Flavopiridol Hydrochloride是一种CDK的广谱抑制剂，与 ATP 竞争性地抑制 CDK1，CDK2 和 CDK4 的活性，IC50值分别为 30, 170, 100 nM。

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.

在SUDHL-4皮下注射淋巴瘤模型的老鼠中静脉注射7.5 mg/kg Flavopiridol,模型鼠的肿瘤大部分（8分之2）或者完全（8分之4）消退,其中两只动物保持无病状持续60天以上,整体生长延迟73.2％.每天以最大耐受剂量10 mg/kg 口服给药Flavopiridol,在第1-4天及7-11天,影响PRXF1337的肿瘤消退,在PRXF1369中肿瘤停滞持续4周.用7.5 mg/kg Flavopiridol静脉内、或腹膜内连续注射Flavopiridol5天后,12个晚期皮下（sc）人HL-60异种移植鼠中的11个肿瘤完全消退,治疗一疗程后移植鼠数月无病.

Flavopiridol以时间和浓度依赖性方式诱导人类乳腺癌细胞G1期阻滞并抑制CDK2和CDK4。 Flavopiridol约12小时的短时处理,会诱导造血细胞系（包括SUDHL4,SUDHL6（B细胞系）,Jurkat和MOLT4（T细胞系）和HL60（骨髓））的细胞凋亡。一项研究Flavopiridol处理可诱导人成胶质细胞瘤T98 g细胞系产生大量的AKT-Ser473磷酸化。在克隆形成实验中,Flavopiridol在23人肿瘤模型中作为高效的细胞毒性化合物,平均IC70是8 ng/mL。

Recombinant CDKs Kinase Reactions: CDKs activities are determined in microtiter plates as follows. Forty μg Gst-Rb are mixed with different amounts of Flavopiridol and unlabeled ATP. Reactions are then started by the addition of an ammonium sulfate cut of the S100 fraction obtained from insect cells expressing recombinant human CDKs. The final reaction conditions are 10 mM MgCl2, 50 mM Tris-HCl (pH 7.5), and 1 mM DTT. The final concentration of ATP is adjusted accordingly. Radiolabeled ATP is used as a phosphoryl donor. The reaction is carried out for 2.5 minutes at 30 °C after addition of enzyme and then terminated with the addition of EDTA. The Gst-Rb is then captured with glutathione-Sepharose and the incorporated radioactivity is determined by liquid scintillation counting.

Cells grown at a density of 1 × 106 cells/mL are exposed to Flavopiridol for different concentrations and time periods. DNA is extracted. Briefly, cells are washed once with cold phosphate-buffered saline (PBS) and lysed with 3 mL lysis buffer (5 mM Tris-HCL [pH 7.5]; 20 mM EDTA; 0.5% Triton X-100) for 15 minutes at 4 °C. The chromatin of the cell lysates is isolated by centrifugation (20 minutes at 26,000 g, 4 °C). The supernatants containing small DNA fragments are extracted sequentially with phenol, phenol:chloroform (1:1), and chloroform. Nucleic acids are precipitated in 0.5 M NaCl, 90% ethanol at -20 °C overnight. RNA is then digested by bovine RNAaseA (60 μg/mL). After sequential reextraction and reprecipitation, DNA is dissolved in 10 mM Tris-HCL (pH 7.5), 1 mM EDTA, 0.5% sodium dodecyl sulfate (SDS) before electrophoresis on 1.6% agarose gel. (Only for Reference)

131740-09-5

C21H21Cl2NO5

438.3

HL 275;Alvocidib Hydrochloride;MDL 107826A;FLAVOPIRIDOL HCL;NSC 649890 HCl;NSC 649890

H2O:43.8 mg/mL (100 mM)
DMSO:43.8 mg/mL (100 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years