Flavopiridol (Alvocidib) HCl

製品コードS2679 バッチS267902

印刷

化学情報

Chemical Structure Synonyms NSC 649890, L86-8275, HMR-1275, DSP-2033 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C21H20ClNO5.HCl
分子量 438.3 CAS No. 131740-09-5
Solubility (25°C)* 体外 DMSO 88 mg/mL (200.77 mM)
Water 88 mg/mL (200.77 mM)
Ethanol 9 mg/mL (20.53 mM)
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 Flavopiridol (Alvocidib) HClcompetes with ATP to inhibit CDKs including CDK1, CDK2, CDK4 and CDK6 with IC50 of ~ 40 nM in cell-free assays. It is 7.5-fold more selective for CDK1/2/4/6 than CDK7. Flavopiridol is initially found to inhibit EGFR and PKA. Flavopiridol HCl induces autophagy and ER stress. Flavopiridol HCl blocks HIV-1 replication. Phase 1/2.
in vitro Flavopiridol is initially found to inhibit the epidermal growth factor receptor and protein kinase A (IC50 = 21 and 122 μM). Flavopiridol is later shown to inhibit cell proliferation, at more physiologically relevant concentrations (IC50 = 66 nM) when Flavopiridol is tested in the National Cancer Institute Development Therapeutics Program panel of 60 human tumor cell lines. [1] Flavopiridol induces G1 arrest with inhibition of CDK2 and CDK4 in human breast carcinoma cells in a time and concentration dependent manner. [2] Short time treatment of Flavopiridol (~12 hours) induce apoptosis in hematopoietic cell lines including SUDHL4, SUDHL6 (B-cell lines), Jurkat and MOLT4 (T-cell lines ), and HL60 (myeloid). [3] In the clonogenic assay, Flavopiridol functions as a highly potent cytotoxic compound with a mean IC70 with 8 ng/mL in 23 human tumor models. [4] A recent study shows Flavopiridol treatment induces a substantial AKT-Ser473 phosphorylation in human glioblastoma T98G cell line. [5]
in vivo At the maximal tolerated dose of 10 mg/kg/day administered p.o. on days 1-4 and 7-11, Flavopiridol effects tumor regression in PRXF1337 and tumor stasis lasting for 4 weeks in PRXF1369. [4] After treatment with 7.5 mg/kg Flavopiridol bolus intravenous (IV) or intraperitoneal on each of 5 consecutive days, 11 out of 12 advanced stage subcutaneous (s.c.) human HL-60 xenografts undergo complete regressions, and animals remain disease-free several months after one course of Flavopiridol treatment. SUDHL-4 s.c. lymphomas treated with flavopiridol at 7.5 mg/kg bolus IV for 5 days undergo either major (two out of eight mice) or complete (four out of eight mice) regression, with two animals remaining disease-free for more than 60 days. The overall growth delay is 73.2%. Daily IV or IP administration of flavopiridol results in peak plasma levels of about 7 µM, followed by a progressive decline to approximately 100 nM in 8 hours.[6]

プロトコル(参考用のみ)

キナーゼアッセイ 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.
細胞アッセイ 細胞株 SUDHL4, SUDHL6, Jurkat, MOLT4, and HL60
濃度 0, 100 500, 5000 nM
反応時間 14 hours
実験の流れ 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 26,000g, 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.
動物実験 動物モデル 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
投薬量 10 mg/kg/d [4]; 7.5 mg/kg/d [6]
投与方法 p.o.[4]; i.p. or i.v. [6]

カスタマーフィードバック

Data from [Br J Cancer, 2014, 110(5), 1189-98]

Data from [Data independently produced by Mol Cancer Ther, 2012, 11(11), 2321-2330]

Data from [PNAS, 2011, 108, 8417]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Monoallelically expressed noncoding RNAs form nucleolar territories on NOR-containing chromosomes and regulate rRNA expression [ Elife, 2024, 13e80684] PubMed: 38240312
From co-delivery to synergistic anti-inflammatory effect: Studies on chitosan-stabilized Janus emulsions having chloroquine phosphate and flavopiridol in Complete Freund's Adjuvant induced arthritis rat model [ Int J Biol Macromol, 2023, 258(Pt 1):128776] PubMed: 38114014
Claspin is Required for Growth Recovery from Serum Starvation through Regulating the PI3K-PDK1-mTOR Pathway in Mammalian Cells [ Mol Cell Biol, 2023, 43(1):1-21] PubMed: 36720467
Lamin A/C phosphorylation at serine 22 is a conserved heat shock response to regulate nuclear adaptation during stress [ J Cell Sci, 2023, 136(4)jcs259788] PubMed: 36695453
Brd4-dependent CDK9 expression induction upon sustained pharmacological inhibition of P-TEFb kinase activity [ Biochem Biophys Res Commun, 2023, 671:75-79] PubMed: 37295357
The super elongation complex drives transcriptional addiction in MYCN-amplified neuroblastoma [ Sci Adv, 2023, 9(13):eadf0005] PubMed: 36989355
Nuclear oligo hashing improves differential analysis of single-cell RNA-seq [ Nat Commun, 2022, 13(1):2666] PubMed: 35562344
p300/CBP sustains Polycomb silencing by non-enzymatic functions [ Mol Cell, 2022, 82(19):3580-3597.e9] PubMed: 36206738
Discovery of a large-scale, cell-state-responsive allosteric switch in the 7SK RNA using DANCE-MaP [ Mol Cell, 2022, S1097-2765(22)00114-9] PubMed: 35320755
ISR8/IRF1-AS1 Is Relevant for IFNα and NF-κB Responses [ Front Immunol, 2022, 13:829335] PubMed: 35860270

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