Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C21H20ClNO5 |
Molecular Weight | 401.84 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 2 / 2 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CN1CC[C@@H]([C@H]1CO)C2=C3OC(=CC(=O)C3=C(O)C=C2O)C4=C(Cl)C=CC=C4
InChI
InChIKey=QLUYMIVVAYRECT-GXTWGEPZSA-N
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
Molecular Formula | C21H20ClNO5 |
Molecular Weight | 401.84 |
Charge | 0 |
Count |
|
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 2 / 2 |
E/Z Centers | 0 |
Optical Activity | UNSPECIFIED |
P276-00 (also known as riviciclib) is a novel, potent, small-molecule, flavone-derived inhibitor of cyclin-dependent kinases (Cdk), Cdk 4 D1, Cdk1 B, and Cdk9 T, with potent cytotoxic effects against chemosensitive and chemoresistant cancer cell lines. P276-00 was in phase II clinical trial for the treatment mantle cell lymphoma, but that study was terminated based on interim results and all subjects were off study at that time. Although, there were not the major safety or tolerability concerns. However, this drug successfully passed phase II clinical trial for the treatment Melanoma, squamous cell carcinoma of head and neck, malignant melanoma and in combination with Gemcitabine in the treatment of advanced pancreatic cancer.
Originator
Sources: https://www.ncbi.nlm.nih.gov/pubmed/25816934
Curator's Comment: Piramal Enterprises Limited (PEL) (formerly known as Piramal Life Sciences Limited)
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: P11802 Gene ID: 1019.0 Gene Symbol: CDK4 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/17363486 |
0.063 µM [IC50] | ||
Target ID: P06493 Gene ID: 983.0 Gene Symbol: CDK1 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/17363486 |
0.079 µM [IC50] | ||
Target ID: P50750 Gene ID: 1025.0 Gene Symbol: CDK9 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/17363486 |
0.02 µM [IC50] | ||
Target ID: CHEMBL308 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17363486 |
0.079 µM [IC50] | ||
Target ID: CHEMBL301 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17363486 |
0.224 µM [IC50] | ||
Target ID: CHEMBL331 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17363486 |
0.063 µM [IC50] | ||
Target ID: CHEMBL3116 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17363486 |
0.02 µM [IC50] | ||
Target ID: CHEMBL2508 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17363486 |
0.396 µM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1818.96 ng/mL |
94.5 mg/m² 1 times / day multiple, intravenous dose: 94.5 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: |
RIVICICLIB HYDROCHLORIDE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
5158.09 ng × h/mL |
94.5 mg/m² 1 times / day multiple, intravenous dose: 94.5 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: |
RIVICICLIB HYDROCHLORIDE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
6.22 h |
94.5 mg/m² 1 times / day multiple, intravenous dose: 94.5 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: |
RIVICICLIB HYDROCHLORIDE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
185 mg/m2 1 times / day multiple, intravenous Recommended Dose: 185 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 185 mg/m2, 1 times / day Sources: Page: p.13 |
unhealthy, ADULT n = 13 Health Status: unhealthy Condition: mantle cell lymphoma Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 13 Sources: Page: p.13 |
Disc. AE: Herpes zoster... Other AEs: Thrombocytopenia... AEs leading to discontinuation/dose reduction: Herpes zoster (grade 2, 7.7%) Other AEs:Thrombocytopenia (grade 4, 7.7%) Sources: Page: p.13 |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Herpes zoster | grade 2, 7.7% Disc. AE |
185 mg/m2 1 times / day multiple, intravenous Recommended Dose: 185 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 185 mg/m2, 1 times / day Sources: Page: p.13 |
unhealthy, ADULT n = 13 Health Status: unhealthy Condition: mantle cell lymphoma Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 13 Sources: Page: p.13 |
Thrombocytopenia | grade 4, 7.7% | 185 mg/m2 1 times / day multiple, intravenous Recommended Dose: 185 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 185 mg/m2, 1 times / day Sources: Page: p.13 |
unhealthy, ADULT n = 13 Health Status: unhealthy Condition: mantle cell lymphoma Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 13 Sources: Page: p.13 |
PubMed
Title | Date | PubMed |
---|---|---|
In vitro antitumor properties of a novel cyclin-dependent kinase inhibitor, P276-00. | 2007 Mar |
|
A phase II, single-arm, open-label, multicenter study to evaluate the efficacy and safety of P276-00, a cyclin-dependent kinase inhibitor, in patients with relapsed or refractory mantle cell lymphoma. | 2015 Jul |
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/25816934
A phase II study of P276-00 was conducted in patients with relapsed or refractory mantle cell lymphoma (MCL) at the recommended dose of 185 mg/m(2)/day from days 1 to 5 of a 21-day cycle.
Route of Administration:
Intravenous
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/17363486
P276-00 was found to be more selective with IC50s <100 nmol/L for Cdk4-D1, Cdk1-B, and Cdk9-T1, as compared with other Cdks, and less selective for non-Cdk kinases. 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
Substance Class |
Chemical
Created
by
admin
on
Edited
Sat Dec 16 01:42:18 GMT 2023
by
admin
on
Sat Dec 16 01:42:18 GMT 2023
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Record UNII |
9EK26WE8QN
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Record Status |
Validated (UNII)
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Record Version |
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NCI_THESAURUS |
C2185
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NCI_THESAURUS |
C129825
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24887371
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300000034452
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9EK26WE8QN
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9792
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C64762
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920113-02-6
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CHEMBL3545283
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TARGET->WEAK INHIBITOR |
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TARGET -> INHIBITOR |
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TARGET->WEAK INHIBITOR |
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TARGET -> INHIBITOR |
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TARGET -> INHIBITOR |
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TARGET -> INHIBITOR |
IC50
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SALT/SOLVATE -> PARENT |
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Related Record | Type | Details | ||
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ACTIVE MOIETY |
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