Synonym
DS-5565; DS 5565; DS5565; A-2000700; Mirogabalin; Mirogabalin besylate.
IUPAC/Chemical Name
2-((1R,5S,6S)-6-(aminomethyl)-3-ethylbicyclo[3.2.0]hept-3-en-6-yl)acetic acid compound with benzenesulfonic acid (1:1)
InChi Key
OKJXJRVWXYRSAN-TXULWXBWSA-N
InChi Code
InChI=1S/C12H19NO2.C6H6O3S/c1-2-8-3-9-5-12(7-13,6-11(14)15)10(9)4-8;7-10(8,9)6-4-2-1-3-5-6/h4,9-10H,2-3,5-7,13H2,1H3,(H,14,15);1-5H,(H,7,8,9)/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.O=S(C3=CC=CC=C3)(O)=O
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 and in water
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
Related CAS#
CAS#1138245-21-2 ( Mirogabalin besylate);
CAS#1138245-13-2 ( Mirogabalin free base).
Biological target:
Mirogabalin besylate is a selective and orally available ligand for the α2δ subunit of voltage-gated calcium channels, with Kds of 13.5 nM, 22.7 nM, 27 nM, and 47.6 nM for human α2δ-1, human α2δ-2, rat α2δ-1, and rat α2δ-2.
In vitro activity:
Mirogabalin showed potent and selective binding affinities for the α2δ subunits, while having no effects on 186 off-target proteins.
Reference: J Pharmacol Exp Ther. 2018 Jun;365(3):573-582. https://pubmed.ncbi.nlm.nih.gov/29563324/
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 |
mg/mL |
mM |
comments |
| Solubility |
| DMSO |
125.0 |
340.17 |
|
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
367.46
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. Yamamura N, Mikkaichi T, Itokawa KI, Hoshi M, Damme K, Geigner S, Baumhauer C. Mirogabalin, a novel α2δ ligand, is not a substrate of LAT1, but of PEPT1, PEPT2, OAT1, OAT3, OCT2, MATE1 and MATE2-K. Xenobiotica. 2022 Sep-Nov;52(9-11):997-1009. doi: 10.1080/00498254.2022.2129517. Epub 2022 Oct 6. PMID: 36170033.
2. Domon Y, Arakawa N, Inoue T, Matsuda F, Takahashi M, Yamamura N, Kai K, Kitano Y. Binding Characteristics and Analgesic Effects of Mirogabalin, a Novel Ligand for the α2δ Subunit of Voltage-Gated Calcium Channels. J Pharmacol Exp Ther. 2018 Jun;365(3):573-582. doi: 10.1124/jpet.117.247551. Epub 2018 Mar 21. PMID: 29563324.
3. 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.
4. 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:
1. Yamamura N, Mikkaichi T, Itokawa KI, Hoshi M, Damme K, Geigner S, Baumhauer C. Mirogabalin, a novel α2δ ligand, is not a substrate of LAT1, but of PEPT1, PEPT2, OAT1, OAT3, OCT2, MATE1 and MATE2-K. Xenobiotica. 2022 Sep-Nov;52(9-11):997-1009. doi: 10.1080/00498254.2022.2129517. Epub 2022 Oct 6. PMID: 36170033.
2. Domon Y, Arakawa N, Inoue T, Matsuda F, Takahashi M, Yamamura N, Kai K, Kitano Y. Binding Characteristics and Analgesic Effects of Mirogabalin, a Novel Ligand for the α2δ Subunit of Voltage-Gated Calcium Channels. J Pharmacol Exp Ther. 2018 Jun;365(3):573-582. doi: 10.1124/jpet.117.247551. Epub 2018 Mar 21. PMID: 29563324.
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.
