Amphiphilic Superspreading Polymer Membranes Prepared by Capillary Force-Driven Self-Assembly.

To overcome the two main obstacles of large-scale application of superspreading material, self assembly is used to prepare superspreading polymer membrane (SPPM) in this work. An amphiphilic SPPM is prepared by capillary force-driven self assembly using PP melt-blown nonwovens and polyvinyl alcohol (PVA). The prepared SPPM has low preparation cost and stable performance since self assembly needs low energy consumption, and the production is thermodynamically stable. By using cryo-electron microscopy, transmission electron microscopy, X-ray photoelectron spectrum and scanning electron microscope with energy dispersive X-ray spectroscopy. It is proved that PVA is successfully assembled on the fiber surface of PP melt-blown nonwovens. The prepared SPPM has excellent spreading performance, the "spreading times" of both water and oil are less than 0.5 s. They showed much superior performance compared to traditional materials when applied in oil-water separation, seawater desalination, and ion separation. This work will definitely promote the development of self assembly, superspreading materials, and related sciences.

FSP1-mediated ferroptosis in cancer: from mechanisms to therapeutic applications.

Ferroptosis is a new discovered regulated cell death triggered by the ferrous ion (Fe2+)-dependent accumulation of lipid peroxides associated with cancer and many other diseases. The mechanism of ferroptosis includes oxidation systems (such as enzymatic oxidation and free radical oxidation) and antioxidant systems (such as GSH/GPX4, CoQ10/FSP1, BH4/GCH1 and VKORC1L1/VK). Among them, ferroptosis suppressor protein 1 (FSP1), as a crucial regulatory factor in the antioxidant system, has shown a crucial role in ferroptosis. FSP1 has been well validated to ferroptosis in three ways, and a variety of intracellular factors and drug molecules can alleviate ferroptosis via FSP1, which has been demonstrated to alter the sensitivity and effectiveness of cancer therapies, including chemotherapy, radiotherapy, targeted therapy and immunotherapy. This review aims to provide important frameworks that, bring the regulation of FSP1 mediated ferroptosis into cancer therapies on the basis of existing studies.

TOP2A modulates signaling via the AKT/mTOR pathway to promote ovarian cancer cell proliferation.

Ovarian cancer (OC) is a form of gynecological malignancy that is associated with worse patient outcomes than any other cancer of the female reproductive tract. Topoisomerase II α (TOP2A) is commonly regarded as an oncogene that is associated with malignant disease progression in a variety of cancers, its mechanistic functions in OC have yet to be firmly established. We explored the role of TOP2A in OC through online databases, clinical samples, in vitro and in vivo experiments. And initial analyses of public databases revealed high OC-related TOP2A expression in patient samples that was related to poorer prognosis. This was confirmed by clinical samples in which TOP2A expression was elevated in OC relative to healthy tissue. Kaplan-Meier analyses further suggested that higher TOP2A expression levels were correlated with worse prognosis in OC patients. In vitro, TOP2A knockdown resulted in the inhibition of OC cell proliferation, with cells entering G1 phase arrest and undergoing consequent apoptotic death. In rescue assays, TOP2A was confirmed to regulate cell proliferation and cell cycle through AKT/mTOR pathway activity. Mouse model experiments further affirmed the key role that TOP2A plays as a driver of OC cell proliferation. These data provide strong evidence supporting TOP2A as an oncogenic mediator and prognostic biomarker related to OC progression and poor outcomes. At the mechanistic level, TOP2A can control tumor cell growth via AKT/mTOR pathway modulation. These preliminary results provide a foundation for future research seeking to explore the utility of TOP2A inhibitor-based combination treatment regimens in platinum-resistant recurrent OC patients.

Event-Triggered Impulsive Control for Input-to-State Stabilization of Nonlinear Time-Delay Systems.

This article investigates the event-triggered impulsive control (ETIC) problem for a class of nonlinear time-delay systems subject to exogenous disturbances. An original event-triggered mechanism (ETM) which utilizes the information of system state and external input is constructed based on Lyapunov function approach. To achieve the input-to-state stability (ISS) of the considered system, some sufficient conditions are presented, in which the underlying relationship among ETM, exogenous input, and impulse action is established. Furthermore, the possible Zeno behavior induced by the proposed ETM is excluded simultaneously. As an application, the design criterion of ETM and impulse gain is put forward for a class of impulsive control systems with delay according to the feasibility of some linear matrix inequalities (LMIs). Finally, two examples with numerical simulations are provided to confirm the effectiveness of the developed theoretical results, where the synchronization issue of delayed Chua's circuit is considered.

