Anrikefon
(Synonyms: HSK21542)
Anrikefon is a peripherally restricted kappa opioid receptor (KOR) agonist, with an IC50 of 0.54 nM, an EC50 of 2.41 pM, and a Ka of 0.068 nM against human KOR, and it exhibits high selectivity over μ and δ opioid receptors. Anrikefon exerts analgesic effects by inhibiting behaviors associated with inflammatory, postoperative and neuropathic pain, and also exerts antipruritic effects by reducing itch-related behaviors. Anrikefon can be used in research on pain, pruritus, and pruritus associated with chronic kidney disease.
It is advisable to consider the stable salt form (Anrikefon acetate) that retains the same biological activity.
For research use only. We do not sell to patients.
- CAS No.: 2269511-95-5
- Formula: C39H57N7O5
- Molecular Weight:703.91
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
Description
Anrikefon is a peripherally restricted kappa opioid receptor (KOR) agonist, with an IC50 of 0.54 nM, an EC50 of 2.41 pM, and a Ka of 0.068 nM against human KOR, and it exhibits high selectivity over μ and δ opioid receptors. Anrikefon exerts analgesic effects by inhibiting behaviors associated with inflammatory, postoperative and neuropathic pain, and also exerts antipruritic effects by reducing itch-related behaviors. Anrikefon can be used in research on pain, pruritus, and pruritus associated with chronic kidney disease[1][2].
IC50 & Target
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κ Opioid Receptor/KOR |
In Vitro
Anrikefon (HSK21542) (0.01-10 nM, 0.123-1.23 nM; 60 min, 120 min) potently binds to human KOR in isolated HEK-293 cell membranes with an IC50 of 0.54 nM, a Kd of 0.068 nM, and a long dissociation half-life of 90.6 min[1].
Anrikefon (HSK21542) (0.001-10 nM; 30 min) potently inhibits forskolin-induced cAMP accumulation in human KOR-expressing HEK-293 cells with an EC50 of 2.41 pM[1].
Anrikefon (HSK21542) (10 μM) exhibits high off-target selectivity, with only weak binding to the cannabinoid CB1 receptor at a high concentration of 10 μM and no activity against 85 other tested targets[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
Anrikefon (HSK21542) (0.03-30 mg/kg; i.v.; single dose) produces potent, dose-dependent, KOR-mediated antinociceptive effects in a Mus musculus acetic acid-induced writhing model, with a minimum effective dose of 0.03 mg/kg at 15 minutes post-dosing and sustained efficacy for at least 24 hours post-administration[1].
Anrikefon (HSK21542) (0.1-10 mg/kg; i.v.; single dose) produces dose-dependent antiallodynic effects in a rat hindpaw incision post-surgical pain model, with efficacy detectable for at least 24 hours post-administration at doses of 3 mg/kg and 10 mg/kg[1].
Anrikefon (HSK21542) (0.1-3 mg/kg; i.v.; single dose) produces sustained, dose-dependent antiallodynic effects in a rat CCI neuropathic pain model, with a minimum effective dose of 0.3 mg/kg and efficacy lasting at least 24 hours post-administration at doses of 1 mg/kg and 3 mg/kg[1].
Anrikefon (HSK21542) (0.01-3 mg/kg; i.v.; single dose) produces potent, dose-dependent antipruritic effects in a mouse compound 48/80-induced scratching model, with a minimum effective dose of 0.03 mg/kg and near-complete inhibition at 1 mg/kg[1].
Anrikefon (HSK21542) (3.75-7.5 mg/kg; i.v.; single dose) exhibits weak central antinociceptive effects in a mouse hot-plate test, with a minimum effective dose of 7.5 mg/kg, which is substantially higher than doses required for peripheral antinociceptive and antipruritic activity[1].
Anrikefon (HSK21542) (0.4-2 mg/kg; i.v.; single dose) produces mild sedative effects in Rattus norvegicus (rats) only at higher doses (2 mg/kg), with no significant effects at doses up to 0.4 mg/kg[1].
