Olaquindox targets bacterial ribosomes and DNA. It binds to bacterial ribosomes, preventing bacterial protein synthesis and inhibiting the production of toxins and enzymes. The compound also binds to nuclear DNA and inhibits the function of RNA polymerase II, thereby inhibiting transcription. In mitochondria, it inhibits the activity of multidrug efflux pumps. Additionally, Olaquindox induces apoptosis through a caspase-9-dependent mitochondrial pathway and induces autophagy, which is upregulated by Beclin 1 but downregulated by ROS-dependent JNK.

Olaquindox induces apoptosis of HepG2 cells through a caspase-9-dependent mitochondrial pathway. It also induces autophagy in HepG2 cells, which is upregulated by Beclin 1 but downregulated by ROS-dependent JNK. Olaquindox-induced apoptosis can be enhanced by 3-methyladenine. The compound has genotoxic activity. It inhibits the activity of multidrug efflux pumps in mitochondria. Olaquindox binds to DNA and inhibits transcription by binding to nuclear DNA and inhibiting the function of RNA polymerase II. It also binds to bacterial ribosomes, preventing protein synthesis.

Olaquindox (100 mg/kg in the baseline diet) raises the feed conversion ratio (FCR) and average daily growth [1].
In vivo, Olaquindox stimulates growth and reduces intestinal mucosal immunity in piglets. At a dose of 100 mg/kg in the baseline diet, it raises feed conversion ratio and average daily growth. Olaquindox decreases E. coli-induced diarrhea and the number of intraepithelial lymphocytes in the ileum and increases body weight in piglets. However, it induces bleeding.

Olaquindox is evaluated in cell-free enzymatic assays to assess its ability to inhibit RNA polymerase II and DNA binding. The compound is incubated with nuclear DNA and RNA polymerase II, and the inhibition of transcription is measured. Mitochondrial efflux pump activity can be assessed by measuring the accumulation of substrates in the presence of Olaquindox.

Olaquindox is assessed in cell-based assays using HepG2 cells. Cells are treated with Olaquindox, and apoptosis is measured by assessing caspase-9 activation and mitochondrial pathway markers. Autophagy is assessed by measuring Beclin 1 levels and ROS-dependent JNK activity. The enhancement of apoptosis by 3-methyladenine is also evaluated. Genotoxic activity is assessed using standard genotoxicity assays.

Olaquindox is administered orally in animal models to evaluate its growth-promoting and antimicrobial effects. In piglets, it is typically administered at a dose of 100 mg/kg in the baseline diet. Efficacy is assessed by measuring feed conversion ratio, average daily growth, and reduction in E. coli-induced diarrhea. Intestinal mucosal immunity is assessed by measuring the number of intraepithelial lymphocytes. Bleeding is monitored as an adverse effect.

