PF299804

• CAT Number: I000449
• CAS Number: 1110813-31-4
• Molecular Formula: C₂₄H₂₅ClFN₅O₂
• Molecular Weight: 469.94
• Purity: ≥95%
• Target: EGFR
• Solubility: DMSO: 19 mg/mL，H2O：< 1 mg/mL
• Storage: 3 years -20℃ powder
• IUPAC Name: (E)-N-[4-(3-chloro-4-fluoroanilino)-7-methoxyquinazolin-6-yl]-4-piperidin-1-ylbut-2-enamide
• InChI: InChI=1S/C24H25ClFN5O2/c1-33-22-14-20-17(24(28-15-27-20)29-16-7-8-19(26)18(25)12-16)13-21(22)30-23(32)6-5-11-31-9-3-2-4-10-31/h5-8,12-15H,2-4,9-11H2,1H3,(H,30,32)(H,27,28,29)/b6-5+
• InChIKey: LVXJQMNHJWSHET-AATRIKPKSA-N
• SMILES: COC1=C(C=C2C(=C1)N=CN=C2NC3=CC(=C(C=C3)F)Cl)NC(=O)C=CCN4CCCCC4

Dacomitinib (PF299804) (Cat.No:I000449) is a potent, orally available, irreversible tyrosine kinase HER 1 (EGFR), HER2 and HER4 inhibitor with IC50 of 6, 45.7 and 73.7 nM for EGFR, ERBB2 and ERBB4, respectively. The phase II clinical trials for Dacomitinib(PF299804) was performing in the treatment of advanced gastric cancer.

Reference

1:Second-line Treatment of Non-Small Cell Lung Cancer: Focus on the Clinical Development of Dacomitinib. Zugazagoitia J, Díaz A, Jimenez E, Nuñez JA, Iglesias L, Ponce-Aix S, Paz-Ares L.Front Med (Lausanne). 2017 Apr 5;4:36. doi: 10.3389/fmed.2017.00036. eCollection 2017. Review. PMID: 28424775 Free PMC Article2:Dacomitinib-induced diarrhoea is associated with altered gastrointestinal permeability and disruption in ileal histology in rats. Van Sebille YZA, Gibson RJ, Wardill HR, Secombe KR, Ball IA, Keefe DMK, Finnie JW, Bowen JM.Int J Cancer. 2017 Jun 15;140(12):2820-2829. doi: 10.1002/ijc.30699. Epub 2017 Mar 28. PMID: 28316082 3:Impact of a planned dose interruption of dacomitinib in the treatment of advanced non-small-cell lung cancer (ARCHER 1042). Kim DW, Garon EB, Jatoi A, Keefe DM, Lacouture ME, Sonis S, Gernhardt D, Wang T, Giri N, Doherty JP, Nadanaciva S, O/’Connell J, Sbar E, Cho BC.Lung Cancer. 2017 Apr;106:76-82. doi: 10.1016/j.lungcan.2017.01.021. Epub 2017 Feb 1. PMID: 28285698 4:Dacomitinib, a new pan-EGFR inhibitor, is effective in killing ovarian cancer cells. Xu L, Wu H, Jiang C, Wang H, Gao B, Yan S, Qi Y, Zhou S.Discov Med. 2016 Nov;22(122):297-309. PMID: 28009971 Free Article5:reply to the letter to the editor /’Possible determinants of VSL#3 probiotic failure in preventing gastrointestinal adverse events associated with dacomitinib in patients with advanced non-small-cell lung cancer enrolled in ARCHER-1042 trial/’ by Ceccarelli et al. Lacouture ME; authors of the publication “A phase II study (ARCHER 1042) to evaluate prophylactic treatment of dacomitinib-induced dermatologic and gastrointestinal adverse events in advanced non-small-cell lung cancer”..Ann Oncol. 2016 Nov;27(11):2138-2139. Epub 2016 Sep 23. No abstract available. PMID: 27664149 6:Possible determinants of VSL#3 probiotic failure in preventing gastrointestinal adverse events associated with dacomitinib in patients with advanced non-small-cell lung cancer enrolled in ARCHER-1042 trial. Ceccarelli G, Schietroma I, Corano Scheri G, d/’Ettorre G, Vullo V.Ann Oncol. 2016 Nov;27(11):2137-2138. Epub 2016 Aug 8. No abstract available. PMID: 27502719 7:A Phase I Clinical Trial and Independent Patient-Derived Xenograft Study of Combined Targeted Treatment with Dacomitinib and Figitumumab in Advanced Solid Tumors. Calvo E, Soria JC, Ma WW, Wang T, Bahleda R, Tolcher AW, Gernhardt D, O/’Connell J, Millham R, Giri N, Wick MJ, Adjei AA, Hidalgo M.Clin Cancer Res. 2017 Mar 1;23(5):1177-1185. doi: 10.1158/1078-0432.CCR-15-2301. Epub 2016 Oct 12. PMID: 27733479 8:Phase I trial of dacomitinib, a pan-human epidermal growth factor receptor (HER) inhibitor, with concurrent radiotherapy and cisplatin in patients with locoregionally advanced squamous cell carcinoma of the head and neck (XDC-001). Prawira A, Brana-Garcia I, Spreafico A, Hope A, Waldron J, Razak AR, Chen EX, Jang R, O/’Sullivan B, Giuliani M, Bayley A, Cho J, Wang L, Perez-Ordonez B, Weinreb I, Siu LL, Hansen AR.Invest New Drugs. 2016 Oct;34(5):575-83. doi: 10.1007/s10637-016-0367-2. Epub 2016 Jun 11. PMID: 27289242 9:A phase II study (ARCHER 1042) to evaluate prophylactic treatment of dacomitinib-induced dermatologic and gastrointestinal adverse events in advanced non-small-cell lung cancer. Lacouture ME, Keefe DM, Sonis S, Jatoi A, Gernhardt D, Wang T, Doherty JP, Giri N, Nadanaciva S, O/’Connell J, Sbar E, Piperdi B, Garon EB.Ann Oncol. 2016 Sep;27(9):1712-8. doi: 10.1093/annonc/mdw227. Epub 2016 Jun 10. PMID: 27287210 10:Dacomitinib versus erlotinib in patients with EGFR-mutated advanced nonsmall-cell lung cancer (NSCLC): pooled subset analyses from two randomized trials. Ramalingam SS, O/’Byrne K, Boyer M, Mok T, Jänne PA, Zhang H, Liang J, Taylor I, Sbar EI, Paz-Ares L.Ann Oncol. 2016 Jul;27(7):1363. doi: 10.1093/annonc/mdw221. Epub 2016 May 30. No abstract available. PMID: 27240994