An allele-agnostic mutant-KRAS inhibitor suppresses tumor maintenance signals and reprograms tumor immunity in pancreatic cancer.

is among the most frequently mutated oncogenes in cancer, and for decades, efforts at pharmacological blockade of its function in solid cancers have been unsuccessful. A notable advance in this endeavor is the recent development of small-molecule KRAS inhibitors, which enable direct targeting of the mutant oncoprotein. Here, we comprehensively evaluated the preclinical efficacy of BI-2493, a first-in-class allele-agnostic mutant-KRAS inhibitor (panKRASi), in pancreatic ductal adenocarcinoma (PDAC).

Monolayer-Defined Flat Colloidal PbSe Quantum Dots in Extreme Confinement.

Colloidal 2D PbX (X = S, Se, Te) nanocrystals are innovative materials pushing the boundaries of quantum confinement by combining crystal thicknesses down to a monolayer with additional confinement in the lateral dimension. These flat PbSe quantum dots (fQDs) exhibit telecommunication band photoluminescence (1.43-0.

When public health emergencies hit the front line: a qualitative study of the patient experience in the emergency department and outpatient infectious disease clinic during the 2022 Mpox clade IIb outbreak.

Background: The World Health Organization (WHO) declared mpox clade IIb a Public Health Emergency of International Concern (PHEIC) in July 2022. During the clade IIb epidemic, patients presented to both Emergency Departments (ED) and Infectious Disease (ID) clinics for care. Given the uncertainty and limited knowledge of mpox in 2022, we sought to understand the patient experience to inform service delivery for future outbreaks.

Pan-KRAS Inhibitors BI-2493 and BI-2865 Display Potent Antitumor Activity in Tumors with KRAS Wild-type Allele Amplification.

KRASG12C selective inhibitors, such as sotorasib and adagrasib, have raised hopes of targeting other KRAS-mutant alleles in patients with cancer. We report that KRAS wild-type (WT)-amplified tumor models are sensitive to treatment with the small-molecule KRAS inhibitors BI-2493 and BI-2865. These pan-KRAS inhibitors directly target the "OFF" state of KRAS and result in potent antitumor activity in preclinical models of cancers driven by KRAS-mutant proteins.

A Comparative Pharmacokinetics Study of Orally and Intranasally Administered 8-Nitro-1,3-benzothiazin-4-one (BTZ043) Amorphous Drug Nanoparticles.

BTZ043 is an 8-nitro-1,3-benzothiazin-4-one with potency against multidrug-resistant . Low solubility and hepatic metabolism are linked to poor oral bioavailability. Amorphous drug nanoparticles (ADN) were formulated to improve the bioavailability.