ChemicalBook Product Catalog Biochemical Engineering Inhibitors Epigenetics HDAC inhibitors CUDC-101

CUDC-101

Product NameCUDC-101
CAS1012054-59-9
MFC24H26N4O4
MW434.49
EINECS
MOL File1012054-59-9.mol

Chemical Properties

Melting point	174-177℃
Density	1.28
storage temp.	-20°C
solubility	DMSO: soluble
pka	9.47±0.20(Predicted)
form	solid
color	White or off-white
Stability	Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 1 month.
InChIKey	PLIVFNIUGLLCEK-UHFFFAOYSA-N
SMILES	N(O)C(=O)CCCCCCOc1cc2c(ncnc2Nc3cc(ccc3)C#C)cc1OC

Safety Information

WGK Germany	3
Storage Class	10 - Combustible liquids

Usage And Synthesis

Description

CUDC-101 (1012054-59-9) is a novel hybrid dual-acting HDAC and receptor tyrosine kinase inhibitor. It is a potent HDAC inhibitor which also inhibits EGFR and HER2, IC50= 4.4, 2.4 and 15.7 nM respectively.1It not only blocks EGFR and HER2 but also attenuates multiple compensatory pathways such as AKT, HER3 and MET which enable tumor cells to escape the effects of conventional EGFR/HER2 inhibitors.1,2

Uses

Inhibitor of HDAC, EGFR, and HER2 with an IC50 of 4.4, 2.4, and 15.7 nM, respectively.

Uses

CUDC-101 is a potent multi-acting HDAC (histone deacetylase), EGFR (epidermal growth factor receptor), and HER2 ( human epidermal growth factor receptor 2) inhibitor for the treatment of cancer.

General Description

A potent multitargeted inhibitor of histone deacetylase (HDAC) and the receptor kinases epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2), with IC50 values of 4.4, 2.4, and 15.7 nM, respectively.

Displays potent antiproliferative and proapoptotic activities against cultured and implanted tumor cells that are sensitive or resistant to several approved single-targeted drugs.

Synthesis

Heptanoic acid, 6-[[4-[(3-ethynylphenyl)amino]-7-methoxy-6-quinazolinyl]oxy]-, ethyl ester

1012920-21-6

1012054-59-9

Step 8b. Synthesis of 7-[[4-(3-ethynylphenylamino)-7-methoxyquinazolin-6-yl]oxy]-N-hydroxyheptanamide (Compound 12): Referring to the method for the preparation of Compound 1 in Example 1 , the target product 7-[[4-(3-ethynylphenylamino)-7-methoxyquinazolin-6-yl]oxy]-N-hydroxyheptanamide (Compound 12) was obtained by reaction of Compound 0113-12 (250 mg, 0.56 mmol). amino)-7-methoxyquinazolin-6-yl]oxy]-N-hydroxyheptanamide (compound 12), the product was a gray solid (100 mg, 41% yield). Melting point: 205 °C (decomposition temperature 171.8-177.2 °C). LC-MS (m/z): 435 [M + H]+. 1H NMR (DMSO-d6, δ): 1.36 (m, 2H), 1.52 (m, 4H), 1.83 (m, 2H), 1.97 (m, 2H), 3.94 (s, 3H), 4.14 (t, J = 6.3 Hz, 2H), 4.20 (s, 1H), 7.21 (m, 2H), 7.41 (t, J = 8.1 Hz, 1H), 7.83 (s, 1H), 7.90 (d, J = 8.1 Hz, 1H), 8.00 (s, 1H), 8.50 (s, 1H), 8.66 (s, 1H), 9.48 (s, 1H), 10.35 (s, 1H).

in vivo

CUDC-101 (120 mg/kg, iv, daily) induces tumor regression in the Hep-G2 liver cancer model and is more efficacious than erlotinib at its maximum tolerated dose (MTD). In the erlotinib-resistant A549 NSCLC xenograft model, CUDC-101 (120 mg/kg) shows potent inhibition of tumor growth. In the erlotinib-sensitive H358 NSCLC models, CUDC-101 (15, 30, 60 mg/kg, i.v.) inhibits tumor growth in a dose-dependent manner. CUDC-101 (120 mg/kg) causes 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. CUDC-101 (120 mg/kg) also inhibits tumor growth in the K-ras mutant HCT116 colorectal and EGFR/HER2 (neu)-expressing HPAC pancreatic cancer models^[1].
In an in vivo mouse model of metastatic ATC, CUDC-101 inhibits tumor growth and metastases, and significantly prolongs survival^[3].
CUDC-101 (120 mg/kg) is effective against a broad range of tumor types in xenograft models^[4].

target

EGFR

IC 50

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

References

[1] CHENG-JUNG LAI. CUDC-101, a multitargeted inhibitor of histone deacetylase, epidermal growth factor receptor, and human epidermal growth factor receptor 2, exerts potent anticancer activity.[J]. Cancer research, 2010, 70 9: 3647-3656. DOI:10.1158/0008-5472.can-09-3360
[2] XIONG CAI*. Discovery of 7-(4-(3-Ethynylphenylamino)-7-methoxyquinazolin-6-yloxy)-N-hydroxyheptanamide (CUDC-101) as a Potent Multi-Acting HDAC, EGFR, and HER2 Inhibitor for the Treatment of Cancer[J]. Journal of Medicinal Chemistry, 2010, 53 5: 2000-2009. DOI:10.1021/jm901453q

CUDC-101

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