Flavopiridol

Pan-cdk inhibitor CAS# 146426-40-6

Flavopiridol

Catalog No. BCC1577----Order now to get a substantial discount!

Product Name & Size Price Stock
Flavopiridol: 5mg $23 In Stock
Flavopiridol: 10mg Please Inquire In Stock
Flavopiridol: 20mg Please Inquire Please Inquire
Flavopiridol: 50mg Please Inquire Please Inquire
Flavopiridol: 100mg Please Inquire Please Inquire
Flavopiridol: 200mg Please Inquire Please Inquire
Flavopiridol: 500mg Please Inquire Please Inquire
Flavopiridol: 1000mg Please Inquire Please Inquire
Related Products

Quality Control of Flavopiridol

Number of papers citing our products

Chemical structure

Flavopiridol

3D structure

Chemical Properties of Flavopiridol

Cas No. 146426-40-6 SDF Download SDF
PubChem ID 5459219 Appearance Powder
Formula C21H20ClNO5 M.Wt 401.85
Type of Compound N/A Storage Desiccate at -20°C
Synonyms L868275; HMR-1275; Alvocidib
Solubility DMSO : 33.33 mg/mL (82.94 mM; Need ultrasonic)
Chemical Name 2-(2-chlorophenyl)-5,7-dihydroxy-8-[(3R,4S)-3-hydroxy-1-methylpiperidin-4-yl]chromen-4-one
SMILES CN1CCC(C(C1)O)C2=C(C=C(C3=C2OC(=CC3=O)C4=CC=CC=C4Cl)O)O
Standard InChIKey BIIVYFLTOXDAOV-PXAZEXFGSA-N
Standard InChI InChI=1S/C21H20ClNO5/c1-23-7-6-12(17(27)10-23)19-14(24)8-15(25)20-16(26)9-18(28-21(19)20)11-4-2-3-5-13(11)22/h2-5,8-9,12,17,24-25,27H,6-7,10H2,1H3/t12-,17+/m1/s1
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months.
Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it.
About Packaging 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial.
2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial.
3. Try to avoid loss or contamination during the experiment.
Shipping Condition Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request.

Biological Activity of Flavopiridol

DescriptionFlavopiridol is a broad inhibitor of CDK, competing with ATP to inhibit CDKs including CDK1, CDK2, CDK4 with IC50s of 30, 170, 100 nM, respectively.In Vitro:Flavopiridol (2 μM) robustly induces a distinct pattern of ER stress in CLL cells that contributes to cell death through IRE1-mediated activation of ASK1 and possibly downstream caspases[1]. Flavopiridol results in potent upregulation of a number of PRGs in treatments lasting 4-24 h. Flavopiridol has and immediate and long-term effect on the expression of several PRGs. In serum starved cells re-stimulated with serum, flavopiridol also inhibits the expression of these genes, but subsequently, JUNB, GADD45B and EGR1 are upregulated in the presence of flavopiridol[2].

References:
[1]. Mahoney E, et al. ER stress and autophagy: new discoveries in the mechanism of action and drug resistance of the cyclin-dependent kinase inhibitor flavopiridol.Blood. 2012 Aug 9;120(6):1262-1273. [2]. Keskin H, et al. Complex effects of flavopiridol on the expression of primary response genes. Cell Div. 2012 Mar 29;7:11. [3]. Kim KS, et al.Thio- and oxoflavopiridols, cyclin-dependent kinase 1-selective inhibitors: synthesis and biological effects. J Med Chem. 2000 Nov 2;43(22):4126-34.

Protocol

Kinase Assay [1]
Briefly, lysates containing approximately 3×106 cells are incubated with 50 μM LEVD-AFC (caspase 4 substrate) or LETD-AFC (caspase 8 substrate) containing 10 mM dithiothretiol (DTT). caspase 4 activity is measured one hour after addition of substrate and caspase 8 activity is measured 30 minutes after addition of substrate. Release of free AFC is measured with a Beckman-Coulter DTX 880 multimode detector.

