BC-LI-0186

BC-LI-0186
Identifiers
	IUPAC name 4-(2,3-dimethyl-5-oxo-4-propan-2-ylpyrazol-1-yl)-N-(2-phenoxyethyl)benzenesulfonamide;
CAS Number	695207-56-8;
PubChem CID	4917788;
ChemSpider	4099704;
CompTox Dashboard (EPA)	DTXSID901336671 ;
Chemical and physical data
Formula	C22H27N3O4S
Molar mass	429.54 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC1=C(C(=O)N(N1C)C2=CC=C(C=C2)S(=O)(=O)NCCOC3=CC=CC=C3)C(C)C;
	InChI InChI=1S/C22H27N3O4S/c1-16(2)21-17(3)24(4)25(22(21)26)18-10-12-20(13-11-18)30(27,28)23-14-15-29-19-8-6-5-7-9-19/h5-13,16,23H,14-15H2,1-4H3; Key:SQYWMHPZMHDCHP-UHFFFAOYSA-N;

BC-LI-0186 is a compound that acts as an inhibitor of the GTPase enzyme leucyl-tRNA synthetase (LRS). This enzyme acts as part of the mTOR complex and acts as a leucine sensor which stimulates mTORC1 in the presence of leucine. BC-LI-0186 blocks the docking site for mTORC1 and thereby prevents the mTOR activation and increased protein synthesis which is usually triggered by branched-chain amino acids such as leucine, yet without inhibiting the separate catalytic activity of LRS.^[1] This may have potential applications in the treatment of cancer,^[2] and BC-LI-0186 has also been shown to promote muscle regeneration after injury.^[3]

References

^ Kim JH, Lee C, Lee M, Wang H, Kim K, Park SJ, et al. (September 2017). "Control of leucine-dependent mTORC1 pathway through chemical intervention of leucyl-tRNA synthetase and RagD interaction". Nature Communications. 8 (1): 732. Bibcode:2017NatCo...8..732K. doi:10.1038/s41467-017-00785-0. PMC 5622079. PMID 28963468.
^ Kim EY, Lee JG, Lee JM, Kim A, Yoo HC, Kim K, et al. (2019). "Therapeutic effects of the novel Leucyl-tRNA synthetase inhibitor BC-LI-0186 in non-small cell lung cancer". Therapeutic Advances in Medical Oncology. 11: 1758835919846798. doi:10.1177/1758835919846798. PMC 6535710. PMID 31205503.
^ Son K, You JS, Yoon MS, Dai C, Kim JH, Khanna N, et al. (April 2019). "Nontranslational function of leucyl-tRNA synthetase regulates myogenic differentiation and skeletal muscle regeneration". The Journal of Clinical Investigation. 129 (5): 2088–2093. doi:10.1172/JCI122560. PMC 6486340. PMID 30985292.

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[1] Kim JH, Lee C, Lee M, Wang H, Kim K, Park SJ, et al. (September 2017). "Control of leucine-dependent mTORC1 pathway through chemical intervention of leucyl-tRNA synthetase and RagD interaction". Nature Communications. 8 (1): 732. Bibcode:2017NatCo...8..732K. doi:10.1038/s41467-017-00785-0. PMC 5622079. PMID 28963468.

[2] Kim EY, Lee JG, Lee JM, Kim A, Yoo HC, Kim K, et al. (2019). "Therapeutic effects of the novel Leucyl-tRNA synthetase inhibitor BC-LI-0186 in non-small cell lung cancer". Therapeutic Advances in Medical Oncology. 11: 1758835919846798. doi:10.1177/1758835919846798. PMC 6535710. PMID 31205503.

[3] Son K, You JS, Yoon MS, Dai C, Kim JH, Khanna N, et al. (April 2019). "Nontranslational function of leucyl-tRNA synthetase regulates myogenic differentiation and skeletal muscle regeneration". The Journal of Clinical Investigation. 129 (5): 2088–2093. doi:10.1172/JCI122560. PMC 6486340. PMID 30985292.

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