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HX-1171, formerly known as HTHQ, is a lipid peroxidation inhibitor potentially for the treatment of hepatic fibrosis. HTHQ and vitamin E attenuated interleukin-1beta-induced iNOS protein expression in cultured hepatocytes, the potency of HTHQ being 10-times higher than that of vitamin E. HTHQ may prevent tumor production induced by AP and NaNO2 more effectively than ascorbic acid.
Physicochemical Properties
| Molecular Formula | C15H24O2 |
| Molecular Weight | 236.355 |
| Exact Mass | 236.177 |
| CAS # | 148081-72-5 |
| Related CAS # | 148081-72-5 |
| PubChem CID | 119193 |
| Appearance | White to off-white solid powder |
| Density | 0.971g/cm3 |
| Boiling Point | 357.8ºC at 760mmHg |
| Melting Point | 72.5-73ºC |
| Flash Point | 154.4ºC |
| Vapour Pressure | 1.29E-05mmHg at 25°C |
| Index of Refraction | 1.507 |
| LogP | 3.609 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 2 |
| Rotatable Bond Count | 6 |
| Heavy Atom Count | 17 |
| Complexity | 205 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | ATMNQRRJNBCQJO-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C15H24O2/c1-5-6-7-8-9-17-14-10-11(2)15(16)13(4)12(14)3/h10,16H,5-9H2,1-4H3 |
| Chemical Name | 4-(hexyloxy)-2,3,6-trimethylphenol |
| Synonyms | HX-1171 HX-1171 HX-1171 HTHQ |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ln Vitro | Treatment of PC12 cells with HTHQ (0-100 μM; 24 hours) enhances cell viability in a dose-dependent manner [1]. HTHQ (10 μM; 0.6-24 hours; PC12 cells) suppresses p38 mitogen activation Phosphorylation of protein kinase (MAPK), c-Jun N-terminal kinase (JNK1/2), and 3,4-L-dihydroxyphenylalanine (L-DOPA)-induced sustained extracellular signal-regulated kinase (ERK1/2). Additionally, HTHQ promotes cell viability by normalizing Bcl-2-associated X protein (Bax) expression and Bcl-2-associated death protein (Bad) phosphorylation that have been decreased by L-DOPA [1]. |
| ln Vivo | Serum chemistry levels and liver weights of male Sprague Dawley rats (specific pathogen-free) considerably improved after 4 weeks of oral HTHQ treatment (50-200 mg/kg). Malondialdehyde and hydroxyproline levels in the liver are lowered by HTHQ. Fibrotic septa are also decreased by HTHQ therapy. When HTHQ was administered to mice with DMN-induced liver fibrosis, the amount of mRNA for TGF-β (transforming growth factor-β), α-SMA (α-smooth muscle actin), and PDGF (platelet-derived growth factor) in the liver tissue decreased[2]. |
| Cell Assay |
Cell Viability Assay[1] Cell Types: PC12 Cell Tested Concentrations: 0 μM, 1 μM, 10 μM and 100 μM Incubation Duration: 24 hrs (hours) Experimental Results: The significant decrease in cell viability induced by 100 and 200 μM L-DOPA at 24 hrs (hours) was attenuated. Western Blot Analysis[1] Cell Types: PC12 Cell Tested Concentrations: 10 μM Incubation Duration: 0.6-24 hrs (hours) Experimental Results: Inhibition of L-DOPA-induced sustained extracellular signal-regulated kinase (ERK1/2), p38 mitogen-activated protein kinase Phosphorylation (MAPK) and c-Jun N-terminal kinase (JNK1/2). And also normalized the diminished Bcl-2-associated death protein (Bad) phosphorylation and Bcl-2-associated X protein (Bax) expression by L-DOPA. |
| Animal Protocol |
Animal/Disease Models: 48 specific pathogen-free male Sprague Dawley (SD) rats (6 weeks old) were given dimethylnitrosamine (DMN) [2] Doses: 50 mg/kg, 100 mg/kg, 200 mg /kg Doses: po (po (oral gavage)) lasted for 4 weeks. Experimental Results: Improved DMN-induced liver fibrosis in male SD rats. |
| References |
[1]. 1-O-Hexyl-2,3,5-Trimethylhydroquinone Ameliorates l-DOPA-Induced Cytotoxicity in PC12 Cells. Molecules. 2019 Mar 1;24(5). pii: E867. [2]. Inhibitory Effect of 1-O-Hexyl-2,3,5-Trimethylhydroquinone on Dimethylnitrosamine-induced Liver Fibrosis in Male SD Rats. Toxicol Res. 2010 Sep;26(3):193-201. |
| Additional Infomation | Hx 1171 is under investigation in clinical trial NCT01548391 (A Phase I Clinical Study Study of the Safety, Tolerability, and Pharmacokinetics of HX-1171 in Healthy Male Subjects). |
Solubility Data
| Solubility (In Vitro) | DMSO : ~100 mg/mL (~423.10 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: 25 mg/mL (105.78 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 250.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (10.58 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 3: ≥ 2.5 mg/mL (10.58 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.2308 mL | 21.1542 mL | 42.3083 mL | |
| 5 mM | 0.8462 mL | 4.2308 mL | 8.4617 mL | |
| 10 mM | 0.4231 mL | 2.1154 mL | 4.2308 mL |