Afatinib dimaleate
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MedKoo CAT#: 120204

CAS#: 850140-73-7 (dimaleate)

Description: Afatinib dimaleate is an orally bioavailable dual receptor tyrosine kinase (RTK) inhibitor with potential antineoplastic activity. EGFR/HER2 tyrosine kinase inhibitor BIBW 2992 irreversibly binds to and inhibits human epidermal growth factor receptors 1 and 2 (EGFR-1; HER2), which may result in the inhibition of tumor growth and angiogenesis. EGFR/HER2 are RTKs that belong to the EGFR superfamily; both play major roles in tumor cell proliferation and tumor vascularization and are overexpressed in many cancer cell types. Afatinib is approved in much of the world (including the United States, Canada, the United Kingdom and Australia) for the treatment of metastatic non-small cell lung carcinoma (NSCLC), developed by Boehringer Ingelheim. It acts as an angiokinase inhibitor.


Chemical Structure

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Afatinib dimaleate
CAS# 850140-73-7 (dimaleate)

Theoretical Analysis

MedKoo Cat#: 120204
Name: Afatinib dimaleate
CAS#: 850140-73-7 (dimaleate)
Chemical Formula: C32H33ClFN5O11
Exact Mass:
Molecular Weight: 718.09
Elemental Analysis: C, 53.52; H, 4.63; Cl, 4.94; F, 2.65; N, 9.75; O, 24.51

Price and Availability

Size Price Availability Quantity
100.0mg USD 90.0 Ready to ship
200.0mg USD 150.0 Ready to ship
500.0mg USD 250.0 Ready to ship
1.0g USD 450.0 Ready to ship
2.0g USD 750.0 Ready to ship
5.0g USD 1650.0 2 Weeks
10.0g USD 2450.0 2 Weeks
20.0g USD 3250.0 2 Weeks
50.0g USD 4650.0 2 Weeks
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Related CAS #: 850140-73-7 (dimaleate)   439081-18-2 (free base)   850140-72-6 (free base)    

Synonym: BIBW-2992; BIBW 2992; BIBW2992. Afatinib dimaleate; trade name: Gilotrif, Tomtovok and Tovok.

IUPAC/Chemical Name: (S,E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-((tetrahydrofuran-3-yl)oxy)quinazolin-6-yl)-4-(dimethylamino)but-2-enamide dimaleate

InChi Key: USNRYVNRPYXCSP-JUGPPOIOSA-N

InChi Code: InChI=1S/C24H25ClFN5O3.2C4H4O4/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;2*5-3(6)1-2-4(7)8/h3-6,10-12,14,16H,7-9,13H2,1-2H3,(H,30,32)(H,27,28,29);2*1-2H,(H,5,6)(H,7,8)/b4-3+;2*2-1-/t16-;;/m0../s1

SMILES Code: O=C(NC1=CC2=C(NC3=CC=C(F)C(Cl)=C3)N=CN=C2C=C1O[C@@H]4COCC4)/C=C/CN(C)C.O=C(O)/C=C\C(O)=O.O=C(O)/C=C\C(O)=O

Appearance: White to off-white solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

Biological target: Afatinib dimaleate is an irreversible EGFR family inhibitor with IC50s of 0.5 nM, 0.4 nM, 10 nM and 14 nM for EGFRwt, EGFRL858R, EGFRL858R/T790M and HER2, respectively.
In vitro activity: To investigate the molecular mechanisms underlying afatinib function, the activity of ERK and the expression levels of VEGF and MMP9 were investigated following treatment with afatinib. RT-qPCR and western blot analysis results suggested that the expression levels of VEGF and MMP9 were decreased by afatinib through EGFR inhibition (Fig. 4A and B). Moreover, the phosphorylation level of ERK was significantly decreased after treatment with afatinib through EGFR inhibition, and the ratio of p-ERK/ERK was significantly decreased after treatment with afatinib through EGFR inhibition (Fig. 4C and D). The present results suggested that afatinib decreased the activity of the ERK-VEGF/MMP9 signaling pathway in vitro. Reference: Mol Med Rep. 2019 Oct; 20(4): 3317–3325. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6755195/
In vivo activity: When this study analyzed the lungs of these mice, this study noticed significantly reduced tumor burden and number in lungs of afatinib treated mice as compared to vehicle treated mice (Fig. S7A and S7B). In accordance to reduced tumor area this study also detected reduced oncogenic K-ras G12D levels in total lung lysates of the afatinib treated group, which reflects the decreased amount of tumor cells in the lungs (Fig. S7C). Reference: Sci Transl Med. 2018 Jun 20; 10(446): eaao2301. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610658/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
Water 32.18 44.81
DMSO 56.97 79.34

