CUDC-101 Chemical Properties

Melting point:

174-177℃

Density 

1.28

storage temp. 

-20°C

solubility 

DMSO: soluble

form 

solid

pka

9.47±0.20(Predicted)

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

Safety Information

WGK Germany 

3

CUDC-101 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.1?It 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

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

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

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