Cell Assay [1]
The cells treated with flavopiridol are washed after 4 hours with PBS and resuspended in regular growth medium (RPMI 1640) supplemented with 10% human serum and antibiotics for the remainder of the incubation time. In the case of flavopiridol/chloroquine samples, chloroquine is re-added in the fresh media after flavopiridol is washed at 4 hours. For all the other conditions, cells are incubated with the respective drugs for 24 hours continuously.

References:
[1]. Mahoney E, et al. ER stress and autophagy: new discoveries in the mechanism of action and drug resistance of the cyclin-dependent kinase inhibitor flavopiridol.Blood. 2012 Aug 9;120(6):1262-1273. [2]. Keskin H, et al. Complex effects of flavopiridol on the expression of primary response genes. Cell Div. 2012 Mar 29;7:11. [3]. Kim KS, et al.Thio- and oxoflavopiridols, cyclin-dependent kinase 1-selective inhibitors: synthesis and biological effects. J Med Chem. 2000 Nov 2;43(22):4126-34.

Flavopiridol Dilution Calculator

Concentration (start)
x
Volume (start)
=
Concentration (final)
x
Volume (final)
 
 
 
C1
V1
C2
V2

calculate

Flavopiridol Molarity Calculator

Mass
=
Concentration
x
Volume
x
MW*
 
 
 
g/mol

calculate

Preparing Stock Solutions of Flavopiridol

1 mg 5 mg 10 mg 20 mg 25 mg
1 mM 2.4885 mL 12.4425 mL 24.8849 mL 49.7698 mL 62.2123 mL
5 mM 0.4977 mL 2.4885 mL 4.977 mL 9.954 mL 12.4425 mL
10 mM 0.2488 mL 1.2442 mL 2.4885 mL 4.977 mL 6.2212 mL
50 mM 0.0498 mL 0.2488 mL 0.4977 mL 0.9954 mL 1.2442 mL
100 mM 0.0249 mL 0.1244 mL 0.2488 mL 0.4977 mL 0.6221 mL
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations.

Organizitions Citing Our Products recently

 
 
 

Calcutta University

University of Minnesota

University of Maryland School of Medicine

University of Illinois at Chicago

The Ohio State University

University of Zurich

Harvard University

Colorado State University

Auburn University

Yale University

Worcester Polytechnic Institute

Washington State University

Stanford University

University of Leipzig

Universidade da Beira Interior

The Institute of Cancer Research

Heidelberg University

University of Amsterdam

University of Auckland
TsingHua University
TsingHua University
The University of Michigan
The University of Michigan
Miami University
Miami University
DRURY University
DRURY University
Jilin University
Jilin University
Fudan University
Fudan University
Wuhan University
Wuhan University
Sun Yat-sen University
Sun Yat-sen University
Universite de Paris
Universite de Paris
Deemed University
Deemed University
Auckland University
Auckland University
The University of Tokyo
The University of Tokyo
Korea University
Korea University

Background on Flavopiridol

Flavopiridol is a potent and selective inhibitor of cyclin-dependent kinases (CDKs) with IC50 values of ~41 nM for CDK1, CDK2, CDK4, CDK6 and 300 nM for CDK7, respectively [1].
CDKs are a family of protein kinases regulating the cell cycle and play an important role in transcription, mRNA processing, and cell differentiation.
Analysis of the crystal structure suggested flavopiridol binded to the ATP-binding pocket of CDK2. In MCF-7 breast cancer cells, flavopiridol reduced the mRNA level of cyclin D1 protein and cyclin D3 protein [1]. In 23 human tumor cell models, flavopiridol significantly inhibited human bone marrow colony formation between 10 and 100 ng/ml [2].
In prostate cancer xenograft PRXFI369, flavopinidol (10 mg/kg/day) had antitumor activity of optimal test/control (T/C) of 33% and a growth delay of 30 days. Also, it reduced tumor volume by 85%. In prostate cancer xenograft PRXFI337, the optimal T/C was 27% and the growth delay was 17 days [2].
References:
[1]. Senderowicz AM. The cell cycle as a target for cancer therapy: basic and clinical findings with the small molecule inhibitors flavopiridol and UCN-01. Oncologist, 2002, 7 Suppl 3: 12-9.
[2]. Drees M, Dengler WA, Roth T, et al. Flavopiridol (L86-8275): selective antitumor activity in vitro and activity in vivo for prostate carcinoma cells. Clin Cancer Res, 1997, 3(2): 273-279.
[3]. Carlson BA, Dubay MM, Sausville EA, et al. Flavopiridol induces G1 arrest with inhibition of cyclin-dependent kinase (CDK) 2 and CDK4 in human breast carcinoma cells. Cancer Res, 1996, 56(13): 2973-2978.

