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TAK-733
| 别名 | example 18 [US8470837], TAK733, compound 17 [PMID: 21310613] |
|---|---|
| Compound Class | Synthetic organic |
| 变动原因 |
TAK-733 is a potent and selective MEK inhibitor with an allosteric binding mode, that was designed as a novel cancer chemotherapeutic |
| Related Product | TAK-733 |
Summary
| 是否批准为药物？ | |
|---|---|
| IUPAC Name | 3-[(2R)-2,3-dihydroxypropyl]-6-fluoro-5-(2-fluoro-4-iodoanilino)-8-methylpyrido[2,3-d]pyrimidine-4,7-dione |
| 别名 | example 18 [US8470837], TAK733, compound 17 [PMID: 21310613] |
数据库链接
| PubChem CID | 24963252 |
|---|---|
| ChEMBL Ligand | CHEMBL1615025 |
| BindingDB Ligand | 50337926 |
| RCSB PDB Ligand | IZG |
生物活性
| 生物活性评价 |
TAK-733 inhibits ERK phosphorylation in cells with an EC50 of 1.9 nM |
|---|---|
| 关联靶标 | mitogen-activated protein kinase kinase 1 |
临床资料
| Summary of Clinical Use |
TAK-733 was advanced to Phase 1 clinical studies for treatment of advanced solid tumours. Trial NCT00948467 was completed |
|---|---|
| 作用机制与药效学效应 |
The mitogen-activated protein kinase (MAPK) pathway (the Ras/Raf/MEK/ERK signaling cascade) is one of the most important pathways involved in cell proliferation and differentiation, and abberant pathway activation driven by K-Ras or B-Raf mutations in tumours is common. Hence, drug companies have long been developing inhibitors of components of the MAPK pathway as cancer chemotherapeutics |
参考文献
| 1. Dong Q, Dougan DR, Gong X, Halkowycz P, Jin B, Kanouni T, O'Connell SM, Scorah N, Shi L, Wallace MB et al.. (2011) Discovery of TAK-733, a potent and selective MEK allosteric site inhibitor for the treatment of cancer.. Bioorg Med Chem Lett, 21 (5): (1315-9). [PMID:21310613] |
| 2. Adjei AA, LoRusso P, Ribas A, Sosman JA, Pavlick A, Dy GK, Zhou X, Gangolli E, Kneissl M, Faucette S et al.. (2017) A phase I dose-escalation study of TAK-733, an investigational oral MEK inhibitor, in patients with advanced solid tumors.. Invest New Drugs, 35 (1): (47-58). [PMID:27650277] |
| 3. Akinleye A, Furqan M, Mukhi N, Ravella P, Liu D. (2013) MEK and the inhibitors: from bench to bedside.. J Hematol Oncol, 6 (13): (27). [PMID:23587417] |
结构
| Canonical SMILES | OCC(Cn1cnc2c(c1=O)c(Nc1ccc(cc1F)I)c(c(=O)n2C)F)O |
|---|---|
| Isomeric SMILES | OC[C@@H](Cn1cnc2c(c1=O)c(Nc1ccc(cc1F)I)c(c(=O)n2C)F)O |
| InChI | InChI=1S/C17H15F2IN4O4/c1-23-15-12(16(27)24(7-21-15)5-9(26)6-25)14(13(19)17(23)28)22-11-3-2-8(20)4-10(11)18/h2-4,7,9,22,25-26H,5-6H2,1H3/t9-/m1/s1 |
| InChI key | RCLQNICOARASSR-SECBINFHSA-N |
危险品化学品经营许可证（带存储）