Absorption, Distribution and Excretion
Experiments in rats with bile duct fistulas involving intraduodenal injection of (3-1)4C-olaquindox showed that approximately 18% of the dose was excreted via bile. Similar results were observed after intravenous administration. Following oral administration, the drug was widely distributed throughout the body, with most radioactivity disappearing within 24 hours. Autoradiography showed the highest drug concentration in the rat kidneys at 4 hours, indicating urinary excretion was comparable to previously observed. Slightly elevated drug concentrations were also observed in the liver, testes, adrenal glands, and hair follicles. During the fattening period, in pigs fed diets containing up to 45 ppm olaquindox, the highest drug concentrations were observed in the liver (0.14 ppm) and kidneys (0.28 ppm) 6 hours after drug withdrawal. After 24 hours, drug concentrations were below the detection limit (0.1 ppm). Similar results were observed when pigs were fed diets containing 10 ppm olaquindox. When pigs were fed the recommended dose (maximum 100 ppm in the diet) for up to 20 weeks, and were sacrificed 6 hours after drug withdrawal, the drug concentration in the kidneys was relatively high (approximately 2000 ppb), while the drug concentration in the liver was relatively low (300 ppb). Two days after withdrawal, when sacrificed, the drug concentrations in the liver, kidneys, and muscles had all decreased to below the detection limit (50 ppb). Pigs fed a diet containing more than the recommended dose (160 or 250 ppm) of olaquindox for up to 4 weeks also had initially high drug concentrations in the kidneys, liver, and muscles, but these concentrations decreased to below the detection limit 2 days after withdrawal. Olaquindox is rapidly absorbed by pigs after oral administration. After an oral dose of 2 mg/kg body weight, over 90% is excreted in the urine within 24 hours, indicating rapid and widespread absorption. The remainder is excreted in the feces. Peak plasma concentrations (1-2 ppm) are reached within 1-2 hours after administration. Plasma concentrations subsequently decreased rapidly, reaching approximately 0.03 ppm after 24 hours and 0.005–0.01 ppm after 48 hours. Two days after administration, radioactivity was detected in all tissues, but at extremely low concentrations. Radioactivity concentrations in the kidneys and liver were 110 ppb and 52 ppb, respectively, while the concentration in muscle was only 9 ppb. After 8 days, radioactivity concentrations in the liver and kidneys decreased to 27 ppb and 12 ppb, respectively, while the concentration in muscle was approximately 2.5 ppb. At 28 days post-administration, low concentrations were detected only in the kidneys and muscle (0.9 ppb and 0.5–0.8 ppb, respectively), with a slightly higher concentration in the liver (2 ppb).
For more complete data on absorption, distribution, and excretion of olaquindos (6 types), please visit the HSDB record page.
Metabolism/Metabolites
Biotransformation of olaquindos was studied only in pigs. Following oral administration of olaquindo, the majority (70%) was excreted unchanged in the urine. The major metabolite appeared to be the reducing compound, namely 1- or 4-mono-N-oxide (16%). The remainder consisted of three compounds believed to be carboxylic acid derivatives. Subsequent studies elucidated the structure of these metabolites in pigs. Following oral administration, the major component in urine remained olaquindo, with approximately 7% present as 4-mono-N-oxide. Omega-oxidation yielded a 2-carboxymethylaminocarbonyl compound and its 4-mono-N-oxide derivative (6%). Additionally, a small amount of the corresponding 1-mono-N-oxide fraction of the 2-carboxymethylaminocarbonyl compound was detected (1%). The remaining metabolite was a dideoxy derivative of the 2-carboxymethylaminocarbonyl compound, namely 2-carboxymethylaminocarbonyl-3-methylquinoxaline (>1%).
Olaquindox is orally active and is administered in the diet. It has a molecular weight of 263.25 and a molecular formula of C12H13N3O4. It is slightly soluble in water. The compound has a melting point >145ºC (dec.). It is typically stored as a solid powder.

The LD50 of Olaquindox in cats (male and female) by subcutaneous administration is 500 mg/kg body weight. The compound has genotoxic activity. It induces bleeding. Due to its toxicity, the use of Olaquindox as a feed additive is no longer authorized in China.

[1]. Ding MX, et al. Olaquindox and cyadox stimulate growth and decrease intestinal mucosal immunityof piglets orally inoculated with Escherichia coli. J Anim Physiol Anim Nutr (Berl). 2006 Jun;90(5-6):238-43.

Olaquindox [BAN:INN] is a quinoxaline derivative.
Olaquindox is a quinoxaline derivative and an orally active antibiotic. It is used as an antimicrobial growth promoter in livestock production. The compound has a CAS number of 23696-28-8. It is also known by synonyms such as N-(2-HYDROXYETHYL)-3-METHYL-2-QUINOXALINECARBOXAMIDE 1,4-DIOXIDE and OLAQUINDOX. The compound is for research use only and is not intended for human therapeutic use.

C12H13N3O4

263.2493

263.09

23696-28-8

Olaquindox-d4;1189487-82-8

71905

Pale yellow crystals

1.4±0.1 g/cm3

343.3ºC

209°C (dec.)

>204.4ºC

1.651

-2.2

2

5

3

19

421

0

O=[N+]1C2=C([H])C([H])=C([H])C([H])=C2N(C(C([H])([H])[H])=C1C(N([H])C([H])([H])C([H])([H])O[H])=O)[O-]

TURHTASYUMWZCC-UHFFFAOYSA-N

InChI=1S/C12H13N3O4/c1-8-11(12(17)13-6-7-16)15(19)10-5-3-2-4-9(10)14(8)18/h2-5,16H,6-7H2,1H3,(H,13,17)

N-(2-hydroxyethyl)-3-methyl-4-oxido-1-oxoquinoxalin-1-ium-2-carboxamide

Bisergon; Bayonox; Bayernox

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 : ~25 mg/mL (~94.97 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (9.50 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 (9.50 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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 (Please use freshly prepared in vivo formulations for optimal results.)