Compound AC1Q3QWB upregulates CDKN1A and SOX17 by interrupting the HOTAIR-EZH2 interaction and enhances the efficacy of tazemetostat in endometrial cancer.

Endometrial cancer (EC) is a common malignancy of the female reproductive system, with an escalating incidence. Recurrent/metastatic EC presents a poor prognosis. The interaction between the long non-coding RNA (lncRNA) HOTAIR and the polycomb repressive complex 2 (PRC2) induces abnormal silencing of tumor suppressor genes, exerting a pivotal role in tumorigenesis. We have previously discovered AC1Q3QWB (AQB), a small-molecule compound targeting HOTAIR-EZH2 interaction. In the present study, we unveil that AQB selectively hampers the interaction between HOTAIR and EZH2 within EC cells, thus reversing the epigenetic suppression of tumor suppressor genes. Furthermore, our findings demonstrate AQB's synergistic effect with tazemetostat (TAZ), an EZH2 inhibitor, significantly boosting the expression of CDKN1A and SOX17. This, in turn, induces cell cycle arrest and impedes EC cell proliferation, migration, and invasion. In vivo experiments further validate AQB's potential by enhancing TAZ's anti-tumor efficacy at lower doses. Our results advocate AQB, a recently discovered small-molecule inhibitor, as a promising agent against EC cells. When combined with TAZ, it offers a novel therapeutic strategy for EC treatment.

TMT-Based Proteomic Analysis of Continuous Cropping Response in Codonopsis tangshen Oliv.

The growth and development of Codonopsis tangshen, an important herb used in Chinese traditional medicine, have been seriously affected by continuous cropping obstacles. Therefore, understanding the molecular responses of C. tangshen to continuous cropping is imperative to improve its resistance to continuous cropping obstacles. Here, physiological and biochemical results showed that the levels of chlorophyll and malonaldehyde (MDA) were higher in the continuous cropping (LZ) group compared with those of the non-continuous cropping (FLZ) group, while superoxide dismutase (SOD) content was lower in the LZ group than in the FLZ group. Tandem mass tag (TMT)-based proteomic analysis was performed to investigate the response mechanism to continuous cropping obstacles in C. tangshen. A total of 70 differentially expressed proteins (DEPs) were significantly involved in relevant pathways, including photosynthesis, oxidative phosphorylation, ribosome activity, and secondary metabolites. The results suggest that these DEPs in C. tangshen might play a critical role in response to continuous cropping. These findings could provide scientific basis for improving C. tangshen's resistance to continuous cropping obstacles.

CCNE1 is a predictive and immunotherapeutic indicator in various cancers including UCEC: a pan-cancer analysis.

BACKGROUND: CCNE1 plays an important oncogenic role in several tumors, especially high-stage serous ovarian cancer and endometrial cancer. Nevertheless, the fundamental function of CCNE1 has not been explored in multiple cancers. Therefore, bioinformatics analyses of pan-cancer datasets were carried out to explore how CCNE1 regulates tumorigenesis. METHODS: A variety of online tools and cancer databases, including GEPIA2, SangerBox, LinkedOmics and cBioPortal, were applied to investigate the expression of CCNE1 across cancers. The pan-cancer datasets were used to search for links between CCNE1 expression and prognosis, DNA methylation, m6A level, genetic alterations, CCNE1-related genes, and tumor immunity. We verified that CCNE1 has biological functions in UCEC cell lines using CCK-8, EdU, and Transwell assays. RESULTS: In patients with different tumor types, a high mRNA expression level of CCNE1 was related to a poor prognosis. Genes related to CCNE1 were connected to the cell cycle, metabolism, and DNA damage repair, according to GO and KEGG enrichment analyses. Genetic alterations of CCNE1, including duplications and deep mutations, have been observed in various cancers. Immune analysis revealed that CCNE1 had a strong correlation with TMB, MSI, neoantigen, and ICP in a variety of tumor types, and this correlation may have an impact on the sensitivity of various cancers to immunotherapy. CCK-8, EdU and Transwell assays suggested that CCNE1 knockdown can suppress UCEC cell proliferation, migration and invasion. CONCLUSION: Our study demonstrated that CCNE1 is upregulated in multiple cancers in the TCGA database and may be a promising predictive biomarker for the immunotherapy response in some types of cancers. Moreover, CCNE1 knockdown can suppress the proliferation, migration and invasion of UCEC cells.

