 또한, 아파티닙은 EGFR 변이가 있는 비소세포 폐암 환자 치료용으로 승인된 EGFR 차단제로 확인되었습니다[3].

References:

1.Eskens FA, Mom CH, Planting AS, Gietema JA, Amelsberg A, Huisman H, et al. A phase I dose escalation study of BIBW 2992, an irreversible dual inhibitor of epidermal growth factor receptor 1 (EGFR) and 2 (HER2) tyrosine kinase in a 2-week on, 2-week off schedule in patients with advanced solid tumours. Br J Cancer 2008,98:80-85.
2.Li D, Ambrogio L, Shimamura T, Kubo S, Takahashi M, Chirieac LR, et al. BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models. Oncogene 2008,27:4702-4711.
3.Engle JA, Kolesar JM. Afatinib: A first-line treatment for selected patients with metastatic non-small-cell lung cancer. Am J Health Syst Pharm 2014,71:1933-1938.

Chemical Properties

Cas No. 439081-18-2 SDF
Chemical Name (E)-N-[4-(3-chloro-4-fluoroanilino)-7-[(3S)-oxolan-3-yl]oxyquinazolin-6-yl]-4-(dimethylamino)but-2-enamide
Canonical SMILES CN(C)CC=CC(=O)NC1=C(C=C2C(=C1)C(=NC=N2)NC3=CC(=C(C=C3)F)Cl)OC4CCOC4
Formula C24H25ClFN5O3 M.Wt 485.94
Solubility ≥ 24.3mg/mL in DMSO, ≥ 42.1 mg/mL in EtOH with ultrasonic Storage Store at -20°C
General tips Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month.
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table

Prepare stock solution
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
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

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리뷰

Review for Afatinib(BIBW2992)

Average Rating: 5 ★★★★★ (Based on Reviews and 30 reference(s) in Google Scholar.)

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