Home Epigenetics HDAC inhibitor - EGFR inhibitor - HER2 inhibitor CUDC-101 For research use only.

CUDC-101

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.

CUDC-101 Chemical Structure

CUDC-101 Chemical Structure

CAS No. 1012054-59-9

Purity & Quality Control

CUDC-101 Related Products

Signaling Pathway

HDAC Signaling Pathways

HDAC Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
human SK-BR-3 cells Proliferation assay Antiproliferative activity against human SK-BR-3 cells after hrs by ATP content assay, IC50=0.04 μM 20143778
MDA-MB-231 cells Proliferation assay Antiproliferative activity against human MDA-MB-231 cells after hrs by ATP content assay, IC50=0.1 μM 20143778
human HepG2 cells Proliferation assay Antiproliferative activity against human HepG2 cells after hrs by ATP content assay, IC50=0.13 μM 20143778
human SKHEP1 cells Proliferation assay Antiproliferative activity against human SKHEP1 cells after hrs by ATP content assay, IC50=0.22 μM 20143778
human Hep3B2 cells Proliferation assay Antiproliferative activity against human Hep3B2 cells after hrs by ATP content assay, IC50=0.23 μM 20143778
human BxPC3 cells Proliferation assay Antiproliferative activity against human BxPC3 cells after hrs by ATP content assay, IC50=0.27 μM 20143778
human NCI-H358 cells Proliferation assay Antiproliferative activity against human NCI-H358 cells after hrs by ATP content assay, IC50=0.4 μM 20143778
human MCF7 cells Proliferation assay Antiproliferative activity against human MCF7 cells after hrs by ATP content assay, IC50=0.55 μM 20143778
human HCC827 cells Proliferation assay Antiproliferative activity against human HCC827 cells after hrs by ATP content assay, IC50=0.6 μM 20143778
human H460 cells Proliferation assay Antiproliferative activity against human H460 cells after hrs by ATP content assay, IC50=0.7 μM 20143778
human Capan1 cells Proliferation assay Antiproliferative activity against human Capan1 cells after hrs by ATP content assay, IC50=0.8 μM 20143778
Click to View More Cell Line Experimental Data

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)		 Click to View More Targets
2.4 nM 4.4 nM 4.5 nM 5.1 nM 9.1 nM
In vitro
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 and combinations of vorinostat in most cases. CUDC-101 potently inhibits cancer cell lines. [1] CUDC-101 inhibits the 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]
Kinase Assay 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 Research 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.
In Vivo
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 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 -sensitive H358 NSCLC xenografts in a dose-dependent manner. CUDC-101 also shows potent inhibition of tumor growth in the -resistant A549 NSCLC xenograft model. CUDC-101 produces significant tumor regression in the -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]
Animal Research 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.
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT01702285 Terminated
Cancer
Curis Inc.
 September 2012 Phase 1
NCT01384799 Completed
Head and Neck Cancer
Curis Inc.
 November 2011 Phase 1
NCT00728793 Completed
Tumors
Curis Inc.
 August 2008 Phase 1

Chemical Information & Solubility

Molecular Weight 434.49 Formula

C24H26N4O4
CAS No. 1012054-59-9 SDF Download CUDC-101 SDF
Smiles COC1=C(C=C2C(=C1)N=CN=C2NC3=CC=CC(=C3)C#C)OCCCCCCC(=O)NO
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 43 mg/mL ( (98.96 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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In vivo
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Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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