PHA-848125
Modify Date: 2024-01-11 15:40:00
PHA-848125 structure
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Common Name | PHA-848125 | ||
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| CAS Number | 802539-81-7 | Molecular Weight | 460.575 | |
| Density | 1.3±0.1 g/cm3 | Boiling Point | N/A | |
| Molecular Formula | C25H32N8O | Melting Point | N/A | |
| MSDS | N/A | Flash Point | N/A | |
Use of PHA-848125Milciclib (PHA-848125) is a potent, dual inhibitor of CDK and Tropomyosin receptor kinase (TRK), with IC50s of 45, 150, 160, 363, 398 nM and 53 nM for cyclin A/CDK2, cyclin H/CDK7, cyclin D1/CDK4, cyclin E/CDK2, cyclin B/CDK1 and TRKA, respectively. |
| Name | N,1,4,4-tetramethyl-8-[4-(4-methylpiperazin-1-yl)anilino]-5H-pyrazolo[4,3-h]quinazoline-3-carboxamide |
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| Synonym | More Synonyms |
| Description | Milciclib (PHA-848125) is a potent, dual inhibitor of CDK and Tropomyosin receptor kinase (TRK), with IC50s of 45, 150, 160, 363, 398 nM and 53 nM for cyclin A/CDK2, cyclin H/CDK7, cyclin D1/CDK4, cyclin E/CDK2, cyclin B/CDK1 and TRKA, respectively. |
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| Related Catalog | |
| Target |
cyclin A/CDK2:45 nM (IC50) cyclin E/CDK2:363 nM (IC50) cyclin H/CDK7:150 nM (IC50) cyclin D1/CDK4:160 nM (IC50) cyclin B/CDK1:398 nM (IC50) TRKA:53 nM (IC50) |
| In Vitro | Milciclib (PHA-848125; 0.156 or 0.625 μM) up-regulates the expression of PDCD4, DDIT4, SESN2/sestrin 2 and DEPDC6/DEPTOR in GL-Mel cells[1]. Milciclib (PHA-848125) potently inhibits the kinase activity of CDK2/cyclin A complex and of TRKA in a biochemical assay, with IC50s of 45 and 53 nM, respectively. Milciclib induces a clear accumulation of cells in G1 phase. Milciclib strongly inhibits NGF-induced phosphorylation of TRKA in a dose-dependent manner[2]. |
| In Vivo | Milciclib (PHA-848125; 5, 10, and 15 mg/kg, p.o.) inhibits the growth of tumor in 7,12-dimethylbenz(a) anthracene (DMBA)-induced rat mammary carcinoma model. Milciclib has significant antitumor activity in various human xenografts and carcinogen-induced tumors as well as in disseminated primary leukemia models, with plasma concentrations in rodents in the same range as those found active in inhibiting cancer cell proliferation[2]. Milciclib (PHA-848125; 40 mg/kg) induces a significant tumor growth inhibition in K-RasG12DLA2 mice, and this is accompanied by a reduction in the cell membrane turnover[3]. |
| Cell Assay | Cells are seeded into 96- or 384-well plates at densities ranging from 10,000 to 30,000/cm2 in appropriate medium plus 10% FCS. After 24 hours, cells are treated in duplicate with serial dilutions of Milciclib, and 72 hours later, viable cell number is assessed using the CellTiter-Glo Assay. IC50s are calculated using a Sigmoidal fitting algorithm. Experiments are done independently at least twice. |
| Animal Admin | Rats are randomized and introduced into the study when at least one mammary tumor attained a diameter of 0.5 cm. Groups of 10 animals are treated orally twice a day continuously for 10 days with vehicle (glucosate) or with 5, 10, and 15 mg/kg of Milciclib, whereas a further group receives two cycles of Milciclib at 20 mg/kg orally twice a day for 5 days with an intervening rest period of 1 week. Tumor volume is measured regularly by caliper for the duration of the experiment. |
| References |
| Density | 1.3±0.1 g/cm3 |
|---|---|
| Molecular Formula | C25H32N8O |
| Molecular Weight | 460.575 |
| Exact Mass | 460.269897 |
| PSA | 94.70000 |
| LogP | 1.75 |
| Index of Refraction | 1.692 |
| Storage condition | -20℃ |
| 1H-Pyrazolo[4,3-h]quinazoline-3-carboxamide, 4,5-dihydro-N,1,4,4-tetramethyl-8-[[4-(4-methyl-1-piperazinyl)phenyl]amino]- |
| Milciclib [INN] |
| N,1,4,4-Tetramethyl-8-{[4-(4-methyl-1-piperazinyl)phenyl]amino}-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide |
| N,1,4,4-tetramethyl-8-(4-(4-methylpiperazin-1-yl)phenylamino)-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide |
| Milciclibum |
| cc-78 |
| Milciclib |
| PHA-848125 |