| Identification | Back Directory | [Name]
P276 | [CAS]
920113-03-7 | [Synonyms]
P276
CS-996
Riviciclib HCl
P276 USP/EP/BP
Riviciclib HCl (P276-00)
Riviciclib hydrochloride
RIVICICLIB HYDROCHLORIDE (P276-00)
inhibit,Inhibitor,Riviciclib,CDK,Riviciclib hydrochloride,Cyclin dependent kinase,Apoptosis
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
4H-1-Benzopyran-4-one, 2-(2-chlorophenyl)-5,7-dihydroxy-8-[(2R,3S)-2-(hydroxymethyl)-1-methyl-3-pyrrolidinyl]-, hydrochloride (1:1)
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) | [Molecular Formula]
C21H20ClNO5.HCl | [MDL Number]
MFCD26960898 | [MOL File]
920113-03-7.mol | [Molecular Weight]
438.3 |
| Hazard Information | Back Directory | [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 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].
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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) | [storage]
Store at -20° C |
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