4-{3-chloro-4-[(cyclopropylcarbamoyl)amino]phenoxy}-7-methoxyquinoline-6-carboxamide
Lenvatinib
CAS: 417716-92-8;956958-53-5
Molecular Formula: C21H16N6O2S2
4-{3-chloro-4-[(cyclopropylcarbamoyl)amino]phenoxy}-7-methoxyquinoline-6-carboxamide - Names and Identifiers
| Name | Lenvatinib |
| Synonyms | XL147 XL-147 SAR245408 Lenvatinib PI3K inhibitorX XL-147(SAR245408) N-[3-(2,1,3-Benzothiadiazol-5-ylamino)-2-quinoxalinyl]-4-methylbenzenesulfonamide, 4-{3-chloro-4-[(cyclopropylcarbamoyl)amino]phenoxy}-7-methoxyquinoline-6-carboxamide N-[3-(Benzo[c][1,2,5]thiadiazol-5-ylaMino)quinoxalin-2-yl]-4-MethylbenzenesulfonaMide N-[3-(2,1,3-Benzothiadiazol-5-ylamino)-2-quinoxalinyl]-4-methylbenzenesulfonamide XL 147 |
| CAS | 417716-92-8 956958-53-5 |
| InChI | InChI=1/C21H19ClN4O4/c1-29-19-10-17-13(9-14(19)20(23)27)18(6-7-24-17)30-12-4-5-16(15(22)8-12)26-21(28)25-11-2-3-11/h4-11H,2-3H2,1H3,(H2,23,27)(H2,25,26,28) |
4-{3-chloro-4-[(cyclopropylcarbamoyl)amino]phenoxy}-7-methoxyquinoline-6-carboxamide - Physico-chemical Properties
| Molecular Formula | C21H16N6O2S2 |
| Molar Mass | 448.52 |
| Density | 1.538 |
| Boling Point | 638.9±65.0 °C(Predicted) |
| Flash Point | 333.144°C |
| Vapor Presure | 0mmHg at 25°C |
| pKa | 6.71±0.30(Predicted) |
| Storage Condition | -20℃ |
| Refractive Index | 1.697 |
| Use | XL147 is a selective, reversible type I PI3K inhibitor, which has an inhibitory effect on PI3Kα/δ/γ. The IC50 is 39 nM/36 nM/23 nM respectively, and the effect on PI3Kβ is slightly weaker. |
| In vitro study | XL147 is a selective, reversible PI3K inhibitor with an IC50 of 40 nM at p110α. XL147 inhibits the PI3K subtype and is a competitive inhibitor of ATP. In human breast cancer cell lines overexpressing HER2, treatment with XL147 inhibits phosphorylation of AKT and S6, and induces expression and phosphorylation of HER3 and other RTKs. In HER2 cells, the HER2 tyrosine kinase catalyzes the phosphorylation of HER3, leading to partial recovery of pAKT, thus limiting the anticancer activity of xl147. In addition, reduction of HER3 or treatment with anti-HER2 agents trastuzumab or lapatinib sensitizes HER2 breast cancer cells to xl147. Treatment with XL147 inhibited monolayer cell growth of all cells tested, including BT474, HCC1937, etc., in a dose-dependent manner. The primary efficacy of XL147 is inhibition of cell proliferation. XL147 induced cell death at a concentration of 20 μm. XL147 inhibited PI3K in a dose-dependent manner. While inhibiting apoptosis, XL147 induced a decrease in cyclin D1 and pRB, and induced an increase in the level of CDK inhibitor p27KIPI, but the change was not obvious when acting on PARP and cleaved PARP. Treatment with XL147 resulted in a dose-dependent reduction in pAKTS473/T308 and pS6S240/244. XL147 also positively regulates the levels of HER3 and/or pher3y1289. In cells overexpressing HER2, phosphorylation and expression of multiple receptor tyrosine kinases, including HER3, are positively regulated, followed by inhibition of PI3K. Inhibition of PI3K, while inducing the production of HER3, InsR, IGF1R, and FGFR2 mRNAs, reduction of FoxO1 and blocking of this induction by the FoxO3a transcription factor. In HER2 cells, reduction of HER3 siRNA or in combination with the HER2 inhibitor Trastuzumab or Lapatinib enhances the induction of cell death by XL147, and enhances the effect of inhibiting pAKT and ps6. Either of Trastuzumab and lapatinib and XL147 synergistically enhanced inhibition of growth of pAKT and BT474 xenografts. XL147 is a selective, reversible PI3K inhibitor with an IC50 of 40 nM at p110α. XL147 inhibits the PI3K subtype and is a competitive inhibitor of ATP. In human breast cancer cell lines overexpressing HER2, treatment with XL147 inhibits phosphorylation of AKT and S6, and induces expression and phosphorylation of HER3 and other RTKs. In HER2 |
| In vivo study | Athymic mice bearing BT474 xenografts were randomly treated with XL147, lapatinib, trastuzumab, or XL147 and each HER2 antagonist. Each monotherapy significantly inhibited tumor growth, with 1/8 of the mice treated with trastuzumab monotherapy having complete tumor regression. The effect of combined administration is much higher than that of single administration. The combination of Trastuzumab and XL147, but not lapatinib and XL147, induced 3/8 of the tumor response. However, no drug-related toxicity was evident with either treatment. Inhibition of pHER3 by the combination of XL147 and trastuzumab was much more effective than the other treatments. Treatment of tumors with XL147 in combination with lapatinib, or XL147 in combination with trastuzumab, resulted in a significantly lower nuclear pAKT than the group administered alone. Of the three groups administered alone, XL147 was the only one that showed inhibition of nuclear pAKT levels. Cytoplasmic pAKT levels did not change significantly. athymic mice bearing BT474 xenografts were randomly treated with XL147, lapatinib, trastuzumab, or XL147 and each HER2 antagonist. Each monotherapy significantly inhibited tumor growth, with 1/8 of the mice treated with trastuzumab monotherapy having complete tumor regression. The effect of combined administration is much higher than that of single administration. The combination of Trastuzumab and XL147, but not lapatinib and XL147, induced 3/8 of the tumor response. However, no drug-related toxicity was evident with either treatment. Inhibition of pHER3 by the combination of XL147 and trastuzumab was much more effective than the other treatments. Treatment of tumors with XL147 in combination with lapatinib, or XL147 in combination with trastuzumab, resulted in a significantly lower nuclear pAKT than the group administered alone. Of the three groups administered alone, XL147 was the only one that showed inhibition of nuclear pAKT levels. Cytoplasmic pAKT levels did not change significantly. |
4-{3-chloro-4-[(cyclopropylcarbamoyl)amino]phenoxy}-7-methoxyquinoline-6-carboxamide - Preparation solution concentration reference
| 1mg | 5mg | 10mg | |
|---|---|---|---|
| 1 mM | 2.23 ml | 11.148 ml | 22.296 ml |
| 5 mM | 0.446 ml | 2.23 ml | 4.459 ml |
| 10 mM | 0.223 ml | 1.115 ml | 2.23 ml |
| 5 mM | 0.045 ml | 0.223 ml | 0.446 ml |
Last Update：2024-01-02 23:10:35
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