| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
Crisugabalin (HSK16149) targets the α2δ subunit of voltage-gated calcium channels (VGCCs).
- Inhibition of [³H]gabapentin binding to the α2δ subunit: IC50 = 3.96 nM (95% CI: 2.28 – 6.63 nM). [1] |
|---|---|
| ln Vitro |
- Binding affinity to VGCC α2δ subunit: In a competitive [³H]gabapentin binding assay using rat cerebral cortical membranes, HSK16149 inhibited [³H]gabapentin binding in a dose-dependent manner with an IC50 of 3.96 nM (95% CI: 2.28 – 6.63 nM), which is 23 times more potent than pregabalin (IC50 = 92.12 nM, 95% CI: 61.40 – 141.2 nM). [1]
- Off-target selectivity profile: HSK16149 was tested at 10 µM against 105 targets (receptors, ion channels, transporters, enzymes). No significant inhibition or stimulation (>50%) was observed on any target, indicating high selectivity for the α2δ subunit. [1] |
| ln Vivo |
- Chronic constriction injury (CCI) neuropathic pain model (rats): Oral administration of HSK16149 (3, 10, 30 mg/kg) dose-dependently increased paw withdrawal threshold (PWT). Minimum effective dose (MED) = 10 mg/kg. At 30 mg/kg, 50% PWT was 3.24-fold higher than vehicle at 2 h, lasting up to 6 h. Efficacy of 10 mg/kg HSK16149 was comparable to 30 mg/kg pregabalin. [1]
- STZ-induced diabetic neuropathy model (rats): HSK16149 (3, 10, 30 mg/kg, oral) dose-dependently increased PWT. MED = 10 mg/kg. At 30 mg/kg, efficacy lasted up to 24 h post-dose (pregabalin lasted only 12 h at same dose). At 10 mg/kg, efficacy persisted up to 8 h. [1] - Intermittent cold stress (ICS) fibromyalgia model (mice): HSK16149 (10, 30 mg/kg, oral, 2 h pre-test) inhibited mechanical allodynia dose-dependently. MED = 30 mg/kg, increasing 50% PWT by 2.6-fold vs. vehicle, comparable to 30 mg/kg pregabalin. [1] - Formalin-induced inflammatory pain model (mice): HSK16149 (10, 30 mg/kg, oral, 2 h pre-formalin) decreased phase II pain behaviors dose-dependently (1.6- and 2.2-fold decrease in motion counts, respectively, both P<0.0001 vs. vehicle). No significant effect on phase I at 30 mg/kg. Effect at 30 mg/kg similar to same dose of pregabalin. [1] |
| Enzyme Assay |
- [³H]gabapentin binding assay: Rat cerebral cortical membranes were homogenized in 10 mM HEPES buffer (pH 7.4). The homogenate was centrifuged at 12,000×g for 20 min at 4°C. Membrane pellets (0.02 mg equivalent) were incubated with 20 nM [³H]gabapentin and varying concentrations of test compounds for 30 min at 25°C. Bound and free fractions were separated by vacuum filtration through GF/B filters pre-treated with 0.3% polyetherimide. Filters were washed with ice-cold buffer. Bound radioactivity was measured by liquid scintillation counting. Non-specific binding was determined using 100 µM gabapentin. Inhibition rate (%) = (CPM_total – CPM_compound) / (CPM_total – CPM_non-specific). IC50 was calculated by non-linear regression using GraphPad Prism. [1]
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| Animal Protocol |
- CCI neuropathic pain model (rats): A 2-mm polyethylene cuff was implanted around the left sciatic nerve under isoflurane anesthesia. On day 17 post-surgery, HSK16149 and pregabalin were suspended in 0.5% carboxymethylcellulose sodium and orally administered at 10 µL/g. PWTs were measured at 2, 4, 6 h post-dose. Satellite groups (N=4) were used for plasma collection at 0, 0.083, 0.25, 0.5, 1, 2, 6, 12, 24 h. [1]
- STZ-induced diabetic neuropathy model (rats): Rats received 70 mg/kg STZ intraperitoneally for 3 consecutive days. After 22 days, rats with fasting glucose >11.1 mmol/L were considered diabetic. Baseline PWTs were measured. Compounds suspended in 0.5% carboxymethylcellulose sodium were orally administered at 10 µL/g. PWTs measured at various time points. Plasma collected at same time points as CCI model. [1] - ICS fibromyalgia model (mice): Mice were exposed to alternating cold (4°C) and room temperature cycles for 3 days. On day 4, mice with baseline 50% PWT >0.5 g were excluded. Compounds suspended in 0.5% methylcellulose were orally administered, and pain thresholds measured at 2 h post-dose. [1] - Formalin-induced nociception (mice): Compounds or vehicle (0.5% methylcellulose) were orally administered. After 2 h, 15 µL of 2.5% formalin was injected subcutaneously into the right hind paw. Nociceptive responses (licking/biting) were recorded from 0-9 min (phase I) and 10-45 min (phase II) using an automatic detector. [1] - Rotarod test (rats): Rats were trained on an accelerating rotarod (6 cm diameter, accelerated to 15 rpm) for 3 days. Those with fall-off latency >90 s on day 3 were used. On day 4, compounds or 0.5% methylcellulose were orally administered. At 2 h post-dose, fall-off latency was recorded (max 120 s). [1] - Locomotor activity test (rats): Rats were acclimatized to the chamber for 2 days. After oral administration of vehicle or compounds, rats were placed into the detection system at 2 h post-dose and allowed to explore for 1 h. Total distance traveled was analyzed using an ANY-maze video tracking system. [1] |
