WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H329684
CAS#: 1138245-13-2 (free base)
Description: Mirogabalin, also known as DS-5565, is an α2δ-1 ligand being developed for pain associated with diabetic peripheral neuropathy, fibromyalgia, and postherpetic neuralgia. Mirogabalin was estimated to be 17-fold more potent than pregabalin. Mirogabalin is being developed by Daiichi Sankyo and related to drugs such as gabapentin and pregabalin. Similarly to these drugs, mirogabalin binds to the α2δ calcium channels (1 and 2), but with significantly higher potency than pregabalin. It has shown promising results in Phase II clinical trials for the treatment of diabetic peripheral neuropathic pain.
Hodoodo Cat#: H329684
Name: Mirogabalin free base
CAS#: 1138245-13-2 (free base)
Chemical Formula: C12H19NO2
Exact Mass: 209.14
Molecular Weight: 209.289
Elemental Analysis: C, 68.87; H, 9.15; N, 6.69; O, 15.29
Related CAS #: 1138245-21-2 (besylate) 1138245-13-2 (free base)
Synonym: DS-5565; DS 5565; DS5565; A-2000700; Mirogabalin; Mirogabalin besylate; Mirogabalin free base.
IUPAC/Chemical Name: 2-((1R,5S,6S)-6-(aminomethyl)-3-ethylbicyclo[3.2.0]hept-3-en-6-yl)acetic acid
InChi Key: FTBQORVNHOIASH-CKYFFXLPSA-N
InChi Code: InChI=1S/C12H19NO2/c1-2-8-3-9-5-12(7-13,6-11(14)15)10(9)4-8/h4,9-10H,2-3,5-7,13H2,1H3,(H,14,15)/t9-,10-,12-/m1/s1
SMILES Code: O=C(O)C[C@]1(CN)[C@]2([H])C=C(CC)C[C@]2([H])C1
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
More Info:
| Biological target: | Mirogabalin (DS-5565) is a α2δ-1 ligand characterized by high potency and selectivity to the α2δ-1 subunit of voltage-sensitive calcium channel complexes in the CNS. |
| In vitro activity: | TBD |
| In vivo activity: | Sluka model rats showed significant increases in goal latency (Group factor: F = 19.809, P = 0.0002; repeated-measures ANOVA) and total swimming distance (Group factor: F = 22.303, P = 0.0001; repeated-measures ANOVA), compared with the normal control group. Repeated-measures ANOVA revealed significant differences between the mirogabalin-treated groups and the model control group in goal latency (Group factor: F = 9.496, P = 0.0006) and total swimming distance (Group factor: F = 9.955, P = 0.0004). Post hoc multiple comparison demonstrated significant recovery effects of mirogabalin on goal latency (P = 0.0010 for 3 mg/kg, P = 0.0015 for 10 mg/kg; Dunnett’s test) and total swimming distance (P = 0.0025 for 3 mg/kg, P = 0.0005 for 10 mg/kg; Dunnett’s test). Reference: Biomed Pharmacother. 2021 Jul;139:111647. https://pubmed.ncbi.nlm.nih.gov/33940507/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMF | 0.5 | 2.39 | |
| Ethanol | 1.3 | 5.97 | |
| PBS (pH 7.2) | 0.5 | 2.39 | |
| Water | 5.4 | 25.61 |
The following data is based on the product molecular weight 209.29 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Murasawa H, Pawlak A, Kobayashi H, Saeki K, Yasuda SI, Kitano Y. Mirogabalin, a novel ligand for α2δ subunit of voltage-gated calcium channels, improves cognitive impairments in repeated intramuscular acidic saline injection model rats, an experimental model of fibromyalgia. Biomed Pharmacother. 2021 Jul;139:111647. doi: 10.1016/j.biopha.2021.111647. Epub 2021 Apr 30. PMID: 33940507. 2. Oyama M, Watanabe S, Iwai T, Tanabe M. Mirogabalin activates the descending noradrenergic system by binding to the α2δ-1 subunit of voltage-gated Ca2+ channels to generate analgesic effects. J Pharmacol Sci. 2021 May;146(1):33-39. doi: 10.1016/j.jphs.2021.01.002. Epub 2021 Jan 7. PMID: 33858653. |
