Synonym
CID23723457; CID-23723457; CID 23723457; ML335; ML-335; ML 335; CYM51010; CYM-51010; CYM 51010;
IUPAC/Chemical Name
1-[[4-(Acetylamino)phenyl]methyl]-4-(2-phenylethyl)-4-Piperidinecarboxylic acid ethyl ester
InChi Key
VUXRYYSKTWDPLO-UHFFFAOYSA-N
InChi Code
InChI=1S/C25H32N2O3/c1-3-30-24(29)25(14-13-21-7-5-4-6-8-21)15-17-27(18-16-25)19-22-9-11-23(12-10-22)26-20(2)28/h4-12H,3,13-19H2,1-2H3,(H,26,28)
SMILES Code
O=C(C1(CCC2=CC=CC=C2)CCN(CC3=CC=C(NC(C)=O)C=C3)CC1)OCC
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
To be determined
Shelf Life
>2 years if stored properly
Drug Formulation
To be determined
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:
CYM51010 is a biased ligand of μ-opioid receptor – δ-opioid receptor heterodimers with an EC50 of 403 nM.
In vitro activity:
This study reports the identification of compounds targeting μOR-δOR heteromers through high-throughput screening of a small-molecule library. Among them, CYM51010 was found to be a μOR-δOR-biased ligand, because its activity is blocked by the μOR-δOR heteromer antibody. Notably, systemic administration of CYM51010 induced antinociceptive activity similar to morphine, and chronic administration of CYM51010 resulted in lesser antinociceptive tolerance compared with morphine. Taken together, these results suggest that CYM51010, a μOR-δOR-biased ligand, could serve as a scaffold for the development of a unique type (heteromer-biased) of drug that is more potent and without the severe side effects associated with conventional clinical opioids.
Reference: Proc Natl Acad Sci U S A. 2013 Jul 16;110(29):12072-7. https://pubmed.ncbi.nlm.nih.gov/23818586/
In vivo activity:
This study examined the effects of spinal nerve injury on µ-δ heteromer expression in dorsal root ganglion (DRG) neurons and the effects of a µ-δ heteromer-targeting agonist, CYM51010, on neuropathic pain behavior in rats and mice. Importantly, in SNL rats, subcutaneous injection of CYM51010 inhibited mechanical hypersensitivity in a dose-related manner (EC50: 1.09 mg/kg) and also reversed heat hyperalgesia and attenuated ongoing pain (2 mg/kg, subcutaneously). Electrophysiologic studies showed that CYM51010 inhibited the C-component and windup phenomenon in spinal wide dynamic range neurons of SNL rats. The pain inhibitory effects of CYM51010 persisted in morphine-tolerant rats but was markedly attenuated in µ-OR knockout mice.
Reference: Pain. 2020 Apr;161(4):842-855. https://pubmed.ncbi.nlm.nih.gov/31815916/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
5.0 |
12.24 |
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
408.54
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. Gomes I, Fujita W, Gupta A, Saldanha SA, Negri A, Pinello CE, Eberhart C, Roberts E, Filizola M, Hodder P, Devi LA. Identification of a μ-δ opioid receptor heteromer-biased agonist with antinociceptive activity. Proc Natl Acad Sci U S A. 2013 Jul 16;110(29):12072-7. doi: 10.1073/pnas.1222044110. Epub 2013 Jul 1. Erratum in: Proc Natl Acad Sci U S A. 2013 Oct 15;110(42):1760. Saldanha, Adrian S [corrected to Saldanha, S Adrian]; Eberhart, Christina [added]. PMID: 23818586; PMCID: PMC3718106.
2. Tiwari V, He SQ, Huang Q, Liang L, Yang F, Chen Z, Tiwari V, Fujita W, Devi LA, Dong X, Guan Y, Raja SN. Activation of µ-δ opioid receptor heteromers inhibits neuropathic pain behavior in rodents. Pain. 2020 Apr;161(4):842-855. doi: 10.1097/j.pain.0000000000001768. PMID: 31815916; PMCID: PMC7085422.
In vitro protocol:
Gomes I, Fujita W, Gupta A, Saldanha SA, Negri A, Pinello CE, Eberhart C, Roberts E, Filizola M, Hodder P, Devi LA. Identification of a μ-δ opioid receptor heteromer-biased agonist with antinociceptive activity. Proc Natl Acad Sci U S A. 2013 Jul 16;110(29):12072-7. doi: 10.1073/pnas.1222044110. Epub 2013 Jul 1. Erratum in: Proc Natl Acad Sci U S A. 2013 Oct 15;110(42):1760. Saldanha, Adrian S [corrected to Saldanha, S Adrian]; Eberhart, Christina [added]. PMID: 23818586; PMCID: PMC3718106.
In vivo protocol:
Tiwari V, He SQ, Huang Q, Liang L, Yang F, Chen Z, Tiwari V, Fujita W, Devi LA, Dong X, Guan Y, Raja SN. Activation of µ-δ opioid receptor heteromers inhibits neuropathic pain behavior in rodents. Pain. 2020 Apr;161(4):842-855. doi: 10.1097/j.pain.0000000000001768. PMID: 31815916; PMCID: PMC7085422.
1: Zyrianova T, Lopez B, Olcese R, Belperio J, Waters CM, Wong L, Nguyen V, Talapaneni S, Schwingshackl A. K2P2.1 (TREK-1) potassium channel activation protects against hyperoxia-induced lung injury. Sci Rep. 2020 Dec 15;10(1):22011. doi: 10.1038/s41598-020-78886-y. PMID: 33319831; PMCID: PMC7738539.
2: Lolicato M, Natale AM, Abderemane-Ali F, Crottès D, Capponi S, Duman R, Wagner A, Rosenberg JM, Grabe M, Minor DL Jr. K2P channel C-type gating involves asymmetric selectivity filter order-disorder transitions. Sci Adv. 2020 Oct 30;6(44):eabc9174. doi: 10.1126/sciadv.abc9174. PMID: 33127683; PMCID: PMC7608817.
3: Lolicato M, Arrigoni C, Mori T, Sekioka Y, Bryant C, Clark KA, Minor DL Jr. K2P2.1 (TREK-1)-activator complexes reveal a cryptic selectivity filter binding site. Nature. 2017 Jul 20;547(7663):364-368. doi: 10.1038/nature22988. Epub 2017 Jul 10. PMID: 28693035; PMCID: PMC5778891.
4: Pinello C, Guerrero M, Eberhart C, Volmar CH, Saldanha SA, Cayanan C, Urbano M, Brown SJ, Ferguson J, Gomes I, Devi LA, Roberts E, Hodder P, Rosen H. Characterization of an agonist probe for opioid receptor mu 1 (OPRM1)-opioid receptor delta 1 (OPRD1) heterodimerization. 2012 Dec 17 [updated 2013 Apr 5]. In: Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010–. PMID: 23833799.