| ADME/Pharmacokinetics |
- CCI model (rats): HSK16149 (10 mg/kg): Cmax = 0.69 µg/mL, AUC0-24h = 1.46 µg•h/mL; (30 mg/kg): Cmax = 1.69 µg/mL, AUC0-24h = 4.27 µg•h/mL. [1]
- STZ model (rats): HSK16149 (10 mg/kg): Cmax = 0.62 µg/mL, AUC0-24h = 1.55 µg•h/mL; (30 mg/kg): Cmax = 1.80 µg/mL, AUC0-24h = 4.75 µg•h/mL. [1] - Comparison with pregabalin: At the same dose, the exposure levels (Cmax and AUC0-24h) of HSK16149 in plasma were 2.25–4.73 times lower than pregabalin in pain models. At 30 mg/kg, brain tissue AUC0-24h of HSK16149 was 18-fold lower than pregabalin. [1] |
| Toxicity/Toxicokinetics |
- Rotarod test (ataxic effects): HSK16149 at 100 mg/kg caused a 1.8-fold decrease in fall-off latency (less severe than pregabalin, which caused a 3.6-fold decrease). At 30 mg/kg, pregabalin significantly reduced fall-off latency (1.4-fold), while HSK16149 showed no significant ataxic effect. MED for ataxia: HSK16149 = 100 mg/kg; pregabalin = 30 mg/kg. [1]
- Locomotor activity test (sedative effects): HSK16149 reduced total distance traveled dose-dependently. MED for sedation = 100 mg/kg for both HSK16149 and pregabalin (3-fold decrease vs. vehicle). [1] - Therapeutic index calculation: Based on MED in CCI model (10 mg/kg) and rotarod test (100 mg/kg for HSK16149 vs. 30 mg/kg for pregabalin), the therapeutic index (rotarod) for HSK16149 is 10, vs. 3 for pregabalin. For locomotor activity: HSK16149 index = 10, pregabalin = 10, mirogabalin = 2.5. [1] |
| References | |
| Additional Infomation |
Crisugabalin is being investigated in the clinical trial NCT06490484 (Efficacy and safety of HSK16149 capsules in Chinese diabetic patients with peripheral neuropathy who do not respond well to pregabalin).
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| Molecular Formula |
C12H19NO2
|
|---|---|
| Molecular Weight |
C12H19NO2
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| Exact Mass |
209.141
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| Elemental Analysis |
C, 68.87; H, 9.15; N, 6.69; O, 15.29
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| CAS # |
2209104-84-5
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| PubChem CID |
139300919
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| Appearance |
White to off-white solid at room temperature
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| LogP |
-0.9
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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 |
3
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| Heavy Atom Count |
15
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| Complexity |
304
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| Defined Atom Stereocenter Count |
5
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| SMILES |
C1C[C@@H]2[C@@H]3C[C@H]1C[C@@H]3[C@@]2(CC(=O)O)CN
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| InChi Key |
WCEFMBSFXJUREW-LIJGXYGRSA-N
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| InChi Code |
InChI=1S/C12H19NO2/c13-6-12(5-11(14)15)9-2-1-7-3-8(9)10(12)4-7/h7-10H,1-6,13H2,(H,14,15)/t7-,8-,9+,10-,12-/m0/s1
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| Chemical Name |
2-[(1S,2S,3R,6S,8S)-2-(aminomethyl)-2-tricyclo[4.2.1.03,8]nonanyl]acetic acid
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| Synonyms |
Crisugabalin; HSK-16149; HSK16149; 2209104-84-5; HSK 16149; Q3MK7E8686; RefChem:1082256; .
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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 (477.8 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.) |
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/NCT07483398
Conditions:Parkinson's Disease With Nociceptive PainLink: https://clinicaltrials.gov/ct2/show/NCT07453862
Conditions:Restless Leg Syndrome (RLS)|Variant Restless Legs SyndromeLink: https://clinicaltrials.gov/ct2/show/NCT07196657
Conditions:Fibromyalgia|Pregabalin|Pain
Title:Crisugabalin for Radiotherapy-Related Neuropathic Pain
Status:Recruiting
updateDate:2025-05-18
Ctid:NCT06766916
Link: https://clinicaltrials.gov/ct2/show/NCT06766916
Conditions:Neuropathic PainLink: https://clinicaltrials.gov/ct2/show/NCT06007066
Conditions:Post-operative PainLink: https://clinicaltrials.gov/ct2/show/NCT05916573
Conditions:Renal ImpairmentLink: https://clinicaltrials.gov/ct2/show/NCT04841720
Conditions:Diabetic Neuropathies|Diabetic Neuropathy PeripheralProducts are for research use only; We do not sell to patients
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