Synonym
NS-11394; NS 11394; NS11394.
IUPAC/Chemical Name
3'-(5-(2-hydroxypropan-2-yl)-1H-benzo[d]imidazol-1-yl)-[1,1'-biphenyl]-2-carbonitrile
InChi Key
HLKYSQGBIIIQJN-UHFFFAOYSA-N
InChi Code
InChI=1S/C23H19N3O/c1-23(2,27)18-10-11-22-21(13-18)25-15-26(22)19-8-5-7-16(12-19)20-9-4-3-6-17(20)14-24/h3-13,15,27H,1-2H3
SMILES Code
N#CC1=CC=CC=C1C2=CC=CC(N3C4=CC=C(C(C)(O)C)C=C4N=C3)=C2
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, not 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
Biological target:
NS11394 is an orally active and unique subtype-selective GABAA positive allosteric receptor (PAM), with a Ki of ~0.5 nM.
In vitro activity:
Specifically, this study show that NS11394 is potent and highly effective in rodent anxiety models. NS11394 impairs memory in both rats and mice, which is possibly attributable to its efficacy at GABA(A)-alpha(5) receptors, albeit activity at this receptor might be relevant to its antinociceptive effects (J Pharmacol Exp Ther 327:doi;10.1124/jpet.108.144, 2008). In conclusion, NS11394 has a unique subtype-selective GABA(A) receptor profile and represents an excellent pharmacological tool to further our understanding on the relative contributions of GABA(A) receptor subtypes in various therapeutic areas.
Reference: J Pharmacol Exp Ther. 2008 Dec;327(3):954-68. https://pubmed.ncbi.nlm.nih.gov/18791063/
In vivo activity:
Oral administration of NS11394 (1-30 mg/kg) to rats attenuated spontaneous nociceptive behaviors in response to hindpaw injection of formalin and capsaicin, effects that were blocked by the benzodiazepine site antagonist flumazenil. Ongoing inflammatory nociception, observed as hindpaw weight-bearing deficits after Freund's adjuvant injection, was also completely reversed by NS11394. Likewise, hindpaw mechanical allodynia was fully reversed by NS11394 in two rat models of peripheral neuropathic pain.
Reference: J Pharmacol Exp Ther. 2008 Dec;327(3):969-81. https://pubmed.ncbi.nlm.nih.gov/18791060/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMF |
33.0 |
93.37 |
| DMSO |
68.0 |
192.40 |
| Ethanol |
52.0 |
147.13 |
| Ethanol:PBS (pH 7.2) (1:5) |
0.2 |
0.45 |
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
353.43
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. Mirza NR, Larsen JS, Mathiasen C, Jacobsen TA, Munro G, Erichsen HK, Nielsen AN, Troelsen KB, Nielsen EØ, Ahring PK. NS11394 [3'-[5-(1-hydroxy-1-methyl-ethyl)-benzoimidazol-1-yl]-biphenyl-2-carbonitrile], a unique subtype-selective GABAA receptor positive allosteric modulator: in vitro actions, pharmacokinetic properties and in vivo anxiolytic efficacy. J Pharmacol Exp Ther. 2008 Dec;327(3):954-68. doi: 10.1124/jpet.108.138859. Epub 2008 Sep 12. PMID: 18791063.
2. Spröte C, Richter F, Bauer A, Gerstenberger J, Richter A. The α2β3γ2 GABAA receptor preferring agonist NS11394 aggravates dystonia in the phenotypic dtsz model. Eur J Pharmacol. 2016 Nov 15;791:655-658. doi: 10.1016/j.ejphar.2016.09.040. Epub 2016 Sep 30. PMID: 27693801.
3. Munro G, Lopez-Garcia JA, Rivera-Arconada I, Erichsen HK, Nielsen EØ, Larsen JS, Ahring PK, Mirza NR. Comparison of the novel subtype-selective GABAA receptor-positive allosteric modulator NS11394 [3'-[5-(1-hydroxy-1-methyl-ethyl)-benzoimidazol-1-yl]-biphenyl-2-carbonitrile] with diazepam, zolpidem, bretazenil, and gaboxadol in rat models of inflammatory and neuropathic pain. J Pharmacol Exp Ther. 2008 Dec;327(3):969-81. doi: 10.1124/jpet.108.144568. Epub 2008 Sep 12. PMID: 18791060.
