Synonym
M22 NEDD8 inhibitor; M22; M-22; M 22; NAE-IN-M22
IUPAC/Chemical Name
1-benzyl-N-(2,4-dichlorophenethyl)piperidin-4-amine
InChi Key
WMEXQHGRMWPOEF-UHFFFAOYSA-N
InChi Code
InChI=1S/C20H24Cl2N2/c21-18-7-6-17(20(22)14-18)8-11-23-19-9-12-24(13-10-19)15-16-4-2-1-3-5-16/h1-7,14,19,23H,8-13,15H2
SMILES Code
ClC1=CC=C(C(Cl)=C1)CCNC2CCN(CC3=CC=CC=C3)CC2
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
Biological target:
M22 NEDD8 inhibitor is a novel, potent, selective reversible NEDD8 activating enzyme (NAE) inhibitor.
In vitro activity:
HMPV M2-2 was the most potent inhibitor of RIG-I/TRIM25-mediated interferon (IFN)-β activation. M2-2 silencing induced the activation of transcription factors (IRF and NF-kB) downstream of RIG-I signaling in A549 cells. Moreover, M2-2 inhibited RIG-I ubiquitination and CARD-dependent interactions with MAVS.
Reference: Front Immunol. 2022 Aug 15;13:970750. https://pubmed.ncbi.nlm.nih.gov/36045682/
In vivo activity:
M22 is reversible for NAE, inhibits multiple cancer cell lines with GI50 values in the low micromolar range, and induces apoptosis in A549 cells. Furthermore, it produces tumor inhibition in AGS xenografts in nude mice and low acute toxicity in a zebrafish model. M22, a novel NAE inhibitor, represents a promising lead structure for the development of new antitumor agents.
Reference: ACS Chem Biol. 2016 Jul 15;11(7):1901-7. https://pubmed.ncbi.nlm.nih.gov/27135934/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
161.5 |
444.50 |
| Ethanol |
73.0 |
200.92 |
| Water |
4.0 |
11.01 |
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
363.33
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. Umetsu A, Sato T, Watanabe M, Ida Y, Furuhashi M, Tsugeno Y, Ohguro H. Unexpected Crosslinking Effects of a Human Thyroid Stimulating Monoclonal Autoantibody, M22, with IGF1 on Adipogenesis in 3T3L-1 Cells. Int J Mol Sci. 2023 Jan 6;24(2):1110. doi: 10.3390/ijms24021110. PMID: 36674625; PMCID: PMC9863235.
2. Tanaka Y, Morita N, Kitagawa Y, Gotoh B, Komatsu T. Human metapneumovirus M2-2 protein inhibits RIG-I signaling by preventing TRIM25-mediated RIG-I ubiquitination. Front Immunol. 2022 Aug 15;13:970750. doi: 10.3389/fimmu.2022.970750. PMID: 36045682; PMCID: PMC9421128.
3. Lu P, Liu X, Yuan X, He M, Wang Y, Zhang Q, Ouyang PK. Discovery of a novel NEDD8 Activating Enzyme Inhibitor with Piperidin-4-amine Scaffold by Structure-Based Virtual Screening. ACS Chem Biol. 2016 Jul 15;11(7):1901-7. doi: 10.1021/acschembio.6b00159. Epub 2016 May 6. PMID: 27135934.
4. Furmaniak J, Sanders J, Young S, Kabelis K, Sanders P, Evans M, Clark J, Wilmot J, Rees Smith B. In vivo effects of a human thyroid-stimulating monoclonal autoantibody (M22) and a human thyroid-blocking autoantibody (K1-70). Auto Immun Highlights. 2011 Sep 14;3(1):19-25. doi: 10.1007/s13317-011-0025-9. PMID: 26000124; PMCID: PMC4389019.
In vitro protocol:
1. Umetsu A, Sato T, Watanabe M, Ida Y, Furuhashi M, Tsugeno Y, Ohguro H. Unexpected Crosslinking Effects of a Human Thyroid Stimulating Monoclonal Autoantibody, M22, with IGF1 on Adipogenesis in 3T3L-1 Cells. Int J Mol Sci. 2023 Jan 6;24(2):1110. doi: 10.3390/ijms24021110. PMID: 36674625; PMCID: PMC9863235.
2. Tanaka Y, Morita N, Kitagawa Y, Gotoh B, Komatsu T. Human metapneumovirus M2-2 protein inhibits RIG-I signaling by preventing TRIM25-mediated RIG-I ubiquitination. Front Immunol. 2022 Aug 15;13:970750. doi: 10.3389/fimmu.2022.970750. PMID: 36045682; PMCID: PMC9421128.
In vivo protocol:
1. Lu P, Liu X, Yuan X, He M, Wang Y, Zhang Q, Ouyang PK. Discovery of a novel NEDD8 Activating Enzyme Inhibitor with Piperidin-4-amine Scaffold by Structure-Based Virtual Screening. ACS Chem Biol. 2016 Jul 15;11(7):1901-7. doi: 10.1021/acschembio.6b00159. Epub 2016 May 6. PMID: 27135934.
2. Furmaniak J, Sanders J, Young S, Kabelis K, Sanders P, Evans M, Clark J, Wilmot J, Rees Smith B. In vivo effects of a human thyroid-stimulating monoclonal autoantibody (M22) and a human thyroid-blocking autoantibody (K1-70). Auto Immun Highlights. 2011 Sep 14;3(1):19-25. doi: 10.1007/s13317-011-0025-9. PMID: 26000124; PMCID: PMC4389019.
1: Ni S, Chen X, Yu Q, Xu Y, Hu Z, Zhang J, Zhang W, Li B, Yang X, Mao F, Huang J, Sun Y, Li J, Jia L. Discovery of candesartan cilexetic as a novel neddylation inhibitor for suppressing tumor growth. Eur J Med Chem. 2020 Jan 1;185:111848. doi: 10.1016/j.ejmech.2019.111848. Epub 2019 Nov 4. PMID: 31732254.
2: Lu P, Liu X, Yuan X, He M, Wang Y, Zhang Q, Ouyang PK. Discovery of a novel NEDD8 Activating Enzyme Inhibitor with Piperidin-4-amine Scaffold by Structure- Based Virtual Screening. ACS Chem Biol. 2016 Jul 15;11(7):1901-7. doi: 10.1021/acschembio.6b00159. Epub 2016 May 6. PMID: 27135934.
