6X3L

Sortilin-Progranulin Interaction With Compound 2

Summary for 6X3L

• Entry DOI: 10.2210/pdb6x3l/pdb
• Descriptor: Sortilin, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 1-benzyl-3-tert-butyl-1H-pyrazole-5-carboxylic acid, ... (5 entities in total)
• Functional Keywords: protein protein interaction, unknown function
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 86190.43

Authors

Parthasarathy, G.,Soisson, S.M. (deposition date: 2020-05-21, release date: 2020-08-12, Last modification date: 2024-10-23)

Primary citation

Stachel, S.J.,Ginnetti, A.T.,Johnson, S.A.,Cramer, P.,Wang, Y.,Bukhtiyarova, M.,Krosky, D.,Stump, C.,Hurzy, D.M.,Schlegel, K.A.,Cooke, A.J.,Allen, S.,O'Donnell, G.,Ziebell, M.,Parthasarathy, G.,Getty, K.L.,Ho, T.,Ou, Y.,Jovanovska, A.,Carroll, S.S.,Pausch, M.,Lumb, K.,Mosser, S.D.,Voleti, B.,Klein, D.J.,Soisson, S.M.,Zerbinatti, C.,Coleman, P.J.
Identification of potent inhibitors of the sortilin-progranulin interaction.
Bioorg.Med.Chem.Lett., 30:127403-127403, 2020

PubMed Abstract: High-throughput screening methods have been used to identify two novel series of inhibitors that disrupt progranulin binding to sortilin. Exploration of structure-activity relationships (SAR) resulted in compounds with sufficient potency and physicochemical properties to enable co-crystallization with sortilin. These co-crystal structures supported observed SAR trends and provided guidance for additional avenues for designing compounds with additional interactions within the binding site.

PubMed: 32738972
DOI: 10.1016/j.bmcl.2020.127403

Experimental method

X-RAY DIFFRACTION (2.7 Å)