CUDC-101

Catalog No.S1194 Batch:S119404

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Technical Data

Formula

C24H26N4O4
Molecular Weight 434.49 CAS No. 1012054-59-9
Solubility (25°C)* In vitro DMSO 44 mg/mL (101.26 mM)
Water Insoluble
Ethanol Insoluble
In vivo (Add solvents to the product individually and in order)
Homogeneous suspension
15% Captisol
10.0mg/ml Taking the 1 mL working solution as an example, take 10 mg of this product, add it to 1 ml of 15% Captisol clear solution, and mix evenly to form a uniform suspension. The mixed solution should be used immediately for optimal results. 
* <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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description 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.
Targets
EGFR [1]
(Cell-free assay)		 HDAC [1]
(Cell-free assay)		 HDAC1 [1]
(Cell-free assay)		 HDAC6 [1]
(Cell-free assay)		 HDAC3 [1]
(Cell-free assay)		 View More
2.4 nM 4.4 nM 4.5 nM 5.1 nM 9.1 nM
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]

Protocol (from reference)

Kinase Assay:[1]
  • HDAC, EGFR and HER2 inhibition assays

    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.
Cell Assay:[1]
  • Cell lines

    HCC827, H358, H460, HepG2, Hep3B2, Sk-Hep-1, Capan1, BxPc3, MCF-7, MDA-MB-231, and Sk-Br-3

  • Concentrations

    Dissolved in DMSO, final concentrations ~10 μM

  • Incubation Time

    72 hours

  • Method

    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.
Animal Study:[1]
  • Animal Models

    Female athymic mice (nude nu/nu CD-1) inoculated with Hep-G2, H358, A549, MDA-MB468, HCT116, CAL-27, HepG2, or HPAC

  • Dosages

    ~120 mg/kg/day

  • Administration

    Administered via i.v.

Customer Product Validation

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's CUDC-101 has been cited by 23 publications

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

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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