Pub. Date : 2019 Jul 5
PMID : 31118272
14 Functional Relationships(s)Download |
Sentence | Compound Name | Protein Name | Organism |
| 1 | Structural basis of resistance of mutant RET protein-tyrosine kinase to its inhibitors nintedanib and vandetanib. | nintedanib | ret proto-oncogene | Homo sapiens |
| 2 | Nintedanib is a RET TKI that inhibits the vandetanib-resistant RET(G810A) mutant. | nintedanib | ret proto-oncogene | Homo sapiens |
| 3 | Nintedanib is a RET TKI that inhibits the vandetanib-resistant RET(G810A) mutant. | nintedanib | ret proto-oncogene | Homo sapiens |
| 4 | Here, we determined the X-ray co-crystal structure of RET kinase domain-nintedanib complex to 1.87 A resolution and a RET(G810A) kinase domain crystal structure to 1.99 A resolution. | nintedanib | ret proto-oncogene | Homo sapiens |
| 5 | Drug-sensitivity profiling of RET(L881V) revealed that it remains sensitive to nintedanib. | nintedanib | ret proto-oncogene | Homo sapiens |
| 6 | The RET-nintedanib co-crystal structure disclosed that Leu-730 in RET engages in hydrophobic interactions with the piperazine, anilino, and phenyl groups of nintedanib, providing a structural basis for explaining that the p.L730V mutation identified in nine independently isolated cell lines resistant to nintedanib. | nintedanib | ret proto-oncogene | Homo sapiens |
| 7 | The RET-nintedanib co-crystal structure disclosed that Leu-730 in RET engages in hydrophobic interactions with the piperazine, anilino, and phenyl groups of nintedanib, providing a structural basis for explaining that the p.L730V mutation identified in nine independently isolated cell lines resistant to nintedanib. | nintedanib | ret proto-oncogene | Homo sapiens |
| 8 | The RET-nintedanib co-crystal structure disclosed that Leu-730 in RET engages in hydrophobic interactions with the piperazine, anilino, and phenyl groups of nintedanib, providing a structural basis for explaining that the p.L730V mutation identified in nine independently isolated cell lines resistant to nintedanib. | nintedanib | ret proto-oncogene | Homo sapiens |
| 9 | The RET-nintedanib co-crystal structure disclosed that Leu-730 in RET engages in hydrophobic interactions with the piperazine, anilino, and phenyl groups of nintedanib, providing a structural basis for explaining that the p.L730V mutation identified in nine independently isolated cell lines resistant to nintedanib. | nintedanib | ret proto-oncogene | Homo sapiens |
| 10 | The RET-nintedanib co-crystal structure disclosed that Leu-730 in RET engages in hydrophobic interactions with the piperazine, anilino, and phenyl groups of nintedanib, providing a structural basis for explaining that the p.L730V mutation identified in nine independently isolated cell lines resistant to nintedanib. | nintedanib | ret proto-oncogene | Homo sapiens |
| 11 | The RET-nintedanib co-crystal structure disclosed that Leu-730 in RET engages in hydrophobic interactions with the piperazine, anilino, and phenyl groups of nintedanib, providing a structural basis for explaining that the p.L730V mutation identified in nine independently isolated cell lines resistant to nintedanib. | nintedanib | ret proto-oncogene | Homo sapiens |
| 12 | Comparisons of RET-nintedanib, RET(G810A), and RET-vandetanib crystal structures suggested that the solvent-front Ala-810 makes hydrophobic contacts with a methyl group and aniline in nintedanib and blocks water access to two oxygen atoms of vandetanib, resulting in an energetic penalty for burying polar groups. | nintedanib | ret proto-oncogene | Homo sapiens |
| 13 | Of note, even though the p.L881V mutation did not affect sensitivity to nintedanib, RET(L881V) was resistant to nintedanib analogs lacking a phenyl group. | nintedanib | ret proto-oncogene | Homo sapiens |
| 14 | These results provide structural insights into resistance of RET mutants against the TKIs nintedanib and vandetanib. | nintedanib | ret proto-oncogene | Homo sapiens |