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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
Structure of RIVICICLIB

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

HIDE SMILES / InChI

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

Curator's Comment: Piramal Enterprises Limited (PEL) (formerly known as Piramal Life Sciences Limited)

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: P11802
Gene ID: 1019.0
Gene Symbol: CDK4
Target Organism: Homo sapiens (Human)
0.063 µM [IC50]
Target ID: P06493
Gene ID: 983.0
Gene Symbol: CDK1
Target Organism: Homo sapiens (Human)
0.079 µM [IC50]
Target ID: P50750
Gene ID: 1025.0
Gene Symbol: CDK9
Target Organism: Homo sapiens (Human)
0.02 µM [IC50]
0.079 µM [IC50]
0.224 µM [IC50]
0.063 µM [IC50]
0.02 µM [IC50]
0.396 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
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

AUC

ValueDoseCo-administeredAnalytePopulation
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

T1/2

ValueDoseCo-administeredAnalytePopulation
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

Doses

DosePopulationAdverse 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

AEs

AESignificanceDosePopulation
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
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer

Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
yes [IC50 5.1735 uM]
PubMed

PubMed

TitleDatePubMed
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
Patents

Sample Use Guides

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
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 Sat Dec 16 01:42:18 GMT 2023
Edited
by admin
on Sat Dec 16 01:42:18 GMT 2023
Record UNII
9EK26WE8QN
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
RIVICICLIB
INN   WHO-DD  
INN  
Official Name English
(+)-RIVICICLIB
Common Name English
4H-1-BENZOPYRAN-4-ONE, 2-(2-CHLOROPHENYL)-5,7-DIHYDROXY-8-((2R,3S)-2-(HYDROXYMETHYL)-1-METHYL-3-PYRROLIDINYL)-
Systematic Name English
Riviciclib [WHO-DD]
Common Name English
P 276-00 FREE BASE
Code English
P-276-00 FREE BASE
Code English
riviciclib [INN]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C2185
Created by admin on Sat Dec 16 01:42:18 GMT 2023 , Edited by admin on Sat Dec 16 01:42:18 GMT 2023
NCI_THESAURUS C129825
Created by admin on Sat Dec 16 01:42:18 GMT 2023 , Edited by admin on Sat Dec 16 01:42:18 GMT 2023
Code System Code Type Description
PUBCHEM
24887371
Created by admin on Sat Dec 16 01:42:18 GMT 2023 , Edited by admin on Sat Dec 16 01:42:18 GMT 2023
PRIMARY
SMS_ID
300000034452
Created by admin on Sat Dec 16 01:42:18 GMT 2023 , Edited by admin on Sat Dec 16 01:42:18 GMT 2023
PRIMARY
FDA UNII
9EK26WE8QN
Created by admin on Sat Dec 16 01:42:18 GMT 2023 , Edited by admin on Sat Dec 16 01:42:18 GMT 2023
PRIMARY
INN
9792
Created by admin on Sat Dec 16 01:42:18 GMT 2023 , Edited by admin on Sat Dec 16 01:42:18 GMT 2023
PRIMARY
NCI_THESAURUS
C64762
Created by admin on Sat Dec 16 01:42:18 GMT 2023 , Edited by admin on Sat Dec 16 01:42:18 GMT 2023
PRIMARY
CAS
920113-02-6
Created by admin on Sat Dec 16 01:42:18 GMT 2023 , Edited by admin on Sat Dec 16 01:42:18 GMT 2023
PRIMARY
ChEMBL
CHEMBL3545283
Created by admin on Sat Dec 16 01:42:18 GMT 2023 , Edited by admin on Sat Dec 16 01:42:18 GMT 2023
PRIMARY
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