8-cyclopentyl-2-((4-(4-methylpiperazin-1-yl)phenyl)amino)-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidine-6-carbonitrile
ON123300
CAS: 1357470-29-1
Molecular Formula: C24H27N7O
8-cyclopentyl-2-((4-(4-methylpiperazin-1-yl)phenyl)amino)-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidine-6-carbonitrile - Names and Identifiers
8-cyclopentyl-2-((4-(4-methylpiperazin-1-yl)phenyl)amino)-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidine-6-carbonitrile - Physico-chemical Properties
| Molecular Formula | C24H27N7O |
| Molar Mass | 429.52 |
| Density | 1.35±0.1 g/cm3(Predicted) |
| Boling Point | 642.7±65.0 °C(Predicted) |
| Solubility | 10 mM in DMSO |
| pKa | 7.88±0.42(Predicted) |
| Storage Condition | -20℃ |
| In vitro study | ON123300 inhibited the proliferation of U87 glioma cells with an IC50 of 3.4±0.1 μmol/L. It reduced the phosphorylation of Akt and induced Erk activation in a concentration-dependent and time-dependent manner, this is attributed to the reduction of Akt-mediated inactivation at position C- Raf S259 by ON123300 and the activation of p70S6K-induced negative feedback regulation of PI3K. ON123300 also inhibits CDK4/6 and PI3K-δ, and has potent inhibitory activity against mantle cell lymphoma (MCLs). It is a potent inhibitor of CDK4 with an IC50 of 3.8 nM and has little activity on CDK1,2,5,8. MCL cell lines treated with low concentrations of ON123300(0.1-1.0 μm) accumulated in the G1 phase of the cell cycle, while most cells passed through the S and G2/M phases under high concentrations of ON123300, and eventually accumulated in the sub-G1 phase, indicating that apoptosis. ON123300 inhibited the phosphorylation of pRB and p130 in a concentration-dependent manner. Its treatment will result in inhibition of phosphorylation of FOXO1, a target of mTOR. |
| In vivo study | In the preclinical brain tumor model (U87MG),ON123300 accumulates in large amounts in the brain and in brain tumors. Consistent with in vitro experiments, ON123300 monotherapy caused a concentration-dependent inhibition of Akt and activation of Erk in brain tumors. ON123300 is highly bound to plasma protein (99.4%) in mice, and quickly enters the brain. It has good blood brain barrier penetration ability and accumulates in normal brain. The pharmacokinetics of ON123300 showed that its plasma concentration was exponential and the overall rapid decline, and the terminal elimination half-life was 1.5 hours. Mouse xenograft tumor experiments showed significant inhibition of MCL tumor growth in ON123300 treated animals. In safety studies in mice, ON123300 is an orally bioactive drug with very little toxic effect when administered by oral route or intraperitoneal route. |
8-cyclopentyl-2-((4-(4-methylpiperazin-1-yl)phenyl)amino)-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidine-6-carbonitrile - Preparation solution concentration reference
| 1mg | 5mg | 10mg | |
|---|---|---|---|
| 1 mM | 2.328 ml | 11.641 ml | 23.282 ml |
| 5 mM | 0.466 ml | 2.328 ml | 4.656 ml |
| 10 mM | 0.233 ml | 1.164 ml | 2.328 ml |
| 5 mM | 0.047 ml | 0.233 ml | 0.466 ml |
Last Update：2024-01-02 23:10:35
8-cyclopentyl-2-((4-(4-methylpiperazin-1-yl)phenyl)amino)-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidine-6-carbonitrile - Reference Information
| use | 8-cyclopentyl -7, 8-dihydro-2-[[4-(4-methyl-1-piperazinyl) phenyl] amino]-7-oxo-pyridino [2,3-D] pyrimidin-6-nitrile can be used as a multi-target kinase inhibitor and intermediate for scientific research and development and laboratory research. |
| biological activity | ON123300 is an effective multi-target kinase inhibitor, and its IC50 for CDK4, Ark5/NUAK1, PDGFRβ, FGFR1, RET (c-RET) and Fyn is 3.9 nM, 5 nM, 26 nM, 26 nM, 9.2 nM and 11nM respectively. |
| target | TargetValue CDK4/CyclinD1 (Cell-free assay) 3.87 nM ARK5 (Cell-free assay) 4.95 nM RET (Cell-free assay) 9.2 nM CDK6/CyclinD1 (Cell-free assay) 9.82 nM Fyn (Cell-free assay) 11 nM |
| Target | Value |
| CDK4/CyclinD1 (Cell-free assay) | 3.87 nM |
| ARK5 (Cell-free assay) | 4.95 nM |
| RET (Cell-free assay) | 9.2 nM |
| CDK6/CyclinD1 (Cell-free assay) | 9.82 nM |
| Fyn (Cell-free assay) | 11 nM |
| in vitro study | ON123300 inhibit the proliferation of U87 glioma cells with IC50 of 3.4±0.1 μmol/L; Reduce Akt phosphorylation and induce Erk activation in a concentration-dependent and time-dependent manner, this is attributed to ON123300 reducing the negative feedback regulation of PI3K caused by Akt-mediated inactivation of C- Raf S259 and activation of p70S6K. ON123300 can also inhibit CDK4/6 and PI3K-δ, and has effective inhibitory activity on mantle cell lymphoma (MCLs). It is an effective inhibitor of CDK4, IC50 is 3.8 nM, and has little activity against CDK1,2,5,8. MCL cell lines treated with low concentration ON123300(0.1-1.0 μM) accumulate in G1 phase of cell cycle, while most cells pass through S and G2/M phases and eventually accumulate in sub-G1 phase under high concentration ON123300 treatment, indicating apoptosis. The phosphorylation of pRB and p130 was inhibited ON123300 concentration-dependently. Its treatment will lead to inhibition of FOXO1 phosphorylation, which is the target of mTOR. |
| in vivo research | in preclinical brain tumor model (U87MG),ON123300 accumulate in large quantities in brain and brain tumors. Consistent with in vitro experiments, ON123300 single drug administration caused Akt concentration-dependent inhibition and activated Erk in brain tumors. ON123300 is highly bound to plasma proteins (99.4%) and quickly enters the brain in mice. It has good blood-brain barrier penetration and accumulates in normal brain. The pharmacokinetics of the ON123300 showed that its blood drug concentration was multi-exponential and decreased rapidly as a whole, with a terminal elimination half-life of 1.5 hours. Mouse xenograft tumor experiments showed that MCL tumor growth was significantly inhibited in ON123300 treated animals. In safety studies in mice, ON123300 is a drug with oral biological activity. When administered by oral route or intraperitoneal injection route, the toxic effect is very small. |
Last Update：2024-04-09 15:16:37
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Product Name: ON123300 Visit Supplier Webpage Request for quotation
CAS: 1357470-29-1
Tel: 18301782025
Email: 3008007409@qq.com
Mobile: 18021002903
QQ: 3008007409
Wechat: 18301782025
CAS: 1357470-29-1
Tel: 18301782025
Email: 3008007409@qq.com
Mobile: 18021002903
QQ: 3008007409
Wechat: 18301782025
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