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C25H33N10O7V2, triclinic, P1‾ $P\overline{1}$ (no. 2), a = 10.3933(4) Å, b = 12.5655(5) Å, c = 14.1841(5) Å, α = 65.373(1)°, β = 70.351(1)∘ $70.351{(1)}^{\circ }$ , γ = 88.052(2)∘ $88.052{(2)}^{\circ }$ , V = 1573.62(11) Å3, Z = 2, R gt(F) = 0.0362, wR ref(F 2) = 0.0885, T = 173 K.

KRAS mutations are highly prevalent in a wide range of lethal cancers, and these mutant forms of KRAS play a crucial role in driving cancer progression and conferring resistance to treatment. While there have been advancements in the development of small molecules to target specific KRAS mutants, the presence of undruggable mutants and the emergence of secondary mutations continue to pose challenges in the clinical treatment of KRAS-mutant cancers. In this study, we developed a novel molecular tool called tumor-targeting KRAS degrader (TKD) that effectively targets a wide range of KRAS mutants. TKD is composed of a KRAS-binding nanobody, a cell-penetrating peptide selectively targeting cancer cells, and a lysosome-binding motif. Our data revealed that TKD selectively binds to KRAS in cancer cells and effectively induces KRAS degradation via a lysosome-dependent process. Functionally, TKD suppresses tumor growth with no obvious side effects and enhances the antitumor effects of PD-1 antibody and cetuximab. This study not only provides a strategy for developing drugs targeting "undruggable" proteins but also reveals that TKD is a promising therapeutic for treating KRAS-mutant cancers. [ABSTRACT FROM AUTHOR]

Chemoresistance is a main reason for treatment failure in patients with nasopharyngeal carcinoma, but the exact regulatory mechanism underlying chemoresistance in nasopharyngeal carcinoma remains to be elucidated. Here, we identify PJA1 as a key E3 ubiquitin ligase involved in nasopharyngeal carcinoma chemoresistance that is highly expressed in nasopharyngeal carcinoma patients with nonresponse to docetaxel-cisplatin-5-fluorouracil induction chemotherapy. We find that PJA1 facilitates docetaxel resistance by inhibiting GSDME-mediated pyroptosis in nasopharyngeal carcinoma cells. Mechanistically, PJA1 promotes the degradation of the mitochondrial protein PGAM5 by increasing its K48-linked ubiquitination at K88, which further facilitates DRP1 phosphorylation at S637 and reduced mitochondrial reactive oxygen species production, resulting in suppression of GSDME-mediated pyroptosis and the antitumour immune response. PGAM5 knockdown fully restores the docetaxel sensitization effect of PJA1 knockdown. Moreover, pharmacological targeting of PJA1 with the small molecule inhibitor RTA402 enhances the docetaxel sensitivity of nasopharyngeal carcinoma in vitro and in vivo. Clinically, high PJA1 expression indicates inferior survival and poor clinical efficacy of TPF IC in nasopharyngeal carcinoma patients. Our study emphasizes the essential role of E3 ligases in regulating chemoresistance and provides therapeutic strategies for nasopharyngeal carcinoma based on targeting the ubiquitin-proteasome system. While chemotherapy may initially be effective in patient with nasopharyngeal carcinoma (NPC), resistance often develops. Here, the authors identify PJA1 as a driver of resistance to docetaxel via inhibition of GSDME-mediated proptosis and target this using a PJA1 inhibitor to restore sensitivity in preclinical models of NPC. [ABSTRACT FROM AUTHOR]

Four kinds of tridentate [OSO] bisphenol titanium complex catalysts [S (2-CH2-4-tBu-6-R-C6H2O)2]TiCl2(R1 = CMe3, R2 = CPhMe2, R3 = CPh2Me, R4 = CPh3) were prepared from 4-tert-butyl phenol through bromination, nucleophilic substitution and metal complexation reaction by changing the ortho-substituent of hydroxyl. The reaction performance of ethylene polymerization was investigated under the conditions of 30, 50, 70 °C, and pressure of 0.6 MPa. Polyolefin products under different conditions were obtained by changing the Al/Ti ratio of the catalyst and the reaction time. The products were characterized and analyzed by gel chromatogram phy (GPC). The four catalysts under different reaction conditions were compared. Due to the effect of R group steric hindrance, the larger the steric hindrance, the higher the activity of the catalyst. Based on the experimental results, it was concluded that the activity of the [S(2-CH2-4-tBu-6-CMePh2-C6H2O)2]TiCl2 catalyst at 50 °C was up to 6.7 x 106 g PE/(mol Ti ⋅ h), and the obtained polyolefin product Mw was 1.68 x 105, with a molecular weight distribution of 3.2. [ABSTRACT FROM AUTHOR]

