Flavopiridol (Alvocidib) HCl

Alias: NSC 649890 HCl; HMR-1275;HMR1275;L-868275; L 868275;HL 275; MDL 107,826A;HL-275;NSC 649890 HCl; NSC649890; NSC-649890; HMR 1275;L 86-8275; L868275; HMR 1274; HMR-1274; HMR1274; Flavoperidol; Alvocidib; HMR 1275; HMR-1275; L 86 8275; L86-8275; MDL 107826A; MDL-107826A; NSC 649890.

Cat No.:V1538 Purity: ≥98%

COA Product Data Instructions for use SDS

Flavopiridol (Alvocidib) HCl Chemical Structure CAS No.: 131740-09-5
Product category: CDK

This product is for research use only, not for human use. We do not sell to patients.

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Other Forms of Flavopiridol (Alvocidib) HCl:

Flavopiridol (Alvocidib)

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Top Publications Citing lnvivochem Products

Nature 2021, 597(7874):119-125.

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J Am Chem Soc 2022,144:21831-21836.

Cell 2020,183:1202-1218.e25.

Science Adv 2022:8,eabm9427.

Nature 2021,597(7874):119-125.

Cell 2020,183:1202-1218.e25.

PNAS Nexus 2022,1(3):pgac063.

ACS Nano 2023,17(10):9110-9125.

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Purity & Quality Control Documentation

Current batch：

Purity: ≥98%

COA

MSDS

NMR

Instructions

Product Description
Bioactivity & Protocols
Physicochemical Properties
Solubility Data
Calculators
Clinical Trial Information
Biological Data

Product Description

Flavopiridol HCl (also known as Alvocidib; NSC 649890; HMR-1275; L-868275; HL-275; MDL-107,826A), the HCl salt of flavopiridol which is a flavanoid, is a broad spectrum and ATP-competitive inhibitor of cyclin-dependent kinases-CDKs with potential antineoplastic activity. It is an ATP-competitive CDK inhibitor with IC50s of less than 40 nM that inhibits CDK1, CDK2, CDK4, and CDK6.

Biological Activity I Assay Protocols (From Reference)

Targets

CDK1 (IC50 = 40 nM); CDK2 (IC50 = 40 nM); CDK4 (IC50 = 40 nM); CDK6 (IC50 = 40 nM); CDK7 (IC50 = 300 nM)

ln Vitro

Flavopiridol is first discovered to inhibit protein kinase A and the epidermal growth factor receptor (IC50 = 21 and 122 μM). Later testing on a panel of 60 human tumor cell lines from the National Cancer Institute Development Therapeutics Program reveals that flavipiridol inhibits cell proliferation at more physiologically relevant concentrations (IC50 = 66 nM).[1] In human breast cancer cells, flavopiridol causes G1 arrest through the time- and concentration-dependent inhibition of CDK2 and CDK4.[2] Apoptosis is induced in hematopoietic cell lines, such as B-cell lines SUDHL4, B-cell lines SUDHL6, T-cell lines Jurkat and MOLT4, and myeloid lines HL60, by a brief treatment with flavopiridol (~12 hours).[3]

ln Vivo

Flavopiridol causes tumor regression in PRXF1337 and tumor stasis that lasts for four weeks in PRXF1365, when given p.o. at the highest tolerated dose of 10 mg/kg/day.[4] One course of Flavopiridol treatment results in complete regressions in 11 out of 12 advanced stage subcutaneous (s.c.) human HL-60 xenografts, and the animals continue to be disease-free for several months after receiving a 7.5 mg/kg Flavopiridol bolus intravenous (IV) or intraperitoneal on each of five consecutive days. Treatment of SUDHL-4 s.c. lymphomas with flavopiridol at 7.5 mg/kg bolus IV for 5 days results in either major regression in 2 out of 8 mice or complete regression in 4 out of 8 mice, with 2 animals remaining disease-free for more than 60 days. There is a 73.2% growth delay overall. When IV or IP administration of rivopiridol is administered daily, the plasma levels peak at approximately 7 µM and then gradually decline to approximately 100 nM within 8 hours.[6]