Preparing Stock Solutions

The following data is based on the product molecular weight 718.09 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Chen Y, Chen X, Ding X, Wang Y. Afatinib, an EGFR inhibitor, decreases EMT and tumorigenesis of Huh‑7 cells by regulating the ERK‑VEGF/MMP9 signaling pathway. Mol Med Rep. 2019 Oct;20(4):3317-3325. doi: 10.3892/mmr.2019.10562. Epub 2019 Aug 6. PMID: 31432165; PMCID: PMC6755195. 2. Chen YJ, Hsu CC, Shiao YJ, Wang HT, Lo YL, Lin AMY. Anti-inflammatory effect of afatinib (an EGFR-TKI) on OGD-induced neuroinflammation. Sci Rep. 2019 Feb 21;9(1):2516. doi: 10.1038/s41598-019-38676-7. Erratum in: Sci Rep. 2021 Jan 25;11(1):2693. PMID: 30792526; PMCID: PMC6385176. 3. Liu Z, Chen Z, Wang J, Zhang M, Li Z, Wang S, Dong B, Zhang C, Gao J, Shen L. Mouse avatar models of esophageal squamous cell carcinoma proved the potential for EGFR-TKI afatinib and uncovered Src family kinases involved in acquired resistance. J Hematol Oncol. 2018 Aug 29;11(1):109. doi: 10.1186/s13045-018-0651-z. PMID: 30157900; PMCID: PMC6114252. 4. Moll HP, Pranz K, Musteanu M, Grabner B, Hruschka N, Mohrherr J, Aigner P, Stiedl P, Brcic L, Laszlo V, Schramek D, Moriggl R, Eferl R, Moldvay J, Dezso K, Lopez-Casas PP, Stoiber D, Hidalgo M, Penninger J, Sibilia M, Győrffy B, Barbacid M, Dome B, Popper H, Casanova E. Afatinib restrains K-RAS-driven lung tumorigenesis. Sci Transl Med. 2018 Jun 20;10(446):eaao2301. doi: 10.1126/scitranslmed.aao2301. PMID: 29925635; PMCID: PMC7610658.
In vitro protocol: 1. Chen Y, Chen X, Ding X, Wang Y. Afatinib, an EGFR inhibitor, decreases EMT and tumorigenesis of Huh‑7 cells by regulating the ERK‑VEGF/MMP9 signaling pathway. Mol Med Rep. 2019 Oct;20(4):3317-3325. doi: 10.3892/mmr.2019.10562. Epub 2019 Aug 6. PMID: 31432165; PMCID: PMC6755195. 2. Chen YJ, Hsu CC, Shiao YJ, Wang HT, Lo YL, Lin AMY. Anti-inflammatory effect of afatinib (an EGFR-TKI) on OGD-induced neuroinflammation. Sci Rep. 2019 Feb 21;9(1):2516. doi: 10.1038/s41598-019-38676-7. Erratum in: Sci Rep. 2021 Jan 25;11(1):2693. PMID: 30792526; PMCID: PMC6385176.
In vivo protocol: 1. Liu Z, Chen Z, Wang J, Zhang M, Li Z, Wang S, Dong B, Zhang C, Gao J, Shen L. Mouse avatar models of esophageal squamous cell carcinoma proved the potential for EGFR-TKI afatinib and uncovered Src family kinases involved in acquired resistance. J Hematol Oncol. 2018 Aug 29;11(1):109. doi: 10.1186/s13045-018-0651-z. PMID: 30157900; PMCID: PMC6114252. 2. Moll HP, Pranz K, Musteanu M, Grabner B, Hruschka N, Mohrherr J, Aigner P, Stiedl P, Brcic L, Laszlo V, Schramek D, Moriggl R, Eferl R, Moldvay J, Dezso K, Lopez-Casas PP, Stoiber D, Hidalgo M, Penninger J, Sibilia M, Győrffy B, Barbacid M, Dome B, Popper H, Casanova E. Afatinib restrains K-RAS-driven lung tumorigenesis. Sci Transl Med. 2018 Jun 20;10(446):eaao2301. doi: 10.1126/scitranslmed.aao2301. PMID: 29925635; PMCID: PMC7610658.

