CDDO methyl ester

CDDO methyl ester is an EGFR degrader.¹ It binds to EGFR (K_d = 5.64 µM) and induces EGFR ubiquitination and degradation in BT-549 breast cancer cells but not in the presence of shRNA targeting the mRNA encoding Kelch-like ECH-associated protein 1 (Keap1). CDDO methyl ester (1 µM) increases the number of autophagosomes in BT-549 cells. It inhibits Ifn-γ-induced increases in levels of nitric oxide (NO) in isolated mouse macrophages (IC₅₀ = 0.11 nM).² CDDO methyl ester (1 µM) inhibits TNF-α-induced NF-κB nuclear translocation in KBM5 cells.³ It disrupts the mitochondrial membrane potential in U937 lymphoma monocytes when used at a concentration of 1 µM.⁴ CDDO methyl ester decreases the viability of SGC-7901, NCI N87, BGC-823, and GES-1 gastric cancer cells (IC₅₀s = 0.6, 0.8, 0.5, and 0.5 µM, respectively).⁵ It reduces plasma levels of triglycerides, free fatty acids, insulin, blood levels of glucose, liver and muscle levels of total lipids, and muscle levels of triglycerides in mice fed a Western diet when administered at a dose of 3 mg/kg per day.⁶ CDDO methyl ester (2 mg/kg every other day), alone or in combination with gefitinib (Item No. 13166), decreases tumor volume and weight and the percentage of EGFR⁺ tumor cells in an HCC1806 breast cancer mouse xenograft model.¹

WARNING This product is not for human or veterinary use.

1. Wang, H., Wang, H., Wang, R., et al. Discovery of a molecular glue for EGFR degradation. Oncogene (2024).

2. Honda, T., Honda, Y., Favaloro, F.G., Jr., et al. A novel dicyanotriterpenoid, 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-onitrile, active at picomolar concentrations for inhibition of nitric oxide production. Bioorg. Med. Chem. Lett. 12(7), 1027-1030 (2002).

3. Shishodia, S., Sethi, G., Konopleva, M., et al. A synthetic triterpenoid, CDDO-Me, inhibits IκBα kinase and enhances apoptosis induced by TNF and chemotherapeutic agents through down-regulation of expression of nuclear factor κB-regulated gene products in human leukemic cells. Clin. Cancer Res. 12(6), 1828-1838 (2006).

4. Konopleva, M., Tsao, T., Ruvolo, P., et al. Novel triterpenoid CDDO-Me is a potent inducer of apoptosis and differentiation in acute myelogenous leukemia. Blood 99(1), 326-335 (2002).

5. Li, N., Wang, J., Zhang, L., et al. New CDDO arylboronate ester derivatives with high selectivity and low toxicity. J. Med. Chem. 67(16), (2024).

6. Saha, P.K., Reddy, V.T., Konopleva, M., et al. The triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic-acid methyl ester has potent anti-diabetic effects in diet-induced diabetic mice and Lepr^db/db mice. The Journal of Biological Chemisty 285(52), 40581-40592 (2010).