CP-724714

製品コードS1167 バッチS116701

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C27H27N5O3
分子量 469.53 CAS No. 537705-08-1
Solubility (25°C)* 体外 DMSO 94 mg/mL (200.2 mM)
Ethanol 94 mg/mL (200.2 mM)
Water Insoluble
* <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 CP-724714 is a potent, selective inhibitor of HER2/ErbB2 with IC50 of 10 nM, >640-fold selectivity against EGFR, InsR, IRG-1R, PDGFR, VEGFR2, Abl, Src, c-Met etc in cell-free assays. Phase 2.
in vitro CP-724,714 is marked selectively against EGFR with IC50 of 6.4 μM. CP-724,714 is >1,000-fold less potent for IR, IGF-1R, PDGFRβ, VGFR2, abl. Src, c-Met c-jun NH2-terminal kinase (JNK)-2, JNK-3, ZAP-70, cyclin-dependent kinase (CDK)-2, and CDK-5. CP-724,714 potently reduces the EGF-induced autophosphorylation of the chimera containing the erbB2 kinase domain with IC50 of 32 nM, but is markedly less potent against EGFR in transfected NIH3T3 cells. CP-724,714 sensitively inhibits the proliferation of erbB2-amplified cells including BT-474 and SKBR3, with IC50 of 0.25 and 0.95 μM. CP-724,714 induces the accumulation of cells in G1 phase and a marked reduction in S-phase in BT-474 cells at 1 μM. [1] CP-724,714 likely exerts its hepatotoxicity via both hepatocellular injury and hepatobiliary cholestatic mechanisms. CP-724,714 displays inhibition of cholyl-lysyl fluorescein and taurocholate (TC) efflux into canaliculi in cryopreserved and fresh cultured human hepatocytes, respectively. CP-724,714 inhibits TC transport in membrane vesicles expressing human bile salt export pump with IC50 of 16 μM and inhibits the major efflux transporter in bile canaliculi, MDR1, with IC50 of ~28 μM. [2]
in vivo CP-724,714 (25 mg/kg) is rapidly absorbed after p.o. administration and causes reduction of tumor erbB2 receptor phosphorylation after dosing in FRE-erbB2 or BT-474 xenografts. CP-724,714 induces apoptosis in FRE-erbB2 xenograft–bearing (s.c.) mice and shows 50% tumor growth inhibition at 50 mg/kg, without weight loss or mortality. CP-724,714 also has great antitumor activity in MDA-MB-453, MDA-MB-231, LoVo (colon), and Colo-205 (colon) xenografts. Furthermore, CP-724,714 (30 or 100 mg/kg) reduces the extracellular signal–regulated kinase and Akt phosphorylation in BT-474 xenografts. [1]

プロトコル(参考用のみ)

