Comprehensive multi-omics analysis identifies NUSAP1 as a potential prognostic and immunotherapeutic marker for lung adenocarcinoma.

While NUSAP1's association with various tumors is established, its predictive value for prognosis and immunotherapy in lung adenocarcinoma (LUAD) remains unconfirmed. We analyzed Nucleolar Spindle-Associated Protein 1 (NUSAP1) gene expression in TCGA and GTEx datasets and validated it in clinicopathological tissues using qRT-PCR and immunohistochemistry. Additionally, we investigated NUSAP1's relationship with patient prognosis across TCGA and five GEO cohorts.

Discovery and Optimization of Potent, Efficacious and Selective Inhibitors Targeting EGFR Exon20 Insertion Mutations.

Herein, we report the identification and optimization of a series of potent inhibitors of EGFR Exon20 insertions with significant selectivity over wild-type EGFR. A strategically designed HTS campaign, multiple iterations of structure-based drug design (SBDD), and tactical linker replacement led to a potent and wild-type selective series of molecules and ultimately the discovery of . Compound is a potent and selective inhibitor of EGFR Exon20 insertions and has demonstrated encouraging efficacy in NSCLC EGFR CRISPR-engineered H2073 xenografts that carry an SVD Exon20 insertion and reduced efficacy in a H2073 wild-type EGFR xenograft model compared to CLN-081 (), indicating that may have lower EGFR wild-type associated toxicity.

Structure-Based Design and Pharmacokinetic Optimization of Covalent Allosteric Inhibitors of the Mutant GTPase KRAS.

Attempts to directly drug the important oncogene KRAS have met with limited success despite numerous efforts across industry and academia. The KRAS mutant represents an "Achilles heel" and has recently yielded to covalent targeting with small molecules that bind the mutant cysteine and create an allosteric pocket on GDP-bound RAS, locking it in an inactive state. A weak inhibitor at this site was optimized through conformational locking of a piperazine-quinazoline motif and linker modification.

Asymmetric Transfer Hydrogenations of 2,3-Disubstituted Quinoxalines with Ammonia Borane.

An asymmetric transfer hydrogenation of 2,3-disubstituted quinoxalines using a chiral frustrated Lewis pair of Piers' borane and (R)-tert-butylsulfinamide as the catalyst with ammonia borane as the hydrogen source has been successfully realized. For 2-alkyl-3-arylquinoxaline substrates, cis-tetrahydroquinoxalines were obtained as the predominant products in high yields with 77-86% ee. In contrast, trans isomers were often furnished as major products for the reactions of 2,3-dialkylquinoxalines with up to >99% ee.

A Frustrated Lewis Pair Catalyzed Asymmetric Transfer Hydrogenation of Imines Using Ammonia Borane.

Inspired by the zwitterion species generated from the splitting of H by frustrated Lewis pairs, we put forward a novel frustrated Lewis pair by the combination of H and H incorporated Lewis acid and base together. Piers' borane and chiral tert-butylsulfinamide were chosen as the FLP, and a metal-free asymmetric transfer hydrogenation of imines was realized with high enantioselectivities. Significantly, with ammonia borane as hydrogen source, a catalytic asymmetric reaction using 10 mol % of Piers' borane, chiral tert-butylsulfinamide, and pyridine additive, has been successfully achieved to furnish optically active amines in 78-99% yields with 84-95% ee's.

Organocatalytic asymmetric biomimetic transamination of aromatic ketone to optically active amine.

An asymmetric biomimetic transamination of aromatic ketones to optically active amines with o-HOPhCH(2)NH(2) as amine source catalyzed by hydroquinine-derived chiral base is described. Up to 85% ee was obtained.

An efficient asymmetric biomimetic transamination of α-keto esters to chiral α-amino esters.

An efficient asymmetric biomimetic transamination of α-keto esters with quinine derivatives as chiral bases was described. A wide variety of α-amino esters containing various functional groups can be synthesized in high yield and enantioselectivity.

Stereoselective construction of the tetracyclic core of Cryptotrione.

An efficient stereoselective approach to the tetracyclic core of Cryptotrione, involving an asymmetric Michael addition, ring-closing metathesis, and subsequent cyclopropanation, is described.

An approach to the hexacyclic skeleton of trigonoliimines.

A strategy to construct the hexacyclic skeleton of trigonoliimines A, B and their derivatives involving a carbanion-triggered intramolecular cyclization of a seven-membered ring and a subsequent six-membered ring formation in one pot is described.