Home Cell Cycle CDK inhibitor - Apoptosis related activator Riviciclib hydrochloride (P276-00) For research use only.

Riviciclib hydrochloride (P276-00)

Riviciclib hydrochloride (P276-00) is a novel CDK1, CDK4 and CDK9 inhibitor with IC50 of 79 nM, 63 nM and 20 nM, respectively. Riviciclib hydrochloride (P276-00) induces apoptosis. Phase 2/3.

Riviciclib hydrochloride (P276-00) Chemical Structure

Riviciclib hydrochloride (P276-00) Chemical Structure

CAS No. 920113-03-7

Purity & Quality Control

Batch: S805801 DMSO]88 mg/mL]false]Water]88 mg/mL]false]Ethanol]7 mg/mL]false Purity: 99.26%
99.26

Riviciclib hydrochloride (P276-00) Related Products

Signaling Pathway

CDK Signaling Pathways

CDK Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
KB-8-5-11 qHTS assay P-glycoprotein substrates identified in KB-8-5-11 adenocarcinoma cell line, qHTS therapeutic library screen, Potency = 5.1735 μM. 31515284
KB-3-1 qHTS assay P-glycoprotein substrates identified in KB-3-1 adenocarcinoma cell line, qHTS therapeutic library screen. 31515284
Click to View More Cell Line Experimental Data

