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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.
Physicochemical Properties
| Molecular Formula | C21H20CLNO5.HCL | |
| Molecular Weight | 438.3 | |
| Exact Mass | 437.079 | |
| 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; | |
| PubChem CID | 9910986 | |
| Appearance | Light yellow to khaki solid powder | |
| Boiling Point | 603.6ºC at 760 mmHg | |
| Melting Point | 169.5-170ºC | |
| Flash Point | 318.8ºC | |
| Vapour Pressure | 2.03E-15mmHg at 25°C | |
| LogP | 4.044 | |
| Hydrogen Bond Donor Count | 4 | |
| Hydrogen Bond Acceptor Count | 6 | |
| Rotatable Bond Count | 2 | |
| Heavy Atom Count | 29 | |
| Complexity | 628 | |
| Defined Atom Stereocenter Count | 2 | |
| 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 | |
| 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 | |
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| 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 |
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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) |
Biological Activity
| 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 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. | |
| 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. |
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| 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. |
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| Additional Infomation |
Alvocidib hydrochloride is a hydrochloride salt resulting from the formal reaction of equimolar amounts of alvocidib and hydrogen chloride. A cyclin-dependent kinase 9 (CDK9) inhibitor, it has been studied for the treatment of acute myeloid leukaemia, arthritis and atherosclerotic plaque formation. It has a role as an antineoplastic agent, an antirheumatic drug, an apoptosis inducer and an EC 2.7.11.22 (cyclin-dependent kinase) inhibitor. It contains an alvocidib(1+). Alvocidib Hydrochloride is a synthetic N-methylpiperidinyl chlorophenyl flavone compound. As an inhibitor of cyclin-dependent kinase, alvocidib induces cell cycle arrest by preventing phosphorylation of cyclin-dependent kinases (CDKs) and by down-regulating cyclin D1 and D3 expression, resulting in G1 cell cycle arrest and apoptosis. This agent is also a competitive inhibitor of adenosine triphosphate activity. |
Solubility Data
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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 |