1942114-09-1
EAI-045
CAS: 1942114-09-1
Molecular Formula: C19H14FN3O3S
1942114-09-1 - Names and Identifiers
1942114-09-1 - Physico-chemical Properties
| Molecular Formula | C19H14FN3O3S |
| Molar Mass | 383.4 |
| Density | 1.546±0.06 g/cm3(Predicted) |
| Solubility | DMSO: ≥ 28 mg/mL |
| pKa | 7.20±0.50(Predicted) |
| Storage Condition | 2-8°C |
| Physical and Chemical Properties | Bioactive EAI045 is an allosteric inhibitor targeting specific drug-resistant EGFR mutants. No effect on wild-type receptors. |
| Use | Application EAI045 is an allosteric inhibitor of EGFR mutants targeting specific drug resistance. No effect on wild-type receptors. It can be used as a pharmaceutical raw material. |
| In vitro study | EAI045 potently inhibited phosphorylation of EGFR(Y1173) in H1975 cells (EC50=2 nM), but not in HaCaT cells with wild EGFR (keratinocyte cell line). Despite the inhibitory effect of EAI045 on EGFR mutants, EAI had no anti-proliferative effect in H1975 and H3255 cells despite reaching concentrations of 10 μm. EAI045 was able to inhibit EGFR(L858R and T790M) mutants with an IC50 of 3 nM. However, it was not able to completely prevent the autophosphorylation of EGFR in H1975 cells with EGFR(L858R/T790M) mutants. The dimerization defective/independent mutant was more sensitive to eai045. Because kinase activation of EGFR requires the formation of dimers, EAI045 may have inhibitory activity against one of the subunits of the EGFR heteromer. |
| In vivo study | Pharmacokinetic studies in mice showed a maximum plasma concentration of 0.57 μm for EAI045 with a half-life of 2.15 hours. At a concentration of 20 mg/kg, the bioavailability was 26%. When EAI045 was used in combination with cetuximab, another compound that prevented EGFR dimerization, EAI045 significantly reduced tumor growth in a mouse model of lung cancer driven by EGFR(L858R/T790M) mutants. Mice dosed with EAI045 alone had no therapeutic effect. EAI045 in combination with cetuximab also induced tumor volume reduction in mice with the L858R/T790M/C797S mutation. EAI045 and cetuximab showed a synergistic effect. |
1942114-09-1 - Preparation solution concentration reference
| 1mg | 5mg | 10mg | |
|---|---|---|---|
| 1 mM | 2.608 ml | 13.041 ml | 26.083 ml |
| 5 mM | 0.522 ml | 2.608 ml | 5.217 ml |
| 10 mM | 0.261 ml | 1.304 ml | 2.608 ml |
| 5 mM | 0.052 ml | 0.261 ml | 0.522 ml |
Last Update：2024-01-02 23:10:35
1942114-09-1 - Reference Information
| application | EAI045 is an allosteric inhibitor targeting EGFR mutants with specific drug resistance. No effect on wild-type receptors. It can be used as a pharmaceutical raw material. |
| biological activity | EAI045 is an allosteric inhibitor targeting EGFR mutants with specific drug resistance. No effect on wild-type receptors. |
| target | TargetValue EGFR mutants () |
| Target | Value |
| In vitro study | EAI045 effectively inhibits the phosphorylation of EGFR(Y1173) in H1975 cells (EC50=2 nM), but has no such effect in HaCaT cells (keratinocytes) with wild EGFR. Although EAI045 had an inhibitory effect on the mutant of EGFR, in H1975 and H3255 cells, EAI also had no antiproliferative effect despite reaching a concentration of 10 μM. EAI045 was able to inhibit EGFR(L858R and T790M) mutants with an IC50 of 3 nM. However, it is not able to completely prevent the autophosphorylation of EGFR in H1975 cells with EGFR(L858R/T790M) mutants. The dimerization-deficient/independent mutants were more sensitive to EAI045. Because EGFR kinase activation requires the formation of dimers, EAI045 may have inhibitory activity on a certain subunit of EGFR heteromers. |
| In vivo studies | Pharmacokinetic studies in mice showed that the maximum plasma concentration of EAI045 is 0.57 μM, and its half-life is 2.15 hours. At an administration concentration of 20 mg/kg, its bioavailability is 26%. When EAI045 is cetuximab combined with another compound that prevents EGFR dimerization, EAI045 can significantly reduce tumor growth in a mouse model of lung cancer driven by EGFR(L858R/T790M) mutants. Mice given EAI045 alone had no therapeutic effect. EAI045 combined with cetuximab also induced tumor volume reduction in mice with L858R/T790M/C797S mutation. This shows that EAI045 and cetuximab have synergistic effect. |
Last Update：2024-04-09 22:09:11
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Product Name: EAI-045 Request for quotation
CAS: 1942114-09-1
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Email: 2853786052@qq.com
Mobile: 86+15671228036
QQ: 2853786052
Wechat: 15671228036
CAS: 1942114-09-1
Tel: 0714-3999186
Email: 2853786052@qq.com
Mobile: 86+15671228036
QQ: 2853786052
Wechat: 15671228036
Product Name: EAI045 Visit Supplier Webpage Request for quotation
CAS: 1942114-09-1
Tel: 18301782025
Email: 3008007409@qq.com
Mobile: 18021002903
QQ: 3008007409
Wechat: 18301782025
CAS: 1942114-09-1
Tel: 18301782025
Email: 3008007409@qq.com
Mobile: 18021002903
QQ: 3008007409
Wechat: 18301782025
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