Discovery of A Chimeric Polyketide Family as Cancer Immunogenic Chemotherapeutic Leads DOI Open Access
Dan Xue, Mingming Xu, Michael R. Madden

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 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.

Language: Английский

Design, synthesis and biological evaluation of novel diphenylamine analogues as NLRP3 inflammasome inhibitors DOI

Tongtong Kang,

Simin Sun,

Huimin Wang

et al.

Bioorganic & Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 113, P. 117927 - 117927

Published: Sept. 19, 2024

Language: Английский

Citations

0
Discovery of A Chimeric Polyketide Family as Cancer Immunogenic Chemotherapeutic Leads DOI Open Access
Dan Xue, Mingming Xu, Michael R. Madden

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 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.

Language: Английский

Citations

0