Page 79 - I. Chemical biology and drug discovery

Effect of MJ22 polymeric micelles
on antidiabetic target protein tyrosine phosphatases

a
Min Ji Kang , and Sang J. Chung a
a College of Pharmacy, Sungkyunkwan University, Suwon, Korea

BACKGROUND AIM

Micelles are nanoparticles as be used for targeted drug delivery. Several protein tyrosine phosphatases (PTPs) play significant roles
Targeting drug delivery systems such as liposomes and polymeric in diabetes. A series of experiments were conducted to see the
micelles make numerous chemotherapeutics available that are too toxic antidiabetic effects of the candidate compounds. We tested whether
to use. Drug-loaded micelles enhance water solubility and circulation MJ12 and MJ14 inhibited the activity of diabetes-related PTPs in
time of drugs. Furthermore, they can target specific tissues via vitro. We found the IC 50 of MJ22 at each PTPs. MJ14 was treated to
enhancing retention effect. observe the Akt level associated with diabetes in C2C12. Thus, to
improve the antidiabetic effect using the benefit of polymeric
micelles, we have made micelles using MJ22, MJ42, and MJ14.
METHODS

PTPs

Non-fluorescent Compound Fluorescent
DiFMUP DiFMU C2C12
RESULTS

Table 1. Kinetics condition, the Michaelis constant K M , IC 50 values of MJ22, and Figure 2. MJ14 enhanced the phosphorylation of Akt
inhibition % of 20 μM MJ14 for each PTPs related to diabetes. when treated with insulin. Western blotting results
obtained by treating MJ14 with C2C12.
SHP2 PTP-MEG2 DUSP9 TC-PTP Insulin
Control MJ14 10 μM (100 nM)
pH 6 7 7 6 p-Akt
[E] (nM) 5 0.1 250 0.15 t-Akt
K M (μM) 91 189 24 34 MJ14 10 μM Insulin
Control + Insulin (100 nM)
IC 50 (μM) 7.5 33 11.5 14.1
p-Akt
% (MJ14) 95 68 23 88
t-Akt
Figure 1. IC 50 graphs of antidiabetic target PTPs. IC 50 is estimated by fitting Figure 3. Size of MJ22 micelles. Dynamic light scattering
the sigmoid plot. % inhibition versus various concentrations of MJ22. (DLS) results of MJ22 micelles.
Z-Average: 111.4 (d.nm); PdI: 0.139. 3 repetitions.
SHP2 PTP-MEG2 DUSP9 TC-PTP

CONCLUSION REFERENCES ACKNOWLEDGEMENTS

PTPs are associated with diverse diseases, 1. Evan M. Cohen, Huiying Ding, PhD, Chase W. This research was supported by the Bio &
such as cancer and diabetes. MJ22 and Kessinger, Chalermchai Khemtong, PhD, Jinming Medical Technology Development Program
MJ14 inhibited the activity of SHP2, PTP- Gao, PhD, and Baran D. Sumer, MD, Otolaryngology- of the National Research Foundation (NRF)
MEG2, DUSP9, TC-PTP in vitro. These Head and Neck Surgery, 2010, 143, 109-115. funded by the Korean government (MSIT)
2. Judy Shapiro, “An easy guide to understanding
PTPs are correlated with diabetes. MJ14 surfactants”, International Products Corporation, (NRF-2012M3A9C4048775 and NRF-
increased insulin-regulated phosphor-Akt 2018, https://www.ipcol.com/blog/an-easy-guide-to- 2017M3A9C8031995)
level when treated with insulin in C2C12. In understanding-surfactants/
conclusion, MJ22 and MJ14 are potential 3. Pavlovic K, Krako Jakovljevic N, Jovanovic M,
Isakovic A, Markovic I, Lalic NM, “Pavlovic 2017 Contact information
anti-diabetes candidates. To increase the
antidiabetic effects of these two substances, MITOEAGLE Obergurgl”, Bioblast, 2018,
as well as to raise solubility and stability, https://www.bioblast.at/index.php/Pavlovic_2017_MIT E-mail: sjchung@skku.edu
OEAGLE_Obergurgl
micelles were made using MJ22, MJ42, and
MJ14. We plan to see the anti-diabetic effect
using this delivery system.