Preparation and Property Characterization of In2YSbO7/BiSnSbO6 Heterojunction Photocatalyst toward Photocatalytic Degradation of Indigo Carmine within Dye Wastewater under Visible-Light Irradiation.

In2YSbO7 and In2YSbO7/BiSnSbO6 heterojunction photocatalyst were prepared by a solvothermal method for the first time. The structural characteristics of In2YSbO7 had been represented. The outcomes showed that In2YSbO7 crystallized well and possessed pyrochlore constitution, a stable cubic crystal system and space group Fd3m. The lattice parameter of In2YSbO7 was discovered to be a = 11.102698 Å and the band gap energy of In2YSbO7 was discovered to be 2.68 eV, separately. After visible-light irradiation of 120 minutes (VLGI-120M), the removal rate (ROR) of indigo carmine (IC) reached 99.42% with In2YSbO7/BiSnSbO6 heterojunction (IBH) as a photocatalyst. The ROR of total organic carbon (TOC) reached 93.10% with IBH as a photocatalyst after VLGI-120M. Additionally, the dynamics constant k which was taken from the dynamic curve toward (DCT) IC density and VLGI time with IBH as a catalyst reached 0.02950 min-1. The dynamics constant k which came from the DCT TOC density and VLGI time with IBH as a photocatalyst reached 0.01783 min-1. The photocatalytic degradation of IC in dye wastewater (DW) with IBH as a photocatalyst under VLGI was in accordance with the first-order kinetic curves. IBH was used to degrade IC in DW for three cycles of experiments under VLGI, and the ROR of IC reached 98.74%, 96.89% and 94.88%, respectively, after VLGI-120M, indicating that IBH had high stability. Compared with superoxide anions or holes, hydroxyl radicals possessed the largest oxidative ability for removing IC in DW, as demonstrated by experiments with the addition of trapping agents. Lastly, the probable degradation mechanism and degradation pathway of IC were revealed in detail. The results showed that a visible-light-responsive heterojunction photocatalyst which possessed high catalytic activity and a photocatalytic reaction system which could effectively remove IC in DW were obtained. This work provided a fresh scientific research idea for improving the performance of a single catalyst.

Effect of Na-ion intercalation on the thermal conductivity of carbon honeycomb nanostructure.

This work studies the thermal conductivity of Na-ion intercalated carbon honeycomb (CHC) via the combination of first-principles calculation and molecular dynamics simulation. The effects of ion concentration, ion charge, temperature, and strain are explored. The simulation results show that the thermal conductivity of CHC presents a nonmonotonic dependence on the ion concentration. The enhanced phonon scattering and increased phonon group velocities of CHC induced by its interaction with the Na ions are responsible for the nonmonotonic dependence. Both the increases in the ion charge and temperature reduce the thermal conductivity. In contrast, a compressive strain of around -3% can increase the thermal conductivity by eliminating the phonon softening effect caused by the volume expansion of CHC during the ion intercalation. However, further increasing the strain negatively or positively from -3% leads to a decrease in the thermal conductivity. The simulation results presented in this work are beneficial in understanding the thermal properties of CHC when it is used as an electrode in ion batteries and supercapacitors.

Synthesis and Property Examination of Er2FeSbO7/BiTiSbO6 Heterojunction Composite Catalyst and Light-Catalyzed Retrogradation of Enrofloxacin in Pharmaceutical Waste Water under Visible Light Irradiation.

