T-0901317
featured

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

MedKoo CAT#: 558247

CAS#: 293754-55-9

Description: T-0901317, also known as T-1317; TO-091317; TO 901317, is a liver X receptor (LXR) agonist. T-0901317 inhibits development of atherosclerosis in LDL receptor-deficient mice. T-0901317 significantly reduced the atherosclerotic lesions in LDLR(-/-) mice without affecting plasma total cholesterol levels. T-0901317 increased expression of ATP binding cassette A1 in the lesions in LDLR(-/-) mice as well as in mouse peritoneal macrophages. T-0901317 also significantly induced cholesterol efflux activity in peritoneal macrophages. T-0901317 may be useful therapeutic agents for the treatment of atherosclerosis.


Chemical Structure

img
T-0901317
CAS# 293754-55-9

Theoretical Analysis

MedKoo Cat#: 558247
Name: T-0901317
CAS#: 293754-55-9
Chemical Formula: C17H12F9NO3S
Exact Mass: 481.0394
Molecular Weight: 481.3326
Elemental Analysis: C, 42.42; H, 2.51; F, 35.52; N, 2.91; O, 9.97; S, 6.66

Price and Availability

Size Price Availability Quantity
10.0mg USD 90.0 Ready to ship
25.0mg USD 150.0 Ready to ship
50.0mg USD 250.0 Ready to ship
100.0mg USD 450.0 Ready to ship
200.0mg USD 750.0 Ready to ship
500.0mg USD 1650.0 Ready to ship
1.0g USD 2950.0 Ready to ship
Bulk inquiry

Synonym: T-0901317; T0901317; T 0901317; T-1317; T1317; T 1317; TO-91317; TO 901317; TO 901317; TO-091317; TO 091317; TO091317;

IUPAC/Chemical Name: N-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl)-N-(2,2,2-trifluoroethyl)benzenesulfonamide

InChi Key: SGIWFELWJPNFDH-UHFFFAOYSA-N

InChi Code: InChI=1S/C17H12F9NO3S/c18-14(19,20)10-27(31(29,30)13-4-2-1-3-5-13)12-8-6-11(7-9-12)15(28,16(21,22)23)17(24,25)26/h1-9,28H,10H2

SMILES Code: OC(C(F)(F)F)(C(F)(F)F)C1=CC=C(N(CC(F)(F)F)S(C2=CC=CC=C2)(=O)=O)C=C1

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).

HS Tariff Code: 2934.99.9001

Biological target: T0901317 is an agonist for both LXR and FXR with EC50 of 50 nM and 5 μM, respectively.
In vitro activity: T0901317 strongly and reversibly depolarized ΔΨ. Accordingly, T0901317 decreased the cytosolic ATP concentration. Wash-out of T0901317 led to a drop in [Ca2+]c, which is due to ATP-dependent sarco/endoplasmic reticulum Ca2+-ATPase activation. In patch-clamp experiments, opening of KATP channels by T0901317 is only found in the cell-attached but not in the excised-patch configuration. These data exclude a direct effect of the drug on KATP channels but rather point to an indirect metabolism-mediated effect. In conclusion, the T0901317-induced depolarization of ΔΨ leads to opening of KATP channels due to ATP depletion, which in turn reduces Ca2+ influx and insulin secretion. Reference: Endocrinology. 2017 Jul 1;158(7):2145-2154. https://academic.oup.com/endo/article/158/7/2145/3754363
In vivo activity: To examine the role of T0901317 on ABCA1 expression in vivo, 11-week-old APP23 mice were treated orally by gastric gavage for 6 days with 50 mg/kg/day T0901317. Control mice received vehicle only. The treatment of APP23 mice resulted in a substantial increase in the expression of ABCA1 (more than 3-fold, p < 0.001), whereas the expression of APP was unchanged (Fig. 6, A and B). The effect of T0901317 on Aβ production was also examined. Because at this age Aβ in the brain of APP23 mice is soluble in SDS, Aβ was extracted from the initial brain homogenate by SDS containing RIPA buffer or diethylamine, and the results from the two determinations compared. Fig. 7, A and B show the levels of RIPA-extracted Aβ40 and Aβ42 in APP23 mice were significantly decreased. Similar results were obtained by ELISA determinations of diethylamine-extracted soluble Aβ40 and Aβ42 (not shown), thus confirming that amyloidogenic processing of human APP in APP23 mice was decreased after T0901317 treatment. Because the ratio of secreted sAPPα over sAPPβ was increased in the brain of T0901317-treated mice and Aβ1–40 and Aβ1–42 was decreased, the results suggest that the synthetic LXR ligand increases the non-amyloidogenic processing of APP. Reference: J Biol Chem. 2005 Feb 11;280(6):4079-88. https://www.jbc.org/article/S0021-9258(20)76044-8/fulltext

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 81.38 169.07
Ethanol 72.07 149.73

Preparing Stock Solutions

The following data is based on the product molecular weight 481.3326 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.

