CUDC-101

製品コードS1194 バッチS119401

化学情報

	Synonyms	N/A	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₂₄H₂₆N₄O₄
	分子量	434.49	CAS No.	1012054-59-9
Solubility (25°C)*	体外	DMSO	43 mg/mL (98.96 mM)
		Water	Insoluble
		Ethanol	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	CUDC-101 is a potent multi-targeted inhibitor against HDAC, EGFR and HER2 with IC50 of 4.4 nM, 2.4 nM, and 15.7 nM, and inhibits class I/II HDACs, but not class III, Sir-type HDACs. Phase 1.
in vitro	Specific for class I and class II HDACs, CUDC-101 does not inhibit class III Sir-type HDACs. CUDC-101 displays weak activity against other protein kinases including KDR/VEGFR2, Lyn, Lck, Abl-1, FGFR-2, Flt-3, and Ret with IC50 of 0.85 μM, 0.84 μM, 5.91 μM, 2.89 μM, 3.43 μM, 1.5 μM, abd 3.2 μM, respectively. CUDC-101 displays broad antiproliferative activity in many human cancer cell types with IC50 of 0.04-0.80 μM, exhibiting a higher potency than erlotinib, lapatinib, and combinations of vorinostat with either erlotinib or lapatinib in most cases. CUDC-101 potently inhibits lapatinib- and erlotinib-resistant cancer cell lines. ^[1] CUDC-101 inhibits the erlotinib-resistant EGFR mutant T790M although its effects are incomplete with an Amax of ~60% of peak enzyme activity after inhibition. CUDC-101 treatment increases the acetylation of histone H3 and H4, as well as the acetylation of non-histone substrates of HDAC such as p53 and α-tubulin, in a dose-dependant manner in various cancer cell lines. CUDC-101 also suppresses HER3 expression, Met amplification, and AKT reactivation in tumor cells. ^[2]
in vivo	Administration of CUDC-101 at 120 mg/kg/day induces tumor regression in the Hep-G2 liver cancer model, which is more efficacious than that of erlotinib at its maximum tolerated dose (25 mg/kg/day) and vorinostat at an equimolar concentration dose (72 mg/kg/day). CUDC-101 inhibits the growth of erlotinib-sensitive H358 NSCLC xenografts in a dose-dependent manner. CUDC-101 also shows potent inhibition of tumor growth in the erlotinib-resistant A549 NSCLC xenograft model. CUDC-101 produces significant tumor regression in the lapatinib-resistant, HER2-negative, EGFR-overexpressing MDA-MB-468 breast cancer model and the EGFR-overexpressing CAL-27 head and neck squamous cell carcinoma (HNSCC) model. Additionally, CUDC-101 inhibits tumor growth in the K-ras mutant HCT116 colorectal and EGFR/HER2 (neu)-expressing HPAC pancreatic cancer models. ^[1]

プロトコル(参考用のみ)

キナーゼアッセイ	HDAC, EGFR and HER2 inhibition assays
キナーゼアッセイ	The activities of Class I and II HDACs are assessed using the Biomol Color de Lys system. Briefly, HeLa cell nuclear extracts are used as a source of HDACs. Different concentrations of CUDC-101 are added to HeLa cell nuclear extracts in the presence of a colorimetric artificial substrate. Developer is added at the end of the assay and enzyme activity is measured in the Wallac Victor II 1420 microplate reader at 405 nM. EGFR and HER2 kinase activity are measured using HTScan EGF receptor and HER2 kinase assay kits. Briefly, the GST-EGFR fusion protein is incubated with synthetic biotinylated peptide substrate and varying concentrations of CUDC-101 in the presence of 400 mM ATP. Phosphorylated substrate is captured with strapavidin-coated 96-well plates. The level of phosphorylation is monitored by antiphospho-tyrosine- and europium-labeled secondary antibodies. The enhancement solution is added at the end of the assay and enzyme activity is measured in the Wallac Victor II 1420 microplate reader at 615 nM.
細胞アッセイ	細胞株	HCC827, H358, H460, HepG2, Hep3B2, Sk-Hep-1, Capan1, BxPc3, MCF-7, MDA-MB-231, and Sk-Br-3
	濃度	Dissolved in DMSO, final concentrations ~10 μM
	反応時間	72 hours
	実験の流れ	Cancer cell lines are plated at 5000 to 10000 cells per well in 96-well flatbottomed plates with varying concentrations of CUDC-101. The cells are incubated with CUDC-101 for 72 hours in the presence of 0.5% of fetal bovine serum. Growth inhibition is assessed by an adenosine triphosphate (ATP) content assay using the Perkin-Elmer ATPlite kit. Apoptosis is routinely assessed by measuring the activities of Caspase-3 and -7 using Apo-ONE Homogeneous Assay Kit.
動物実験	動物モデル	Female athymic mice (nude nu/nu CD-1) inoculated with Hep-G2, H358, A549, MDA-MB468, HCT116, CAL-27, HepG2, or HPAC
	投薬量	~120 mg/kg/day
	投与方法	Administered via i.v.

参考

カスタマーフィードバック

: Data from [Data independently produced by ACS Med Chem Lett, 2013, 4(9), 858-62]

: , , Dr. Zhang of Tianjin Medical University

: , , Dr. Xiangbing Meng of University of Iowa

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：

Histone 4 lysine 5/12 acetylation enables developmental plasticity of Pristionchus mouth form [ Nat Commun, 2023, 14(1):2095]	PubMed: 37055396
Histone 4 lysine 5/12 acetylation enables developmental plasticity of Pristionchus mouth form [ Nat Commun, 2023, 14(1):2095]	PubMed: 37055396
CUDC-907, a dual PI3K/histone deacetylase inhibitor, increases meta-iodobenzylguanidine uptake (123/131I-mIBG) in vitro and in vivo: a promising candidate for advancing theranostics in neuroendocrine tumors [ J Transl Med, 2023, 21(1):604]	PubMed: 37679770
CUDC‑101 is a potential target inhibitor for the EGFR‑overexpression bladder cancer cells [ Int J Oncol, 2023, 10.3892/ijo.2023.5579]	PubMed: 37830158
Non-oncology drug (meticrane) shows anti-cancer ability in synergy with epigenetic inhibitors and appears to be involved passively in targeting cancer cells [ Front Oncol, 2023, 13:1157366]	PubMed: 37274234
High-throughput screen in vitro identifies dasatinib as a candidate for combinatorial treatment with HER2-targeting drugs in breast cancer [ PLoS One, 2023, 18(1):e0280507]	PubMed: 36706086
Development and implementation of the SUM breast cancer cell line functional genomics knowledge base [ NPJ Breast Cancer, 2020, 6:30]	PubMed: 32715085
Prolonged unfolded protein reaction is involved in the induction of chronic myeloid leukemia cell death upon oprozomib treatment [ Cancer Sci, 2020, 112(1):133-143]	PubMed: 33067904
CUDC-101 overcomes arsenic trioxide resistance via caspase-dependent promyelocytic leukemia-retinoic acid receptor alpha degradation in acute promyelocytic leukemia. [ Anticancer Drugs, 2020, 31(2):158-168]	PubMed: 31584454
Activation of PP2A and Inhibition of mTOR Synergistically Reduce MYC Signaling and Decrease Tumor Growth in Pancreatic Ductal Adenocarcinoma [ Cancer Res, 2019, 79(1):209-219]	PubMed: 30389701

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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