| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
hNav1.7 22.8 nM (IC50) mNav1.7 59.4 nM (IC50)
The primary target of DS-1971a is the voltage-gated sodium channel NaV1.7, which is predominantly expressed in peripheral sensory neurons and plays a critical role in pain signaling. By inhibiting NaV1.7, DS-1971a blocks the initiation and propagation of action potentials in pain-sensing neurons, thereby exerting analgesic effects. It is a potent and selective inhibitor of NaV1.7 with IC50 values of 22.8 nM for hNaV1.7 and 59.4 nM for mNaV1.7. The compound's selectivity and oral bioavailability make it an attractive candidate for pain research and development. |
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| ln Vitro |
In vitro, DS-1971a potently inhibits NaV1.7 channels with IC50 values of 22.8 nM for hNaV1.7 and 59.4 nM for mNaV1.7. It is a potent, homozygous form-selective aryl sulfonamide NaV1.7 inhibitor. The compound's high selectivity for NaV1.7 over other sodium channels is a key feature that contributes to its potential as a non-opioid analgesic. DS-1971a is soluble in DMSO at ≥60 mg/mL and is available with a purity of ≥98%.
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| ln Vivo |
A positive toxicological profile is shown by DS-1971a[1]. In mice with partial sciatic nerve ligation (PSL), DS-1971a (0.1–1 mg/kg; po) exhibits dose-dependently reduced heat hyperalgesia[1].
In vivo, DS-1971a is orally active and exerts analgesic effects. It is a promising non-opioid therapeutic candidate for chronic pain conditions, including neuropathic pain. The compound's favorable pharmacological properties, including its oral bioavailability and selectivity for NaV1.7, make it an important research tool in neuroscience, pain biology, and the development of novel analgesic strategies. However, detailed in vivo efficacy data in specific pain models are not extensively reported in the available literature. |
| Enzyme Assay |
In vitro assays for DS-1971a typically involve measuring its inhibition of NaV1.7 channel activity using electrophysiological techniques such as patch-clamp recording in cell lines expressing recombinant hNaV1.7 or mNaV1.7 channels. The compound is applied to the cells at varying concentrations (typically 0.1-1000 nM), and the resulting inhibition of sodium current is measured. The IC50 values of 22.8 nM (hNaV1.7) and 59.4 nM (mNaV1.7) are determined by fitting concentration-response curves. Selectivity assays against other sodium channel subtypes (NaV1.1-1.8) are also performed to assess the compound's specificity.
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| Cell Assay |
Cellular assays for DS-1971a typically use cell lines expressing recombinant NaV1.7 channels, such as HEK293 or CHO cells. The compound is applied to the cells, and its effects on channel activity are assessed using electrophysiological techniques such as patch-clamp recording. Fluorescent-based membrane potential assays using voltage-sensitive dyes can also be used for higher-throughput screening of channel activity. Cells are treated with DS-1971a at various concentrations (e.g., 1-1000 nM), and the inhibition of sodium current or changes in membrane potential are measured. The IC50 for channel inhibition is determined from the concentration-response data.
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| Animal Protocol |
Animal/Disease Models: Male Slc:ddY mice (PSL model)[1]
Doses: 0.1, 0.3, and 1 mg/kg Route of Administration: Po Experimental Results: A significant dose-dependent suppression of thermal hyperalgesiain 0.3 and 1 mg/kg administered groups. The ED50 of DS-1971a at the peak efficacy was 0.32 mg/kg. In vivo animal studies for DS-1971a would typically involve the administration of the compound to rodent models of pain, such as the formalin test, complete Freund's adjuvant (CFA)-induced inflammatory pain model, or neuropathic pain models (e.g., chronic constriction injury or spinal nerve ligation). The compound is administered orally or via other routes, and its analgesic effects are assessed by measuring pain-related behaviors such as paw withdrawal latency, mechanical allodynia, or thermal hyperalgesia. Pharmacokinetic parameters and the compound's ability to penetrate the central nervous system may also be evaluated. |
| ADME/Pharmacokinetics |
DS-1971a is orally active with favorable pharmacokinetic properties. It has a molecular weight of 465.93 g/mol and is soluble in DMSO at ≥60 mg/mL. For research purposes, the compound is typically stored as a powder at -20°C for up to 3 years or at 4°C for up to 2 years. Detailed parameters such as half-life, volume of distribution, and bioavailability are not fully available in the public domain but are characteristic of orally active small molecule NaV1.7 inhibitors.