Featured Products
New Products
 

References on Flavopiridol

Intrathecal Administration of Flavopiridol Promotes Regeneration in Experimental Model of Spinal Cord Injury.[Pubmed:27476919]

Turk Neurosurg. 2016;26(6):922-929.

AIM: Spinal cord injury (SCI) is a serious condition of the central nervous system and it affects the quality of life and even hampers the day-to-day activity of the patient. In the current study, we investigated the efficacy of intrathecal administration of Flavopiridol in an experimental animal model of SCI. The study also aimed at exploring the physiological effects of Flavopiridol on neurons, astrocytes and cell cycle regulatory proteins. MATERIAL AND METHODS: In vitro scratch wound experiments were performed on female Sprague-Dawley rats (n=23). A complete hemisection to the right of T10 was made, and Flavopiridol solution (200 mM, 0.8 nmol Flavopiridol/animal) was delivered topically to the lesion site. Cell viability assay, in vitro scratch injury assay, cell cycle analysis using flow cytometry and behavioural assessments were performed. RESULTS: The local delivery of Flavopiridol reduced cavity formation and improved regeneration of neurons with improvement in physiological performance. Flavopiridol also inhibited the migration and proliferation of astrocytes, and at the same time, promoted the survival of neurons. CONCLUSION: Intrathecal administration of Flavopiridol can be a promising treatment strategy in patients with SCI and it needs to be validated in patient setting.

Exposure-Response Analysis of Alvocidib (Flavopiridol) Treatment by Bolus or Hybrid Administration in Newly Diagnosed or Relapsed/Refractory Acute Leukemia Patients.[Pubmed:28174232]

Clin Cancer Res. 2017 Jul 15;23(14):3592-3600.

Purpose: To elucidate any differences in the exposure-response of alvocidib (Flavopiridol) given by 1-hour bolus or a hybrid schedule (30-minute bolus followed by a 4-hour infusion) using a Flavopiridol/cytosine arabinoside/mitoxantrone sequential protocol (FLAM) in patients with acute leukemia. The hybrid schedule was devised to be pharmacologically superior in chronic leukemia based on unbound exposure.Experimental Design: Data from 129 patients in three FLAM studies were used for pharmacokinetic/pharmacodynamic modeling. Newly diagnosed (62%) or relapsed/refractory (38%) patients were treated by bolus (43%) or hybrid schedule (57%). Total and unbound Flavopiridol concentrations were fit using nonlinear mixed-effect population pharmacokinetic methodologies. Exposure-response relationships using unbound Flavopiridol AUC were explored using recursive partitioning.Results: Flavopiridol pharmacokinetic parameters were estimated using a two-compartment model. No pharmacokinetic covariates were identified. Flavopiridol fraction unbound was 10.9% and not different between schedules. Partitioning found no association between dosing schedule and clinical response. Clinical response was associated with AUC >/= 780 h*ng/mL for newly diagnosed patients and AUC >/= 1,690 h*ng/mL for relapsed/refractory patients. Higher exposures were not associated with increases in severe adverse events (>/= grade 3).Conclusions: Pharmacokinetic modeling showed no difference in Flavopiridol plasma protein binding for bolus versus hybrid dosing. Further trials in newly diagnosed patients with acute leukemia should utilize the bolus FLAM regimen at the MTD of 50 mg/m(2)/day. Trials in relapsed/refractory patients should use the hybrid dosing schedule at the MTD (30/60 mg/m(2)/day) to achieve the higher exposures required for maximal efficacy in this population. Clin Cancer Res; 23(14); 3592-600. (c)2017 AACR.