キナーゼアッセイ Kinase assays
Recombinant erbB2 (amino acid residues 675-1255) and EGFR (amino acid residues 668-1211) intracellular domains are expressed in baculovirus-infected Sf9 cells as glutathione S-transferase fusion proteins. The proteins are purified by affinity chromatography on glutathione Sepharose beads for use in the assay. Nunc MaxiSorp 96-well plates are coated by incubation overnight at 37 °C with 100 μL/well of 0.25 mg/mL poly(Glu:Tyr, 4:1), PGT in PBS. Excess PGT is removed by aspiration and the plate is washed 3 times with wash buffer (0.1% Tween 20 in PBS). The kinase reaction is performed in 50 μL of 50 mm HEPES (pH 7.4) containing 125 mm sodium chloride, 10 mm magnesium chloride, 0.1 mm sodium orthovanadate, 1 mm ATP, and ∼15 ng of recombinant protein. Inhibitors in DMSO are added; the final DMSO concentration is 2.5%. Phosphorylation is initiated by addition of ATP and proceeded for 6 min at room temperature, with constant shaking. The kinase reaction is terminated by aspiration of the reaction mixture and washing four times with wash buffer. Phosphorylated PGT is measured after a 25-min incubation with 50 μL/well HRP conjugated-PY54 antiphosphotyrosine antibody, diluted to 0.2 μg/mL in blocking buffer (3% BSA, 0.05% Tween 20 in PBS). Antibody is removed by aspiration and the plate is washed four times with wash buffer. The colorimetric signal is developed by addition of 50 μL/well Tetramethylbenzidine Microwell Peroxidase Substrate and stopped by the addition of 50 μL/well 0.09 m sulfuric acid. The phosphotyrosine product formed is estimated by measurement of absorbance at 450 nm. The signal for controls is typically A0.6–1.2, with essentially no background in wells without ATP, kinase protein, or PGT, and is proportional to the time of incubation for 6 min.
細胞アッセイ 細胞株 ZR-75-30, HCC-1419, MDA-MB-175, BT-474, SKBR3, MDA-MB-361, UACC-812, T-47D, MDA-MB-453, MDA-MB-468, CAMA-1, MDA-MB-157, MCF-7, MDA-MB-435, ZR-75-1, BT-20, and MDA-MB-231.
濃度 0.1 nM - 10 μM.
反応時間 6 to 7 days.
実験の流れ Cells are seeded in duplicate at 5~10 × 103 per well in 24-well plates. The day after plating, CP-724,714 is added by titrating over six or more dilutions from 0.1 nM to 10 μM. Control wells without CP-724,714 are seeded as well. Cells are grown for 6 to 7 days, at which time surviving cells are counted. After trypsinization, cells are placed in isotone solution and counted immediately using a Coulter Z2 particle counter. Growth inhibition is calculated [(1− experimental value / control value) × 100] for each concentration. Dose-response curves are repeated at least twice and averaged. IC50 values are calculated using Calcusyn Software.
動物実験 動物モデル FRE-erbB2 BT-474, MDA-MB-453, MDA-MB-231, LoVo (colon), and Colo-205 (colon) xenografts are established in athymic female mice (CD-1 nu/nu).
投薬量 ~100 mg/kg.
投与方法 Administered via p.o.

カスタマーフィードバック

Data from [Cancer Res, 2014, 74(1), 341-52]

Data from [Cancer Res, 2013, 74(1), 341-52]

, 2012, Dr. Yong-Weon Yi from Georgetown University Medical Center

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：

ErbB2/HER2 receptor tyrosine kinase regulates human papillomavirus promoter activity [ Front Immunol, 2024, 15:1335302] PubMed: 38370412
The adaptor protein VEPH1 interacts with the kinase domain of ERBB2 and impacts EGF signaling in ovarian cancer cells [ Cell Signal, 2023, 106:110634] PubMed: 36828346
Sphingosine kinase 1 promotes tumor immune evasion by regulating the MTA3-PD-L1 axis [ Cell Mol Immunol, 2022, 19(10):1153-1167.] PubMed: 36050478
The adenosine analog prodrug ATV006 is orally bioavailable and has preclinical efficacy against parental SARS-CoV-2 and variants [ Sci Transl Med, 2022, 14(661):eabm7621] PubMed: 35579533
Blocking glycine utilization inhibits multiple myeloma progression by disrupting glutathione balance [ Nat Commun, 2022, 13(1):4007] PubMed: 35817773
SHF Acts as a Novel Tumor Suppressor in Glioblastoma Multiforme by Disrupting STAT3 Dimerization [ Adv Sci (Weinh), 2022, e2200169] PubMed: 35843865
ROS generation attenuates the anti-cancer effect of CPX on cervical cancer cells by inducing autophagy and inhibiting glycophagy [ Redox Biol, 2022, 53:102339] PubMed: 35636017
CD147 mediates epidermal malignant transformation through the RSK2/AP-1 pathway [ J Exp Clin Cancer Res, 2022, 41(1):246] PubMed: 35964097
Multifunctional photodynamic/photothermal nano-agents for the treatment of oral leukoplakia [ J Nanobiotechnology, 2022, 20(1):106] PubMed: 35246146
A spark to the powder keg: Microneedle-based antitumor nanomedicine targeting reactive oxygen species accumulation for chemodynamic/photothermal/chemotherapy [ J Colloid Interface Sci, 2022, 628(Pt B):189-203] PubMed: 35994900

長期の保管のために-20°Cの下で製品を保ってください。

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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