P276
P276 Basic information
- Product Name:
- P276
- Synonyms:
-
- 4H-1-Benzopyran-4-one, 2-(2-chlorophenyl)-5,7-dihydroxy-8-[(2R,3S)-2-(hydroxymethyl)-1-methyl-3-pyrrolidinyl]-, hydrochloride (1:1)
- Riviciclib hydrochloride
- CS-996
- Riviciclib HCl
- RIVICICLIB HYDROCHLORIDE (P276-00)
- P276-00 4H-1-Benzopyran-4-one, 2-(2-chlorophenyl)-5,7-dihydroxy-8-((2R,3S)-2-(hydroxymethyl)-1-methyl-3-pyrrolidinyl)-, hydrochloride (1:1)
- 2-(2-chlorophenyl)-5,7-dihydroxy-8-[(2R,3S)-2-(hydroxymethyl)-1-methylpyrrolidin-3-yl]chromen-4-one:hydrochloride
- 2-(2-chlorophenyl)-5,7-dihydroxy-8-((2R,3S)-2-(hydroxymethyl)-1-methylpyrrolidin-3-yl)-4H-chromen-4-one hydrochloride
- CAS:
- 920113-03-7
- MF:
- C21H21Cl2NO5
- MW:
- 438.3
- Product Categories:
-
- Inhibitors
- Mol File:
- 920113-03-7.mol
P276 Chemical Properties
- storage temp.
- Store at -20° C
- solubility
- Soluble in DMSO
- form
- Solid
- color
- Off-white to light yellow
P276 Usage And Synthesis
Uses
P276-00 is a cyclin-dependent kinase (CDK) inhibitor. P276-00 has shown to be highly selective for cancer cells and has shown to produce potent inhibition of Cdk4-D1 activity. P276-00 also induces apoptosis in human promyelocytic leukemia (HL-60) cells.
Enzyme inhibitor
This cell cycle-inhibiting flavone and anticancer agent (FW = 438.30 g/mol; CAS 920113-03-7), also named 2-(2-chlorophenyl)-5,7-dihydroxy-8- [(2R,3S)-2-(hydroxymethyl)-1-methyl-3-pyrrolidinyl]-4H-1-benzopyran-4- one, targets the Cyclin-Dependent Kinases CDK1 (IC50 = 79 nM), CDK4 (IC50 = 63 nM) and CDK9 (IC50 = 20 nM). p276-00 showed potent antiproliferative effects against various human cancer cell lines (IC50 values ranging from 300 to 800 nmol/L), but has little effect on cultured fibroblasts. A significant down-regulation of cyclin D1 and Cdk4 and a decrease in Cdk4-specific pRb Ser(780) phosphorylation is observed. P276-00 produces potent inhibition of Cdk4-D1 activity that is competitive with ATP, and not with retinoblastoma protein. The compound also induced apoptosis in human promyelocytic leukemia (HL-60) cells, as evidenced by the induction of caspase-3 and DNA ladder studies. In 22 human cancer xenografts, P276-00 is approximately 26x more potent than cisplatin, and is also active against cisplatin-resistant tumors of central nervous system, melanoma, prostate, and renal cancers. Synchronized human non-small cell lung carcinoma (H-460) and human normal lung fibroblast (WI-38) cells are arrested in G1
in vivo
Riviciclib hydrochloride (administered i.p.; 35 kg/mg daily for 10 days, in human xenograft mode with severe combined immunodeficient mice) shows significant inhibition in the growth of human colon carcinoma HCT-116 xenograft[3].
?
Riviciclib hydrochloride (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) significantly inhibited growth[3].
| Animal Model: | Human xenograft mode with HCT-116 tumor model (severe combined immunodeficient mice)[3] |
| Dosage: | 35 mg/kg |
| Administration: | Administered i.p.; daily for 10 days |
| Result: | Given 35 mg/kg showed significant inhibition in the growth. |
| Animal Model: | Human xenograft model with H-460 tumor xenograft (severe combined immunodeficient mice)[3] |
| Dosage: | 50 mg/kg; 30 mg/kg |
| Administration: | Administered i.p.; 50 mg/kg once daily for 20 days; Administered i.p.; 30 mg/kg twice daily for 18 treatments |
| Result: | Given 50 mg/kg and 30 mg/kg twice daily significantly inhibited growth. |
IC 50
CDK9- Cyclin T1: 0.020 μM (IC50); cdk4-cyclin D1: 0.063 μM (IC50); CDK1-Cyclin B: 0.079 μM (IC50); cdk2-cyclin A: 0.224 μM (IC50); cdk2-cyclin E: 2.500 μM (IC50); cdk6-cyclin D3: 0.396 μM (IC50); CDK9-cyclin H: 2.900 μM (IC50)
P276Supplier
- Tel
- 18210857532; 18210857532
- jkinfo@jkchemical.com
- Tel
- 025-83697070
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- 0531-88811783
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- 400-6206333 13167063860
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