Pactimibe free base

    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 329597

CAS#: 189198-30-9 (free base)

Description: Pactimibe is a ACAT inhibitor. Pactimibe stabilizes atherosclerotic plaque through macrophage acyl-CoA:cholesterol acyltransferase inhibition in WHHL rabbits. Pactimibe sulfate reduces and stabilizes atherosclerotic lesions by cholesterol-lowering and direct effects in apolipoprotein E-deficient mice.


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Pactimibe free base is not in stock, may be available through custom synthesis. For cost-effective reason, minimum 1 gram order is requested. The product will be characterized by NMR, HPLC and MS analysis. Purity (HPLC) is usually >98%. CoA, QC data, MSDS will be provided when product is successfully made. The estimated lead time is 2-3 months. Please send email to sales@medkoo.com to inquire quote.


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 329597
Name: Pactimibe free base
CAS#: 189198-30-9 (free base)
Chemical Formula: C25H40N2O3
Exact Mass: 416.3039
Molecular Weight: 416.606
Elemental Analysis: C, 72.08; H, 9.68; N, 6.72; O, 11.52


Related CAS #: 608510-47-0 (sulfate)   189198-30-9 (free base)  

Synonym: Pactimibe; CS-505; CS505; CS 505.

IUPAC/Chemical Name: (7-(2,2-Dimethylpropanamido)-4,6-dimethyl-1-octylindolin-5-yl)acetic acid

InChi Key: TXIIZHHIOHVWJD-UHFFFAOYSA-N

InChi Code: InChI=1S/C25H40N2O3/c1-7-8-9-10-11-12-14-27-15-13-19-17(2)20(16-21(28)29)18(3)22(23(19)27)26-24(30)25(4,5)6/h7-16H2,1-6H3,(H,26,30)(H,28,29)

SMILES Code: O=C(O)CC1=C(C)C2=C(N(CCCCCCCC)CC2)C(NC(C(C)(C)C)=O)=C1C


Technical Data

Appearance:
Solid powder

Purity:
>98% (or refer to the Certificate of Analysis)

Shipping Condition:
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition:
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility:
Soluble in DMSO

Shelf Life:
>2 years if stored properly

Drug Formulation:
This drug may be formulated in DMSO

Stock Solution Storage:
0 - 4 C for short term (days to weeks), or -20 C for long term (months).

Harmonized System Code:
293490


References

1: Kotsuma M, Tokui T, Freudenthaler S, Nishimura K. Effect of CYP2D6 polymorphism on pharmacokinetics of a novel ACAT inhibitor, pactimibe and its unique metabolite, R-125528. Int J Clin Pharmacol Ther. 2008 Nov;46(11):545-55. PubMed PMID: 19000552.

2: Kotsuma M, Tokui T, Freudenthaler S, Nishimura K. Effects of ketoconazole and quinidine on pharmacokinetics of pactimibe and its plasma metabolite, R-125528, in humans. Drug Metab Dispos. 2008 Aug;36(8):1505-11. doi: 10.1124/dmd.108.021394. PubMed PMID: 18448569.

3: Kotsuma M, Hanzawa H, Iwata Y, Takahashi K, Tokui T. Novel binding mode of the acidic CYP2D6 substrates pactimibe and its metabolite R-125528. Drug Metab Dispos. 2008 Sep;36(9):1938-43. doi: 10.1124/dmd.108.020776. PubMed PMID: 18524873.

4: Kitayama K, Tanimoto T, Koga T, Terasaka N, Fujioka T, Inaba T. Importance of acyl-coenzyme A:cholesterol acyltransferase 1/2 dual inhibition for anti-atherosclerotic potency of pactimibe. Eur J Pharmacol. 2006 Jul 1;540(1-3):121-30. PubMed PMID: 16730694.

5: Kitayama K, Koga T, Inaba T, Fujioka T. Multiple mechanisms of hypocholesterolemic action of pactimibe, a novel acyl-coenzyme A:cholesterol acyltransferase inhibitor. Eur J Pharmacol. 2006 Aug 14;543(1-3):123-32. PubMed PMID: 16814766.

6: Kotsuma M, Tokui T, Ishizuka-Ozeki T, Honda T, Iwabuchi H, Murai T, Ikeda T, Saji H. CYP2D6-Mediated metabolism of a novel acyl coenzyme A:cholesterol acyltransferase inhibitor, pactimibe, and its unique plasma metabolite, R-125528. Drug Metab Dispos. 2008 Mar;36(3):529-34. PubMed PMID: 18056254.

7: Kitayama K, Koga T, Maeda N, Inaba T, Fujioka T. Pactimibe stabilizes atherosclerotic plaque through macrophage acyl-CoA:cholesterol acyltransferase inhibition in WHHL rabbits. Eur J Pharmacol. 2006 Jun 6;539(1-2):81-8. PubMed PMID: 16690054.