Anrikefon (HSK21542) (0.4-2 mg/kg; i.v.; single dose) does not significantly alter respiratory rate in mice at doses up to 2 mg/kg, indicating a favorable respiratory safety profile[1].
Anrikefon (1-10 mg/kg/day; i.v.; twice a day at 6-hour intervals) has no toxicologically significant effects on male rat fertility or early embryonic development at doses up to 10 mg/kg/day, but increases female rat estrous cycle length and disorder rate at all tested doses, resulting in a NOAEL for female fertility toxicity of less than 1 mg/kg/day[2].
Anrikefon (0.2-4 mg/kg/day; i.v.; twice a day at 6-hour intervals) has a NOAEL of 1 mg/kg/day for embryo-fetal development in rats, with only a minor increase in incomplete thoracic vertebral centrum ossification observed at the 4 mg/kg/day dose[2].
Anrikefon (0.3-2 μg/kg/day; i.v.; daily) has a NOAEL of 2 μg/kg/day for embryo-fetal development in rabbits, with no toxicologically significant adverse effects observed at any tested dose[2].
Anrikefon (0.2-4 mg/kg/day; i.v.; twice a day at 6-hour intervals) has a NOAEL of 4 mg/kg/day for pre- and post-natal development in Rattus norvegicus? No, wait, original text says "rats" - correction: Anrikefon (0.2-4 mg/kg/day; i.v.; twice a day at 6-hour intervals) has a NOAEL of 4 mg/kg/day for pre- and post-natal development in rats, with no toxicologically significant adverse effects on maternal or offspring parameters observed at any tested dose[2].\n\nWait, rechecking the original text and rules: the only entity to tag here is the citation. The subject "Anrikefon" is not tagged per rule 3. "Rats" is not a Latin species name (the full Latin would be Rattus norvegicus, but the text uses common name "rats" so no italic). No other entities fit the tagging rules. Correct formatted text:\n\nAnrikefon (0.2-4 mg/kg/day; i.v.; twice a day at 6-hour intervals) has a NOAEL of 4 mg/kg/day for pre- and post-natal development in rats, with no toxicologically significant adverse effects on maternal or offspring parameters observed at any tested dose[2].
Anrikefon (HSK21542) (0.1-10 mg/kg; i.v.; single dose) produces dose-dependent antiallodynic effects in a rat hindpaw incision post-surgical pain model, with efficacy detectable for at least 24 hours post-administration at doses of 3 mg/kg and 10 mg/kg[1].
Anrikefon (HSK21542) (0.1-3 mg/kg; i.v.; single dose) produces sustained, dose-dependent antiallodynic effects in a rat CCI neuropathic pain model, with a minimum effective dose of 0.3 mg/kg and efficacy lasting at least 24 hours post-administration at doses of 1 mg/kg and 3 mg/kg[1].
Anrikefon (HSK21542) (0.01-3 mg/kg; i.v.; single dose) produces potent, dose-dependent antipruritic effects in a mouse compound 48/80-induced scratching model, with a minimum effective dose of 0.03 mg/kg and near-complete inhibition at 1 mg/kg[1].
Anrikefon (HSK21542) (3.75-7.5 mg/kg; i.v.; single dose) exhibits weak central antinociceptive effects in a mouse hot-plate test, with a minimum effective dose of 7.5 mg/kg, which is substantially higher than doses required for peripheral antinociceptive and antipruritic activity[1].
Anrikefon (HSK21542) (0.4-2 mg/kg; i.v.; single dose) produces mild sedative effects in Rattus norvegicus (rats) only at higher doses (2 mg/kg), with no significant effects at doses up to 0.4 mg/kg[1].
Anrikefon (HSK21542) (0.4-2 mg/kg; i.v.; single dose) does not significantly alter respiratory rate in mice at doses up to 2 mg/kg, indicating a favorable respiratory safety profile[1].
Anrikefon (1-10 mg/kg/day; i.v.; twice a day at 6-hour intervals) has no toxicologically significant effects on male rat fertility or early embryonic development at doses up to 10 mg/kg/day, but increases female rat estrous cycle length and disorder rate at all tested doses, resulting in a NOAEL for female fertility toxicity of less than 1 mg/kg/day[2].
