Home Epigenetics HDAC inhibitor - EGFR inhibitor - HER2 inhibitor CUDC-101

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CUDC-101 HDAC inhibitor

Cat.No.S1194

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 this compound inhibits class I/II HDACs, but not class III, Sir-type HDACs. Phase 1.
CUDC-101 HDAC inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 434.49

Jump to Mechanism of Action Cell Culture & Working Concentration Solubility Chemical Information, Storage & Stability Specificity

Quality Control

Cell Culture, Treatment & Working Concentration

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
MDA-MB-231 cells Proliferation assay Antiproliferative activity against human MDA-MB-231 cells after hrs by ATP content assay, IC50=0.1 μM
human HepG2 cells Proliferation assay Antiproliferative activity against human HepG2 cells after hrs by ATP content assay, IC50=0.13 μM
human SKHEP1 cells Proliferation assay Antiproliferative activity against human SKHEP1 cells after hrs by ATP content assay, IC50=0.22 μM
human Hep3B2 cells Proliferation assay Antiproliferative activity against human Hep3B2 cells after hrs by ATP content assay, IC50=0.23 μM
human BxPC3 cells Proliferation assay Antiproliferative activity against human BxPC3 cells after hrs by ATP content assay, IC50=0.27 μM
human NCI-H358 cells Proliferation assay Antiproliferative activity against human NCI-H358 cells after hrs by ATP content assay, IC50=0.4 μM
human MCF7 cells Proliferation assay Antiproliferative activity against human MCF7 cells after hrs by ATP content assay, IC50=0.55 μM
human HCC827 cells Proliferation assay Antiproliferative activity against human HCC827 cells after hrs by ATP content assay, IC50=0.6 μM
human H460 cells Proliferation assay Antiproliferative activity against human H460 cells after hrs by ATP content assay, IC50=0.7 μM
human Capan1 cells Proliferation assay Antiproliferative activity against human Capan1 cells after hrs by ATP content assay, IC50=0.8 μM
Click to View More Cell Line Experimental Data

Chemical Information, Storage & Stability

Molecular Weight 434.49 Formula

C24H26N4O4

 Storage (From the date of receipt)
CAS No. 1012054-59-9 Download SDF Storage of Stock Solutions

Synonyms N/A Smiles COC1=C(C=C2C(=C1)N=CN=C2NC3=CC=CC(=C3)C#C)OCCCCCCC(=O)NO

Solubility

In vitro
Batch:

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

Water : Insoluble

Ethanol : Insoluble

Molarity Calculator

Mass Concentration Volume Molecular Weight

In vivo
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Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

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Mechanism of Action

Targets/IC50/Ki
EGFR [1]
(Cell-free assay)
2.4 nM
HDAC [1]
(Cell-free assay)
4.4 nM
HDAC1 [1]
(Cell-free assay)
4.5 nM
HDAC6 [1]
(Cell-free assay)
5.1 nM
HDAC3 [1]
(Cell-free assay)
9.1 nM
HDAC5 [1]
(Cell-free assay)
11.4 nM
HDAC2 [1]
(Cell-free assay)
12.6 nM
HDAC4 [1]
(Cell-free assay)
13.2 nM
HER2 [1]
(Cell-free assay)
15.7 nM
HDAC10 [1]
(Cell-free assay)
26.1 nM
HDAC9 [1]
(Cell-free assay)
67.2 nM
HDAC8 [1]
(Cell-free assay)
79.8 nM
HDAC7 [1]
(Cell-free assay)
373 nM
In vitro

Specific for class I and class II HDACs, CUDC-101 does not inhibit class III Sir-type HDACs. This compound 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. It 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. This chemical potently inhibits cancer cell lines. [1] It inhibits the resistant EGFR mutant T790M although its effects are incomplete with an Amax of ~60% of peak enzyme activity after inhibition. This compound 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. It 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 this compound 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.
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). This compound inhibits the growth of -sensitive H358 NSCLC xenografts in a dose-dependent manner. It also shows potent inhibition of tumor growth in the -resistant A549 NSCLC xenograft model. This chemical 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, it inhibits tumor growth in the K-ras mutant HCT116 colorectal and EGFR/HER2 (neu)-expressing HPAC pancreatic cancer models. [1]
References

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

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

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