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Synonyms | N/A | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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化学式 | C21H20ClNO5.HCl |
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分子量 | 438.3 | CAS No. | 920113-03-7 | ||||
Solubility (25°C)* | 体外 | DMSO | 88 mg/mL (200.77 mM) | ||||
Water | 88 mg/mL (200.77 mM) | ||||||
Ethanol | 7 mg/mL (15.97 mM) | ||||||
体内 (毎回新しく調製した物を用意してください) |
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* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. |
製品説明 | Riviciclib hydrochloride (P276-00) is a novel CDK1, CDK4 and CDK9 inhibitor with IC50 of 79 nM, 63 nM and 20 nM, respectively. Riviciclib hydrochloride (P276-00) induces apoptosis. Phase 2/3. |
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in vitro | P276-00 shows 40-fold selectivity toward Cdk4-D1, compared with Cdk2-E[1]. It shows potent antiproliferative effects against various human cancer cell lines, including HCT-116, U2OS, H-460, HL-60, HT-29, SiHa, MCF-7, Colo-205, SW-480, PC-3, Caco2, T-24 with an IC50 ranging from 300 to 800 nmol/L, and is found to be highly selective for cancer cells as compared with normal fibroblast cells[1]. P276-00 can down-regulate cyclin D1 and Cdk4 in an ATP- competitive manner and decrease Cdk4-specific pRb Ser780 phosphorylation. P276-00 also induces apoptosis by actving cellular caspase-3 activity and DNA ladder formation[1]. |
in vivo | P276-00, administered i.p. at 50 mg/kg daily for 20 treatments can significantly induce growth inhibition of murine colon cancer (CA-51). However, in murine lung carcinoma model (Lewis lung), an increased dose of 60 mg/kg (30 mg/kg twice daily) administered every alternate day i.p. for 7 treatments shows significant inhibition in the growth[2]. And it also inhibit the growth of human colon carcinoma HCT-116 xenograft and human non-small cell lung carcinoma H-460 xenograft[2]. Efficacy Studies show its maximum tolerated dose is 78 mg/kg/d[2]. |
キナーゼアッセイ | Cdk4-D1/Cdk2-E enzyme assay | |
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The Cdk4-D1/Cdk2-E enzyme assay is run in 96-well format using Millipore Multiscreen filtration plates. All assay steps are done in a single filter plate. The filtration wells are prewetted with 100 μL of kinase buffer [50 mmol/L HEPES (pH, 7.5), 10 mmol/L MgCl2, 1 mmol/L EGTA], and then the solution is removed by vacuum. With filter plate on vacuum manifold, 50 μL GST-Rb bound to GSH-Sepharose beads in kinase buffer (0.5 μg GST-Rb/50 μL) is added to each well, and vacuum is applied to the filter plate. About 25 μL of a reaction mix containing ATP (cold + hot) and 4× phosphatase inhibitor mix (40 μmol/L unlabeled ATP, 10 μCi/mL γ32P-ATP, 40 mmol/L h-glycerophosphate, 4 mmol/L DTT, 0.4 mmol/L NaF, 0.4 mmol/L sodium orthovanadate) diluted in kinase buffer is added to each well. The test compound (4×final concentration in kinase buffer) or kinase buffer alone (control) is then added in an additional 25 μL volume. To each well, 50 μL (100 ng) of human Cdk4-D1/Cdk2-E enzyme in kinase buffer is added to initiate the reaction, which is allowed to continue for 30 min at 30°C. When the reaction is completed, vacuum is applied again, and the plate is washed with the TNEN buffer [20 mmol/L Tris (pH, 8.0), 100 mmol/L NaCl, 1 mmol/L EDTA, 0.5% nonidet-P40] thrice; the filter plate is air-dried and is placed in a Multiscreen adapter plate. Packard Microscint-O cocktail (30 μL) is added, and the plate is covered with a Top-Seal A film. Quantitation of 32P-GST-Rb in 96-well filter plates is carried out by Top Count scintillation counter. All compounds are tested initially at 1 μmol/L concentration. Compounds showing more than or equal to 50% inhibition are further profiled for IC50 determination. | ||
細胞アッセイ | 細胞株 | HCT-116, U2OS, H-460, HL-60, HT-29, SiHa, MCF-7, Colo-205, SW-480, PC-3, Caco2, T-24 |
濃度 | ~5.0 μM | |
反応時間 | 48 h | |
実験の流れ | The cells are seeded at a density of 3,000-5,000 cells per well, depending on cell type in 180 μL of culture medium in 96-well plate and incubated overnight to allow the cells to adhere. Varying concentrations of compounds are added to the wells and incubated for 48 h at 37°C. 3H-thymidine (0.25 μCi) is added to each well, and incorporation of the radiolabel is allowed to proceed for 5 to 7 h. Following this incubation, cells are harvested onto GF/B unifilter plates using a Packard Filtermate Universal harvester, and the plates are counted in a Packard Top Count 96-well liquid scintillation counter. | |
動物実験 | 動物モデル | H-460 xenograft |
投薬量 | 50 mg/kg once daily or 30 mg/kg twice daily | |
投与方法 | i.p. |
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, , Mod Pathol, 2016, 29(6):616-29.
Polysaccharide from Angelica sinensis attenuates SNP-induced apoptosis in osteoarthritis chondrocytes by inducing autophagy via the ERK1/2 pathway [ Arthritis Res Ther, 2021, 23(1):47] | PubMed: 33514407 |
Key metabolism pathways and regulatory mechanisms of high polysaccharide yielding in Hericium erinaceus [ BMC Genomics, 2021, 22(1):160] | PubMed: 33676419 |
Localized Inhibition of Protein Phosphatase 1 by NUAK1 Promotes Spliceosome Activity and Reveals a MYC-Sensitive Feedback Control of Transcription. [ Mol Cell, 2020, 77(6):1322-1339] | PubMed: 32006464 |
An ATR and CHK1 kinase signaling mechanism that limits origin firing during unperturbed DNA replication. [ Proc Natl Acad Sci U S A, 2019, 116(27):13374-13383] | PubMed: 31209037 |
Overcoming resistance to the THZ series of covalent transcriptional CDK inhibitors [Gao Y, et al. Cell Chem Biol, 2018, 10.1016/j.chembiol.2017.11.007] | PubMed: 29276047 |
Expression profiling of small intestinal neuroendocrine tumors identifies subgroups with clinical relevance, prognostic markers and therapeutic targets [Andersson E, et al. Mod Pathol, 2016, 10.1038/modpathol.2016.48.] | PubMed: 26965582 |
長期の保管のために-20°Cの下で製品を保ってください。
人間や獣医の診断であるか治療的な使用のためにでない。
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