| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 250mg | |||
| Other Sizes |
| Targets |
MK-2295 specifically targets the TRPV1 channel, a member of the TRP family of ion channels. TRPV1 is a ligand-gated ion channel that, upon activation by its agonists (capsaicin, heat, or protons), opens to allow the influx of cations, primarily calcium (Ca²⁺) and sodium (Na⁺), into the neuron. This depolarization triggers the generation of action potentials, which are transmitted to the central nervous system to signal pain. MK-2295 acts as a potent antagonist, meaning it binds to the TRPV1 channel and blocks its activation by these stimuli. By preventing the channel from opening, MK-2295 inhibits the transmission of pain signals from the periphery to the brain, thereby producing analgesia. Its mechanism is distinct from that of opioids, offering a potential non-addictive approach to pain management.
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| ln Vitro |
In vitro studies have confirmed that MK-2295 is a potent antagonist of the TRPV1 channel. Its activity is typically assessed using calcium imaging assays in cells that heterologously express human TRPV1. In these assays, cells are loaded with a fluorescent calcium indicator and then stimulated with a TRPV1 agonist, such as capsaicin. The increase in intracellular calcium is measured as a proxy for channel activation. MK-2295 is added at various concentrations, and its ability to inhibit the agonist-induced calcium influx is determined, allowing for the calculation of its IC50. Patch-clamp electrophysiology is also used to directly measure the compound's ability to block TRPV1-mediated currents in single cells. These in vitro studies are fundamental for characterizing the compound's potency and mechanism of action as a TRPV1 antagonist.
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| ln Vivo |
In vivo, MK-2295 has been evaluated in animal models of chronic pain to assess its analgesic efficacy. In these models, such as the formalin test, the complete Freund's adjuvant (CFA) model of inflammatory pain, or neuropathic pain models like the chronic constriction injury (CCI) model, MK-2295 is typically administered orally or intraperitoneally. Pain responses are then measured, for example, by assessing paw withdrawal thresholds to mechanical or thermal stimuli. The ability of MK-2295 to reduce pain-related behaviors in these models demonstrates its potential as an analgesic. Its development was pursued by the pharmaceutical industry for the treatment of chronic pathological pain, though like many TRPV1 antagonists, its clinical advancement may have been limited by side effects such as hyperthermia (elevated body temperature) and impaired noxious heat sensation, which are on-target effects due to the physiological role of TRPV1 in thermoregulation and heat pain perception.
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| Enzyme Assay |
The in vitro receptor binding and functional assays for MK-2295 are centered on its interaction with the TRPV1 channel. Radioligand binding assays can be used to measure its affinity for the channel. However, the primary functional assay is the measurement of its antagonist activity, typically using calcium imaging in cells expressing TRPV1. In this assay, cells are pre-incubated with MK-2295 and then stimulated with a TRPV1 agonist, and the inhibition of the calcium signal is measured. This functional assay directly measures the compound's ability to block the channel's activity and is the standard method for characterizing TRPV1 antagonists.
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| Cell Assay |
Cellular assays for MK-2295 are performed in cell lines that heterologously express the human TRPV1 channel. These cells are loaded with a calcium-sensitive fluorescent dye, and the change in intracellular calcium concentration is monitored in real-time using a fluorescence plate reader. The compound's ability to inhibit capsaicin-, heat-, or acid-induced calcium influx is measured, providing a quantitative measure of its antagonist potency. These cell-based assays are critical for confirming the compound's mechanism of action and for screening and characterizing its activity.
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| Animal Protocol |
In vivo animal experiments for MK-2295 are conducted in standard preclinical pain models. The compound is typically administered orally, and its analgesic effect is evaluated using behavioral tests. For example, in the formalin test, the reduction of pain behaviors in the late (inflammatory) phase is measured. In neuropathic pain models like the spinal nerve ligation or CCI model, the increase in paw withdrawal thresholds to mechanical stimuli (von Frey test) or thermal stimuli (Hargreaves test) is measured. These in vivo studies are essential for demonstrating the efficacy of MK-2295 in a living system and for evaluating its pharmacokinetic and safety profile.
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| ADME/Pharmacokinetics |
MK-2295 has a molecular weight of 490.57 g/mol and a molecular formula of C27H31FN6O2. It is a solid and is typically soluble in DMSO. For in vivo studies, it is formulated for oral administration. Its mesylate salt (CAS# 573678-04-3) is also available. The compound should be stored at -20°C for long-term stability.
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| Toxicity/Toxicokinetics |
The toxicity profile of MK-2295 is characteristic of the TRPV1 antagonist class. On-target side effects include hyperthermia (a rise in core body temperature) and a loss of sensitivity to noxious heat, which are direct consequences of blocking the physiological functions of TRPV1. These side effects have been a significant challenge in the clinical development of TRPV1 antagonists. Other potential side effects may include gastrointestinal disturbances. Comprehensive toxicological evaluations would have been conducted as part of its preclinical development program.
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| Additional Infomation |
MK-2295 is a potent TRPV1 antagonist developed as a potential analgesic for the treatment of chronic pain. Its mechanism of action involves blocking the TRPV1 ion channel, which is a key integrator of pain signals in sensory neurons. While the compound demonstrated analgesic efficacy in preclinical models, the clinical development of TRPV1 antagonists, including MK-2295, has been challenged by on-target side effects such as hyperthermia and impaired heat pain sensation. As such, MK-2295 remains an important research tool for studying TRPV1 biology and pain mechanisms, and its development has contributed to a deeper understanding of the therapeutic potential and limitations of targeting this channel for pain management.
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| Molecular Formula |
C27H31FN6O2
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|---|---|
| Molecular Weight |
490.572448968887
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| Exact Mass |
490.249
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| CAS # |
878811-00-8
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| Related CAS # |
878811-00-8;1855897-95-8 (mesylate);
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| PubChem CID |
11670376
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
5
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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 |
5
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| Heavy Atom Count |
36
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| Complexity |
752
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C[C@@H]1CCCN1C2=NC(=CC(=N2)N3CCN(C[C@H]3C)C4=NC=C(C=C4C)C(=O)O)C5=CC=C(C=C5)F
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| InChi Key |
ZCCXMOUUPUIVNZ-RTBURBONSA-N
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| InChi Code |
InChI=1S/C27H31FN6O2/c1-17-13-21(26(35)36)15-29-25(17)32-11-12-33(19(3)16-32)24-14-23(20-6-8-22(28)9-7-20)30-27(31-24)34-10-4-5-18(34)2/h6-9,13-15,18-19H,4-5,10-12,16H2,1-3H3,(H,35,36)/t18-,19-/m1/s1
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| Chemical Name |
6-[(3R)-4-[6-(4-fluorophenyl)-2-[(2R)-2-methylpyrrolidin-1-yl]pyrimidin-4-yl]-3-methylpiperazin-1-yl]-5-methylpyridine-3-carboxylic 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)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 2.0384 mL | 10.1922 mL | 20.3845 mL | |
| 5 mM | 0.4077 mL | 2.0384 mL | 4.0769 mL | |
| 10 mM | 0.2038 mL | 1.0192 mL | 2.0384 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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