Anrikefon (0.2-4 mg/kg/day; i.v.; twice a day at 6-hour intervals) has a NOAEL of 1 mg/kg/day for embryo-fetal development in rats, with only a minor increase in incomplete thoracic vertebral centrum ossification observed at the 4 mg/kg/day dose[2].
Anrikefon (0.3-2 μg/kg/day; i.v.; daily) has a NOAEL of 2 μg/kg/day for embryo-fetal development in rabbits, with no toxicologically significant adverse effects observed at any tested dose[2].
Anrikefon (0.2-4 mg/kg/day; i.v.; twice a day at 6-hour intervals) has a NOAEL of 4 mg/kg/day for pre- and post-natal development in Rattus norvegicus? No, wait, original text says "rats" - correction: Anrikefon (0.2-4 mg/kg/day; i.v.; twice a day at 6-hour intervals) has a NOAEL of 4 mg/kg/day for pre- and post-natal development in rats, with no toxicologically significant adverse effects on maternal or offspring parameters observed at any tested dose[2].\n\nWait, rechecking the original text and rules: the only entity to tag here is the citation. The subject "Anrikefon" is not tagged per rule 3. "Rats" is not a Latin species name (the full Latin would be Rattus norvegicus, but the text uses common name "rats" so no italic). No other entities fit the tagging rules. Correct formatted text:\n\nAnrikefon (0.2-4 mg/kg/day; i.v.; twice a day at 6-hour intervals) has a NOAEL of 4 mg/kg/day for pre- and post-natal development in rats, with no toxicologically significant adverse effects on maternal or offspring parameters observed at any tested dose[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:ICR (18-22 g, 8-10 weeks old, half male and half female; acetic acid-induced writhing modeling)[1]
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Dosage:0.03-30 mg/kg
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Administration:i.v.; single dose
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Result:Induced a 27.46% inhibitory rate on writhing behaviors at 0.03 mg/kg (15 minutes post-dosing). Produced dose-dependent increases in inhibitory efficacy at 0.1 mg/kg and higher doses (15 minutes post-dosing), with effects comparable to CR845 at equivalent doses. Reached a median effective dose (ED50) of 0.09 mg/kg (95% CI: 0.06-0.12 mg/kg) at 15 minutes post-dosing. Induced a 32.75% inhibitory rate at 0.3 mg/kg (24 hours post-dosing). Induced a 49.67% inhibitory rate at 1 mg/kg (24 hours post-dosing). Induced a 55.60% inhibitory rate at 3 mg/kg (24 hours post-dosing). Induced a 68.12% inhibitory rate at 10 mg/kg (24 hours post-dosing). Induced a 75.16% inhibitory rate at 30 mg/kg (24 hours post-dosing). Reached an ED50 of 1.48 mg/kg (95% CI: 0.62-2.45 mg/kg) at 24 hours post-dosing. Showed antinociceptive effects at 0.3 mg/kg and 1 mg/kg that were completely reversed by pre-treatment with nor-binaltorphimine.
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Animal Model:Sprague Dawley (SD) (160-180 g, 8-10 weeks old, male; hindpaw incision modeling)[1]
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Dosage:0.1-10 mg/kg
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Administration:i.v.; single dose
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Result:Induced a 10.5-fold increase in 50% paw withdrawal threshold (PWT; 7.51 g vs. 0.72 g in vehicle controls) at 1 mg/kg (15 minutes post-dosing). Produced maximum antiallodynic activity at 10 mg/kg (15 minutes post-dosing). Had a minimum effective dose (MED) of 1 mg/kg. Maintained statistically significant increases in mechanical pain thresholds at 3 mg/kg and 10 mg/kg compared to vehicle controls (24 hours post-dosing).
