Acta Pharmacologica Sinica 2008 February; 29 (2): 278-284; doi: 10.1111/j.1745-7254.2008.00737.x

Acta Pharmacologica Sinica 2008 February; 29 (2): 278-284; doi: 10.1111/j.1745-7254.2008.00737.x

Original Article

Discovery of a novel competitive inhibitor of PTP1B by high-throughput screening¹

Lei SHI^2,3, Hai-ping YU^2,3, Yue-yang ZHOU², Jun-qin DU², Qiang SHEN², Jing-ya LI², Jia LI^2,4

²National Center for Drug Screening, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, China

Aim: To characterize the functional and pharmacological features of agonist-induced hump currents in human α4β2-nicotinic acetylcholine receptors (nAChR).

Results: HTS was finished with an averaged Z´ factor of 0.63, and LGH00081, a competitive inhibitor of PTP1B with novel structure and relatively good selectivity for receptor-type protein tyrosine phosphatases, was identified.

Conclusion: We established a molecular level assay which is useful for the screening of PTP1B inhibitors with therapeutic potential. The novel competitive PTP1B inhibitor LGH00081 offers a good start for structure modification and cellular functional activity study.

Keywords: high throughput screening; PTP1B; insulin receptor; phosphoryaltion; competitive inhibitor

¹Project supported by National Natural Science Foundation of China grants (No 30623008, 30200341, and 30400560) and a Shanghai Commission of Science and Technology grant (No 054319910).

³ These authors contributed equally to this work.
⁴ Correspondence to Prof Jia LI.
Phn 86-21-5080-1313.
Fax 86-21-5080-1552.
E-mail jli@mail.shcnc.ac.cn
Received 2007-05-13 Accepted 2007-08-31

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