Masoprocol targets multiple enzymes and receptors. It is a potent inhibitor of lipoxygenase (LOX), particularly 5-lipoxygenase (5LOX), which is involved in the synthesis of inflammatory mediators such as leukotrienes. It also directly inhibits the activation of two receptor tyrosine kinases (RTKs): the insulin-like growth factor receptor (IGF-1R) and the c-erbB2/HER2/neu receptor. Additionally, it inhibits formyltetrahydrofolate synthetase, carboxylesterase, and cyclooxygenase.

Adipocytes treated with 30 µM of mastoprocol for 90 minutes exhibit high basal and insulin-stimulated glucose clearance [2].
In vitro, Masoprocol demonstrates potent lipoxygenase inhibitory activity. It interferes with arachidonic acid metabolism, thereby reducing the production of inflammatory mediators. It also inhibits the activation of IGF-1R and HER2 receptors, which can lead to decreased proliferation of susceptible tumor cell populations. The compound may induce apoptosis through disruption of the actin cytoskeleton and activation of stress-activated protein kinases (SAPKs).

Masoprocol (150 mg/kg; ir; twice daily for 12 days) displays anti-hyperglycemic action and decreases plasma glucose concentrations in male C57BL/ks-db/db mice [1]. Masoprocol (0.83 mmol/kg; twice daily for 4 days) reduced glucose concentrations by an average of 35% and triglyceride concentrations by 80% compared with vehicle in a rat model of type II diabetes [2]. Masoprocol (40-80 mg/kg; oral; twice daily for 8 days) significantly reduces hepatic triglycerides (TG) in a non-diabetic rat model of diet-induced hypertriglyceridemia (HTG) ) secretion (P<.01) and liver TG content [3].
In vivo, Masoprocol has antihyperglycemic activity and decreases glucose concentration and hepatic triglyceride levels. It has been used clinically for the treatment of actinic keratoses (precancerous skin growths). As a potent and orally active lipoxygenase inhibitor, it shows potential for type II diabetes research. Its anti-inflammatory and antineoplastic activities have also been observed in vivo.

A cell-free assay for Masoprocol would involve measuring its inhibition of lipoxygenase enzymatic activity. In such assays, the enzyme is incubated with a substrate (e.g., arachidonic acid) in the presence of varying concentrations of the compound. The production of lipoxygenase products is measured, and the IC50 is calculated. Its inhibition of receptor tyrosine kinases can be assessed using kinase assays with purified enzymes and peptide substrates.

Cellular assays for Masoprocol typically involve assessing its effects on cancer cell proliferation and signaling. Cells are treated with the compound, and cell viability is measured. The inhibition of IGF-1R and HER2 phosphorylation can be assessed by Western blotting. The compound's effects on inflammatory mediator production can also be measured in immune cells stimulated with appropriate agonists.

In vivo animal experiments for Masoprocol have been conducted in models of type II diabetes, where it demonstrated antihyperglycemic activity. Specific protocols and dosing regimens are not detailed in the available sources. Its clinical use for actinic keratoses indicates that it has been evaluated in human subjects.

Absorption, Distribution and Excretion
Less than 1%-2% of the product is absorbed through the skin within 4 days of application.
Masoprocol has a molecular formula of C18H22O4 and a molecular weight of 302.4 g/mol. It is a solid. Specific pharmacokinetic parameters, such as half-life and bioavailability, are not provided in the available sources. The compound is orally active. For storage, the powder should be kept at -20°C for up to 3 years or at 4°C for up to 2 years.

Toxicity Summary
While the exact mechanism of action remains unclear, studies have shown that Masoprocol is a potent inhibitor of 5-lipoxygenase and exhibits anti-proliferative activity against keratinocytes in tissue culture. However, the relationship between this activity and its therapeutic effect in actinic keratosis is unclear. Masoprocol also inhibits prostaglandins, but the significance of this effect is uncertain.
Toxicity data for Masoprocol are not detailed in the available sources. As a compound used for the treatment of actinic keratoses, its safety profile has been evaluated in clinical settings. However, specific toxicological information, such as LD50 values or common adverse effects, is not provided in the references cited. The compound is intended for research use and is not for human consumption as a standalone agent.

[1]. Masoprocol (nordihydroguaiaretic acid): a new antihyperglycemic agent isolated from the creosote bush (Larrea tridentata). Eur J Pharmacol. 1998 Apr 3;346(1):77-9.

[2]. Effect of masoprocol on carbohydrate and lipid metabolism in a rat model of Type II diabetes. Diabetologia. 1999 Jan;42(1):102-6.