In vitro protocol:
1. Mirza NR, Larsen JS, Mathiasen C, Jacobsen TA, Munro G, Erichsen HK, Nielsen AN, Troelsen KB, Nielsen EØ, Ahring PK. NS11394 [3'-[5-(1-hydroxy-1-methyl-ethyl)-benzoimidazol-1-yl]-biphenyl-2-carbonitrile], a unique subtype-selective GABAA receptor positive allosteric modulator: in vitro actions, pharmacokinetic properties and in vivo anxiolytic efficacy. J Pharmacol Exp Ther. 2008 Dec;327(3):954-68. doi: 10.1124/jpet.108.138859. Epub 2008 Sep 12. PMID: 18791063.
In vivo protocol:
1. Spröte C, Richter F, Bauer A, Gerstenberger J, Richter A. The α2β3γ2 GABAA receptor preferring agonist NS11394 aggravates dystonia in the phenotypic dtsz model. Eur J Pharmacol. 2016 Nov 15;791:655-658. doi: 10.1016/j.ejphar.2016.09.040. Epub 2016 Sep 30. PMID: 27693801.
2. Munro G, Lopez-Garcia JA, Rivera-Arconada I, Erichsen HK, Nielsen EØ, Larsen JS, Ahring PK, Mirza NR. Comparison of the novel subtype-selective GABAA receptor-positive allosteric modulator NS11394 [3'-[5-(1-hydroxy-1-methyl-ethyl)-benzoimidazol-1-yl]-biphenyl-2-carbonitrile] with diazepam, zolpidem, bretazenil, and gaboxadol in rat models of inflammatory and neuropathic pain. J Pharmacol Exp Ther. 2008 Dec;327(3):969-81. doi: 10.1124/jpet.108.144568. Epub 2008 Sep 12. PMID: 18791060.
1: Hofmann M, Kordás KS, Gravius A, Bölcskei K, Parsons CG, Dekundy A, Danysz W, Dézsi L, Wittko-Schneider IM, Sághy K, Gyertyán I, Horváth C. Assessment of the effects of NS11394 and L-838417, α2/3 subunit-selective GABA(A) [corrected] receptor-positive allosteric modulators, in tests for pain, anxiety, memory and motor function. Behav Pharmacol. 2012 Dec;23(8):790-801. doi: 10.1097/FBP.0b013e32835a7c7e. Erratum in: Behav Pharmacol. 2013 Apr;24(2):153. PubMed PMID: 23075708.
2: Hansen RR, Erichsen HK, Brown DT, Mirza NR, Munro G. Positive allosteric modulation of GABA-A receptors reduces capsaicin-induced primary and secondary hypersensitivity in rats. Neuropharmacology. 2012 Dec;63(8):1360-7. doi: 10.1016/j.neuropharm.2012.08.002. Epub 2012 Aug 17. PubMed PMID: 22985969.
3: Mirza NR, Larsen JS, Mathiasen C, Jacobsen TA, Munro G, Erichsen HK, Nielsen AN, Troelsen KB, Nielsen EØ, Ahring PK. NS11394 [3'-[5-(1-hydroxy-1-methyl-ethyl)-benzoimidazol-1-yl]-biphenyl-2-carbonitrile], a unique subtype-selective GABAA receptor positive allosteric modulator: in vitro actions, pharmacokinetic properties and in vivo anxiolytic efficacy. J Pharmacol Exp Ther. 2008 Dec;327(3):954-68. doi: 10.1124/jpet.108.138859. Epub 2008 Sep 12. PubMed PMID: 18791063.
4: Munro G, Lopez-Garcia JA, Rivera-Arconada I, Erichsen HK, Nielsen EØ, Larsen JS, Ahring PK, Mirza NR. Comparison of the novel subtype-selective GABAA receptor-positive allosteric modulator NS11394 [3'-[5-(1-hydroxy-1-methyl-ethyl)-benzoimidazol-1-yl]-biphenyl-2-carbonitrile] with diazepam, zolpidem, bretazenil, and gaboxadol in rat models of inflammatory and neuropathic pain. J Pharmacol Exp Ther. 2008 Dec;327(3):969-81. doi: 10.1124/jpet.108.144568. Epub 2008 Sep 12. PubMed PMID: 18791060.
