Presentation (CTI)

OBJECTIVES: The study aims to understand the expression of IDH1/2 in the normal and glioblastoma (GBM) conditions using various bioinformatics databases. Also, to identify the dual inhibitor for mutant IDH1/2 using Schrödinger software. Further, invitro and invivo studies were performed to explore the therapeutic efficacy of the identified molecule against the GBM.
METHODS: The expression of IDH1/2 was analyzed using various bioinformatics databases including GEPIA2, and UALCAN. Insilco analysis was performed to predict the potent dual inhibitor for mutant IDH1/2 targeting GBM using Schrödinger software. For the invitro study, SRB cell viability assay was performed to analyze the tumor cell death. The therapeutic efficacy of the identified potent molecule was further explored in the C6 GBM cell line-induced animal model using female Wistar rats.
RESULTS: Bioinformatics study revealed that the expression of IDH1/2 is highly expressed in GBM patients compared to healthy individuals. Moreover, the GBM patients with IDH1/2 mutation reported a very low survival rate. Using the insilico Schrödinger tool, the identified compound showed maximum contact with Gln 277 for 99% in IDH1 and Gln 316 for 100% in IDH2. Gln277 and Gln 316 are the important amino acids required for the inhibitory function of IDH1/2 to target GBM. Invitro cell viability study revealed that the identified molecule causes GBM tumor cell death. Tumor-induced using intracerebroventricular injection in the female Wistar rats shows reduced tumor growth and proliferation marker.
CONCLUSIONS: In conclusion, the identified molecule showed good interaction and stability with the target protein IDH1/2. Also, the molecule showed a promising tumor cell death invitro and therapeutic efficacy and reduced D-2HG in the animal models.