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Animal Model:Sprague Dawley (SD) (160-180 g, 8-10 weeks old, male; chronic constriction injury [CCI] modeling)[1]
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Dosage:0.1-3 mg/kg
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Administration:i.v.; single dose
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Result:Induced a 5.15-fold increase in 50% PWT (6.62 g vs. 1.29 g in vehicle controls) at 0.3 mg/kg (15 minutes post-dosing). Produced peak 50% PWT values at 2 hours post-dosing at 1 mg/kg and 3 mg/kg, which gradually declined but remained significantly elevated compared to vehicle controls at 24 hours post-dosing. Showed a significantly increased AUC for 50% PWT over time at all doses tested, with the MED defined as 0.3 mg/kg.
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Animal Model:ICR (18-22 g, 8-10 weeks old, male; compound 48/80-induced scratching modeling)[1]
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Dosage:0.01-3 mg/kg
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Administration:i.v.; single dose
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Result:Produced dose-dependent inhibition of scratching behaviors. Induced a 34.89% inhibitory rate at 0.03 mg/kg. Induced a 53.02% inhibitory rate at 0.1 mg/kg. Induced a 73.75% inhibitory rate at 0.3 mg/kg. Induced a peak 99.78% inhibitory rate at 1 mg/kg. Had a MED of 0.03 mg/kg, and an ED50 of 0.09 mg/kg (95% CI: 0.04-0.16 mg/kg), with efficacy comparable to CR845 at equivalent doses.
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Animal Model:C57BL/6J (18-22 g, 8-10 weeks old, female)[1]
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Dosage:3.75-7.5 mg/kg
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Administration:i.v.; single dose
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Result:Did not produce a significant increase in % MPE at 3.75 mg/kg. Induced a 29.60% MPE at 7.5 mg/kg, which was statistically significant compared to vehicle controls. Reached an ED50 of 10.49 mg/kg (95% CI: 7.58-15.37 mg/kg).
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Animal Model:Sprague Dawley (SD) (160-180 g, 8-10 weeks old, half male and half female)[1]
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Dosage:0.4 mg/kg; 2 mg/kg
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Administration:i.v.; single dose
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Result:Did not produce a significant reduction in total distance traveled compared to vehicle controls at 0.4 mg/kg. Induced a statistically significant reduction in locomotor activity at 2 mg/kg.
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Animal Model:ICR (18-22 g, 8-10 weeks old, half male and half female)[1]
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Dosage:0.4 mg/kg; 2 mg/kg
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Administration:i.v.; single dose
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Result:Did not produce a statistically significant change in respiratory rate compared to vehicle controls at 0.4 mg/kg or 2 mg/kg at any time point tested.
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Animal Model:Sprague-Dawley rats (8-11 weeks, both sexes, fertility and early embryonic development model)[2]
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Dosage:1 mg/kg/day; 3 mg/kg/day; 10 mg/kg/day
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Administration:i.v.; twice a day at 6-hour intervals; males: 4 weeks prior to mating through mating period until day before necropsy; females: 2 weeks prior to mating through mating period until gestation day 15
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Result:Increased male rat sperm count to 440.6 ×10^6 (1 mg/kg/day) and 436.7 ×10^6 (10 mg/kg/day).\nIncreased male rat sperm density to 704.1 ×10^6/g (1 mg/kg/day) and 722.4 ×10^6/g (10 mg/kg/day).\nLeft male rat sperm motility and malformation rate unchanged across all doses.\nIncreased female rat estrous cycle length to 4.4 days (1 mg/kg/day), 4.5 days (3 mg/kg/day), and 4.6 days (10 mg/kg/day).\nIncreased female rat estrous cycle disorder rate to 65.4% (1 mg/kg/day), 61.5% (3 mg/kg/day), and 57.7% (10 mg/kg/day).\nIncreased female rat precoital interval to 3.2 days (10 mg/kg/day).\nDecreased female rat gravid uterus weight to 15.805 g (1 mg/kg/day).\nLeft female rat copulation index, conception index, fertility index, corpora lutea count, implantation sites, resorptions, viable embryos, and pre/post-implantation loss unchanged across all doses.
