Flavopiridol (Alvocidib)

製品コードS1230 バッチS123009

印刷

化学情報

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

C21H20ClNO5
分子量 401.84 CAS No. 146426-40-6
Solubility (25°C)* 体外 DMSO 80 mg/mL (199.08 mM)
Water Insoluble
Ethanol Insoluble
体内 （毎回新しく調製した物を用意してください）
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <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) competes with ATP to inhibit CDKs including CDK1, CDK2, CDK4, CDK6, and CDK9 with IC50 values in the 20-100 nM range. It is more selective for CDK1, 2, 4, 6, 9 versus CDK7. Flavopiridol is initially found to inhibit EGFR and PKA. Flavopiridol induces autophagy and ER stress. Flavopiridol blocks HIV-1 replication. Phase 1/2.
in vitro Flavopiridol (Alvocidib) displays less activity against unrelated kinases such as MAP, PAK, PKC, and EGFR with IC50 of >14 μM. It significantly inhibits the colony growth of HCT116, A2780, PC3, and Mia PaCa-2 cells with IC50 of 13 nM, 15 nM, 10 nM and 36 nM, respecitively. [1] This compound also potently inhibits the activity of Glycogen synthase kinase-3 (GSK-3) with an IC50 of 280 nm. [2] Compared with other CDKs, it inhibits the activity of CDK7 less potently with IC50 of 875 nM. At 0.5 μM, it inhibits both pSer807/811 Rb and pThr199 NPM, whereas mild changes are observed at pThr821 Rb. It also decreases the overall RNA polymerase II level, as well as the phosphorylation of RNA polymerase II on the CTD repeats at Ser2 Ser5. [3] As a broad spectrum CDK inhibitor, it can inhibit cell cycle progression in either G1 or G2. At 0.3 μM, it induces G1 arrest in either MCF-7 or MDA-MB-468 cells by inhibition of the CDK4 or CDK2 kinase activity. [4] It exhibits potent cytotoxicity against a wide variety of tumor cell lines with IC50 values ranging form 16 nM for LNCAP to 130 nM for K562. [5]
in vivo Administration of Flavopiridol (Alvocidib) at 7.5 mg/kg for 7 days displays slight antitumor activity against P388 murine leukemia, resulting in %T/C value of 110, and active against the human A2780 ovarian carcinoma implanted sc in nude mice, producing 1.5 log cell kill (LCK). [5] Treatment with this compound at 1-2.5 mg/kg for 10 days significantly suppresses collagen-induced arthritis in mice in a dose-dependent manner, by inhibiting synovial hyperplasia and joint destruction, whereas serum concentrations of anti-collagen type II (CII) Abs and proliferative responses to CII are maintained. [6] In the p21-intact Hct116 xenografts in nude mice, administration of CPT-11 (100 mg/kg) followed by it (3 mg/kg) 7 and 16 hours later significantly inhibits tumor regression by 86% and 82%, respectively, displaying >2 fold inhibition compared with CPT-11 alone by 40 %. The combination produces ~30% complete response rate (CR) in contrast to CPT-11 alone where no CR is found. [7]
特徴 First CDK inhibitor to be used in human clinical trials.

プロトコル(参考用のみ)

キナーゼアッセイ CDK kinase assay
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細胞アッセイ 細胞株 MCF-7, LNCAP, PC3, HCT116, CACO-2, A549, HL60, K562 cells and et al.
濃度 Dissolved in DMSO, final concentrations ~10 μM
反応時間 72 hours
実験の流れ

Cells are exposed to various concentrations of Flavopiridol (Alvocidib) for 72 hours at which time the tetrazolium dye, MTS in combination with phenazine methosulfate, is added. After 3 hours, the absorbency is measured at 492 nm, which is proportional to the number of viable cells. The results are expressed as IC50 values. For cell Cycle analysis, cells are fixed in paraformaldehyde and ethanol, washed, resuspended in staining solution of TdT enzyme and FITC-dUTP, washed, stained with PI following RNase treatment, and then analyzed by flow cytometry.
動物実験 動物モデル Female Balb/c×DBA/2J F1 mice inoculated ip with P388 ascites leukemic cells, and Balb/c nu/nu nude mice subcutaneous implanted with A2780, Br-cycE, or A431 cells
投薬量 ~7.5 mg/kg/day
投与方法 Injection i.p.

参考

  • https://pubmed.ncbi.nlm.nih.gov/11063609/
  • https://pubmed.ncbi.nlm.nih.gov/15689157/
  • https://pubmed.ncbi.nlm.nih.gov/18469809/
  • https://pubmed.ncbi.nlm.nih.gov/8674031/
  • https://pubmed.ncbi.nlm.nih.gov/12190313/
  • https://pubmed.ncbi.nlm.nih.gov/18209094/
  • https://pubmed.ncbi.nlm.nih.gov/11751522/
  • https://pubmed.ncbi.nlm.nih.gov/18469809/
  • https://pubmed.ncbi.nlm.nih.gov/11311660/

カスタマーフィードバック

Data from [PNAS, 2011, 108, 8417]

Data from [Data independently produced by , , Science, 2018, 11(530), doi: 10.1126/scisignal.aai8669]

Data from [Data independently produced by , , Cancer Res, 2016, 76(5):1158-69]

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：

SLFN11-mediated ribosome biogenesis impairment induces TP53-independent apoptosis [ Mol Cell, 2025, S1097-2765(25)00042-5] PubMed: 39909041
Combined therapy with DR5-targeting antibody-drug conjugate and CDK inhibitors as a strategy for advanced colorectal cancer [ Cell Rep Med, 2025, S2666-3791(25)00231-9] PubMed: 40449480
Identification of modulators of the ALT pathway through a native FISH-based optical screen [ Cell Rep, 2025, 44(1):115114] PubMed: 39729394
Identifying Age-Modulating Compounds Using a Novel Computational Framework for Evaluating Transcriptional Age [ Aging Cell, 2025, e70075] PubMed: 40307992
Protection of infant mice against pertussis, tuberculosis and influenza by co-administration of nasal pertussis vaccine candidate BPZE1 and BCG [ iScience, 2025, 28(7):112839] PubMed: 40612502
Replication-competent adenovirus reporters utilizing endogenous viral expression architecture [ J Virol, 2025, 99(10):e0114625] PubMed: 40928252
BET degraders reveal BRD4 disruption of 7SK and P-TEFb is critical for effective reactivation of latent HIV in CD4+ T-cells [ J Virol, 2025, 99(4):e0177724] PubMed: 40067013
Repurposing flavopiridol as an inhaled therapeutic for pulmonary fibrosis [ Eur J Pharmacol, 2025, 1005:178058] PubMed: 40816528
Bacterial ubiquitin ligase engineered for small molecule and protein target identification [ bioRxiv, 2025, 2025.03.20.644192] PubMed: 40166235
Correlated protein-RNA associations reveal a requirement for HNRNPU in long-range Polycomb recruitment by the lncRNAs Airn , Kcnq1ot1 , and Xist [ bioRxiv, 2025, 2025.07.16.665154] PubMed: 40791421

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人間や獣医の診断であるか治療的な使用のためにでない。

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