C25H33N10O7V2, triclinic, P 1 ‾ (no. 2), a = 10.3933(4) Å, b = 12.5655(5) Å, c = 14.1841(5) Å, α = 65.373(1)°, β = 70.351 (1) ∘ , γ = 88.052 (2) ∘ , V = 1573.62(11) Å3, Z = 2, Rgt(F) = 0.0362, wRref(F2) = 0.0885, T = 173 K. [ABSTRACT FROM AUTHOR]

Abstract A new quinone compound, p-hydroxymethoxybenzobijuglone (HMBBJ), isolated from Juglans mandshurica by bioassay-guided fractionation, showed cytotoxic activity against HeLa cell line. Its chemical structure was determined by NMR and HREIMS [...]

Comprehensive Summary: A visible‐light‐induced tandem radical intramolecular cyclization/arylation of quinoxalin‐2(1H)‐ones with bromodifluoroacetamides is described. This protocol allows efficient access to a variety of valuable α,α‐difluoro‐γ‐lactam‐fused quinoxalin‐2(1H)‐ones in moderate to good yields under metal‐free, mild and redox neutral reaction conditions. This strategy is tolerant of various functional groups and a broad range of substrates. The mechanism experiments suggested an involvement of 5‐exo‐trig cyclization and a radical process in this transformation. [ABSTRACT FROM AUTHOR]

The effect of substituting Mn for Fe on the structure and magnetic properties of Pr2Fe(sub 17-x)Mnx compounds, with x equal to or greater than zero but less than or equal to nine, has been studied. Results indicate the substitution does not change the structure of Pr2Fe17. The unit-cell volume remains unchanged even if manganese content increases up to x = 2 but increases linearly by 2.5 cubic angstroms per Mn atom up to x =8. Cell volume increases significantly at x = 9. It was also observed that the saturation magnetic moment at 5k decreases with increasing Mn concentration.

X-ray diffraction and magnetization measurements were used to examine the structure and the magnetic anisotropy of R2Co15Al2 compounds. Findings showed that the compounds are in the single phase, having the hexagonal Th2Ni17-type structure for R=Y, Ho, Er and Tm and the rhombohedral Th2Zn17-type structure for R=Ce, Pr, Nd, Gd, Tb and Dy. The Ce compound was found to exhibit an anomalous lattice parameter and magnetic characteristic which are relative to the mixed-valence behavior of the Ce ion.

This work reports the photocatalytic application of an anthraquinone‐containing polymeric photosensitizer (AQ‐PHEMA) in the visible light‐induced cross‐dehydrogenative‐coupling of N‐aryl tetrahydroisoquinolines with several nucleophiles, including nitromethane, 1‐methyl‐2‐alkyl ketone and dialkyl (aryl) phosphine oxide. The results revealed that the reaction could be catalyzed by AQ‐PHEMA efficiently to afford a series of 1‐substituted‐2‐aryl‐1,2,3,4‐tetrahydroisoquinolines in good to excellent yields with nice substrate tolerance under aerobic conditions at room temperature. The practical application potential was also showcased by a gram‐scale synthesis. More importantly, the utilization of AQ‐PHEMA as a heterogeneous photosensitizer also showed nice recyclability and reusability of the catalyst, whereas AQ‐PHEMA can be easily separated and reused for at least 8 times without significant loss of photocatalytic activity. [ABSTRACT FROM AUTHOR]

A study was conducted to analyze the structure and magnetic characteristics of (Nd(sub 1-x)Ce(sub x))(sub 6)Fe(sub 13)Al compounds. The compounds were prepared from 99.9% pure elements by arc melting carried out under at atmosphere of high-purity argon. The samples were then quenched in water after heat treatment. Experimental results indicated a complex temperature dependence of magnetization.

A study was conducted to analyze the structure and magnetocrystalline anisotropy of Ce2Co(sub 17-x)Al(sub x), where x = 0, 1, 2, and 3, compounds. X-ray diffraction and magnetization measurements were carried out. Experimental results indicated that the unit-cell volume, saturation magnetization and Curie temperature of the compounds were anomalously low in comparison with values determined from an extrapolation by the R2Co(sub 17-x)Al(sub x) compounds.