8: Terasaka N, Miyazaki A, Kasanuki N, Ito K, Ubukata N, Koieyama T, Kitayama K, Tanimoto T, Maeda N, Inaba T. ACAT inhibitor pactimibe sulfate (CS-505) reduces and stabilizes atherosclerotic lesions by cholesterol-lowering and direct effects in apolipoprotein E-deficient mice. Atherosclerosis. 2007 Feb;190(2):239-47. PubMed PMID: 16626720.

9: Meuwese MC, de Groot E, Duivenvoorden R, Trip MD, Ose L, Maritz FJ, Basart DC, Kastelein JJ, Habib R, Davidson MH, Zwinderman AH, Schwocho LR, Stein EA; CAPTIVATE Investigators.. ACAT inhibition and progression of carotid atherosclerosis in patients with familial hypercholesterolemia: the CAPTIVATE randomized trial. JAMA. 2009 Mar 18;301(11):1131-9. doi: 10.1001/jama.301.11.1131. PubMed PMID: 19293413.

10: Shoji Y, Takahashi K, Ohta M, Kasai M, Kunishiro K, Kanda M, Yogai S, Takeuchi Y, Shirahase H. Novel indoline-based acyl-CoA: cholesterol acyltransferase inhibitor: Effects of introducing a methanesulfonamide group on physicochemical properties and biological activities. Bioorg Med Chem. 2009 Aug 15;17(16):6020-31. doi: 10.1016/j.bmc.2009.06.047. PubMed PMID: 19608421.

11: Takahashi K, Ohta M, Shoji Y, Kasai M, Kunishiro K, Miike T, Kanda M, Shirahase H. Novel acyl-CoA: cholesterol acyltransferase inhibitor: indoline-based sulfamide derivatives with low lipophilicity and protein binding ratio. Chem Pharm Bull (Tokyo). 2010 Aug;58(8):1057-65. PubMed PMID: 20686260.

12: Nissen SE, Tuzcu EM, Brewer HB, Sipahi I, Nicholls SJ, Ganz P, Schoenhagen P, Waters DD, Pepine CJ, Crowe TD, Davidson MH, Deanfield JE, Wisniewski LM, Hanyok JJ, Kassalow LM; ACAT Intravascular Atherosclerosis Treatment Evaluation (ACTIVATE) Investigators.. Effect of ACAT inhibition on the progression of coronary atherosclerosis. N Engl J Med. 2006 Mar 23;354(12):1253-63. Erratum in: N Engl J Med. 2006 Aug 10;355(6):638. PubMed PMID: 16554527.

13: Nicholls SJ, Sipahi I, Schoenhagen P, Wisniewski L, Churchill T, Crowe T, Goormastic M, Wolski K, Tuzcu EM, Nissen SE; ACTIVATE Investigators.. Intravascular ultrasound assessment of novel antiatherosclerotic therapies: rationale and design of the Acyl-CoA:Cholesterol Acyltransferase Intravascular Atherosclerosis Treatment Evaluation (ACTIVATE) Study. Am Heart J. 2006 Jul;152(1):67-74. PubMed PMID: 16824833.

14: Yoshinaka Y, Shibata H, Kobayashi H, Kuriyama H, Shibuya K, Tanabe S, Watanabe T, Miyazaki A. A selective ACAT-1 inhibitor, K-604, stimulates collagen production in cultured smooth muscle cells and alters plaque phenotype in apolipoprotein E-knockout mice. Atherosclerosis. 2010 Nov;213(1):85-91. doi: 10.1016/j.atherosclerosis.2010.08.048. PubMed PMID: 20843517.

15: Ohta M, Takahashi K, Kasai M, Shoji Y, Kunishiro K, Miike T, Kanda M, Mukai C, Shirahase H. Novel tetrahydroisoquinoline derivatives with inhibitory activities against acyl-CoA: cholesterol acyltransferase and lipid peroxidation. Chem Pharm Bull (Tokyo). 2010 Aug;58(8):1066-76. PubMed PMID: 20686261.

16: Parini P, Eriksson M, Rudel LL. Carotid atherosclerosis progression and ACAT inhibition. JAMA. 2009 Jul 15;302(3):255; author reply 256-7. doi: 10.1001/jama.2009.1000. PubMed PMID: 19602681.

17: Atherosclerosis drug fails to meet Phase III trial end point. Nat Rev Drug Discov. 2009 May;8(5):348. doi: 10.1038/nrd2879. PubMed PMID: 19404306.

18: Wiklund O. [New agents against atherosclerosis tested. Alarming findings, ACAT inhibitors seem to have proatherogenic effects]. Lakartidningen. 2006 Oct 25-31;103(43):3270. Swedish. PubMed PMID: 17117657.

19: Rudel LL, Farese RV Jr. ACAT inhibition and the progression of coronary atherosclerosis. N Engl J Med. 2006 Jun 15;354(24):2616-7; author reply 2616-7. PubMed PMID: 16775245.

20: Fazio S, Linton M. Failure of ACAT inhibition to retard atherosclerosis. N Engl J Med. 2006 Mar 23;354(12):1307-9. PubMed PMID: 16554534.