1110813-31-4
dacomitinib
CAS: 1110813-31-4
Molecular Formula: C24H25ClFN5O2
1110813-31-4 - Names and Identifiers
| Name | dacomitinib |
| Synonyms | pf-299 PF299804 DACOMITINIB Dacomitinib dacomitinib PF-00299804 pf-00299804-03 PF-00299804-03 DacoMitinib,PF299804 DacoMitinib (PF-00299804) DacoMitinib (PF299804, PF299) DacoMitinib (PF299804,PF-00299804) (E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-Methoxyquinazolin-6-yl)-4-(piperidin-1-yl)but-2-enamide (2e)-n-(4-((3-chloro-4-fluorophenyl)amino)-7-methoxy-6-quinazolinyl)-4-(1-piperidinyl)-2-butenamide |
| CAS | 1110813-31-4 |
| 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+ |
1110813-31-4 - Physico-chemical Properties
| Molecular Formula | C24H25ClFN5O2 |
| Molar Mass | 469.94 |
| Density | 1.344 |
| Melting Point | 184-187°C |
| Boling Point | 665.7±55.0 °C(Predicted) |
| Solubility | DMSO ≥21mg/mL Water <1.2mg/mL Ethanol <1.2mg/mL |
| Appearance | White solid. |
| Color | White to Pale Yellow |
| pKa | 12.05±0.43(Predicted) |
| Storage Condition | Refrigerator |
| Use | A potent and selective inhibitor of EGFR and ERBB phosphorylation. |
| In vitro study | PF299804 is a specific inhibitor of ERBB family kinases. PF299804 inhibits EGFR signaling and induces apoptosis in the H3255 GR cell line containing EGFR T790M. PF299804 is effective against gefitinib-sensitive and resistant NSCLC cell lines. PF299804 inhibits the growth of H3255 and HCC827 cells expressing the T790M mutant. PF299804 inhibits EGFR phosphorylation in the presence of T790M mutant. PF-299804 is capable of irreversibly inhibiting ERBB tyrosine kinase activity by binding at the ATP site and covalent modification of nucleophilic cysteine residues in the catalytic domain of ERBB family members. PF299804 showed significant growth inhibition in her2-amplified gastric cancer cells (SNU216, N87), and compared with other EGFR tyrosine kinase inhibitors, including gefitinib,lapatinib,BIBW-2992, and CI-1033, PF299804 has a 50% lower inhibitory concentration value. In her2-amplified gastric cancer cells, PF299804 induces apoptosis and G1 arrest, and inhibits the HER family and downstream signaling pathways, including STAT3,AKT, and extracellular signal-regulated kinase (ERK) receptor phosphorylation. PF299804 also blocks EGFR/HER2,HER2/HER3, and HER3/HER4 heterodimer formation and HER3 binding to p85α in SNU216 cells. A recent study using 47 human breast cancer and immortalized mammary epithelial cell lines to evaluate the inhibitory effect of PF299804 showed that, relative to non-expanded cell lines (RR = 3.39, p < 0.0001),PF299804 preferentially inhibits the growth of HER-2-amplified breast cancer cell lines. In most sensitive cell lines, PF299804 reduced the phosphorylation of HER2,EGFR,HER4,AKT and ERK. PF299804 exerts its anti-proliferative effects through G0/G1 phase arrest and induction of apoptosis. |
| In vivo study | Oral administration of PF299804 effectively inhibited the growth of HCC827 Del/T790M xenografts. Low dose oral administration of PF-299804 (15 mg/kg) resulted in significant antitumor activity, including significant tumor regression in various human tumor xenograft models, for example, ERBB1 (EGFR) xenograft models that express and/or over-express members of the ERBB family, or contain double mutations (L858R/T790M) associated with resistance to gefitinib and erlotinib. |
1110813-31-4 - Risk and Safety
| HS Code | 29335990 |
1110813-31-4 - Introduction
Dacomitinib (PF299804, PF299) is an effective and irreversible pan-ErbB inhibitor, which acts most effectively on EGFR with IC50 of 6 nM, and acts efficiently on NSCLCs carrying EGFR or ERBB2 mutant (anti-Gefitinib) and EGFR T790M mutant.
Last Update：2022-10-16 17:12:05
1110813-31-4 - Reference Information
| introduction | dactinib (Dacomitinib) is the second generation and irreversible EGFR tyrosine kinase inhibitor (TKI) developed by Pfizer in the United States. the mechanism of action of this drug is similar to afatinib and can irreversibly inhibit three different ERBB family molecular members, including EGFR(HER1),HER2 and HER4. Perhaps because it can inhibit multiple ERBB family proteins, it shows a better effect. |
| pharmacological effects | dactinib is an oral small molecule EGFR-TKI that can inhibit wild-type EGFR and EGFR mutation T790M) in NSCLC patients. The Pfizer clinical trial of dactinib in patients with locally advanced or metastatic NSCLC showed failure to prolong OS. The company is conducting another clinical trial (ARCHER1050) to compare with gefitinib for advanced NSCLC patients with EGFR mutation. This trial will be a key trial for the future approval of dactinib. |
| biological activity | dactinib (Dacomitinib,PF299804) is an effective and irreversible pan-ErbB inhibitor, most effective on EGFR, with IC50 of 6 nM, and highly effective on NSCLCs carrying EGFR or ERBB2 mutant (anti-Gefitinib) and EGFR T790M mutant. Phase 2. Dacomitinib (PF299804, PF299) is an effective and irreversible pan-ErbB inhibitor, which acts most effectively on EGFR. IC50 is 6 nM in cell-free test. Dacomitinib inhibit ERBB2 and ERBB4, the corresponding IC50 values are 45.7 nM and 73.7 nM respectively. Dacomitinib can efficiently act on NSCLCs carrying EGFR or ERBB2 mutant (Gefitinib resistant) and EGFR T790M mutant. Dacomitinib can inhibit cell growth and induce apoptosis. Phase 2. |
| Target | Value |
| EGFR (Cell-free assay) | 6.0 nM |
| ErbB2 (Cell-free assay) | 45.7 nM |
| ErbB4 (Cell-free assay) | 73.7 nM |
Last Update：2024-04-09 21:32:03
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Product Name: Dacomitinib Visit Supplier Webpage Request for quotationCAS: 1110813-31-4
Tel: 0714-3999186
Email: 2853786052@qq.com
Mobile: 86+15671228036
QQ: 2853786052
Wechat: 15671228036
Spot supply
Product Name: Dacomitinib (PF299804, PF299) Visit Supplier Webpage Request for quotationCAS: 1110813-31-4
Tel: 18301782025
Email: 3008007409@qq.com
Mobile: 18021002903
QQ: 3008007409
Wechat: 18301782025
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