Enzyme Assay

The following is how CDK activities are measured in microtiter plates. A combination of 40 μg Gst-Rb, varying concentrations of Flavopiridol, and unlabeled ATP is prepared. Subsequently, an ammonium sulfate cut of the S100 fraction obtained from insect cells expressing human CDK recombinant is added to initiate the reactions. A final mixture of 10 mM MgCl2, 50 mM Tris-HCl (pH 7.5), and 1 mM DTT is used. As a result, the final ATP concentration is modified. A phosphoryl donor is employed, which is radiolabeled ATP. After the enzyme is added, the reaction is run for 2.5 minutes at 30 °C before being stopped with the addition of EDTA. Following the Gst-Rb'scapturewith glutathione-Sepharose, liquid scintillation counting is used to calculate the radioactivity that has been incorporated.

Cell Assay

Different concentrations and durations of exposure to flavopiridol are given to cells grown at a density of 1 × 10⁶ cells/mL. It extracts DNA. In a nutshell, cells are lysed for 15 minutes at 4 °C in 3 mL of lysis buffer (5 mM Tris-HCL [pH 7.5]; 20 mM EDTA; 0.5% Triton X-100). This process involves one cold wash with phosphate-buffered saline (PBS). Centrifugation is used to separate the chromatin from the cell lysates (20 minutes at 26,000g, 4 °C). The following methods are used in order to extract the supernatants containing small DNA fragments: phenol, phenol:chloroform (1:1), and chloroform. Overnight at -20°C, nucleic acids are precipitated in 0.5 M NaCl and 90% ethanol. After that, bovine RNAaseA (60 μg/mL) breaks down the RNA. DNA is dissolved in 10 mM Tris-HCL (pH 7.5), 1 mM EDTA, and 0.5% sodium dodecyl sulfate (SDS) prior to electrophoresis on 1.6% agarose gel after successive reextraction and reprecipitation.

Animal Protocol

Human prostate cancer xenografts, PRXFI337 and PRXFI369, grown s.c. in nude mice [4] Human promyelocytic leukemia HL-60, human B-cell follicular lymphoma SUDHL-4, and acquired immunodeficiency syndrome (AIDS)-r
10 mg/kg/d; 7.5 mg/kg/d
p.o.[4]; i.p. or i.v.

References

[1]. A short and efficient synthesis of the pharmacological research tool GW501516 for the peroxisome proliferator-activated receptor delta. J Org Chem. 2003 Nov 14;68(23):9116-8.

[2]. Effects of the peroxisome proliferator-activated receptor (PPAR)-δ agonist GW 501516 on bone and muscle in ovariectomized rats. Endocrinology. 2014 Jun;155(6):2178-89.

[3]. GW 501516, a PPARδ agonist, ameliorates tubulointerstitial inflammation in proteinuric kidney disease via inhibition of TAK1-NFκB pathway in mice. PLoS One. 2011;6(9):e25271.

[4]. A metabolomic study of the PPARδ agonist GW 501516 for enhancing running endurance in Kunming mice. Sci Rep. 2015 May 6;5:9884.

[5]. PPARβ/δ Agonist GW501516 Inhibits Tumorigenicity of Undifferentiated Nasopharyngeal Carcinoma in C666-1 Cells by Promoting Apoptosis. Front Pharmacol. 2018 Jun 28;9:648.

These protocols are for reference only. InvivoChem does not independently validate these methods.

