Mirogabalin (DS-5565) is a potent, selective and orally bioavailable α2δ-1 ligand under development for treating pain associated with diabetic peripheral neuropathy, fibromyalgia, and postherpetic neuralgia. It has affinities 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, respectively. 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.

Physicochemical Properties

Molecular Formula	C12H19NO2
Molecular Weight	209.2848
Exact Mass	209.142
CAS #	1138245-13-2
Related CAS #	1138245-21-2 (besylate);1138245-13-2;
PubChem CID	59509752
Appearance	Light yellow to light brown solid powder
LogP	2.482
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	4
Heavy Atom Count	15
Complexity	311
Defined Atom Stereocenter Count	3
SMILES	CCC1=C[C@@H]2[C@H](C1)C[C@@]2(CC(=O)O)CN
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
Chemical Name	2-((1R,5S,6S)-6-(aminomethyl)-3-ethylbicyclo[3.2.0]hept-3-en-6-yl)acetic acid
Synonyms	DS-5565 DS 5565 DS5565 A-2000700 A2000700A 2000700Mirogabalin besylate Mirogabalin free base.
HS Tariff Code	2934.99.9001
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)

Biological Activity

ln Vitro	Mirogabalin (DS-5565) is a newly developed, highly potent, and selective α2δ-1 ligand for the α2δ-1 subunit of the voltage-sensitive calcium channel complex in the central nervous system (CNS). Milopalin dissociates from α2δ-1 more slowly than α2δ-2 and, in particular, α2δ-1 more slowly than pregabalin, according to in vitro investigations conducted with membrane preparations from human and rat α2δ subunit-expressing cells. In addition, compared to pregabalin, milopalin showed greater analgesic efficacy and broader central nervous system safety while demonstrating strong and prolonged analgesia in streptozotocin-induced diabetic rats. Its selectivity for α2δ-1 and slower dissociation as compared to pregabalin are the reasons for the range [1]. DS-5565, an α2δ-1 ligand, is being developed to treat postherpetic neuralgia, fibromyalgia, and diabetic peripheral neuropathy pain. Milopalin specifically targets α2δ-1, an auxiliary protein linked to voltage-sensitive calcium channel complexes in the brain. Numerous pain neurotransmitters are released less often as a result of this binding's reduction of calcium input into nerve terminals. Milopaline's estimated ED50 (converted scale) is 20.5 mg, with a 90% confidence interval (CI) ranging from 10.1-41.7 mg [2].
ln Vivo	Furthermore, milopalin demonstrated strong and long-lasting analgesic effects in streptozotocin-induced diabetic rats. Its selectivity for α2δ-1 and slow dissociation are responsible for its superior analgesic efficacy and wider central nervous system (CNS) effects as compared to pregabalin safety margin. In contrast to pregabalin [1].
References	[1]. 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. [2]. Exposure-response modeling of average daily pain score, and dizziness and somnolence, forMirogabalin (DS-5565) in patients with diabetic peripheral neuropathic pain. J Clin Pharmacol. 2016 Jan;56(1):67-77.
Additional Infomation	Mirogabalin has been used in trials studying the treatment of Post-herpetic Neuralgia, Pain Associated With Fibromyalgia, and Diabetic peripheral neuropathic pain. See also: Mirogabalin Besylate (annotation moved to).

Solubility Data

Solubility (In Vitro)

H2O : ~7.71 mg/mL (~36.84 mM) DMSO :< 1 mg/mL

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 0.83 mg/mL (3.97 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 8.3 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of 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: ≥ 0.83 mg/mL (3.97 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 8.3 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. Solubility in Formulation 3: ≥ 0.83 mg/mL (3.97 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 8.3 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 4: 10 mg/mL (47.78 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	4.7783 mL	23.8914 mL	47.7829 mL
	5 mM	0.9557 mL	4.7783 mL	9.5566 mL
	10 mM	0.4778 mL	2.3891 mL	4.7783 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.