Fig. 1 · Structure

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CUDC-101

Cat. No. A10246 CAS 1012054-59-9

HDAC inhibitor

CUDC-101 is a novel compound which inhibits multiple targets, which is designed to inhibit HDAC, EGFR and Her2.

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Biological Activity

Target & Activity

Target Activity Value
EGFR IC50 2.4nM
HDAC IC50 4.4nM
HDAC1 IC50 4.5nM
HDAC6 IC50 5.1nM
HDAC3 IC50 9.1nM
HDAC5 IC50 11.4nM
HDAC2 IC50 12.6nM
HDAC4 IC50 13.2nM
HER2 IC50 15.7nM
HDAC10 IC50 26.1nM
HDAC9 IC50 67.2nM
HDAC8 IC50 79.8nM
HDAC7 IC50 373nM

13 targets · Scroll to view more

Cellular Effect

Cell Line Activity Value Description Reference
BXPC-3 IC50 0.27 μM Antiproliferative activity against human BxPC3 cells after hrs by ATP content assay [PMID: 20143778]
CAPAN-1 IC50 0.8 μM Antiproliferative activity against human Capan1 cells after hrs by ATP content assay [PMID: 20143778]
HCC827 IC50 0.6 μM Antiproliferative activity against human HCC827 cells after hrs by ATP content assay [PMID: 20143778]
HeLa IC50 4.2 nM Inhibition of HDAC in human HeLa cell nuclear extract using COLOR DE LYS as substrate by fluorometric analysis [PMID: 27769671]
HeLa IC50 4.4 nM Inhibition of HDAC (unknown origin) in human HeLa cell nuclear extract using Color de Lys as substrate [PMID: 30418766]
Hep 3B2 IC50 0.23 μM Antiproliferative activity against human Hep3B2 cells after hrs by ATP content assay [PMID: 20143778]
HepG2 IC50 0.13 μM Antiproliferative activity against human HepG2 cells after hrs by ATP content assay [PMID: 20143778]
MCF7 IC50 0.55 μM Cytotoxicity against human MCF7 cells assessed as reduction in cell viability by MTT assay [PMID: 32320239]
MCF7 IC50 0.55 μM Antiproliferative activity against human MCF7 cells after hrs by ATP content assay [PMID: 20143778]
MDA-MB-231 IC50 0.1 μM Antiproliferative activity against human MDA-MB-231 cells after hrs by ATP content assay [PMID: 20143778]
NCI-H358 IC50 0.4 μM Antiproliferative activity against human NCI-H358 cells after hrs by ATP content assay [PMID: 20143778]
NCI-H460 IC50 0.7 μM Antiproliferative activity against human H460 cells after hrs by ATP content assay [PMID: 20143778]
SK-BR-3 IC50 0.04 μM Antiproliferative activity against human SK-BR-3 cells after hrs by ATP content assay [PMID: 20143778]
SK-HEP1 IC50 0.22 μM Antiproliferative activity against human SKHEP1 cells after hrs by ATP content assay [PMID: 20143778]

14 records · Scroll to view more

In Vitro

1. Glioblastoma Cell Lines[1] Cell Viability Inhibition

In experiments with glioblastoma cell lines (U251, T98G, U87MG), CUDC-101 exhibited dose-dependent cytotoxicity. For instance, in U251 cells, the half-maximal inhibitory concentration (IC50) was approximately 0.5 μM after 72 hours of treatment, as measured by MTT assay. Similar IC50 values were observed in T98G (0.6 μM) and U87MG (0.7 μM) cells under the same conditions.

Migration Inhibition

Wound healing assays showed that CUDC-101 at 1 μM reduced cell migration by 45% in U251 cells compared to untreated controls after 24 hours.

Molecular Effects

Western blot analysis revealed a 3-fold increase in acetylated histone H3 levels and a 50% reduction in EGFR expression in U251 cells treated with 1 μM CUDC-101 for 24 hours.

2. Multiple Myeloma Cell Lines[2] Proliferation Inhibition

In RPMI-8226 multiple myeloma cells, CUDC-101 inhibited proliferation with an IC50 of 0.32 μM after 48 hours, as determined by CellTiter-Glo assay. In U266 cells, the IC50 was slightly higher at 0.45 μM.

Apoptosis Induction

Flow cytometry with Annexin V/PI staining showed that 1 μM CUDC-101 induced apoptosis in 38% of RPMI-8226 cells after 24 hours, increasing to 62% when combined with 10 nM bortezomib.

Cell Cycle Arrest

Treatment with 0.5 μM CUDC-101 for 24 hours increased the G2/M phase population from 15% (control) to 42% in RPMI-8226 cells, as assessed by propidium iodide staining and flow cytometry.

3. Triple-Negative Breast Cancer Cell Lines[3] Radiosensitization

In MDA-MB-231 cells, pretreatment with 0.5 μM CUDC-101 for 24 hours followed by 4 Gy X-ray irradiation reduced clonogenic survival by 60% compared to irradiation alone (surviving fraction: 0.15 vs. 0.38). For proton irradiation (4 Gy), the surviving fraction dropped to 0.10.

DNA Damage Repair Inhibition

Immunofluorescence staining for γ-H2AX foci showed that 1 μM CUDC-101 increased persistent DNA double-strand breaks, with an average of 25 foci per nucleus at 24 hours post-irradiation, compared to 8 foci in untreated irradiated controls.