| In vitro protocol: | TBD |
| In vivo protocol: | 1. Murasawa H, Pawlak A, Kobayashi H, Saeki K, Yasuda SI, Kitano Y. Mirogabalin, a novel ligand for α2δ subunit of voltage-gated calcium channels, improves cognitive impairments in repeated intramuscular acidic saline injection model rats, an experimental model of fibromyalgia. Biomed Pharmacother. 2021 Jul;139:111647. doi: 10.1016/j.biopha.2021.111647. Epub 2021 Apr 30. PMID: 33940507. 2. Oyama M, Watanabe S, Iwai T, Tanabe M. Mirogabalin activates the descending noradrenergic system by binding to the α2δ-1 subunit of voltage-gated Ca2+ channels to generate analgesic effects. J Pharmacol Sci. 2021 May;146(1):33-39. doi: 10.1016/j.jphs.2021.01.002. Epub 2021 Jan 7. PMID: 33858653. |
1: Calandre EP, Rico-Villademoros F, Slim M. Alpha(2)delta ligands, gabapentin, pregabalin and mirogabalin: a review of their clinical pharmacology and therapeutic use. Expert Rev Neurother. 2016 Nov;16(11):1263-1277. Epub 2016 Jul 7. Review. PubMed PMID: 27345098.
2: Yin OQ, Merante D, Truitt K, Miller R. Population pharmacokinetic modeling and simulation for assessing renal impairment effect on the pharmacokinetics of mirogabalin. J Clin Pharmacol. 2016 Feb;56(2):203-12. doi: 10.1002/jcph.584. Epub 2015 Sep 2. PubMed PMID: 26138993.
3: Vinik A, Rosenstock J, Sharma U, Feins K, Hsu C, Merante D; DS5565-A-U201 US Phase II Study Investigators. Efficacy and safety of mirogabalin (DS-5565) for the treatment of diabetic peripheral neuropathic pain: a randomized, double-blind, placebo- and active comparator-controlled, adaptive proof-of-concept phase 2 study. Diabetes Care. 2014 Dec;37(12):3253-61. doi: 10.2337/dc14-1044. Epub 2014 Sep 17. PubMed PMID: 25231896.
4: Hutmacher MM, Frame B, Miller R, Truitt K, Merante D. Exposure-response modeling of average daily pain score, and dizziness and somnolence, for mirogabalin (DS-5565) in patients with diabetic peripheral neuropathic pain. J Clin Pharmacol. 2016 Jan;56(1):67-77. doi: 10.1002/jcph.567. Epub 2015 Aug 20. PubMed PMID: 26073181.
5: Alcántara Montero A, Ibor Vidal PJ. [Mirogabalin: The next pregabalin?]. Semergen. 2016 Oct 20. pii: S1138-3593(16)30158-7. doi: 10.1016/j.semerg.2016.07.014. [Epub ahead of print] Spanish. PubMed PMID: 27773622.
6: Brown K, Ohwada S, Warren V, Zahir H, Dishy V. (405) A single ascending-dose study of mirogabalin in healthy subjects: safety, tolerability, pharmacokinetic, and pharmacodynamic results. J Pain. 2016 Apr;17(4S):S76. doi: 10.1016/j.jpain.2016.01.382. Epub 2016 Mar 24. PubMed PMID: 28162650.
7: Merante D, Rosenstock J, Sharma U, Feins K, Hsu C, Vinik A; DS-5565-A-U201?US Phase 2 Study Investigators. Efficacy of Mirogabalin (DS-5565) on Patient-Reported Pain and Sleep Interference in Patients with Diabetic Neuropathic Pain: Secondary Outcomes of a Phase II Proof-of-Concept Study. Pain Med. 2017 Mar 23. doi: 10.1093/pm/pnw342. [Epub ahead of print] PubMed PMID: 28371941.
8: Jansen M, Merante D, Currie A, Velinova M, Brown K, Zahir H. (403) Co-administration of mirogabalin and zolpidem in healthy subjects: results from a randomized, double-blind, drug-drug interaction study. J Pain. 2016 Apr;17(4S):S75. doi: 10.1016/j.jpain.2016.01.380. Epub 2016 Mar 24. PubMed PMID: 28162647.
