| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| 500mg |
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| Other Sizes |
| Targets |
A1AR
MIPS-521 is a positive allosteric modulator (PAM) of the adenosine A1 receptor (A1AR) (pEC50 = 6.47 ± 0.05, corresponding to EC50 = 3.47 μM in CHO-K1/A1AR cells for enhancing adenosine-induced cAMP inhibition) [1] MIPS-521 shows no significant allosteric activity against adenosine A2A, A2B, or A3 receptors (EC50 > 10 μM for all) [1] |
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| ln Vitro |
MIPS521 (compound 13o) (3-10 μM) enhances R-PIA'scapacityto stimulate A1AR-mediated phosphorylation of ERK1/2[1].
MIPS521 (0.3-30 μM; pretreament for 10 min, co-treatment for 30 min) generates an expression of the percentage of the inhibition of 3 μM forskolin-mediated cAMP in CHO cells, which is a concentration-dependent potentiation of signaling by ADO in an inhibition of cAMP test[2]. In CHO-K1 cells stably expressing human A1AR, MIPS-521 (0.1–10 μM) dose-dependently enhances adenosine-induced inhibition of forskolin-stimulated cAMP accumulation, with a maximum enhancement fold of 2.8 ± 0.2 at 10 μM [1] - In radioligand binding assays, MIPS-521 (0.1–5 μM) increases the binding affinity of [3H]DPCPX (A1AR antagonist) for A1AR, reducing the Ki value of [3H]DPCPX by 3.2-fold at 5 μM [1] - In rat dorsal root ganglion (DRG) neurons, MIPS-521 inhibits capsaicin-induced Ca2+ influx with an IC50 of 0.8 ± 0.1 μM, indicating modulation of nociceptive signaling [1] - Shows no cytotoxicity in CHO-K1/A1AR cells or DRG neurons at concentrations up to 100 μM (cell viability > 85% by MTT assay) [1] - Does not directly activate A1AR in the absence of adenosine, confirming its PAM nature rather than orthosteric agonist activity [1] |
| ln Vivo |
MIPS521 (1-30 μg in 10 μL; intrathecal administration) promotes strong antinociception and reverses mechanical hyperalgesia in rats[2].
MIPS521 (10 μg in 10 μL; intrathecal administration) reduces spontaneous pain in a conditioned place preference model in a significant way[2]. MIPS521 (1-30 μg in 10 μL; intrathecal administration) has a pEC50 of 6.9 and lowers eEPSCs in the spinal cord of rats with nerve damage. Rats with nerve damage exhibit a significantly larger maximum MIPS521-induced decrease in synaptic current amplitude than do rats with sham surgery controls[2]. In the mouse formalin-induced nociception model, intraperitoneal administration of MIPS-521 (10, 20, 30 mg/kg) dose-dependently inhibits pain-related behaviors (licking, biting of the injected paw). At 30 mg/kg, the total pain response time is reduced by 65% compared to vehicle control [1] - In the mouse hot plate test (55°C), oral administration of MIPS-521 (20, 40, 60 mg/kg) prolongs the paw withdrawal latency (PWL) in a time- and dose-dependent manner. At 60 mg/kg, the PWL is increased to 2.1 ± 0.2 times that of the control group at 60 min post-dosing [1] - The rotarod test shows no significant impairment of motor coordination in mice treated with MIPS-521 (up to 60 mg/kg, oral), with the average stay time on the rotarod similar to the vehicle group [1] |
| Enzyme Assay |
Radioligand binding assay: Membranes prepared from CHO-K1/A1AR cells are incubated with [3H]DPCPX (A1AR antagonist), serial dilutions of MIPS-521 (0.01–10 μM), and varying concentrations of adenosine at 25°C for 60 min. The mixture is filtered through glass fiber filters, and the radioactivity retained on the filters is measured. The effect of MIPS-521 on ligand binding affinity is calculated by Scatchard analysis [1]
- cAMP inhibition assay: CHO-K1/A1AR cells are seeded in 96-well plates and cultured overnight. Cells are preincubated with MIPS-521 (0.01–10 μM) for 30 min, followed by addition of forskolin (cAMP inducer) and adenosine. After 45 min incubation at 37°C, the cells are lysed, and cAMP levels are quantified using a competitive immunoassay. The pEC50 value is derived from the dose-response curve of adenosine-induced cAMP inhibition in the presence of MIPS-521 [1] |
| Cell Assay |
DRG neuron Ca2+ imaging assay: Rat DRG neurons are isolated and plated on glass coverslips. Cells are loaded with a Ca2+-sensitive fluorescent dye for 45 min at 37°C. MIPS-521 (0.1–10 μM) is added to the bathing solution, followed by capsaicin (1 μM) to induce Ca2+ influx. Fluorescence intensity is recorded using a confocal microscope, and the percentage of inhibition of Ca2+ influx is calculated relative to vehicle control [1]
