7myr

BACE-1 in complex with compound #18BACE-1 in complex with compound #18

Structural highlights

Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.72Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Publication Abstract from PubMed

The beta-site APP cleaving enzyme 1, known as BACE1, has been a widely pursued Alzheimer's disease drug target owing to its critical role in the production of amyloid-beta. We have previously reported the clinical development of LY2811376 and LY2886721. LY2811376 advanced to Phase I before development was terminated due to nonclinical retinal toxicity. LY2886721 advanced to Phase II, but development was halted due to abnormally elevated liver enzymes. Herein, we report the discovery and clinical development of LY3202626, a highly potent, CNS-penetrant, and low-dose BACE inhibitor, which successfully addressed these key development challenges.

Discovery and Early Clinical Development of LY3202626, a Low-Dose, CNS-Penetrant BACE Inhibitor.,McKinzie DL, Winneroski LL, Green SJ, Hembre EJ, Erickson JA, Willis BA, Monk SA, Aluise CD, Baker TK, Lopez JE, Hendle J, Beck JP, Brier RA, Boggs LN, Borders AR, Cocke PJ, Garcia-Losada P, Lowe SL, Mathes BM, May PC, Porter WJ, Stout SL, Timm DE, Watson BM, Yang Z, Mergott DJ J Med Chem. 2021 Jun 24;64(12):8076-8100. doi: 10.1021/acs.jmedchem.1c00489. Epub, 2021 Jun 3. PMID:34081466^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ McKinzie DL, Winneroski LL, Green SJ, Hembre EJ, Erickson JA, Willis BA, Monk SA, Aluise CD, Baker TK, Lopez JE, Hendle J, Beck JP, Brier RA, Boggs LN, Borders AR, Cocke PJ, Garcia-Losada P, Lowe SL, Mathes BM, May PC, Porter WJ, Stout SL, Timm DE, Watson BM, Yang Z, Mergott DJ. Discovery and Early Clinical Development of LY3202626, a Low-Dose, CNS-Penetrant BACE Inhibitor. J Med Chem. 2021 Jun 24;64(12):8076-8100. PMID:34081466 doi:10.1021/acs.jmedchem.1c00489

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OCA

[1] McKinzie DL, Winneroski LL, Green SJ, Hembre EJ, Erickson JA, Willis BA, Monk SA, Aluise CD, Baker TK, Lopez JE, Hendle J, Beck JP, Brier RA, Boggs LN, Borders AR, Cocke PJ, Garcia-Losada P, Lowe SL, Mathes BM, May PC, Porter WJ, Stout SL, Timm DE, Watson BM, Yang Z, Mergott DJ. Discovery and Early Clinical Development of LY3202626, a Low-Dose, CNS-Penetrant BACE Inhibitor. J Med Chem. 2021 Jun 24;64(12):8076-8100. PMID:34081466 doi:10.1021/acs.jmedchem.1c00489

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