Biological Activity

Description Riviciclib hydrochloride (P276-00) is a novel CDK1, CDK4 and CDK9 inhibitor with IC50 of 79 nM, 63 nM and 20 nM, respectively. Riviciclib hydrochloride (P276-00) induces apoptosis. Phase 2/3.
Targets
CDK9/CyclinT1 [1] CDK4/CyclinD1 [1] CDK1/CyclinB [1] CDK2/CyclinA [1] CDK6/CyclinD3 [1] Click to View More Targets
20 nM 63 nM 79 nM 224 nM 396 nM
In vitro
In vitro P276-00 shows 40-fold selectivity toward Cdk4-D1, compared with Cdk2-E[1]. 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[1]. P276-00 can down-regulate cyclin D1 and Cdk4 in an ATP- competitive manner and decrease Cdk4-specific pRb Ser780 phosphorylation. P276-00 also induces apoptosis by actving cellular caspase-3 activity and DNA ladder formation[1].
Kinase Assay Cdk4-D1/Cdk2-E enzyme assay
The Cdk4-D1/Cdk2-E enzyme assay is run in 96-well format using Millipore Multiscreen filtration plates. All assay steps are done in a single filter plate. The filtration wells are prewetted with 100 μL of kinase buffer [50 mmol/L HEPES (pH, 7.5), 10 mmol/L MgCl2, 1 mmol/L EGTA], and then the solution is removed by vacuum. With filter plate on vacuum manifold, 50 μL GST-Rb bound to GSH-Sepharose beads in kinase buffer (0.5 μg GST-Rb/50 μL) is added to each well, and vacuum is applied to the filter plate. About 25 μL of a reaction mix containing ATP (cold + hot) and 4× phosphatase inhibitor mix (40 μmol/L unlabeled ATP, 10 μCi/mL γ32P-ATP, 40 mmol/L h-glycerophosphate, 4 mmol/L DTT, 0.4 mmol/L NaF, 0.4 mmol/L sodium orthovanadate) diluted in kinase buffer is added to each well. The test compound (4×final concentration in kinase buffer) or kinase buffer alone (control) is then added in an additional 25 μL volume. To each well, 50 μL (100 ng) of human Cdk4-D1/Cdk2-E enzyme in kinase buffer is added to initiate the reaction, which is allowed to continue for 30 min at 30°C. When the reaction is completed, vacuum is applied again, and the plate is washed with the TNEN buffer [20 mmol/L Tris (pH, 8.0), 100 mmol/L NaCl, 1 mmol/L EDTA, 0.5% nonidet-P40] thrice; the filter plate is air-dried and is placed in a Multiscreen adapter plate. Packard Microscint-O cocktail (30 μL) is added, and the plate is covered with a Top-Seal A film. Quantitation of 32P-GST-Rb in 96-well filter plates is carried out by Top Count scintillation counter. All compounds are tested initially at 1 μmol/L concentration. Compounds showing more than or equal to 50% inhibition are further profiled for IC50 determination.
Cell Research Cell lines HCT-116, U2OS, H-460, HL-60, HT-29, SiHa, MCF-7, Colo-205, SW-480, PC-3, Caco2, T-24
Concentrations ~5.0 μM
Incubation Time 48 h
Method The cells are seeded at a density of 3,000-5,000 cells per well, depending on cell type in 180 μL of culture medium in 96-well plate and incubated overnight to allow the cells to adhere. Varying concentrations of compounds are added to the wells and incubated for 48 h at 37°C. 3H-thymidine (0.25 μCi) is added to each well, and incorporation of the radiolabel is allowed to proceed for 5 to 7 h. Following this incubation, cells are harvested onto GF/B unifilter plates using a Packard Filtermate Universal harvester, and the plates are counted in a Packard Top Count 96-well liquid scintillation counter.
In Vivo
In vivo P276-00, administered i.p. at 50 mg/kg daily for 20 treatments can significantly induce growth inhibition of murine colon cancer (CA-51). However, in murine lung carcinoma model (Lewis lung), an increased dose of 60 mg/kg (30 mg/kg twice daily) administered every alternate day i.p. for 7 treatments shows significant inhibition in the growth[2]. And it also inhibit the growth of human colon carcinoma HCT-116 xenograft and human non-small cell lung carcinoma H-460 xenograft[2]. Efficacy Studies show its maximum tolerated dose is 78 mg/kg/d[2].
Animal Research Animal Models H-460 xenograft
Dosages 50 mg/kg once daily or 30 mg/kg twice daily
Administration i.p.
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT00899054 Completed
Squamous Cell Carcinoma of Head and Neck
Piramal Enterprises Limited
 August 2009 Phase 1|Phase 2
NCT00898287 Completed
Pancreatic Cancer
Piramal Enterprises Limited
 May 2009 Phase 1|Phase 2
NCT00547404 Withdrawn
Multiple Myeloma
Piramal Enterprises Limited
 December 2008 Phase 1
NCT00882063 Completed
Relapsed and/or Refractory Multiple Myeloma
Piramal Enterprises Limited
 January 2008 Phase 1|Phase 2
NCT00407498 Completed
Neoplasm
Piramal Enterprises Limited
 May 2005 Phase 1

Chemical Information & Solubility

Molecular Weight 438.3 Formula

C21H20ClNO5.HCl
CAS No. 920113-03-7 SDF Download Riviciclib hydrochloride (P276-00) SDF
Smiles CN1CCC(C1CO)C2=C(C=C(C3=C2OC(=CC3=O)C4=CC=CC=C4Cl)O)O.Cl
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 88 mg/mL ( (200.77 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : 88 mg/mL

Ethanol : 7 mg/mL


Molecular Weight Calculator

In vivo
Batch:

Add solvents to the product individually and in order.


In vivo Formulation Calculator

Preparing Stock Solutions

Molarity Calculator

Mass Concentration Volume Molecular Weight

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3
If you have any other enquiries, please leave a message.

* Indicates a Required Field

Please enter your name.
Please enter your email. Please enter a valid email address.
Please write something to us.
Tags: buy Riviciclib hydrochloride (P276-00) | Riviciclib hydrochloride (P276-00) supplier | purchase Riviciclib hydrochloride (P276-00) | Riviciclib hydrochloride (P276-00) cost | Riviciclib hydrochloride (P276-00) manufacturer | order Riviciclib hydrochloride (P276-00) | Riviciclib hydrochloride (P276-00) distributor