Physicochemical Properties

Molecular Formula

C21H20CLNO5.HCL

Molecular Weight

438.3

Exact Mass

437.0796782

Elemental Analysis

C, 57.55; H, 4.83; Cl, 16.18; N, 3.20; O, 18.25

CAS #

131740-09-5

Related CAS #

131740-09-5 (HCl);146426-40-6;

Appearance

Solid powder

SMILES

CN1CC[C@@H]([C@@H](C1)O)C2=C(C=C(C3=C2OC(=CC3=O)C4=CC=CC=C4Cl)O)O.Cl

InChi Key

LGMSNQNWOCSPIK-LWHGMNCYSA-N

InChi Code

InChI=1S/C21H20ClNO5.ClH/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;1H/t12-,17+;/m0./s1

Chemical Name

2-(2-chlorophenyl)-5,7-dihydroxy-8-[(3S,4R)-3-hydroxy-1-methylpiperidin-4-yl]chromen-4-one;hydrochloride

Synonyms

NSC 649890 HCl; HMR-1275;HMR1275;L-868275; L 868275;HL 275; MDL 107,826A;HL-275;NSC 649890 HCl; NSC649890; NSC-649890; HMR 1275;L 86-8275; L868275; HMR 1274; HMR-1274; HMR1274; Flavoperidol; Alvocidib; HMR 1275; HMR-1275; L 86 8275; L86-8275; MDL 107826A; MDL-107826A; NSC 649890.

HS Tariff Code

2934.99.9001

Storage

Powder -20°C 3 years

4°C 2 years

In solvent -80°C 6 months

-20°C 1 month

Shipping Condition

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility Data

Solubility (In Vitro)

DMSO: ~88 mg/mL (~200.8 mM)

Water: <1 mg/mL

Ethanol: <1 mg/mL

Solubility (In Vivo)

30%Propylene glycol, 5%Tween 80, 65% D5W: 30 mg/mL

(Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.2815 mL	11.4077 mL	22.8154 mL
	5 mM	0.4563 mL	2.2815 mL	4.5631 mL
	10 mM	0.2282 mL	1.1408 mL	2.2815 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

Calculator

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What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?

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The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

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Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

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Molecular formula

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Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4 c12h18n3o4
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In vivo Formulation Calculator (Clear solution)

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

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Calculation results

Working concentration： mg/mL；

Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O，mix and clarify.

Note： (1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.

Clinical Trial Information

NCT Number	Recruitment	interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT00098579	Completed	Drug: doxorubicin hydrochloride Drug: alvocidib	Gastrointestinal Stromal Tumor Stage IV Adult Soft Tissue Sarcoma	National Cancer Institute (NCI)	October 2004	Phase 1
NCT00047307	Completed	Drug: gemcitabine hydrochloride Drug: alvocidib	Stage IV Pancreatic Cancer Stage III Pancreatic Cancer	National Cancer Institute (NCI)	August 2002	Phase 1
NCT00407966	Completed	Drug: alvocidib Drug: cytarabine	Adult Acute Monocytic Leukemia (M5b) Adult Erythroleukemia (M6a)	National Cancer Institute (NCI)	October 2006	Phase 2
NCT01349972	Completed	Drug: alvocidib Drug: cytarabine	Adult Acute Monocytic Leukemia (M5b) Adult Erythroleukemia (M6a)	National Cancer Institute (NCI)	April 2011	Phase 2
NCT00470197	Completed	Drug: alvocidib Drug: cytarabine	Adult Erythroleukemia (M6a) Malignant Neoplasm	National Cancer Institute (NCI)	April 2007	Phase 1

Biological Data

Effect of FVP on the expression of PRGs and IRGs in BJ-TERT fibroblasts.Cell Div.2012 Mar 29;7:11. doi: 10.1186/1747-1028-7-11.
Biphasic effect of FVP in the expression of certain PRG/IRGs.Cell Div.2012 Mar 29;7:11. doi: 10.1186/1747-1028-7-11.
Certain PRG/IRGs are significantly expressed in the presence of FVP during a mitogenic response.Cell Div.2012 Mar 29;7:11. doi: 10.1186/1747-1028-7-11.