850140-72-6 | Afatinib

Packsize	Purity	Availability	Price	Discounted Price
5mg	95%	in stock	$34.00	$24.00
1g	95%	in stock	$42.00	$29.00

Description

• Catalog Number: AC33984
• Chemical Name: Afatinib
• CAS Number: 850140-72-6
• Molecular Formula: C24H25ClFN5O3
• Molecular Weight: 485.9384
• MDL Number: MFCD12407405
• SMILES: CN(C/C=C/C(=O)Nc1cc2c(ncnc2cc1O[C@@H]1COCC1)Nc1ccc(c(c1)Cl)F)C
• NSC Number: 750691

Computed Properties

• Complexity: 702
• Covalently-Bonded Unit Count: 1
• Defined Atom Stereocenter Count: 1
• Defined Bond Stereocenter Count: 1
• Heavy Atom Count: 34
• Hydrogen Bond Acceptor Count: 8
• Hydrogen Bond Donor Count: 2
• Rotatable Bond Count: 8
• XLogP3: 3.6

Upstream Synthesis Route

Afatinib, a potent irreversible inhibitor of tyrosine kinases, is widely used in chemical synthesis for its ability to target specific signaling pathways. In organic chemistry, Afatinib is utilized for the design and development of novel compounds with potential therapeutic properties. Its unique molecular structure allows for precise modifications that can enhance the biological activity of the synthesized molecules. Researchers leverage Afatinib in medicinal chemistry to create analogs and derivatives for studying receptor interactions and drug-receptor binding mechanisms. Additionally, Afatinib serves as a valuable tool in drug discovery efforts aimed at combating diseases such as cancer, where it plays a crucial role in inhibiting the overactivation of tyrosine kinases involved in tumor growth and metastasis. By incorporating Afatinib into chemical synthesis strategies, scientists can accelerate the identification of promising drug candidates with improved efficacy and selectivity profiles.

Literature

• YM155 as an inhibitor of cancer stemness simultaneously inhibits autophosphorylation of epidermal growth factor receptor and G9a-mediated stemness in lung cancer cells.

  PloS one 20170101

• Discovery of (R,E)-N-(7-Chloro-1-(1-[4-(dimethylamino)but-2-enoyl]azepan-3-yl)-1H-benzo[d]imidazol-2-yl)-2-methylisonicotinamide (EGF816), a Novel, Potent, and WT Sparing Covalent Inhibitor of Oncogenic (L858R, ex19del) and Resistant (T790M) EGFR Mutants for the Treatment of EGFR Mutant Non-Small-Cell Lung Cancers.

  Journal of medicinal chemistry 20160728

• EGF816 Exerts Anticancer Effects in Non-Small Cell Lung Cancer by Irreversibly and Selectively Targeting Primary and Acquired Activating Mutations in the EGF Receptor.

  Cancer research 20160315

• Treatment approaches for EGFR-inhibitor-resistant patients with non-small-cell lung cancer.

  The Lancet. Oncology 20150901

• Targeted therapies: Afatinib--new therapy option for EGFR-mutant lung cancer.

  Nature reviews. Clinical oncology 20131001

• Identification of novel scaffold of benzothiazepinones as non-ATP competitive glycogen synthase kinase-3β inhibitors through virtual screening.

  Bioorganic & medicinal chemistry letters 20121201

• Target binding properties and cellular activity of afatinib (BIBW 2992), an irreversible ErbB family blocker.

  The Journal of pharmacology and experimental therapeutics 20121101

• Activation of IL-6R/JAK1/STAT3 signaling induces de novo resistance to irreversible EGFR inhibitors in non-small cell lung cancer with T790M resistance mutation.

  Molecular cancer therapeutics 20121001

• Second-generation irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs): a better mousetrap? A review of the clinical evidence.

  Critical reviews in oncology/hematology 20120901

• Monitoring reversible and irreversible EGFR inhibition with erlotinib and afatinib in a patient with EGFR-mutated non-small cell lung cancer (NSCLC) using sequential [18F]fluorothymidine (FLT-)PET.

  Lung cancer (Amsterdam, Netherlands) 20120901

• New therapies in HER2-positive breast cancer: a major step towards a cure of the disease?

  Cancer treatment reviews 20120801

• A phase II trial to assess efficacy and safety of afatinib in extensively pretreated patients with HER2-negative metastatic breast cancer.

  Breast cancer research and treatment 20120801

• Irreversible protein kinase inhibitors: balancing the benefits and risks.

  Journal of medicinal chemistry 20120726

• Structural analysis of the EGFR TK domain and potential implications for EGFR targeted therapy.

  International journal of oncology 20120601

• A phase II study of afatinib (BIBW 2992), an irreversible ErbB family blocker, in patients with HER2-positive metastatic breast cancer progressing after trastuzumab.

  Breast cancer research and treatment 20120601

• Afatinib for patients with lung adenocarcinoma and epidermal growth factor receptor mutations (LUX-Lung 2): a phase 2 trial.

  The Lancet. Oncology 20120501

• Afatinib versus placebo for patients with advanced, metastatic non-small-cell lung cancer after failure of erlotinib, gefitinib, or both, and one or two lines of chemotherapy (LUX-Lung 1): a phase 2b/3 randomised trial.