A new photocatalyst, Er2FeSbO7, was prepared by solid phase sintering using the high-temperature synthesis method for the first time in this paper. Er2FeSbO7/BiTiSbO6 heterojunction (EBH) catalyst was prepared by the solvent thermal method for the first time. Er2FeSbO7 compound crystallized in the pyrochlore-type architecture and cubelike crystal system; the interspace group of Er2FeSbO7 was Fd3m and the crystal cellular parameter a of Er2FeSbO7 was 10.179902 Å. The band gap (BDG) width of Er2FeSbO7 was 1.88 eV. After visible light irradiation of 150 minutes (VLGI-150min) with EBH as a photocatalyst, the removal rate (RR) of enrofloxacin (ENR) concentration was 99.16%, and the total organic carbon (TOC) concentration RR was 94.96%. The power mechanics invariable k toward ENR consistency and visible light irradiation (VLGI) time with EBH as a photocatalyzer attained 0.02296 min−1. The power mechanics invariable k which was involved with TOC attained 0.01535 min−1. The experimental results showed that the photocatalytic degradation (PCD) of ENR within pharmaceutical waste water with EBH as a photocatalyzer under VLGI was in keeping with the single-order reactivity power mechanics. The RR of ENR with EBH as a photocatalyzer was 1.151 times, 1.269 times or 2.524 times that with Er2FeSbO7 as a photocatalyst, BiTiSbO6 as a photocatalyst, or N-doping TiO2 (N-TO) as a photocatalyst after VLGI-150min. The photocatalytic activity, which ranged from high to low among above four photocatalysts, was as follows: EBHP > Er2FeSbO7 > BiTiSbO6 > N-TO. After VLGI-150min toward three periods of the project with EBH as a photocatalyst, the RR of ENR attained 98.00%, 96.76% and 95.60%. The results showed that the stability of EBH was very high. With appending trapping agent, it could be proved that the oxidative capability for degrading ENR, which ranged from strong to weak among three oxidic radicals, was as follows: superoxide anion > hydroxyl radicals (HRS) > holes. This work provides a scientific basis for the research and oriented leader development of efficient heterojunction catalysts.

Synthesis, Performance Measurement of Bi2SmSbO7/ZnBiYO4 Heterojunction Photocatalyst and Photocatalytic Degradation of Direct Orange within Dye Wastewater under Visible Light Irradiation.

Originally, the new catalyst Bi2SmSbO7 was synthesized by the hydrothermal synthesis method or by the solid-phase sintering method at a lofty temperature. A solvothermal method was utilized to prepare a Bi2SmSbO7/ZnBiYO4 heterojunction photocatalyst (BZHP). The crystal structure of Bi2SmSbO7 belonged to the pyrochlore structure and face-centered cubic crystal system by the space group of Fd3m. The cell parameter a was equivalent to 10.835(1) Å (Bi2SmSbO7). With Bi2SmSbO7/ZnBiYO4 heterojunction (BZH) as the photocatalyst, the removal rate (RR) of direct orange (DO) and the total organic carbon were 99.10% and 96.21% after visible light irradiation of 160 min (VLI-160M). The kinetic constant k toward DO concentration and visible light irradiation time (VLI) with BZH as photocatalyst reached 2.167 min−1. The kinetic constant k, which was concerned with total organic carbon, reached 0.047 min−1. The kinetic curve that came from DO degradation with BZH as a catalyst under VLI conformed to the second-order reaction kinetics. After VLI-160M, the photocatalytic degradation (PD) removal percentage of DO with BZH as the photocatalyst was 1.200 times, 1.268 times or 3.019 times that with Bi2SmSbO7 as the photocatalyst, ZnBiYO4 as the photocatalyst or with nitrogen-doped titanium dioxide as the photocatalyst. The photocatalytic activity (PA) was as following: BZH > Bi2SmSbO7 > ZnBiYO4 > nitrogen-doped titanium dioxide. After VLI-160M for three cycles of experiments with BZH as the photocatalyst, the RR of DO reached 98.03%, 96.73% and 95.43%, respectively, which meant that BZHP possessed high stability. By using the experiment of adding a trapping agent, the oxidative purifying capability for degradation of direct orange, which was in gradual depressed order, was as following: hydroxyl radical > superoxide anion > holes. Finally, the possible degradation pathway and degradation mechanism of DO were discussed systematically. A new high active heterojunction catalyst BZHP, which could efficiently remove toxic organic pollutants such as DO from dye wastewater after VLI, was obtained. Our research was meant to improve the photocatalytic property of the single photocatalyst.

Endometrial cancer in Lynch syndrome.

Lynch syndrome (LS) is an autosomal dominant inherited disease caused by germline pathogenic variants (PVs) in mismatch repair (MMR) genes. LS-associated endometrial cancer (LS-EC) is the most common extraintestinal sentinel cancer caused by germline PVs in MMR genes, including MLH1, MSH2, MSH6 and PMS2. The clinicopathologic features of LS-EC include early age of onset, lower body mass index (BMI), endometrioid carcinoma and lower uterine segment involvement. There has been significant progress in screening, diagnosis, surveillance, prevention and treatment of LS-EC. Many studies support universal screening for LS among patients with EC. Screening mainly involves a combination of traditional clinical criteria and molecular techniques, including MMR-immunohistochemistry (MMR-IHC), microsatellite instability (MSI) testing, MLH1 promoter methylation testing and gene sequencing. The effectiveness of endometrial biopsy and transvaginal ultrasound (TVS) for clinical monitoring of asymptomatic women with LS are uncertain yet. Preventive strategies include hysterectomy and bilateral salpingo-oophorectomy (BSO) as well as chemoprophylaxis using exogenous progestin or aspirin. Recent research has revealed the benefits of immunotherapy for LS-EC. The NCCN guidelines recommend pembrolizumab and nivolumab for treating patients with advanced or recurrent microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) EC.