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1: Prim N, Fore M, Mennecier B. [Afatinib (BIBW 2992).]. Rev Pneumol Clin. 2014 May 27. pii: S0761-8417(14)00047-9. doi: 10.1016/j.pneumo.2014.03.002. [Epub ahead of print] Review. French. PubMed PMID: 24878189.

2: D'Arcangelo M, Hirsch FR. Clinical and comparative utility of afatinib in non-small cell lung cancer. Biologics. 2014 Apr 23;8:183-92. doi: 10.2147/BTT.S40567. eCollection 2014. Review. PubMed PMID: 24790411; PubMed Central PMCID: PMC4003149.

3: Bowles DW, Weickhardt A, Jimeno A. Afatinib for the treatment of patients with EGFR-positive non-small cell lung cancer. Drugs Today (Barc). 2013 Sep;49(9):523-35. doi: 10.1358/dot.2013.49.9.2016610. Review. PubMed PMID: 24086949.

4: Köhler J, Schuler M. Afatinib, erlotinib and gefitinib in the first-line therapy of EGFR mutation-positive lung adenocarcinoma: a review. Onkologie. 2013;36(9):510-8. doi: 10.1159/000354627. Epub 2013 Aug 19. Review. PubMed PMID: 24051929.

5: Yap TA, Popat S. The role of afatinib in the management of non-small cell lung carcinoma. Expert Opin Drug Metab Toxicol. 2013 Nov;9(11):1529-39. doi: 10.1517/17425255.2013.832755. Epub 2013 Aug 28. Review. PubMed PMID: 23985030.

6: Dungo RT, Keating GM. Afatinib: first global approval. Drugs. 2013 Sep;73(13):1503-15. doi: 10.1007/s40265-013-0111-6. Review. PubMed PMID: 23982599.

7: Chen X, Zhu Q, Zhu L, Pei D, Liu Y, Yin Y, Schuler M, Shu Y. Clinical perspective of afatinib in non-small cell lung cancer. Lung Cancer. 2013 Aug;81(2):155-61. doi: 10.1016/j.lungcan.2013.02.021. Epub 2013 May 10. Review. PubMed PMID: 23664448.

8: Yang JC, Reguart N, Barinoff J, Köhler J, Uttenreuther-Fischer M, Stammberger U, O'Brien D, Wolf J, Cohen EE. Diarrhea associated with afatinib: an oral ErbB family blocker. Expert Rev Anticancer Ther. 2013 Jun;13(6):729-36. doi: 10.1586/era.13.31. Epub 2013 Mar 18. Review. PubMed PMID: 23506556.

9: Lacouture ME, Schadendorf D, Chu CY, Uttenreuther-Fischer M, Stammberger U, O'Brien D, Hauschild A. Dermatologic adverse events associated with afatinib: an oral ErbB family blocker. Expert Rev Anticancer Ther. 2013 Jun;13(6):721-8. doi: 10.1586/era.13.30. Epub 2013 Mar 18. Review. PubMed PMID: 23506519.

10: Geuna E, Montemurro F, Aglietta M, Valabrega G. Potential of afatinib in the treatment of patients with HER2-positive breast cancer. Breast Cancer (Dove Med Press). 2012 Aug 27;4:131-7. doi: 10.2147/BCTT.S25868. Review. PubMed PMID: 24367201; PubMed Central PMCID: PMC3846413.



Additional Information

Related CAS#
850140-73-7 (Afatinib dimaleate)
439081-18-2 (Afatinib free base).