Recalculate based on batch purity %
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
Formulation protocol: 1. Maczewsky J, Sikimic J, Bauer C, Krippeit-Drews P, Wolke C, Lendeckel U, Barthlen W, Drews G. The LXR Ligand T0901317 Acutely Inhibits Insulin Secretion by Affecting Mitochondrial Metabolism. Endocrinology. 2017 Jul 1;158(7):2145-2154. doi: 10.1210/en.2016-1941. PMID: 28449117. 2. Koldamova RP, Lefterov IM, Staufenbiel M, Wolfe D, Huang S, Glorioso JC, Walter M, Roth MG, Lazo JS. The liver X receptor ligand T0901317 decreases amyloid beta production in vitro and in a mouse model of Alzheimer's disease. J Biol Chem. 2005 Feb 11;280(6):4079-88. doi: 10.1074/jbc.M411420200. Epub 2004 Nov 22. PMID: 15557325.
In vitro protocol: 1. Maczewsky J, Sikimic J, Bauer C, Krippeit-Drews P, Wolke C, Lendeckel U, Barthlen W, Drews G. The LXR Ligand T0901317 Acutely Inhibits Insulin Secretion by Affecting Mitochondrial Metabolism. Endocrinology. 2017 Jul 1;158(7):2145-2154. doi: 10.1210/en.2016-1941. PMID: 28449117. 2. Koldamova RP, Lefterov IM, Staufenbiel M, Wolfe D, Huang S, Glorioso JC, Walter M, Roth MG, Lazo JS. The liver X receptor ligand T0901317 decreases amyloid beta production in vitro and in a mouse model of Alzheimer's disease. J Biol Chem. 2005 Feb 11;280(6):4079-88. doi: 10.1074/jbc.M411420200. Epub 2004 Nov 22. PMID: 15557325.
In vivo protocol: 1. Maczewsky J, Sikimic J, Bauer C, Krippeit-Drews P, Wolke C, Lendeckel U, Barthlen W, Drews G. The LXR Ligand T0901317 Acutely Inhibits Insulin Secretion by Affecting Mitochondrial Metabolism. Endocrinology. 2017 Jul 1;158(7):2145-2154. doi: 10.1210/en.2016-1941. PMID: 28449117. 2. Koldamova RP, Lefterov IM, Staufenbiel M, Wolfe D, Huang S, Glorioso JC, Walter M, Roth MG, Lazo JS. The liver X receptor ligand T0901317 decreases amyloid beta production in vitro and in a mouse model of Alzheimer's disease. J Biol Chem. 2005 Feb 11;280(6):4079-88. doi: 10.1074/jbc.M411420200. Epub 2004 Nov 22. PMID: 15557325.

Molarity Calculator

Calculate the mass, volume, or concentration required for a solution.
=
x
x
g/mol

*When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and SDS / CoA (available online).

Reconstitution Calculator

The reconstitution calculator allows you to quickly calculate the volume of a reagent to reconstitute your vial. Simply enter the mass of reagent and the target concentration and the calculator will determine the rest.

=
÷

Dilution Calculator

Calculate the dilution required to prepare a stock solution.
x
=
x

1: Xu H, Ma X, Song D, Xue D, He X, Zhang X. Comparison of Tolerogenic Dendritic Cells Induced by Liver X Receptor Agonist from Bone Marrow-derived Cells and Natural Tolerogenic Dendritic Cells. Clin Lab. 2016;62(3):249-61. PubMed PMID: 27156312.

2: Lu X, Wang F, Xu C, Soodvilai S, Peng K, Su J, Zhao L, Yang KT, Feng Y, Zhou SF, Gustafsson JÅ, Yang T. Soluble (pro)renin receptor via β-catenin enhances urine concentration capability as a target of liver X receptor. Proc Natl Acad Sci U S A. 2016 Mar 29;113(13):E1898-906. doi: 10.1073/pnas.1602397113. Epub 2016 Mar 16. PubMed PMID: 26984496; PubMed Central PMCID: PMC4822598.