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| Toxicity/Toxicokinetics |
There is no specific toxicity data reported for DS-1971a in the available literature. As a research chemical intended for laboratory use only, it should be handled with standard safety precautions for handling chemical reagents. The compound is not approved for human therapeutic use. Researchers should consult the material safety data sheet (MSDS) for detailed safety and handling information. Any potential toxicity would need to be assessed through formal toxicological studies if the compound were to be developed further.
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| References | |
| Additional Infomation |
DS-1971a is a potent, selective, and orally active NaV1.7 inhibitor with IC50s of 22.8 nM (hNaV1.7) and 59.4 nM (mNaV1.7). It has a molecular formula of C20H21ClFN5O3S and a molecular weight of 465.93 g/mol. DS-1971a is a homozygous form-selective aryl sulfonamide NaV1.7 inhibitor and exerts analgesic effects. It is a promising non-opioid therapeutic candidate for chronic pain conditions and is soluble in DMSO.
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| Molecular Formula |
C20H21CLFN5O3S
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|---|---|
| Molecular Weight |
465.92884516716
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| Exact Mass |
465.103
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| CAS # |
1450595-86-4
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| PubChem CID |
71711862
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| Appearance |
White to off-white solid powder
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| LogP |
3.3
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
31
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| Complexity |
699
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| Defined Atom Stereocenter Count |
2
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| SMILES |
ClC1C=C(C(=CC=1O[C@H]1CCCC[C@@H]1C1=CC=NN1C)F)S(NC1C=CN=CN=1)(=O)=O
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| InChi Key |
OJKONCJPCULNOW-DYVFJYSZSA-N
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| InChi Code |
InChI=1S/C20H21ClFN5O3S/c1-27-16(6-9-25-27)13-4-2-3-5-17(13)30-18-11-15(22)19(10-14(18)21)31(28,29)26-20-7-8-23-12-24-20/h6-13,17H,2-5H2,1H3,(H,23,24,26)/t13-,17+/m1/s1
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| Chemical Name |
5-chloro-2-fluoro-4-[(1S,2R)-2-(2-methylpyrazol-3-yl)cyclohexyl]oxy-N-pyrimidin-4-ylbenzenesulfonamide
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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: 100 mg/mL (214.62 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.37 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. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.37 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.37 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1462 mL | 10.7312 mL | 21.4625 mL | |
| 5 mM | 0.4292 mL | 2.1462 mL | 4.2925 mL | |
| 10 mM | 0.2146 mL | 1.0731 mL | 2.1462 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.
Link: https://clinicaltrials.gov/ct2/show/NCT02266940
Conditions:HealthyLink: https://clinicaltrials.gov/ct2/show/NCT02261376
Conditions:HealthyLink: https://clinicaltrials.gov/ct2/show/NCT02190058
Conditions:Healthy
Title:Single Ascending Dose Study Using DS-1971 to Assess Safety, Tolerability, and Pharmacokinetics in Healthy Participants.
Status:Completed
updateDate:2018-12-24
Ctid:NCT02107885
Link: https://clinicaltrials.gov/ct2/show/NCT02107885
Conditions:Safety|Tolerability|PharmacokineticsLink: https://clinicaltrials.gov/ct2/show/NCT02564861
Conditions:HealthyLink: https://clinicaltrials.gov/ct2/show/NCT02673866
Conditions:Neuropathic Pain|DiabetesLink: https://clinicaltrials.gov/ct2/show/NCT02473627
Conditions:HealthyProducts are for research use only; We do not sell to patients
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