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Purity: ≥98%
Riviciclib (formerly P 276-00; P-27600; P276-00) is a flavonoid analog which acts as a potent inhibitor of CDK1 (cyclin-dependent kinase), CDK4 and CDK9 with potential antitumor activity. It has IC50s of 79 nM, 63 nM, and 20 nM for CDK1/4/9 inhibition, respectively.
| Targets |
CDK9- Cyclin T1 (IC50 = 0.02 μM); cdk4-cyclin D1 (IC50 = 0.063 μM); CDK1-Cyclin B (IC50 = 0.079 μM); cdk2-cyclin A (IC50 = 0.224 μM); cdk2-cyclin E (IC50 = 2.540 μM); cdk6-cyclin D3 (IC50 = 0.396 μM); CDK9-cyclin H (IC50 = 2.900 μM)
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| ln Vitro |
Riviciclib (1.5-5 μM; 72 hours) exhibits cell arrest in G1 in synchronized human non-small cell lung carcinoma (H-460) and human normal lung fibroblast (WI-38) cells, as well as no detectable cells in G1 and G2 in promyelocytic leukemia cells[3].
Riviciclib (3–24 hours; 1.5 μM) lowers H-460 cell levels of cyclin D1, Cdk4, and Rb. At three hours, Rb (retinoblastoma) phosphorylation at Ser780 decreases[2]. Riviciclib demonstrates activity in human cancer cell lines, including those from the bladder, colon, osteosarcoma, and cervical cancers[2]. |
| ln Vivo |
Riviciclib (administered i.p.; 35 kg/mg daily for 10 days, in human xenograft mode with severe combined immunodeficient mice) significantly inhibits the HCT-116 human colon cancer xenograft's growth[3].
Riviciclib (administered via i.p.; 50 mg/kg once daily; 30 mg/kg twice daily for 18 treatments, in human xenograft mode with severe combined immunodeficient mice) dramatically reduces growth[3].
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| Enzyme Assay |
The Cdk4-D1/Cdk2-E enzyme assay is conducted using Millipore Multiscreen filtration plates in a 96-well format. A single filter plate is used for each step of the assay. After prewetting the filtration wells with 100 μL of kinase buffer (which contains 50 mmol/L HEPES (pH of 7.5), 10 mmol/L MgCl2, and 1 mmol/L EGTA), the solution is vacuum-withdrawn. Vacuum is applied to the filter plate while it is on the vacuum manifold. Each well receives 50 μL of GST-Rb bound to GSH-Sepharose beads in kinase buffer (0.5 μg GST-Rb/50 μL). 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 in approximately 25 μL. An additional 25 μL volume is then added containing either the test compound (4×final concentration in kinase buffer) or kinase buffer alone (control). To start the reaction, add 50 μL (100 ng) of human Cdk4-D1/Cdk2-E enzyme in kinase buffer to each well. The reaction is then allowed to run at 30°C for 30 minutes. The filter plate is air-dried and put in a Multiscreen adapter plate after the reaction is finished and vacuum is applied once more. The plate is then cleaned three times using the TNEN buffer, which is composed of 20 mmol/L Tris (pH, 8.0), 100 mmol/L NaCl, 1 mmol/L EDTA, and 0.5% nonidet-P40. The plate is covered with a Top-Seal A film after adding 30 μL of Packard Microscint-O cocktail. With a Top Count scintillation counter, 32P-GST-Rb is quantified in 96-well filter plates. The initial concentration of each compound tested is 1 μmol/L. More profiling is done on compounds exhibiting 50% or more inhibition in order to determine their IC50.
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| Cell Assay |
Cell Line: Promyelocytic leukemia cells (HL-60 cells), non-small cell carcinoma (H-460) cells, human normal lung fibroblast (WI-38) cells
Concentration: 1.5, 5 μM Incubation Time: 72 hours Result: Showed apoptosis at the end of 24 h and no detectable cells were present in G1 and G2 in HL-60 cells. Caused an exclusive G1 arrest of synchronous population of cancerous cells H-460 cells and normal cells WI-38. |
| Animal Protocol |
Human xenograft mode with HCT-116 tumor model (severe combined immunodeficient mice)[3]
35 mg/kg Administered i.p.; daily for 10 days |
| References |
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| Additional Infomation |
Riviciclib is a synthetic dihydroxyflavone that is 5,7-dihydroxyflavone which is substituted by a (2R,3S)-2-(hydroxymethyl)-1-methylpyrrolidin-3-yl group at position 8 and by a chlorine at the 2' position. A cyclin-dependent kinase inhibitor that exhibits anti-cancer properties. It has a role as an EC 2.7.11.22 (cyclin-dependent kinase) inhibitor and an antineoplastic agent. It is a dihydroxyflavone, a member of monochlorobenzenes, a N-alkylpyrrolidine and a primary alcohol.
Riviciclib is a flavone and cyclin dependent kinase (CDK) inhibitor with potential antineoplastic activity. Riviciclib selectively binds to and inhibits Cdk4/cyclin D1, Cdk1/cyclin B and Cdk9/cyclin T1, serine/threonine kinases that play key roles in the regulation of the cell cycle and cellular proliferation. Inhibition of these kinases leads to cell cycle arrest during the G1/S transition, thereby leading to an induction of apoptosis, and inhibition of tumor cell proliferation. |
| Molecular Formula |
C21H20CLNO5
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| Molecular Weight |
401.84
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| Exact Mass |
401.103
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| Elemental Analysis |
C, 62.77; H, 5.02; Cl, 8.82; N, 3.49; O, 19.91
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| CAS # |
920113-02-6
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| Related CAS # |
Riviciclib hydrochloride;920113-03-7
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| PubChem CID |
23643976
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| Appearance |
Solid powder
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| LogP |
3.242
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
28
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| Complexity |
628
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| Defined Atom Stereocenter Count |
2
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| SMILES |
ClC1C=CC=CC=1C1=CC(C2=C(C=C(C(=C2O1)C1CCN(C)C1CO)O)O)=O
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| InChi Key |
QLUYMIVVAYRECT-GXTWGEPZSA-N
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| InChi Code |
InChI=1S/C21H20ClNO5/c1-23-7-6-12(14(23)10-24)19-15(25)8-16(26)20-17(27)9-18(28-21(19)20)11-4-2-3-5-13(11)22/h2-5,8-9,12,14,24-26H,6-7,10H2,1H3/t12-,14+/m0/s1
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| Chemical Name |
2-(2-chlorophenyl)-5,7-dihydroxy-8-[(2S,3R)-2-(hydroxymethyl)-1-methylpyrrolidin-3-yl]chromen-4-one
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4886 mL | 12.4428 mL | 24.8855 mL | |
| 5 mM | 0.4977 mL | 2.4886 mL | 4.9771 mL | |
| 10 mM | 0.2489 mL | 1.2443 mL | 2.4886 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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