Identification of medicinal compounds as potential inhibitors for mutated isocitrate dehydrogenases against chondrosarcoma

Abstract

Highlights Virtual screening of 5000 novel medicinal compounds procured two compounds (5-galloylquinic acid and artocarpetin) capable of establishing interaction with both mutated IDH1 and IDH2 proteins implicated in chondrosarcoma. Cell lining prediction studies revealed that both 5-galloylquinic acid and artocarpetin sensitizes chondrosarcoma cell lines and has good cytotoxic influence on CHSA8926 and CHSA0011 cells. These compounds possess high acute toxicity values to incite adverse reaction and organ damage in rodents. ITGAV , CAPRIN-1 , CCL5 COG5 and TNFRSF10B gene are successfully downregulated that are involved in the metastasis inflammation and chondrogenesis by these compounds. TP53 expression enhancer, free radical scavenger, MAP kinase stimulant, MM9 expression inhibitor and chemo preventive agent were some biological properties predicted by Prediction of Activity Spectra for substances (PASS) database. Artocarpetin had good ADME and druglikness properties as compared to 5-galloylquinic acid, as this compound had low bioavailability score and one lipinski violation for druglikness.

Crosstalk of Redox-Related Subtypes, Establishment of a Prognostic Model and Immune Responses in Endometrial Carcinoma

“…PHKA1 is a regulator of glycogen metabolism [ 46 ], but its role in cancer has been less studied. COG5 is involved in metastatic inflammation and cartilage formation and can represent a prospective treatment target for chondrosarcoma [ 47 ]. NRIP1 exerts a carcinogenic effect in various solid tumors [ 48 , 49 , 50 ].…”

Chondrosarcoma Resistance to Radiation Therapy: Origins and Potential Therapeutic Solutions

“…Nonconventional treatments for chondrosarcoma include molecularly-targeted therapies, epigenetic approaches, immunotherapy, and herbal therapies [ 33 , 36 ]. Some of the targets for chondrosarcoma therapies involve mutations of isocitrate dehydrogenases IDH1 and IDH2 [ 37 , 38 , 39 , 40 ], angiogenesis [ 41 , 42 ], cyclin-dependent kinases (CDK) [ 43 ], tyrosine kinase inhibitor [ 44 ], mechanisms involved in the signaling pathway of Rapamycin (mTOR) [ 45 , 46 ], agents of hypomethylation, and histone deacetylase (HDAC) [ 47 , 48 , 49 ]. Clinical studies involving immune checkpoint inhibition are in the early stages and show promising results despite patients’ mixed responses to some inhibitors [ 50 , 51 , 52 ].…”