Synonym
TCV-116; TCV 116; TCV116; Candesartan cilexetil
IUPAC/Chemical Name
1-(((cyclohexyloxy)carbonyl)oxy)ethyl 1-((2'-(1H-tetrazol-5-yl)-[1,1'-biphenyl]-4-yl)methyl)-2-ethoxy-1H-benzo[d]imidazole-7-carboxylate
InChi Key
GHOSNRCGJFBJIB-UHFFFAOYSA-N
InChi Code
InChI=1S/C33H34N6O6/c1-3-42-32-34-28-15-9-14-27(31(40)43-21(2)44-33(41)45-24-10-5-4-6-11-24)29(28)39(32)20-22-16-18-23(19-17-22)25-12-7-8-13-26(25)30-35-37-38-36-30/h7-9,12-19,21,24H,3-6,10-11,20H2,1-2H3,(H,35,36,37,38)
SMILES Code
O=C(OC(C)OC(C1=CC=CC2=C1N(CC3=CC=C(C4=C(C5=NN=NN5)C=CC=C4)C=C3)C(OCC)=N2)=O)OC6CCCCC6
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, not in water
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).
HS Tariff Code
2934.99.9001
Biological target:
Candesartan Cilexetil (TCV-116) is an angiotensin II receptor antagonist with IC50 of 0.26 nM, used in the treatment of hypertension.
In vitro activity:
The objective of this study was to determine whether AT1 receptor inhibition would reduce the innate inflammatory response induced
by bacterial lipopolysaccharide (LPS). Monocytes were studied in vitro after incubation with LPS (50 ng/ml) with and without 1
mumol/l candesartan, an AT1 receptor blocker. Human monocytes did not express detectable AT1 receptors, and angiotensin II did
not induce inflammatory factor mRNA expression or cytokine release. However, candesartan substantially reduced the LPS-induced
expression of the mRNAs for the LPS recognition protein cluster of differentiation 14, the proinflammatory cytokines tumor necrosis
factor alpha, interleukin-1 beta and interleukin-6 and the lectin-like oxidized low-density lipoprotein receptor. In addition, candesartan
reduced the activation of the nuclear factor kappa B pathway, the tumor necrosis factor alpha and interleukin-6 secretion, and the ROS
formation induced by LPS, without affecting the secretion of interleukin-10. It is hypothesized that the anti-inflammatory effects of
candesartan in these cells are likely mediated by mechanisms unrelated to AT1 receptor blockade. The results demonstrate that
candesartan significantly reduces the innate immune response to LPS in human circulating monocytes. The anti-inflammatory effects
of candesartan may be of importance not only in hypertension but also in other inflammatory disorders.
Reference: J Hypertens. 2009 Dec;27(12):2365-76. https://pubmed.ncbi.nlm.nih.gov/19730394/
In vivo activity:
To better understand the mechanisms underlying the protective effects of candesartan on the intestinal integrity, fecal SCFAs (shortchain fatty acids) were further quantified. As shown in Fig. 7A, at 12 weeks of age, the amount of acetic acid in the vehicle-treated SHRs was decreased to about 60% of that from the vehicle-treated WKY rats while other SCFA species remained unchanged. No significant changes in the amount of fecal acetic acid were observed in 12-week old candesartan-treated SHRs compared to that from the age-matched vehicle-treated SHRs. By 20 weeks of age, the amount of fecal acetic acid, propionic acid and butyric acid was found to be decreased in the vehicle-treated SHRs compared to that from the age-matched vehicle-treated WKY rats. In distinct contrast, the amount of fecal acetic acid, propionic acid and butyric acid was significantly increased in the candesartan-treated SHRs compared to that from the vehicle-treated SHRs. Meanwhile, although no changes in the amount of fecal isobutyric acid, valeric acid, and isovaleric acid were observed in the vehicle-treated SHRs, candesartan treatment increased the amount of these SCFA species (Fig.7B). These results indicate that prolonged treatment of candesartan results in increased microbial production of SCFAs in SHRs.
Reference: Biomed Pharmacother. 2019 Aug;116:109040. https://pubmed.ncbi.nlm.nih.gov/31170664/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
50.0 |
81.88 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
610.67
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
In vitro protocol:
1. Torika N, Asraf K, Apte RN, Fleisher-Berkovich S. Candesartan ameliorates brain inflammation associated with Alzheimer's
disease. CNS Neurosci Ther. 2018 Mar;24(3):231-242. doi: 10.1111/cns.12802. Epub 2018 Jan 24. PMID: 29365370; PMCID:
PMC6489976.
2. Larrayoz IM, Pang T, Benicky J, Pavel J, Sánchez-Lemus E, Saavedra JM. Candesartan reduces the innate immune response to
lipopolysaccharide in human monocytes. J Hypertens. 2009 Dec;27(12):2365-76. doi: 10.1097/HJH.0b013e3283314bc7. PMID:
19730394; PMCID: PMC2928995.
In vivo protocol:
1. Torika N, Asraf K, Apte RN, Fleisher-Berkovich S. Candesartan ameliorates brain inflammation associated with Alzheimer's
disease. CNS Neurosci Ther. 2018 Mar;24(3):231-242. doi: 10.1111/cns.12802. Epub 2018 Jan 24. PMID: 29365370; PMCID:
PMC6489976.
