| Size | Price | Stock | Qty |
|---|---|---|---|
| 250mg |
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| Other Sizes |
| Targets |
GPR81 (HCA1, lactate receptor) with EC50 = 16 ± 9 μM (human); GPR109a (nicotinic acid receptor) with EC50 > 1 mM (inactive at concentrations tested) [1]
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|---|---|
| ln Vitro |
3-Chloro-5-hydroxybenzoic acid is efficient against mice (EC50=22 μM), rats (EC50=7 μM), dogs (EC50=67 μM), monkeys (EC50=17 μM), and humans (EC50=16 μM). shows hamster GPR81 (EC50=27 μM) and potency[1].
Activated human GPR81 in GTPγS binding assay with EC50 ~16 μM [1] Showed no activity at GPR109a (EC50 > 1 mM) [1] Activity at GPR81 was conserved across species: monkey EC50 = 17 μM, dog EC50 = 67 μM, rat EC50 = 7 μM, mouse EC50 = 22 μM, hamster EC50 = 27 μM [1] |
| ln Vivo |
At all tested dosages, 3-chloro-5-hydroxybenzoic acid (30, 100, and 300 mg/kg; PO given to C57Bl6/J mice fed a high-fat diet for 10 weeks) significantly reduced the amount of free fatty acids, with a minimum efficacious dose of 30 mg/kg[1]. Three-chloro-5-hydroxybenzoic acid pharmacokinetic characteristics in mice [1]. AUCinf (h ng/mL) Cmax (ng/mL) Cmax (μM) dose (mg/kg) tmax (h) t1/2 (h) 30 0.5 9356 11689.50 67.2 1.47 100 0.5 51312 55252.80 341.9 1.10
In overnight fasted C57Bl6/J mice fed high fat chow for 10 weeks (diet-induced obesity mice), oral administration of 5-Chloro-m-Salicylic Acid at 30, 100, and 300 mg/kg significantly reduced nonesterified free fatty acid cholesterol (NEFA) as a marker of lipolysis. The minimum efficacious dose was 30 mg/kg, comparable to that of niacin [1] |
| Enzyme Assay |
GTPγS binding assays were performed to determine agonist activity at GPR81 and GPR109a. Membranes expressing the respective receptors were incubated with [35S]GTPγS and varying concentrations of the compound. The assay was repeated at least twice, and EC50 values were calculated from the concentration-response curves [1]
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| Animal Protocol |
Animal/Disease Models: C57Bl6/ J mice (DIO mice) [1]
Doses: 30, 100 and 300 mg/kg Route of Administration: Oral high-fat diet overnight fasted C57Bl6/J mice 10 weeks Experimental Results: Non-esterified free fatty acid cholesterol (NEFAc ) were Dramatically diminished at all doses tested. For pharmacodynamic study: Overnight fasted C57Bl6/J mice that had been fed a high-fat diet for 10 weeks (DIO mice) were treated orally with 5-Chloro-m-Salicylic Acid at doses of 30, 100, or 300 mg/kg, or with niacin at 30 mg/kg. Nonesterified free fatty acid cholesterol (NEFA) levels were measured as an indicator of lipolysis [1] For pharmacokinetic study: Male mice were given oral doses of 30 mg/kg or 100 mg/kg of the compound. Blood samples were collected at various time points to determine plasma concentrations and calculate pharmacokinetic parameters [1] |
| ADME/Pharmacokinetics |
In mice after oral administration at 30 mg/kg: Cmax = 67 μM (approximately 3-fold over in vitro EC50), AUCinf = 54 h·μM, t1/2 = 1.5 h [1]
After oral administration at 100 mg/kg: Cmax = 342 μM (>15-fold over in vitro EC50), t1/2 = 1.1 h [1] |
| References |
[1]. Dvorak CA, et al. Identification of Hydroxybenzoic Acids as Selective Lactate Receptor (GPR81) Agonists with Antilipolytic Effects. ACS Med Chem Lett. 2012;3(8):637-639. Published 2012 Jun 11.
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| Additional Infomation |
5-Chloro-m-Salicylic Acid is a selective GPR81 agonist that does not activate GPR109a. It inhibits lipolysis in adipocytes, leading to reduced free fatty acids. Unlike niacin, it is not expected to cause flushing (pruritus and skin redness) because flushing is mediated by GPR109a-dependent production of prostaglandins in immune cells. This compound may provide a novel treatment for dyslipidemia without the undesirable side effects associated with niacin [1]
|
| Molecular Formula |
C7H5O3CL
|
|---|---|
| Molecular Weight |
172.5658
|
| Exact Mass |
171.992
|
| CAS # |
53984-36-4
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| PubChem CID |
13071646
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| Appearance |
White to light brown solid powder
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| Density |
1.5±0.1 g/cm3
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| Boiling Point |
364.8±27.0 °C at 760 mmHg
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| Flash Point |
174.4±23.7 °C
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| Vapour Pressure |
0.0±0.9 mmHg at 25°C
|
| Index of Refraction |
1.630
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| LogP |
2.83
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
11
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| Complexity |
160
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(O)C1=CC(O)=CC(Cl)=C1
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| InChi Key |
RJOLIYHZZKAIET-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C7H5ClO3/c8-5-1-4(7(10)11)2-6(9)3-5/h1-3,9H,(H,10,11)
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| Chemical Name |
3-chloro-5-hydroxybenzoic acid
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| HS Tariff Code |
2934.99.9001
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| 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)
|
| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~579.47 mM)
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 5.7947 mL | 28.9737 mL | 57.9475 mL | |
| 5 mM | 1.1589 mL | 5.7947 mL | 11.5895 mL | |
| 10 mM | 0.5795 mL | 2.8974 mL | 5.7947 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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