3: Banerjee M, Chai SC, Wu J, Robbins D, Chen T. Tryptophan 299 is a conserved residue of human pregnane X receptor critical for the functional consequence of ligand binding. Biochem Pharmacol. 2016 Mar 15;104:131-8. doi: 10.1016/j.bcp.2016.02.009. Epub 2016 Feb 18. PubMed PMID: 26902414; PubMed Central PMCID: PMC4778391.

4: Furumoto H, Nanthirudjanar T, Hirata T, Sugawara T. Dietary Effects of Oxidized Eicosapentaenoic Acid (EPA) and Intact EPA on Hepatic Steatosis Induced by a High-sucrose Diet and Liver-X-receptor α Agonist in Mice. J Oleo Sci. 2016;65(3):233-40. doi: 10.5650/jos.ess15227. Epub 2016 Feb 15. PubMed PMID: 26876675.

5: Briand O, Touche V, Colin S, Brufau G, Davalos A, Schonewille M, Bovenga F, Carrière V, de Boer JF, Dugardin C, Riveau B, Clavey V, Tailleux A, Moschetta A, Lasunción MA, Groen AK, Staels B, Lestavel S. Liver X Receptor Regulates Triglyceride Absorption Through Intestinal Down-regulation of Scavenger Receptor Class B, Type 1. Gastroenterology. 2016 Mar;150(3):650-8. doi: 10.1053/j.gastro.2015.11.015. Epub 2015 Nov 18. PubMed PMID: 26602218.

6: Tamehiro N, Park MH, Hawxhurst V, Nagpal K, Adams ME, Zannis VI, Golenbock DT, Fitzgerald ML. LXR Agonism Upregulates the Macrophage ABCA1/Syntrophin Protein Complex That Can Bind ApoA-I and Stabilized ABCA1 Protein, but Complex Loss Does Not Inhibit Lipid Efflux. Biochemistry. 2015 Nov 24;54(46):6931-41. doi: 10.1021/acs.biochem.5b00894. Epub 2015 Nov 9. PubMed PMID: 26506427; PubMed Central PMCID: PMC4874254.

7: Courtaut F, Derangère V, Chevriaux A, Ladoire S, Cotte AK, Arnould L, Boidot R, Rialland M, Ghiringhelli F, Rébé C. Liver X receptor ligand cytotoxicity in colon cancer cells and not in normal colon epithelial cells depends on LXRβ subcellular localization. Oncotarget. 2015 Sep 29;6(29):26651-62. doi: 10.18632/oncotarget.5791. PubMed PMID: 26450852; PubMed Central PMCID: PMC4694942.

8: Pinto CL, Kalasekar SM, McCollum CW, Riu A, Jonsson P, Lopez J, Swindell EC, Bouhlatouf A, Balaguer P, Bondesson M, Gustafsson JÅ. Lxr regulates lipid metabolic and visual perception pathways during zebrafish development. Mol Cell Endocrinol. 2016 Jan 5;419:29-43. doi: 10.1016/j.mce.2015.09.030. PubMed PMID: 26427652; PubMed Central PMCID: PMC4684448.

9: Nanthirudjanar T, Furumoto H, Zheng J, Kim YI, Goto T, Takahashi N, Kawada T, Park SB, Hirata A, Kitamura N, Kishino S, Ogawa J, Hirata T, Sugawara T. Gut Microbial Fatty Acid Metabolites Reduce Triacylglycerol Levels in Hepatocytes. Lipids. 2015 Nov;50(11):1093-102. doi: 10.1007/s11745-015-4067-z. Epub 2015 Sep 23. PubMed PMID: 26399511.

10: Matsuo K, Yamamoto S, Wakamatsu T, Takahashi Y, Kawamura K, Kaneko Y, Goto S, Kazama JJ, Narita I. Increased Proinflammatory Cytokine Production and Decreased Cholesterol Efflux Due to Downregulation of ABCG1 in Macrophages Exposed to Indoxyl Sulfate. Toxins (Basel). 2015 Aug 14;7(8):3155-66. doi: 10.3390/toxins7083155. PubMed PMID: 26287243; PubMed Central PMCID: PMC4549743.

11: Lee J, Hong SW, Park SE, Rhee EJ, Park CY, Oh KW, Park SW, Lee WY. AMP-activated protein kinase suppresses the expression of LXR/SREBP-1 signaling-induced ANGPTL8 in HepG2 cells. Mol Cell Endocrinol. 2015 Oct 15;414:148-55. doi: 10.1016/j.mce.2015.07.031. Epub 2015 Aug 4. PubMed PMID: 26254015.

