曲拉西利
| 中文名称 | 曲拉西利 |
|---|---|
| 中文同义词 | G1T28 ; G1T-28 ; G1T 28 ; TRILACICLIB.;曲拉西利;骨髓保护剂;化合物 T13202L;曲拉西利 (NMN);2'-[[5-(4-甲基哌嗪-1-基)吡啶-2-基]氨基}-7',8'-二氢-6'H-螺环[环己烷-1,9'-吡嗪[1',2':1,5]吡咯[2,3-D]嘧啶]-6'-酮;曲拉西利相关杂质;2'-((5-(4-甲基哌嗪-1-基)吡啶-2-基)氨基)-7',8'-二氢-6'H-吡唑并[环己烷-1,9'-吡嗪并[1',2':1,5]吡咯并[2,3-D]嘧啶]-6'-酮 |
| 英文名称 | trilaciclib |
| 英文同义词 | 2'-((5-(4-methylpiperazin-1-yl)pyridin-2-yl)amino)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-pyrazino[1',2':1,5]pyrrolo[2,3-d]pyrimidin]-6'-one;2'-((5-(4-methylpiperazin-1-yl) yridine-2-yl)amino)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-pyrazino[1',2':1,5]pyrrolo[2,3-d]pyrimidin]-6'-one;Spiro[cyclohexane-1,9'(6'H)-pyrazino[1',2':1,5]pyrrolo[2,3-d]pyrimidin]-6'-one, 7',8'-dihydro-2'-[[5-(4-methyl-1-piperazinyl)-2-pyridinyl]amino]-;2'-[4-(4-methylpiperazin-1-yl)anilino]-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-pyrazino[1',2':1,5]pyrrolo[2,3-d]pyrimidin]-6'-one;Trilaciclib (G1T28);Trilaciclib;2'-((5-(4-Methylpiperazin-1-yl)pyridin-2-yl)amino)-7',8'-dihydro-6'H-spiro[cyclohexane-1,9'-pyrazino[1',2':1,5]pyrrolo[2,3-d]pyrimidin]-6'-one;trilaciclib impurity |
| CAS号 | 1374743-00-6 |
| 分子式 | C24H30N8O |
| 分子量 | 446.55 |
| EINECS号 | |
| 相关类别 | 抑制剂;医药原料;医用原料 |
| Mol文件 | 1374743-00-6.mol |
| 结构式 |  |
曲拉西利 性质
| 密度 | 1.46±0.1 g/cm3(Predicted) |
|---|---|
| 溶解度 | H2O:15.0(最大浓度 mg/mL);33.59(最大浓度 mM) |
| 酸度系数(pKa) | 13.33±0.20(Predicted) |
| 形态 | 固体 |
| 颜色 | 白色至黄色 |
| Target | Value |
|
CDK4/cyclin D1
(Cell-free assay) | 1 nM |
|
CDK6/cyclin D3
(Cell-free assay) | 4 nM |
Incubation with Trilaciclib (G1T28) for 24 hours induces a robust G 1 cell-cycle arrest (time=0). By 16 hours after Trilaciclib hydrochloride washout, cells have reentered the cell cycle and demonstrate cell-cycle kinetics similar to untreated control cells. These results demonstrate that Trilaciclib causes a transient, and reversible G 1 arrest. A transient Trilaciclib-mediated G 1 cell-cycle arrest in CDK4/6-sensitive cells decreases the in vitro toxicity of a variety of commonly used cytotoxic chemotherapy agents associated with myelosuppression.
Trilaciclib (G1T28) treatment results in a robust and dose-dependent suppression of proliferation in HSPCs at 12 hours, with EdU incorporation returning near baseline levels in a dose-dependent manner by 24 hours after administration. These data demonstrate that a single oral dose of Trilaciclib can produce reversible cell-cycle arrest in HSPCs in a dose-dependent manner in vivo . Mice given 100 mg/kg Trilaciclib 30 minutes prior to etoposide treatment, exhibits only background levels of caspase-3/7 activity. These data demonstrate that Trilaciclib can protect the bone marrow from chemotherapy-induced apoptosis in vivo . The data demonstrate that treatment with Trilaciclib prior to 5-FU likely decreases 5-FU-induced damage by chemotherapy in HSPCs, thus accelerating blood count recovery after chemotherapy.