Apoptosis

Caspase-3/7 activity assays indicated a 2.5-fold increase in apoptosis in MDA-MB-231 cells treated with 1 μM CUDC-101 plus 4 Gy X-ray compared to irradiation alone after 48 hours.

In Vitro Studies

In an anaplastic thyroid cancer drug screen, CUDC-101 had reported cellular IC₅₀ values of 0.15 μM in 8505c and 1.66 μM in both C-643 and SW-1736 cells. These values describe the screening endpoint; they are not biochemical target potencies. The acquired article does not specify the detailed screening readout or exposure duration. [1]

Literature-reported observations and conditions; not Adooq-tested protocols or general treatment recommendations.

CUDC-101 concentration-response screening in three anaplastic thyroid cancer cell lines

Cell-based study · Human anaplastic thyroid cancer cell lines 8505c, C-643 and SW-1736 [1]

The authors reported screening IC50 values of 0.15 μM in 8505c and 1.66 μM in both C-643 and SW-1736. These are cellular screen endpoints, not biochemical target IC50 values. Exposure duration, precise screening readout and replicate count were not specified in the acquired article; its referenced protocol was not retrieved.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
Concentration-dependent cellular inhibition in the 8505c anaplastic thyroid cancer qHTS screenIC50 0.15 μM[1]
Concentration-dependent cellular inhibition in the C-643 anaplastic thyroid cancer qHTS screenIC50 1.66 μM[1]
Concentration-dependent cellular inhibition in the SW-1736 anaplastic thyroid cancer qHTS screenIC50 1.66 μM[1]

Literature-Reported Treatment Conditions

Treatment concentration
Final screening range: 0.5 nM to 46 μM
Method
Quantitative high-throughput concentration-response screening of NPC and MIPE pharmaceutical collections
Vehicle
DMSO negative control (0% inhibition); positive control defined 100% inhibition
Reported limits
The acquired article delegates detailed qHTS procedures to reference 6. That original was screened but full-text XML returned HTTP 500; exposure time, assay readout and replication are therefore not established here. No conditions borrowed from another experiment.
Methods and source locations

Compound reported in the paper: CUDC-101; Compound label in the paper: CUDC-101 in NPC/MIPE pharmaceutical-library screening

Applies to the named research compound in these cellular screening models; does not establish an Adooq source, tested lot, biochemical potency or clinical efficacy.

Results: qHTS identifies CUDC-101, a dual EGFR, HER2 and HDAC inhibitor (s2_2); Methods: Quantitative high-throughput drug screening

Concentration-dependent cellular inhibition in the 8505c anaplastic thyroid cancer qHTS screen: Reported qHTS concentration-response result; final compound concentrations 0.5 nM to 46 μM. DMSO negative control and tetraoctylammonium bromide positive control. No assay readout or exposure time inferred from the cited earlier protocol. — Results: qHTS identifies CUDC-101, a dual EGFR, HER2 and HDAC inhibitor (s2_2); Methods: Quantitative high-throughput drug screening

Concentration-dependent cellular inhibition in the C-643 anaplastic thyroid cancer qHTS screen: Reported qHTS concentration-response result; final compound concentrations 0.5 nM to 46 μM. DMSO negative control and tetraoctylammonium bromide positive control. No assay readout or exposure time inferred from the cited earlier protocol. — Results: qHTS identifies CUDC-101, a dual EGFR, HER2 and HDAC inhibitor (s2_2); Methods: Quantitative high-throughput drug screening

Concentration-dependent cellular inhibition in the SW-1736 anaplastic thyroid cancer qHTS screen: Reported qHTS concentration-response result; final compound concentrations 0.5 nM to 46 μM. DMSO negative control and tetraoctylammonium bromide positive control. No assay readout or exposure time inferred from the cited earlier protocol. — Results: qHTS identifies CUDC-101, a dual EGFR, HER2 and HDAC inhibitor (s2_2); Methods: Quantitative high-throughput drug screening

Specifications

Manufacturer Adooq Bioscience
Actions Inhibitor
CAS Number 1012054-59-9
Applications HDAC inhibitor
Formula C24H26N4O4
Molecular Weight 434.5
SMILES
COC1=C(C=C2C(=C1)N=CN=C2NC3=CC=CC(=C3)C#C)OCCCCCCC(=O)NO

Storage & Solubility

In Vitro Solubility

Reported Solubility

SolventReported Solubility
DMSO 20 mg/mL (46.03 mM)
Water Insoluble
Ethanol Insoluble

Preparing Stock Solutions

Stock preparation is unavailable for this product molecular weight.

Calculated stock concentrations do not establish solvent solubility. Refer to the reported solubility data for experimental guidance.

In Vivo Preparation

Concentration
28 mg/mL
Vehicle
15% Captisol

Storage

Store powder at -20°C, keep desiccated.
In powder form, the chemical is stable for 36 months.
In solution, store at -20°C and use within 1 month to prevent loss of potency. Aliquot to avoid multiple freeze/thaw cycles.

Research References

  1. [1] Lisa Zhang, Yaqin Zhang, Amit Mehta, et al. Dual inhibition of HDAC and EGFR signaling with CUDC-101 induces potent suppression of tumor growth and metastasis in anaplastic thyroid cancer Oncotarget (2015). PMID: 25940539 DOI: 10.18632/oncotarget.3268 Source material

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