12: He K, Dai ZY, Li PZ, Zhu XW, Gong JP. Association between liver X receptor-α and neuron-derived orphan nuclear receptor-1 in Kupffer cells of C57BL/6 mice during inflammation. Mol Med Rep. 2015 Oct;12(4):6098-104. doi: 10.3892/mmr.2015.4155. Epub 2015 Jul 30. PubMed PMID: 26239564.

13: Jin X, Freeman SR, Vaisman B, Liu Y, Chang J, Varsano N, Addadi L, Remaley A, Kruth HS. ABCA1 contributes to macrophage deposition of extracellular cholesterol. J Lipid Res. 2015 Sep;56(9):1720-6. doi: 10.1194/jlr.M060053. Epub 2015 Jul 22. PubMed PMID: 26203076; PubMed Central PMCID: PMC4548776.

14: Ramezani A, Dubrovsky L, Pushkarsky T, Sviridov D, Karandish S, Raj DS, Fitzgerald ML, Bukrinsky M. Stimulation of Liver X Receptor Has Potent Anti-HIV Effects in a Humanized Mouse Model of HIV Infection. J Pharmacol Exp Ther. 2015 Sep;354(3):376-83. doi: 10.1124/jpet.115.224485. Epub 2015 Jun 30. PubMed PMID: 26126533; PubMed Central PMCID: PMC4538872.

15: Yang M, Wang R, Sun J, Yu K, Chen B, Xu L, Zhao B, Wang H. The liver X receptor agonist TO901317 protects mice against cisplatin-induced kidney injury. Exp Biol Med (Maywood). 2015 Dec;240(12):1717-27. doi: 10.1177/1535370215589906. Epub 2015 Jun 9. PubMed PMID: 26062799.

16: Meffre D, Shackleford G, Hichor M, Gorgievski V, Tzavara ET, Trousson A, Ghoumari AM, Deboux C, Nait Oumesmar B, Liere P, Schumacher M, Baulieu EE, Charbonnier F, Grenier J, Massaad C. Liver X receptors alpha and beta promote myelination and remyelination in the cerebellum. Proc Natl Acad Sci U S A. 2015 Jun 16;112(24):7587-92. doi: 10.1073/pnas.1424951112. Epub 2015 May 28. PubMed PMID: 26023184; PubMed Central PMCID: PMC4475952.

17: Koura M, Matsuda T, Okuda A, Watanabe Y, Yamaguchi Y, Kurobuchi S, Matsumoto Y, Shibuya K. Design, synthesis and pharmacology of 1,1-bistrifluoromethylcarbinol derivatives as liver X receptor β-selective agonists. Bioorg Med Chem Lett. 2015 Jul 1;25(13):2668-74. doi: 10.1016/j.bmcl.2015.04.080. Epub 2015 May 5. PubMed PMID: 25998501.

18: Botez G, Piraino G, Hake PW, Ledford JR, O'Connor M, Cook JA, Zingarelli B. Age-dependent therapeutic effects of liver X receptor-α activation in murine polymicrobial sepsis. Innate Immun. 2015 Aug;21(6):609-18. doi: 10.1177/1753425915569367. Epub 2015 May 8. PubMed PMID: 25956304; PubMed Central PMCID: PMC4509881.

19: Lim RK, Yu S, Cheng B, Li S, Kim NJ, Cao Y, Chi V, Kim JY, Chatterjee AK, Schultz PG, Tremblay MS, Kazane SA. Targeted Delivery of LXR Agonist Using a Site-Specific Antibody-Drug Conjugate. Bioconjug Chem. 2015 Nov 18;26(11):2216-22. doi: 10.1021/acs.bioconjchem.5b00203. Epub 2015 May 20. PubMed PMID: 25945727; PubMed Central PMCID: PMC4651790.

20: Dong Y, Gao G, Fan H, Li S, Li X, Liu W. Activation of the Liver X Receptor by Agonist TO901317 Improves Hepatic Insulin Resistance via Suppressing Reactive Oxygen Species and JNK Pathway. PLoS One. 2015 Apr 24;10(4):e0124778. doi: 10.1371/journal.pone.0124778. eCollection 2015. PubMed PMID: 25909991; PubMed Central PMCID: PMC4409387.