Synonym
MS402; MS-402; MS 402;
IUPAC/Chemical Name
3-Chloro-N-(4-methoxyphenyl)-4-((2-methyl-3-oxocyclopent-1-en-1-yl)amino)benzamide
InChi Key
VZTVTSICPINUNG-UHFFFAOYSA-N
InChi Code
InChI=1S/C20H19ClN2O3/c1-12-17(9-10-19(12)24)23-18-8-3-13(11-16(18)21)20(25)22-14-4-6-15(26-2)7-5-14/h3-8,11,23H,9-10H2,1-2H3,(H,22,25)
SMILES Code
O=C(NC1=CC=C(OC)C=C1)C2=CC=C(NC3=C(C)C(CC3)=O)C(Cl)=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
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:
MS402 is a BD1-selective BET BrD inhibitor with Kis of 77 nM, 718 nM, 110 nM, 200 nM, 83 nM, and 240 nM for BRD4(BD1), BRD4(BD2), BRD3(BD1), BRD3(BD2), BRD2(BD1) and BRD2(BD2), respectively.
In vitro activity:
To study the role of BET proteins in Th cell differentiation, murine primary naïve CD4+ T cells were isolated from mouse spleen and lymph nodes and treated with IL-12, IL-4 plus α-IL-12, TGF-β plus IL-6, or TGF-β plus IL-2, respectively, to promote Th1, Th2, Th17, or Treg linage-specific differentiation over 3.5 d with or without MS402 added daily to cell culture (Fig. 2A). Strikingly, as shown by flow cytometry analysis, MS402, in a dose-dependent manner, inhibited IL-17 release from 18.6 to 8.0% in the Th17 polarizing condition and to a lesser extent IFN-γ production from 49.7 to 38.6% in the Th1 condition; it had little, if any, effect on IL-4 and Foxp3 expression during Th2 and Treg cell differentiation, respectively (Fig. 2B).
Reference: Proc Natl Acad Sci U S A. 2017 Mar 14;114(11):2952-2957. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5358349/
In vivo activity:
An in vivo experimental colitis study to explore therapeutic potential of MS402 was conducted. Mice treated with MS402 exhibited a reversal of weight loss after 1 wk (Fig. 4G). Consistently, the MS402-treated mice showed an almost minimal degree of inflammation in the colon, as demonstrated by much improved colon length and appearance (Fig. S4A), a lower disease score of 0–1 (Fig. S4B), and markedly reduced inflammatory cell infiltrates in colon sections as compared with those of the disease-group mice (Fig. 4H). Further, the MS402-treated mice also had a lower population of IFN-γ–producing CD4+ T cells and exhibited a much more dramatic reduction of IL-17–producing CD4+ T cells in colon than the group of T-cell-transfer disease mice (Fig. 4I). Finally, the MS402-treated mice had much lower mRNA expression levels of key cytokines and Th17- and Th1-specific transcription factors including il17, il21, il22, il6, rorc, Tbet, and ifng compared with the disease-group mice (Fig. 4J). Collectively, these results show that MS402 is an effective inhibitor of Th17 cell development and ameliorates adaptive T-cell transfer-induced colitis in mice.
Reference: Proc Natl Acad Sci U S A. 2017 Mar 14;114(11):2952-2957. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5358349/
Preparing Stock Solutions
The following data is based on the
product
molecular weight
370.83
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. Cheung K, Lu G, Sharma R, Vincek A, Zhang R, Plotnikov AN, Zhang F, Zhang Q, Ju Y, Hu Y, Zhao L, Han X, Meslamani J, Xu F, Jaganathan A, Shen T, Zhu H, Rusinova E, Zeng L, Zhou J, Yang J, Peng L, Ohlmeyer M, Walsh MJ, Zhang DY, Xiong H, Zhou MM. BET N-terminal bromodomain inhibition selectively blocks Th17 cell differentiation and ameliorates colitis in mice. Proc Natl Acad Sci U S A. 2017 Mar 14;114(11):2952-2957. doi: 10.1073/pnas.1615601114. Epub 2017 Mar 6. PMID: 28265070; PMCID: PMC5358349.
In vitro protocol:
1. Cheung K, Lu G, Sharma R, Vincek A, Zhang R, Plotnikov AN, Zhang F, Zhang Q, Ju Y, Hu Y, Zhao L, Han X, Meslamani J, Xu F, Jaganathan A, Shen T, Zhu H, Rusinova E, Zeng L, Zhou J, Yang J, Peng L, Ohlmeyer M, Walsh MJ, Zhang DY, Xiong H, Zhou MM. BET N-terminal bromodomain inhibition selectively blocks Th17 cell differentiation and ameliorates colitis in mice. Proc Natl Acad Sci U S A. 2017 Mar 14;114(11):2952-2957. doi: 10.1073/pnas.1615601114. Epub 2017 Mar 6. PMID: 28265070; PMCID: PMC5358349.
In vivo protocol:
1. Cheung K, Lu G, Sharma R, Vincek A, Zhang R, Plotnikov AN, Zhang F, Zhang Q, Ju Y, Hu Y, Zhao L, Han X, Meslamani J, Xu F, Jaganathan A, Shen T, Zhu H, Rusinova E, Zeng L, Zhou J, Yang J, Peng L, Ohlmeyer M, Walsh MJ, Zhang DY, Xiong H, Zhou MM. BET N-terminal bromodomain inhibition selectively blocks Th17 cell differentiation and ameliorates colitis in mice. Proc Natl Acad Sci U S A. 2017 Mar 14;114(11):2952-2957. doi: 10.1073/pnas.1615601114. Epub 2017 Mar 6. PMID: 28265070; PMCID: PMC5358349.
1: Cheung K, Lu G, Sharma R, Vincek A, Zhang R, Plotnikov AN, Zhang F, Zhang Q, Ju Y, Hu Y, Zhao L, Han X, Meslamani J, Xu F, Jaganathan A, Shen T, Zhu H, Rusinova E, Zeng L, Zhou J, Yang J, Peng L, Ohlmeyer M, Walsh MJ, Zhang DY, Xiong H, Zhou MM. BET N-terminal bromodomain inhibition selectively blocks Th17 cell differentiation and ameliorates colitis in mice. Proc Natl Acad Sci U S A. 2017 Mar 14;114(11):2952-2957. doi: 10.1073/pnas.1615601114. Epub 2017 Mar 6. PubMed PMID: 28265070; PubMed Central PMCID: PMC5358349.
