| Size | Price | Stock | Qty |
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Purity: ≥98%
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.
| Targets |
CDK1 (IC50 = 40 nM); CDK2 (IC50 = 40 nM); CDK4 (IC50 = 40 nM); CDK6 (IC50 = 40 nM); CDK7 (IC50 = 300 nM)
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| ln Vitro |
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| ln Vivo |
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| 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.
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| 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.
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| 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. |
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| ADME/Pharmacokinetics |
Metabolism / Metabolites
The known human metabolites of flavonoid pyridinol include (2S,3S,4S,5R)-6-[2-(2-chlorophenyl)-5-hydroxy-8-[(3S,4R)-3-hydroxy-1-methylpiperidin-4-yl]-4-oxochromen-7-yl]oxy-3,4,5-trihydroxyoxacyclohexane-2-carboxylic acid. Oral bioavailability: Approximately 20% in humans; approximately 30% in rats after oral administration of 25 mg/kg[1][5] -Elimination half-life: 6-8 hours in humans; 4.5 hours in rats (intraperitoneal injection); 7.2 hours in mice (oral administration)[1][5] -Plasma protein binding: >99% in human plasma (concentration range: 0.1-10 μg/mL)[1][9] -Distribution: Volume of distribution (Vd) in rats = 3.5 L/kg, widely distributed in tumor tissues, bone marrow and lymphoid organs[5][9] -Metabolism: Mainly metabolized in the liver by CYP3A4 to inactive metabolites (e.g., monohydroxylated derivatives)[1][5] -Excretion: 70% of the dose is excreted in feces as metabolites; 25% is excreted in urine; <2% is excreted unchanged[1][5] |
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| Toxicity/Toxicokinetics |
Acute toxicity: Oral LD50 in rats > 200 mg/kg; in mice > 150 mg/kg. - Intraperitoneal LD50 = 50 mg/kg in rats; 40 mg/kg in mice. - Subchronic toxicity (oral administration in rats over 28 days): No significant hepatotoxicity or nephrotoxicity was observed at doses up to 25 mg/kg/day; mild neutropenia (neutrophil count decrease ≤15%) and thrombocytopenia (platelet count decrease ≤10%) occurred at 50 mg/kg/day. - In xenograft mice, therapeutic doses (10-25 mg/kg/day) did not cause significant weight loss or behavioral abnormalities. - Drug interactions: Potent CYP3A4 inhibitors (e.g., ketoconazole) can inhibit this product, increasing AUC by 2.2-fold. Synergistic toxicity with high-dose chemotherapeutic agents (e.g., doxorubicin).
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| References |
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| Additional Infomation |
Alvocidib hydrochloride is the hydrochloride salt formed by the reaction of equimolar amounts of avacidil with hydrogen chloride. It is a cyclin-dependent kinase 9 (CDK9) inhibitor and has been investigated for the treatment of acute myeloid leukemia, arthritis, and atherosclerotic plaque formation. It possesses antitumor, antirheumatic, apoptosis-inducing, and cyclin-dependent kinase (EC 2.7.11.22) inhibitory effects. It contains the avacidil (1+) ion. Avacidil hydrochloride is a synthetic N-methylpiperidinylchlorophenylflavonoid compound. As a cyclin-dependent kinase inhibitor, avacidil induces cell cycle arrest by preventing the phosphorylation of CDKs and downregulating the expression of cyclins D1 and D3, ultimately leading to G1 phase cell cycle arrest and apoptosis. This drug is also a competitive inhibitor of adenosine triphosphate (ATP) activity.
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| Molecular Formula |
C21H20CLNO5.HCL
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| Molecular Weight |
438.3
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| Exact Mass |
437.079
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| Elemental Analysis |
C, 57.55; H, 4.83; Cl, 16.18; N, 3.20; O, 18.25
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| CAS # |
131740-09-5
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| Related CAS # |
131740-09-5 (HCl);146426-40-6;
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| PubChem CID |
9910986
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| Appearance |
Light yellow to khaki solid powder
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| Boiling Point |
603.6ºC at 760 mmHg
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| Melting Point |
169.5-170ºC
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| Flash Point |
318.8ºC
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| Vapour Pressure |
2.03E-15mmHg at 25°C
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| LogP |
4.044
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
29
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| Complexity |
628
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| Defined Atom Stereocenter Count |
2
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| SMILES |
ClC1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C(C2C(=C([H])C(=C(C=2O1)[C@@]1([H])C([H])([H])C([H])([H])N(C([H])([H])[H])C([H])([H])[C@@]1([H])O[H])O[H])O[H])=O.Cl[H]
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| InChi Key |
LGMSNQNWOCSPIK-LWHGMNCYSA-N
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| 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
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| Chemical Name |
2-(2-chlorophenyl)-5,7-dihydroxy-8-[(3S,4R)-3-hydroxy-1-methylpiperidin-4-yl]chromen-4-one;hydrochloride
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
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| 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.
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.
(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.
| 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 |
 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. |
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