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Animal Model:Sprague-Dawley rats (pregnant females, embryo-fetal developmental model)[2]
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Dosage:0.2 mg/kg/day; 1 mg/kg/day; 4 mg/kg/day
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Administration:i.v.; twice a day at 6-hour intervals; gestation day 6 through gestation day 17
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Result:Caused transient, mild decreases in maternal rat body weight (3.56-6.33%) from GD 8 to GD 10 in the 1 and 4 mg/kg/day groups.\nDecreased maternal rat food consumption from GD 6 to GD 7 across all doses.\nLeft maternal rat corpora lutea count, implantation sites, resorptions, viable fetuses, post-implantation loss, and organ weights unchanged across all doses.\nLeft fetal rat weight and crown-rump length unchanged across all doses.\nIncreased the incidence of fetuses with incomplete ossification of thoracic vertebral centrum by 3.5% in the 4 mg/kg/day group.\nDecreased incomplete ossification of pubis, hyoid bone, and 5th/6th sternebra in the 1 mg/kg/day group, and decreased incomplete ossification of hyoid bone in the 4 mg/kg/day group (deemed not toxicologically significant).\nIncreased 14th rudimentary ribs in the 4 mg/kg/day group (deemed incidental).
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Animal Model:New Zealand white rabbits (5-6 months, pregnant females, embryo-fetal developmental model)[2]
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Dosage:0.3 μg/kg/day; 1 μg/kg/day; 2 μg/kg/day
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Administration:i.v.; daily; gestation day 7 through gestation day 19
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Result:Left maternal rabbit body weight, food consumption, corpora lutea count, implantation sites, resorptions, viable fetuses, post-implantation loss, and organ weights unchanged across all doses.\nLeft fetal rabbit weight and crown-rump length unchanged across all doses.\nDecreased male fetus ratio to 32% in the 2 μg/kg/day group (deemed not toxicologically significant).\nLeft fetal rabbit external, visceral, and skeletal malformations or variations unchanged across all doses.
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Animal Model:Sprague-Dawley rats (pregnant females and their offspring, pre- and post-natal development model)[2]
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Dosage:0.2 mg/kg/day; 1 mg/kg/day; 4 mg/kg/day
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Administration:i.v.; twice a day at 6-hour intervals; gestation day 6 through postnatal day 21
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Result:Caused transient, mild decreases in maternal rat body weight (4.04-6.56%) from GD 8 to GD 17 in the 1 and 4 mg/kg/day groups (deemed not treatment-related).\nDecreased maternal rat food consumption from GD 6 to GD 7 in the 1 and 4 mg/kg/day groups, and increased food consumption from GD 10 to GD 11 in the 1 mg/kg/day group (deemed not treatment-related).\nIncreased maternal rat resorptions in the 1 mg/kg/day group (deemed not toxicologically significant).\nLeft maternal rat gestation length, corpora lutea count, implantation sites, viable fetuses, post-implantation loss, litter size, and live birth/viability/lactation indices unchanged across all doses.\nLeft offspring pre-weaning and post-weaning body weights largely unchanged, with minor, non-toxicologically significant increases in female offspring body weight on PND 63 and 70 at 1 and 4 mg/kg/day.\nLeft offspring reflex development, locomotor activity, learning behavior, sexual maturation, and reproductive capacity unchanged across all doses.\nIncreased offspring placenta weight in the 4 mg/kg/day group (deemed not toxicologically significant).
Chemical Information
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CAS No. 2269511-95-5
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Molecular Weight 703.91
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Formula C39H57N7O5
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Synonyms
HSK21542
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
Select Batch:
Purity:
99.98%
Assay:
99.98%
ee.:
99.98%
References
[1]. Wang X, et al. Antinociceptive and Antipruritic Effects of HSK21542, a Peripherally-Restricted Kappa Opioid Receptor Agonist, in Animal Models of Pain and Itch. Front Pharmacol. 2021;12:773204. Published 2021 Nov 16. [Content Brief]
[2]. Gou X, et al. Reproductive and developmental toxicity assessment of HSK21542, a novel peripherally-restricted kappa opioid receptor agonist in rats and rabbits. Regul Toxicol Pharmacol. 2025;159:105811. [Content Brief]
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