Targeting INSM1 in Order to Prevent the Growth of Small Cell Lung Cancer

Small cell lung cancer (SCLC) is a very aggressive form of cancer because of its poor survival and high rate of tumour progression. There are very few commercial drugs that can specifically target SCLC tumours and inhibit their progression. Thus, there is an urgent and unmet need to identify novel and effective drugs that can specifically target the SCLC tumour progression. In this study, we have selected Insulinoma associated protein 1 (INSM1), a transcription factor responsible for neuro-endocrinal differentiation. It has also been studied as a marker for neuro-endocrinal tumours like SCLC. It also plays a role in activation of several key pathways that are responsible for SCLC progression. N-myc which is an intermediate of the Sonic Hedgehog (Shh) pathway, helps in the overexpression of INSM1 which in turn activates PI3K/AKT and MEK/ERK1/2 pathways. The activation of these pathways results in further stabilization of N-myc and this cycle repeats. Thus, INSM1 acts as a key intermediate molecule between the Shh, PI3K/AKT and MEK/ERK1/2 pathways which have been reported to play an important role in tumour progression. It has already been reported that the knockdown of INSM1 can significantly reduce the SCLC tumour progression. Thus, we have screened the target INSM1 against our library of plant based anti-cancerous compounds to obtain a suitable drug. The top compounds having better docking score were studied for their ADME properties. The best compound obtained is then simulated for 50 ns in order to study the stability of the protein-ligand interaction. From this study, we try to identify novel plant-based therapeutics to inhibit SCLC tumour progression by inhibiting INSM1.

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