  The Lancet. Oncology 20120501

• Phase I study of continuous afatinib (BIBW 2992) in patients with advanced non-small cell lung cancer after prior chemotherapy/erlotinib/gefitinib (LUX-Lung 4).

  Cancer chemotherapy and pharmacology 20120401

• Afatinib pharmacokinetics and metabolism after oral administration to healthy male volunteers.

  Cancer chemotherapy and pharmacology 20120401

• Clinical activity of afatinib (BIBW 2992) in patients with lung adenocarcinoma with mutations in the kinase domain of HER2/neu.

  Lung cancer (Amsterdam, Netherlands) 20120401

• EGFR exon 19 insertions: a new family of sensitizing EGFR mutations in lung adenocarcinoma.

  Clinical cancer research : an official journal of the American Association for Cancer Research 20120315

• The EGFR T790M mutation in acquired resistance to an irreversible second-generation EGFR inhibitor.

  Molecular cancer therapeutics 20120301

• Targeting the epidermal growth factor receptor in non-small cell lung cancer cells: the effect of combining RNA interference with tyrosine kinase inhibitors or cetuximab.

  BMC medicine 20120101

• Anti-tumour activity of afatinib, an irreversible ErbB family blocker, in human pancreatic tumour cells.

  British journal of cancer 20111108

• Comprehensive analysis of kinase inhibitor selectivity.

  Nature biotechnology 20111030

• EGFR- and VEGF(R)-targeted small molecules show synergistic activity in colorectal cancer models refractory to combinations of monoclonal antibodies.

  Clinical cancer research : an official journal of the American Association for Cancer Research 20111015

• Growth response of human colorectal tumour cell lines to treatment with afatinib (BIBW2992), an irreversible erbB family blocker, and its association with expression of HER family members.

  International journal of oncology 20110801

• Afatinib (BIBW 2992) development in non-small-cell lung cancer.

  Future oncology (London, England) 20110701

• The search for improved systemic therapy of non-small cell lung cancer--what are today's options?

  Lung cancer (Amsterdam, Netherlands) 20110601

• Phase II trial of weekly alternating sequential BIBF 1120 and afatinib for advanced colorectal cancer.

  Anticancer research 20110601

• The LUX-Lung clinical trial program of afatinib for non-small-cell lung cancer.

  Expert review of anticancer therapy 20110501

• Genotype-driven therapies for non-small cell lung cancer: focus on EGFR, KRAS and ALK gene abnormalities.

  Therapeutic advances in medical oncology 20110501

• Cysteine mapping in conformationally distinct kinase nucleotide binding sites: application to the design of selective covalent inhibitors.

  Journal of medicinal chemistry 20110310

• BIBW 2992 in non-small cell lung cancer.

  Expert opinion on investigational drugs 20110301

• Irreversible EGFR inhibitor EKB-569 targets low-LET γ-radiation-triggered rel orchestration and potentiates cell death in squamous cell carcinoma.

  PloS one 20110101

• EGFR inhibitors in non-small cell lung cancer (NSCLC): the emerging role of the dual irreversible EGFR/HER2 inhibitor BIBW 2992.

  Targeted oncology 20101201

• New drugs in advanced non-small-cell lung cancer: searching for the correct clinical development.

  Expert opinion on investigational drugs 20101201

• Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry.

  Chemistry & biology 20101124

• Phase I trial of the irreversible EGFR and HER2 kinase inhibitor BIBW 2992 in patients with advanced solid tumors.

  Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20100901

• Fast-forwarding hit to lead: aurora and epidermal growth factor receptor kinase inhibitor lead identification.

  Journal of medicinal chemistry 20100708

• Enhanced anticancer effect of the combination of BIBW2992 and thymidylate synthase-targeted agents in non-small cell lung cancer with the T790M mutation of epidermal growth factor receptor.

  Molecular cancer therapeutics 20100601

• The role of irreversible EGFR inhibitors in the treatment of non-small cell lung cancer: overcoming resistance to reversible EGFR inhibitors.

  Cancer investigation 20100501

• Chemogenomic profiling provides insights into the limited activity of irreversible EGFR Inhibitors in tumor cells expressing the T790M EGFR resistance mutation.

  Cancer research 20100201

• Irreversible pan-ErbB tyrosine kinase inhibitors and breast cancer: current status and future directions.

  Cancer treatment reviews 20091201

• Dual targeting of EGFR can overcome a major drug resistance mutation in mouse models of EGFR mutant lung cancer.

  The Journal of clinical investigation 20091001

• Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancers dependent on the epidermal growth factor receptor pathway.

  Clinical lung cancer 20090701

• Synthesis and stereochemical effects of pyrrolidinyl-acetylenic thieno[3,2-d]pyrimidines as EGFR and ErbB-2 inhibitors.

  Bioorganic & medicinal chemistry letters 20090101

• BIBW-2992, a dual receptor tyrosine kinase inhibitor for the treatment of solid tumors.

  Current opinion in investigational drugs (London, England : 2000) 20081201

• Acquired resistance to epidermal growth factor receptor kinase inhibitors associated with a novel T854A mutation in a patient with EGFR-mutant lung adenocarcinoma.

  Clinical cancer research : an official journal of the American Association for Cancer Research 20081115

• BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models.

  Oncogene 20080807

• 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.

  British journal of cancer 20080115