CES2 Inhibitor

Miltirone is an orally active natural compound found in the root of Salvia miltiorrhiza. Miltirone is a central benzodiazepine receptor partial agonist, with an IC₅₀ of 0.3 μM. Miltirone induces ROS - and-p53 dependent apoptosis. Miltirone inhibits carboxylesterase 2 (CES2; K_i = 0.04 μM) and SARS-CoV main protease (Mpro).

CES2-IN-1 (Compound 24) is a reversible and selective CES2 inhibitor (IC₅₀: 6.72 μM for human CES2). CES2-IN-1 reduces the level of CES2 in living cells. CES2-IN-1 is effective against Irinotecan (HY-16562)-induced delayed diarrhea and DSS-induced ulcerative colitis.

CES2A-IN-2 (compound 14n) is an orally active, highly specific, irreversible and covalent CES2A inhibitor with an IC₅₀ of 0.04 nM for human CES2A. CES2A-IN-2 covalently binds to CES2A by specifically targeting the catalytic serine residue (Ser-228). CES2A-IN-2 can significantly ameliorate Irinotecan-triggered gut toxicity (ITGT) without diminishing the anti-tumor effects of Irinotecan (HY-16562) in tumor-bearing mice.

Alisol G (25-Anhydroalisol A) is a human carboxylesterase 2 (hCES2) inhibitor with an IC₅₀ of 3.85 μM. Alisol G exhibits cytotoxic activity against human cancer cells, antibacterial activity against Gram-positive strains, and anti-hepatitis B virus activity. Alisol G can be used in research related to lung cancer, breast cancer, prostate cancer, bacterial infections, and HBV infections.

CES2A-IN-3 (Compound 9d) is a potent serine-targeting covalent human carboxylesterase 2A (hCES2A) inhibitor with an IC₅₀ value of 0.12 nM. CES2A-IN-3 is promising for research of diarrhea and ulcerative colitis.

Carboxylesterase 2-IN-1 is a potent carboxylesterase CES2 inhibitor with an IC₅₀ of 0.13 μM. Carboxylesterase 2-IN-1 blocks the hydrolysis of fluorescein diacetate by CES2 via non-competitive inhibition. Carboxylesterase 2-IN-1 also effectively inhibits adipogenesis induced in mouse preadipocytes.