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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=CC=CC=C4Cl

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

Description

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

Piramal Life Sciences
5
Curator's Comment: Piramal Enterprises Limited (PEL) (formerly known as Piramal Life Sciences Limited)

Approval Year

Unknown
149124
Targets

Targets

Primary TargetPharmacologyConditionPotency
Cyclin-dependent kinase 4
26
Target ID: P11802
Gene ID: 1019.0
Gene Symbol: CDK4
Target Organism: Homo sapiens (Human)
Inhibitor
8504
 0.063 µM [IC50]
Cyclin-dependent kinase 1
27
Target ID: P06493
Gene ID: 983.0
Gene Symbol: CDK1
Target Organism: Homo sapiens (Human)
Inhibitor
8504
 0.079 µM [IC50]
Cyclin-dependent kinase 9
24
Target ID: P50750
Gene ID: 1025.0
Gene Symbol: CDK9
Target Organism: Homo sapiens (Human)
Inhibitor
8504
 0.02 µM [IC50]
Inhibitor
8504
 0.079 µM [IC50]
Inhibitor
8504
 0.224 µM [IC50]
Inhibitor
8504
 0.063 µM [IC50]
Inhibitor
8504
 0.02 µM [IC50]
Inhibitor
8504
 0.396 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Phase II
1147
Unknown

Approved Use

Unknown
Primary
Phase II
1147
Unknown

Approved Use

Unknown
Primary
Phase II
1147
Unknown

Approved Use

Unknown
Primary
Phase II
1147
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1818.96 ng/mL
EXPERIMENT
https://cancerres.aacrjournals.org/content/68/9_Supplement/5079
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
EXPERIMENT
https://cancerres.aacrjournals.org/content/68/9_Supplement/5079
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
EXPERIMENT
https://cancerres.aacrjournals.org/content/68/9_Supplement/5079
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:
https://pubmed.ncbi.nlm.nih.gov/25816934
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/25816934
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:
https://pubmed.ncbi.nlm.nih.gov/25816934
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:
https://pubmed.ncbi.nlm.nih.gov/25816934
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/25816934
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:
https://pubmed.ncbi.nlm.nih.gov/25816934
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/25816934
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer
P-gp
1741
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
P-gp
1932
 yes [IC50 5.1735 uM]
PubMed

PubMed

TitleDatePubMed
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.
2015-07
In vitro antitumor properties of a novel cyclin-dependent kinase inhibitor, P276-00.
2007-03
P276-00, a novel cyclin-dependent inhibitor induces G1-G2 arrest, shows antitumor activity on cisplatin-resistant cells and significant in vivo efficacy in tumor models.
2007-03
Patents

Patents

07951961
2
20070015802
2
20100113803
2
20100179210
5
20100305057
2

Sample Use Guides

In Vivo Use Guide
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
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 Mon Mar 31 20:58:34 GMT 2025
Edited
by admin
on Mon Mar 31 20:58:34 GMT 2025
Record UNII
9EK26WE8QN
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
RIVICICLIB
INN   WHO-DD  
INN  
Official Name English
riviciclib [INN]
Preferred 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
Classification Tree Code System Code
NCI_THESAURUS C2185
Created by admin on Mon Mar 31 20:58:34 GMT 2025 , Edited by admin on Mon Mar 31 20:58:34 GMT 2025
NCI_THESAURUS C129825
Created by admin on Mon Mar 31 20:58:34 GMT 2025 , Edited by admin on Mon Mar 31 20:58:34 GMT 2025
Code System Code Type Description
PUBCHEM
24887371
Created by admin on Mon Mar 31 20:58:34 GMT 2025 , Edited by admin on Mon Mar 31 20:58:34 GMT 2025
PRIMARY
SMS_ID
300000034452
Created by admin on Mon Mar 31 20:58:34 GMT 2025 , Edited by admin on Mon Mar 31 20:58:34 GMT 2025
PRIMARY
FDA UNII
9EK26WE8QN
Created by admin on Mon Mar 31 20:58:34 GMT 2025 , Edited by admin on Mon Mar 31 20:58:34 GMT 2025
PRIMARY
INN
9792
Created by admin on Mon Mar 31 20:58:34 GMT 2025 , Edited by admin on Mon Mar 31 20:58:34 GMT 2025
PRIMARY
NCI_THESAURUS
C64762
Created by admin on Mon Mar 31 20:58:34 GMT 2025 , Edited by admin on Mon Mar 31 20:58:34 GMT 2025
PRIMARY
CAS
920113-02-6
Created by admin on Mon Mar 31 20:58:34 GMT 2025 , Edited by admin on Mon Mar 31 20:58:34 GMT 2025
PRIMARY
ChEMBL
CHEMBL3545283
Created by admin on Mon Mar 31 20:58:34 GMT 2025 , Edited by admin on Mon Mar 31 20:58:34 GMT 2025
PRIMARY
Related Record Type Details
Cyclin T1-CDK9 COMPLEX
TARGET -> INHIBITOR
CYCLIN-DEPENDENT KINASE 6
TARGET->WEAK INHIBITOR
IC50
CYCLIN-DEPENDENT KINASE 9
TARGET -> INHIBITOR
IC50
CYCLIN-DEPENDENT KINASE 2
TARGET->WEAK INHIBITOR
IC50
CYCLIN D1-CDK4 COMPLEX
TARGET -> INHIBITOR
CYCLIN-DEPENDENT KINASE 1
TARGET -> INHIBITOR
IC50
CYCLIN-DEPENDENT KINASE 4
TARGET -> INHIBITOR
IC50
Structure of RIVICICLIB HYDROCHLORIDE
SALT/SOLVATE -> PARENT
Related Record Type Details
Structure of RIVICICLIB
ACTIVE MOIETY
NIH
NCATS
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