bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 6, 2024

Abstract Discovery of cancer immunogenic chemotherapeutics represents an emerging, highly promising direction for treatment that uses a chemical drug to achieve the efficacy both chemotherapy and immunotherapy. Herein we report high-throughput screening platform subsequent discovery new class chemotherapeutic leads. Our integrates informatics-based activity metabolomics rapid identification microbial natural products with novel structures potent activities. Additionally, demonstrate use microcrystal electron diffraction (MicroED) direct structure elucidation lead compounds from partially purified mixtures. Using this strategy screen geographically phylogenetically diverse metabolites against pseudomyxoma peritonei, rare severe cancer, discovered leads, aspercyclicins. The aspercyclicins feature unprecedented tightly packed polycyclic polyketide scaffold comprises continuous fused, bridged, spiro rings. biogenesis involves two distinct biosynthetic pathways, leading formation chimeric cannot be predicted by bottom-up approaches mining genes. With comparable potency some clinically used anticancer drugs, are active multiple cell types inducing death (ICD), including release damage-associated molecular patterns phagocytosis cells. broad-spectrum ICD-inducing aspercyclicins, combined their low toxicity normal cells, potential particularly first peritonei treatment.

Язык: Английский