| Kinase Assay: |
| Biol Pharm Bull. 2005 Sep;28(9):1795-7. | | PTP1B inhibitory effect of abietane diterpenes isolated from Salvia miltiorrhiza.[Pubmed: 16141564 ] | Protein tyrosine phosphatase 1B (PTP1B) acts as a negative regulator of insulin signaling, and selective inhibition of PTP1B has served as a potential drug target for the treatment of type 2 diabetes.
METHODS AND RESULTS:
In the course of screening for PTP1B inhibitory natural products, the MeOH extract of the dried root of Salvia miltiorrhiza BUNGE (Labiatae) was found to exhibit significant inhibitory effect. Bioassay-guided fractionation and purification afforded three related abietane-type diterpene metabolites 1-3. Compounds 1-3 were identified as isotanshinone IIA (1), dihydroisotanshinone I (2), and Isocryptotanshinone (3) mainly by analysis of NMR and MS data.
CONCLUSIONS:
Compounds 1-3 non-competitively inhibited PTP1B activity with 50% inhibitory concentration values of 11.4+/-0.6 microM, 22.4+/-0.6 microM and 56.1+/-6.3 microM, respectively. | | J Drug Target. 2016 Dec;24(10):934-942. | | Isocryptotanshinone, a STAT3 inhibitor, induces apoptosis and pro-death autophagy in A549 lung cancer cells.[Pubmed: 26904961 ] | Signal transducer and activator of transcription 3 (STAT3) is a potential drug target for chemotherapy. Cryptotanshinone (CTS) was identified as a potent STAT3 inhibitor, while the effect of other tanshinones remains unknown.
METHODS AND RESULTS:
In this study, the influence of eight tanshinones on STAT3 activity was initially screened and Isocryptotanshinone (ICTS) significantly inhibited STAT3 activity in a dual luciferase assay. ICTS inhibited the constitutive and inducible phosphorylation of STAT3 at Y705 without affecting the phosphorylation of STAT3 at S727 in A549 lung cancer cells. Furthermore, ICTS inhibited the nuclear translocation of STAT3. Compared with CTS, ICTS exhibited a stronger inhibitory effect on STAT3 phosphorylation and on A549 cytotoxicity. ICTS induced autophagy as evidenced by the accumulation of autophagic vacuoles and the increased expression of LC3 protein and autophagosomes. ICTS-induced cell death was partially reversed by the autophagy inhibitor chloroquine. The docking assay predicted that both ICTS and CTS bind the SH2 domain of STAT3. ICTS formed hydrogen bonds and pi-pi interaction with the nearby amino acid residues of Lys591, Arg609, and Ser636.
CONCLUSIONS:
These findings suggested that ICTS, a natural compound, is a potent STAT3 inhibitor. ICTS induced apoptosis and pro-death autophagy in A549 cells. |
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