Uncemented versus cemented arthroplasty after metal-on-metal total hip replacement in patients with femoral neck fractures: a retrospective study.

OBJECTIVE: To compare the clinical outcomes of primary metal-on-metal total hip replacement (MoM-TR) converted to uncemented total hip replacement (UTR) or cemented total hip replacement (CTR) in patients with femoral neck fractures (AO/OTA: 31B/C). METHODS: Patient data of 234 UTR or CTR revisions after primary MoM-TR failure from March 2007 to January 2018 were retrospectively identified. Clinical outcomes, including the Harris hip score (HHS) and key orthopaedic complications, were collected at 3, 6, and 12 months following conversion and every 12 months thereafter. RESULTS: The mean follow-up was 84.12 (67-100) months for UTR and 84.23 (66-101) months for CTR. At the last follow-up, the HHS was better in the CTR- than UTR-treated patients. Noteworthy dissimilarities were correspondingly detected in the key orthopaedic complication rates (16.1% for CTR vs. 47.4% for UTR). Statistically significant differences in specific orthopaedic complications were also detected in the re-revision rate (10.3% for UTR vs. 2.5% for CTR), prosthesis loosening rate (16.3% for UTR vs. 5.9% for CTR), and periprosthetic fracture rate (12.0% for UTR vs. 4.2% for CTR). CONCLUSION: In the setting of revision of failed primary MoM-TR, CTR may demonstrate advantages over UTR in improving functional outcomes and reducing key orthopaedic complications.

Chemical Recycling of Plastics by Microwave-Assisted High-Temperature Pyrolysis.

Use of plastics faces much criticism because of its shocking and increasing impact on the environment. But banning plastic will not help the environment. Only appropriate recycling of plastic waste can give satisfying solution. A lab-scale chemical recycling method, in which a mixture of plastic wastes and plant oil is continuously cracked into ethylene, propylene, and other useful chemicals by using microwave-assisted high-temperature pyrolysis, is developed. The method has delivered interesting leads that provide the basis for setting up a new process. Based on the encouraging results, a "drop-in" method for a renewable and circular polymer industry is also proposed. If it is commercially realized, plastic waste and plant oils will be the feedstock for the polymer industry and this industry will become renewable and circular.

Investigation of stereoisomeric bisarylethenesulfonic acid esters for discovering potent and selective PTP1B inhibitors.

Protein tyrosine phosphatase 1B (PTP1B) has been considered as a promising therapeutic target for type 2 diabetes mellitus (T2DM) and obesity due to its key regulating effects in insulin signaling and leptin receptor pathways. In this work, a series of cis- and trans-pyrrolidine bisarylethenesulfonic acid esters were prepared and their PTP1B inhibitory potency, selectivity and membrane permeability were evaluated. These novel stereoisomeric molecules especially trans-isomers exhibited remarkable inhibitory activity, significant selectivity as well as good membrane permeability (e.g. compound 28a, IC50 = 120, 1940 and 2670 nM against PTP1B, TCPTP and SHP2 respectively, and Papp = 1.74 × 10-6 cm/s). Molecular simulations indicated that trans-pyrrolidine bisarylethenesulfonic acid esters yielded the stronger binding affinity than their cis-isomers by constructing more interactions with non-catalytic sites of PTP1B. Further biological activity studies revealed that compound 28a could enhance insulin-stimulated glucose uptake and insulin-mediated insulin receptor ß (IRß) phosphorylation with no significant cytotoxicity.

Conductive Graphene-Melamine Sponge Prepared via Microwave Irradiation.