[3]. Masoprocol decreases serum triglyceride concentrations in rats with fructose-induced hypertriglyceridemia. Metabolism. 2000 Sep;49(9):1106-10.

Masoprocol is the meso compound of nordihydroguaiac acid. It is an antioxidant found in the shrub Larrea divaricata and a potent lipoxygenase inhibitor that interferes with arachidonic acid metabolism. It also inhibits (though to a lesser extent) formyltetrahydrofolate synthase, carboxylesterase, and cyclooxygenase. Masoprocol possesses various effects, including antitumor activity, lipoxygenase inhibition, hypoglycemic activity, and metabolic regulation. It has been reported to exist in Larrea divaricata, Schisandra chinensis, and Larrea tridentata, with relevant data available. Masoprocol is a naturally occurring antioxidant belonging to the dicatechin class of compounds, originally derived from the shrub Larrea divaricata, and exhibits antitumor, anti-inflammatory, and antitumor activities. Masoprol directly inhibits the activation of two receptor tyrosine kinases (RTKs), namely the insulin-like growth factor receptor (IGF-1R) and the c-erbB2/HER2/neu receptor, thereby reducing the proliferation of susceptible tumor cell populations. This drug may induce apoptosis in susceptible tumor cell populations by disrupting the actin cytoskeleton and activating stress-activated protein kinase (SAPK). Furthermore, masoprol inhibits arachidonic acid 5-lipoxygenase (5LOX), thereby reducing the synthesis of inflammatory mediators such as prostaglandins and leukotrienes. It may prevent leukocyte infiltration into tissues and the release of reactive oxygen species. Masoprol is a potent lipoxygenase inhibitor that interferes with arachidonic acid metabolism. This compound also has weak inhibitory effects on formyltetrahydrofolate synthase, carboxylesterase, and cyclooxygenase. It also acts as an antioxidant in fats and oils. This compound also inhibits formyltetrahydrofolate synthase, carboxylesterase, and cyclooxygenase, but to a mild degree. It also acts as an antioxidant in fats and oils. Drug Indications: For the treatment of actinic keratosis (precancerous skin hyperplasia that may develop into malignancy if left untreated). Mechanism of Action: While the exact mechanism of action is unclear, studies have shown that masoprol is a potent 5-lipoxygenase inhibitor and exhibits antiproliferative activity against keratinocytes in tissue culture, but the relationship between this activity and its efficacy in actinic keratosis is unclear. Masoprol also inhibits prostaglandins, but the significance of this effect is not yet understood. Pharmacodynamics: Masoprol is a novel antitumor drug. Its exact mechanism of action is unclear. Laboratory studies have shown that masoprol can inhibit cell proliferation similar to that found in actinic keratosis. Masoprol was withdrawn from the US market in June 1996.
Masoprocol (CAS: 27686-84-6) is a potent lipoxygenase inhibitor and antioxidant. It is also known as meso-nordihydroguaiaretic acid and Actinex. The compound has anti-inflammatory, antineoplastic, and antihyperglycemic activities. It has been used for the treatment of actinic keratoses. Its mechanism involves inhibition of lipoxygenase, IGF-1R, and HER2. It is not an approved drug in many countries and is primarily used as a research tool.

C18H22O4

302.36488

302.152

27686-84-6

500-38-9 (stereoisomers);27686-84-6 (RS-isomer);500-38-9 (NGDA);180634-64-4 (pivalate);

71398

Off-white to light yellow solid powder

1.241 g/cm3

526.5ºC at 760 mmHg

185.5ºC

247.8ºC

1.06E-11mmHg at 25°C

1.626

3.566

4

4

5

22

303

2

C[C@H](CC1=CC(=C(C=C1)O)O)[C@@H](C)CC2=CC(=C(C=C2)O)O

HCZKYJDFEPMADG-TXEJJXNPSA-N

InChI=1S/C18H22O4/c1-11(7-13-3-5-15(19)17(21)9-13)12(2)8-14-4-6-16(20)18(22)10-14/h3-6,9-12,19-22H,7-8H2,1-2H3/t11-,12+

4-[(2S,3R)-4-(3,4-dihydroxyphenyl)-2,3-dimethylbutyl]benzene-1,2-diol

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product requires protection from light (avoid light exposure) during transportation and storage.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ≥ 100 mg/mL (~330.73 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (8.27 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.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (8.27 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 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.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (8.27 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.

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 (Please use freshly prepared in vivo formulations for optimal results.)