2. Wu D, Tang X, Ding L, Cui J, Wang P, Du X, Yin J, Wang W, Chen Y, Zhang T. Candesartan attenuates hypertension-associated
pathophysiological alterations in the gut. Biomed Pharmacother. 2019 Aug;116:109040. doi: 10.1016/j.biopha.2019.109040. Epub
2019 Jun 3. PMID: 31170664.
1: Yasuno S, Fujimoto A, Nakagawa Y, Kuwahara K, Ueshima K. Fixed-dose combination therapy of candesartan cilexetil and amlodipine besilate for the treatment of hypertension in Japan. Expert Rev Cardiovasc Ther. 2012 May;10(5):577-83. doi: 10.1586/erc.12.34. Review. PubMed PMID: 22651833.
2: Ardiana F, Lestari ML, Indrayanto G. Candesartan cilexetil. Profiles Drug Subst Excip Relat Methodol. 2012;37:79-112. doi: 10.1016/B978-0-12-397220-0.00003-9. Epub 2012 Mar 19. Review. PubMed PMID: 22469317.
3: Joost A, Schunkert H, Radke PW. Candesartan cilexetil: an update. Expert Opin Pharmacother. 2011 Aug;12(11):1769-80. doi: 10.1517/14656566.2011.587000. Epub 2011 Jun 9. Review. PubMed PMID: 21651457.
4: Hoy SM, Keating GM. Candesartan cilexetil: in children and adolescents aged 1 to <17 years with hypertension. Am J Cardiovasc Drugs. 2010;10(5):335-42. doi: 10.2165/11206300-000000000-00000. Review. PubMed PMID: 20860416.
5: Mengden T, Uen S, Bramlage P. Management of hypertension with fixed dose combinations of candesartan cilexetil and hydrochlorothiazide: patient perspectives and clinical utility. Vasc Health Risk Manag. 2009;5:1043-58. Epub 2009 Dec 29. Review. PubMed PMID: 20057897; PubMed Central PMCID: PMC2801628.
6: Kusumoto K, Mori M, Tanokashira J, Totsuka N. [Pharmacological and clinical properties of ECARD combination tablets LD & HD, fixed-dose combination of candesartan cilexetil and hydrochlorothiazide]. Nihon Yakurigaku Zasshi. 2009 Oct;134(4):217-24. Review. Japanese. PubMed PMID: 19828927.
7: Baguet JP, Barone-Rochette G, Neuder Y. Candesartan cilexetil in the treatment of chronic heart failure. Vasc Health Risk Manag. 2009;5(1):257-64. Epub 2009 Apr 8. Review. PubMed PMID: 19436650; PubMed Central PMCID: PMC2672439.
8: Meredith PA. Candesartan cilexetil--a review of effects on cardiovascular complications in hypertension and chronic heart failure. Curr Med Res Opin. 2007 Jul;23(7):1693-705. Review. PubMed PMID: 17588300.
9: Féghali RE, Nisse-Durgeat S, Asmar R. Effect of candesartan cilexetil on diabetic and non-diabetic hypertensive patients: meta-analysis of five randomized double-blind clinical trials. Vasc Health Risk Manag. 2007;3(1):165-71. Review. PubMed PMID: 17583187; PubMed Central PMCID: PMC1994048.
10: Plosker GL, Keam SJ. Candesartan cilexetil: a pharmacoeconomic review of its use in chronic heart failure and hypertension. Pharmacoeconomics. 2006;24(12):1249-72. Review. PubMed PMID: 17129078.
11: Bönner G, Fuchs W. Long-acting blood pressure reduction by candesartan cilexetil in patients with hypertension. Curr Med Res Opin. 2005 Jun;21(6):935-40. Review. PubMed PMID: 15969893.
12: Fenton C, Scott LJ. Candesartan cilexetil: a review of its use in the management of chronic heart failure. Drugs. 2005;65(4):537-58. Review. PubMed PMID: 15733014.
13: Ross A, Papademetriou V. Candesartan cilexetil in cardiovascular disease. Expert Rev Cardiovasc Ther. 2004 Nov;2(6):829-35. Review. Erratum in: Expert Rev Cardiovasc Ther. 2005 May;3(3):543-4. PubMed PMID: 15500428.
14: Andersen NH, Knudsen ST, Poulsen PL, Poulsen SH, Helleberg K, Eiskjaer H, Hansen KW, Bek T, Mogensen CE. Dual blockade with candesartan cilexetil and lisinopril in hypertensive patients with diabetes mellitus: rationale and design. J Renin Angiotensin Aldosterone Syst. 2003 Jun;4(2):96-9. Review. PubMed PMID: 12806591.
15: Easthope SE, Jarvis B. Candesartan cilexetil: an update of its use in essential hypertension. Drugs. 2002;62(8):1253-87. Review. PubMed PMID: 12010090.
16: Melian EB, Jarvis B. Candesartan cilexetil plus hydrochlorothiazide combination: a review of its use in hypertension. Drugs. 2002;62(5):787-816. Review. PubMed PMID: 11929332.
17: Naka T, Kubo K, Nishikawa K, Inada Y, Furukawa Y. [Angiotensin II receptor antagonists: candesartan cilexetil]. Yakugaku Zasshi. 2000 Dec;120(12):1261-75. Review. Japanese. PubMed PMID: 11193378.
18: Mallion JM, Badguet JP. Putting the efficacy of candesartan cilexetil into perspective: a review of new comparative data. J Hum Hypertens. 2000 Oct;14 Suppl 2:S33-41. Review. PubMed PMID: 11086634.
19: Mancia G, Grassi G. The role of angiotensin II receptor antagonists in hypertension management: focus on candesartan cilexetil. J Hum Hypertens. 2000 Oct;14 Suppl 2:S3-10. Review. PubMed PMID: 11086630.
20: Zannad F. Preserving target-organ function with candesartan cilexetil in patients with hypertension. Blood Press Suppl. 2000;1:36-9. Review. PubMed PMID: 11059635.