Effects of flavopiridol on critical regulation pathways of CD133high/CD44high lung cancer stem cells.[Pubmed:27787370]

Medicine (Baltimore). 2016 Oct;95(43):e5150.

BACKGROUND: Flavopiridol a semisynthetic flavone that inhibits cyclin-dependent kinases (CDKs) and has growth-inhibitory activity and induces a blockade of cell-cycle progression at G1-phase and apoptosis in numerous human tumor cell lines and is currently under investigation in phase II clinical trials. Cancer stem cells (CSCs) are comprised of subpopulation of cells in tumors that have been proposed to be responsible for recurrence and resistance to chemotherapy. The aim of the present study was to investigate the effects of Flavopiridol in cancer stem cell cytoskeleton, cell adhesion, and epithelial to mesenchymal transition in CSCs. METHODS: The cells were treated with Flavopiridol to determine the inhibitory effect. Cell viability and proliferation were determined by using the WST-1 assay. Caspase activity and immunofluorescence analyses were performed for the evaluation of apoptosis, cell cytoskeleton, and epithelial-mesenchymal transition (EMT) markers. The effects of Flavopiridol on the cell cycle were also evaluated. Flow cytometric analysis was used to detect the percentages of CSCs subpopulation. We analyzed the gene expression patterns to predict cell cycle and cell cytoskeleton in CSCs by RT-PCR. RESULTS: Flavopiridol-induced cytotoxicity and apoptosis at the IC50 dose, resulting in a significant increase expression of caspases activity. Cell cycle analyses revealed that Flavopiridol induces G1 phase cell cycle arrest. Flavopiridol significantly decreased the mRNA expressions of the genes that regulate the cell cytoskeleton and cell cycle components and cell motility in CSCs. CONCLUSION: Our results suggest that Flavopiridol has activity against lung CSCs and may be effective chemotherapeutic molecule for lung cancer treatment.

Flavopiridol: An Old Drug With New Perspectives? Implication for Development of New Drugs.[Pubmed:27171480]

J Cell Physiol. 2017 Feb;232(2):312-322.

Glioblastoma, the most common brain tumor, is characterized by high proliferation rate, invasion, angiogenesis, and chemo- and radio-resistance. One of most remarkable feature of glioblastoma is the switch toward a glycolytic energetic metabolism that leads to high glucose uptake and consumption and a strong production of lactate. Activation of several oncogene pathways like Akt, c-myc, and ras induces glycolysis and angiogenesis and acts to assure glycolysis prosecution, tumor proliferation, and resistance to therapy. Therefore, the high glycolytic flux depends on the overexpression of glycolysis-related genes resulting in an overproduction of pyruvate and lactate. Metabolism of glioblastoma thus represents a key issue for cancer research. Flavopiridol is a synthetic flavonoid that inhibits a wide range of Cyclin-dependent kinase, that has been demonstrate to inactivate glycogen phosphorylase, decreasing glucose availability for glycolysis. In this work the study of glucose metabolism upon Flavopiridol treatment in the two different glioblastoma cell lines. The results obtained point towards an effect of Flavopiridol in glycolytic cells, thus suggesting a possible new use of this compound or Flavopiridol-derived formulations in combination with anti-proliferative agents in glioblastoma patients. J. Cell. Physiol. 232: 312-322, 2017. (c) 2016 Wiley Periodicals, Inc.

Description

Flavopiridol (Alvocidib) is a broad spectrum and competitive inhibitor of CDKs, inhibiting CDK1, CDK2, CDK4 with IC50s of 30, 170, 100 nM, respectively.

Keywords:

Flavopiridol,146426-40-6,L868275; HMR-1275; Alvocidib,Natural Products,Cyclin-Dependent Kinases, buy Flavopiridol , Flavopiridol supplier , purchase Flavopiridol , Flavopiridol cost , Flavopiridol manufacturer , order Flavopiridol , high purity Flavopiridol

Online Inquiry for:

      Fill out the information below

      • Size:Qty: - +

      * Required Fields

                                      Result: