Avasimibe information

Avasimibe
Clinical data
Other names	2,6-diisopropylphenyl (2-(2,4,6-triisopropylphenyl)acetyl)sulfamate
Routes of; administration	Oral
ATC code	C10AX (WHO) ;
Legal status
Legal status	Investigational;
Pharmacokinetic data
Metabolism	Hepatic (CYP3A4, 2C9)
Elimination half-life	15–24 hours
Excretion	Fecal (predominant), renal (<2%)
Identifiers
	IUPAC name [2,6-di(propan-2-yl)phenyl] N-[2-[2,4,6-tri(propan-2-yl)phenyl]acetyl]sulfamate;
CAS Number	166518-60-1;
PubChem CID	166558;
DrugBank	06442;
ChemSpider	145759;
UNII	28LQ20T5RC;
KEGG	D03012;
ChEBI	CHEBI:177719;
ChEMBL	ChEMBL101309;
Chemical and physical data
Formula	C29H43NO4S
Molar mass	501.73 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC(C)C1=C(C(=CC=C1)C(C)C)OS(=O)(=O)NC(=O)CC2=C(C=C(C=C2C(C)C)C(C)C)C(C)C;
	InChI InChI=1S/C29H43NO4S/c1-17(2)22-14-25(20(7)8)27(26(15-22)21(9)10)16-28(31)30-35(32,33)34-29-23(18(3)4)12-11-13-24(29)19(5)6/h11-15,17-21H,16H2,1-10H3,(H,30,31); Key:PTQXTEKSNBVPQJ-UHFFFAOYSA-N;

Avasimibe (INN), codenamed CI 1011, is a drug that inhibits sterol O-acyltransferases (SOAT1 and SOAT2, also known as ACAT1 and ACAT2), enzymes involved in the metabolism and catabolism of cholesterol. It was discovered by Parke-Davis (later Pfizer) and developed as a possible lipid-lowering agent and treatment for atherosclerosis.^[1]

The first description of avasimibe was published in 1996.^[2] Clinical trials began in 1997.^[1] However, development was halted in 2003 due to a high potential for interactions with other medicines,^[3] and a pivotal study found it had no favorable effect on atherosclerosis and actually increased LDL cholesterol levels significantly.^[4]

SOAT/ACAT inhibition has since been discredited as a viable strategy for treating high cholesterol and atherosclerosis,^[5] but renewed interest in avasimibe has arisen due to its potential antitumor utility through other mechanisms.

It has never been marketed or used outside clinical trials.^[6]

^ ^a ^b [No authors listed] (2002). "Avasimibe. CI 1011". Drugs in R&D. 3 (3): 173–4. doi:10.2165/00126839-200203030-00005. PMID 12099161.
^ Lee HT, Sliskovic DR, Picard JA, Roth BD, Wierenga W, Hicks JL, Bousley RF, Hamelehle KL, Homan R, Speyer C, Stanfield RL, Krause BR (December 1996). "Inhibitors of acyl-CoA: cholesterol O-acyl transferase (ACAT) as hypocholesterolemic agents. CI-1011: an acyl sulfamate with unique cholesterol-lowering activity in animals fed noncholesterol-supplemented diets". J Med Chem. 39 (26): 5031–4. doi:10.1021/jm960674d. PMID 8978833.
^ "Avasimibe (Code C75252)". NCI Thesaurus. Retrieved 2022-05-09. This article incorporates text from this source, which is in the public domain.
^ Tardif JC, Grégoire J, L'Allier PL, Anderson TJ, Bertrand O, Reeves F, Title LM, Alfonso F, Schampaert E, Hassan A, McLain R, Pressler ML, Ibrahim R, Lespérance J, Blue J, Heinonen T, Rodés-Cabau J (November 2004). "Effects of the acyl coenzyme A:cholesterol acyltransferase inhibitor avasimibe on human atherosclerotic lesions". Circulation. 110 (21): 3372–7. doi:10.1161/01.CIR.0000147777.12010.EF. PMID 15533865. S2CID 9821021.
^ Cite error: The named reference Rau was invoked but never defined (see the help page).
^ "Drug Profile: Avasimibe" (PDF). AdisInsight. 2003-10-28. Retrieved 2022-05-09.

[DRD-1] [No authors listed] (2002). "Avasimibe. CI 1011". Drugs in R&D. 3 (3): 173–4. doi:10.2165/00126839-200203030-00005. PMID 12099161.

[Lee-2] Lee HT, Sliskovic DR, Picard JA, Roth BD, Wierenga W, Hicks JL, Bousley RF, Hamelehle KL, Homan R, Speyer C, Stanfield RL, Krause BR (December 1996). "Inhibitors of acyl-CoA: cholesterol O-acyl transferase (ACAT) as hypocholesterolemic agents. CI-1011: an acyl sulfamate with unique cholesterol-lowering activity in animals fed noncholesterol-supplemented diets". J Med Chem. 39 (26): 5031–4. doi:10.1021/jm960674d. PMID 8978833.

[C75252-3] "Avasimibe (Code C75252)". NCI Thesaurus. Retrieved 2022-05-09. This article incorporates text from this source, which is in the public domain.

[4] Tardif JC, Grégoire J, L'Allier PL, Anderson TJ, Bertrand O, Reeves F, Title LM, Alfonso F, Schampaert E, Hassan A, McLain R, Pressler ML, Ibrahim R, Lespérance J, Blue J, Heinonen T, Rodés-Cabau J (November 2004). "Effects of the acyl coenzyme A:cholesterol acyltransferase inhibitor avasimibe on human atherosclerotic lesions". Circulation. 110 (21): 3372–7. doi:10.1161/01.CIR.0000147777.12010.EF. PMID 15533865. S2CID 9821021.

[Rau-5] Cite error: The named reference Rau was invoked but never defined (see the help page).

[AdisInsight-6] "Drug Profile: Avasimibe" (PDF). AdisInsight. 2003-10-28. Retrieved 2022-05-09.

Clinical data

Other names	2,6-diisopropylphenyl (2-(2,4,6-triisopropylphenyl)acetyl)sulfamate
Routes of administration	Oral
ATC code	C10AX (WHO)
Legal status
Legal status	Investigational
Pharmacokinetic data
Metabolism	Hepatic (CYP3A4, 2C9)
Elimination half-life	15–24 hours
Excretion	Fecal (predominant), renal (<2%)
Identifiers
IUPAC name [2,6-di(propan-2-yl)phenyl] N-[2-[2,4,6-tri(propan-2-yl)phenyl]acetyl]sulfamate
CAS Number	166518-60-1
PubChem CID	166558
DrugBank	06442
ChemSpider	145759
UNII	28LQ20T5RC
KEGG	D03012
ChEBI	CHEBI:177719
ChEMBL	ChEMBL101309
Chemical and physical data
Formula	C₂₉H₄₃NO₄S
Molar mass	501.73 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES CC(C)C1=C(C(=CC=C1)C(C)C)OS(=O)(=O)NC(=O)CC2=C(C=C(C=C2C(C)C)C(C)C)C(C)C
InChI InChI=1S/C29H43NO4S/c1-17(2)22-14-25(20(7)8)27(26(15-22)21(9)10)16-28(31)30-35(32,33)34-29-23(18(3)4)12-11-13-24(29)19(5)6/h11-15,17-21H,16H2,1-10H3,(H,30,31) Key:PTQXTEKSNBVPQJ-UHFFFAOYSA-N