ACAT1 Inhibitor

Avasimibe (CI-1011; PD-148515) is an orally active acyl coenzyme A-cholesterol acyltransferase (ACAT; also called SOAT)) inhibitor with IC₅₀s of 24 and 9.2 µM for ACAT1 and ACAT2, respectively. Avasimibe can be used for the research of prostate cancer.

K-604 dihydrochloride is a potent and selective acyl-CoA:cholesterol acyltransferase 1 (ACAT-1) inhibitor with an IC₅₀ of 0.45±0.06 μM.

Nevanimibe hydrochloride (PD-132301 hydrochloride) is an orally active and selective acyl-coenzyme A:cholesterol O-acyltransferase 1 (ACAT1) inhibitor with an EC₅₀ of 9 nM. Nevanimibe hydrochloride inhibits ACAT2 with an EC₅₀ of 368 nM. Nevanimibe hydrochloride induces cell apoptosis and has the potential for adrenocortical cancer.

Pactimibe (CS-505 free base) is a dual ACAT1/2 inhibitor with IC₅₀s of 4.9 μM and 3.0 μM, respectively. Pactimibe (CS-505 free base) inhibits ACAT with IC₅₀s of 2.0 μM, 2.7 μM, 4.7 μM in the liver, macrophages and THP-1 cells, respectively. Pactimibe (CS-505 free base) noncompetitively inhibits oleoyl-CoA with a K_i value of 5.6 μM. Moreover, Pactimibe (CS-505 free base) obviously inhibits cholesteryl ester formation with an IC₅₀ of 6.7 μM. Pactimibe (CS-505 free base) possesses anti-atherosclerotic potential with lowering plasma cholesterol activity.

Nevanimibe (PD-132301) is an orally active and selective acyl-coenzyme A:cholesterol O-acyltransferase 1 (ACAT1) inhibitor with an EC₅₀ of 9 nM. Nevanimibe inhibits ACAT2 with an EC₅₀ of 368 nM. Nevanimibe induces cell apoptosis and has the potential for adrenocortical cancer.

Esculeogenin A is the sapogenol of tomato saponin Esculeoside A (HY-N18067). Esculeogenin A is an orally active hepatoprotective, hypolipidemic, and antioxidant agent. Esculeogenin A regulates molecular targets like PPARα, SREBP1, Nrf2, NF-κB, ACAT1/ACAT2 to promote hepatic fatty acid oxidation, suppress de novo lipogenesis, enhance antioxidant defense, and inhibit inflammation. Esculeogenin A improves liver function, alleviates hyperlipidemia, and inhibits hepatic steatosis and foam cell formation, preventing nonalcoholic fatty liver disease in high-fat-diet-fed rats and reducing atherosclerotic lesions in apoE-deficient mice. Esculeogenin A can be used for the research of nonalcoholic fatty liver disease, atherosclerosis, and hyperlipidemia.

Pactimibe sulfate (CS-505) is a dual ACAT1/2 inhibitor with IC₅₀s of 4.9 μM and 3.0 μM, respectively. Pactimibe sulfate (CS-505) inhibits ACAT with IC₅₀s of 2.0 μM, 2.7 μM, 4.7 μM in the liver, macrophages and THP-1 cells, respectively. Pactimibe sulfate (CS-505) noncompetitively inhibits oleoyl-CoA with a K_i value of 5.6 μM. Moreover, Pactimibe sulfate (CS-505) obviously inhibits cholesteryl ester formation with an IC₅₀ of 6.7 μM. Pactimibe sulfate (CS-505) possesses anti-atherosclerotic potential with lowering plasma cholesterol activity.