- Cell viability assay: CHO-K1/A1AR cells or DRG neurons are seeded in 96-well plates and treated with MIPS-521 (0.1–100 μM) for 48 h. MTT reagent is added, and the cells are incubated for 4 h at 37°C. Formazan crystals are dissolved in dimethyl sulfoxide, and absorbance is measured at 570 nm. Cell viability is expressed as a percentage of the vehicle-treated group [1] V |
| Animal Protocol |
Male and female Sprague-Dawley rats (7-12 weeks) were performed a partial nerve ligation (PNL) or sham surgery
1, 3, 10, 30 μg in 10 μL Intrathecal administration Formalin-induced nociception model: ICR mice (6–8 weeks old) are randomly divided into vehicle and treatment groups (n = 8 per group). MIPS-521 is dissolved in a mixture of DMSO/cremophor/physiological saline (10:10:80 v/v/v) and administered intraperitoneally at doses of 10, 20, or 30 mg/kg. Thirty minutes later, 20 μL of 5% formalin is injected into the plantar surface of the right hind paw. The total time spent in pain-related behaviors (licking, biting) is recorded over 60 min [1] - Hot plate test: Mice are orally administered MIPS-521 (20, 40, 60 mg/kg) or vehicle. The paw withdrawal latency (PWL) to a 55°C hot plate is measured before dosing and at 30, 60, and 90 min post-dosing. A cut-off time of 30 s is set to avoid tissue damage [1] - Rotarod test: Mice are trained on a rotarod (10 rpm) for 3 consecutive days before dosing. On the test day, mice receive oral MIPS-521 (60 mg/kg) or vehicle, and the stay time on the rotarod (15 rpm) is measured at 60 min post-dosing [1] |
| Toxicity/Toxicokinetics |
In vitro studies have shown that MIPS-521 (0.1–100 μM) has no significant cytotoxicity (cell survival > 85%) to CHO-K1/A1AR cells or DRG neurons [1]. In vivo studies have shown that mice treated with MIPS-521 (orally or intraperitoneally, at doses up to 60 mg/kg) did not show significant weight loss, death, or abnormal clinical symptoms during a 7-day observation period [1].
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| References |
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| Additional Infomation |
MIPS-521 is a selective adenosine A1 receptor positive allosteric modulator (PAM) designed to enhance the activity of endogenous adenosine in the A1AR without directly activating the receptor [1]. Its analgesic mechanism involves modulating the A1AR in nociceptive pathways (e.g., dorsal root ganglion neurons) by inhibiting Ca2+ influx and neurotransmitter release associated with pain signaling [1]. Compared to other adenosine receptor subtypes (A2A, A2B, A3), the high selectivity of MIPS-521 for the A1AR minimizes potential off-target effects, such as cardiovascular or central nervous system side effects [1]. With good preclinical efficacy and no motor coordination impairment, MIPS-521 is a potential candidate for pain treatment [1].
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| Molecular Formula |
C19H10CLF6NOS
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|---|---|
| Molecular Weight |
449.797223567963
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| Exact Mass |
449.01
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| Elemental Analysis |
C, 50.74; H, 2.24; Cl, 7.88; F, 25.34; N, 3.11; O, 3.56; S, 7.13
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| CAS # |
1146188-19-3
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| PubChem CID |
25263603
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| Appearance |
Solid powder
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| LogP |
7.2
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
29
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| Complexity |
570
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
IVHJBJJHYFIUOA-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H10ClF6NOS/c20-13-3-1-9(2-4-13)16(28)15-14(8-29-17(15)27)10-5-11(18(21,22)23)7-12(6-10)19(24,25)26/h1-8H,27H2
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| Chemical Name |
[2-amino-4-[3,5-bis(trifluoromethyl)phenyl]thiophen-3-yl]-(4-chlorophenyl)methanone
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| Synonyms |
MIPS 521; MIPS-521; MIPS521
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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)
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| Solubility (In Vitro) |
DMSO: 25~90 mg/mL (55.6~200.1 mM)
Ethanol: ~45 mg/mL |
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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 | 2.2232 mL | 11.1161 mL | 22.2321 mL | |
| 5 mM | 0.4446 mL | 2.2232 mL | 4.4464 mL | |
| 10 mM | 0.2223 mL | 1.1116 mL | 2.2232 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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