A conductive graphene-melamine sponge (MS) prepared via microwave irradiation is reported in this paper. Graphene oxide supported on the MS was prereduced first at 100 °C and then further reduced in a household microwave oven at over 1000 °C. It was surprising to find that graphene oxide on the MS was reduced perfectly while the three-dimensional structure of the MS was kept well after high-temperature reduction via microwave irradiation. Slight pyrolysis of MS was also found during 5 s microwave irradiation, resulting in nitrogen generation from the pyrolysis of the MS being doped into graphene, which could benefit the electric conductivity of the prepared graphene-MS. The electric conductivity of the prepared graphene-MS is about 0.12-1.0 S/m because of the high reduction degree of graphene oxide and nitrogen doping. On the other hand, different from the pure MS, the newly developed conductive graphene-MS possesses superhydrophobic and superoleophilic properties. Overall, the newly developed conductive graphene-MS contained 94.3 wt % MS and 5.7 wt % N-doped graphene and is a cost-effective material with good elasticity, high conductivity, superhydrophobicity, and superoleophilicity.

Y-shaped bis-arylethenesulfonic acid esters: Potential potent and membrane permeable protein tyrosine phosphatase 1B inhibitors.

Known PTP1B inhibitors with bis-anionic moieties exhibit potent inhibitory activity, good selectivity, however, they are incapable of penetrating cellular membranes. Based upon our finding of a new pharmacophoric group in inhibition of PTP1B and the structural characteristics of the binding pocket of PTP1B, a series of bis-arylethenesulfonic acid ester derivatives were designed and synthesized. These novel molecules, particularly Y-shaped bis-arylethenesulfonic acid ester derivatives, exhibited high PTP1B inhibitory activity, moderate selectivity, and great potential in penetrating cellular membranes (compound 7p, CLogP=9.73, Papp=9.6×10-6cm/s; IC50=140, 1290 and 920nM on PTP1B, TCPTP and SHP2, respectively). Docking simulations suggested that these Y-shaped inhibitors might interact with multiple secondary binding sites in addition to the catalytic site of PTP1B.

Design, synthesis and antimicrobial evaluation of novel benzoxazole derivatives.

The synthesis of (S)-2-(4-tert-butylphenoxy)-3-(benzoxazol-5-yl) propanoic acid derivatives (2a-k) were described and their in vitro antibacterial activities were determined against Gram-negative and -positive bacteria. These compounds were found to exert a broad spectrum of activity against the screened bacteria, but poor MIC values were found for Candida albicans fungi. Compound 2b bearing a hydrophobic aromatic tie was the most active derivative against all bacteria studied with MIC values ranging from 0.098 to 0.78 µg/mL. The activity of 2b against B. subtilis was 2-fold higher than Penicillin, and 8- to 510-fold higher than other control antibiotics.

Design, synthesis, and biological evaluation of 2-substituted ethenesulfonic acid ester derivatives as selective PTP1B inhibitors.

Fifteen 2-substituted ethenesulfonic acid ester derivatives were designed, synthesized, and evaluated for the inhibitory activities against protein tyrosine phosphatase 1B (PTP1B) and T-Cell protein tyrosine phosphatase (TCPTP). The structural activity relationship (SAR) of these compounds are discussed to clarify the impact of the linker and the optimized tail on the inhibitory activity of PTP1B and selectivity over TCPTP. Most of the compounds exhibit excellent inhibitory activities against PTP1B with IC50 values of 1.5-8.9 µM. SAR analysis reveal that the substituents at the hydrophobic tail significantly alter the inhibitory activity against PTP1 B and selectivity over TCPTP, e.g. compound 5d showed excellent inhibitory activity to PTP1B with IC50 = 7.8 µM, and -6-fold selectivity over TCPTP. Combined with our previous findings, we confirm that the linker length and the substituted hydrophobic tail have decisive influence on the PTP1B inhibitory activity and selectivity.

Identification of 2-substituted ethenesulfonic acid ester derivatives as novel, potent and selective inhibitors of protein tyrosine phosphatase 1B.

Sixteen 2-substituted ethenesulfonic acid ester derivatives were designed, synthesized and evaluated for the inhibitory activity against tyrosine phosphatase 1B (PTP1B) and T-Cell protein tyrosine phosphatase (TCPTP). The structural activity relationship (SAR) of these compounds demonstrated that the hydrophilic head, aromatic center and the hydrophobic tail affected the inhibitory activities against PTP1B and the selectivity over TCPTP. Most of the compounds exhibited excellent inhibitory activity against PTP1B with IC50 value of 1.0 µM - 31.2 µM. SAR analysis revealed that the hydrophilic head was indispensable in the maintain of inhibitory activity against PTP1B, the aromatic center significantly altered the selectivity of PTP1B over TCPTP, and the hydrophobic tail significantly altered the inhibitory activity against PTP1B.