6GVH

Crystal structure of PI3K alpha in complex with 3-(2-Amino-benzooxazol-5-yl)-4-chloro-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine

Summary for 6GVH

• Entry DOI: 10.2210/pdb6gvh/pdb
• Descriptor: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform, 5-(6-azanyl-4-chloranyl-1-propan-2-yl-pyrazolo[3,4-d]pyrimidin-3-yl)-1,3-benzoxazol-2-amine (3 entities in total)
• Functional Keywords: lipid kinase, inhibitor, pi3k alpha, transferase-transferase inhibitor complex, transferase-transferase regulator complex, transferase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 112397.27

Authors

Ouvry, G.,Aurelly, M.,Bonnary, L.,Borde, E.,Bouix-Peter, C.,Chantalat, L.,Clary, L.,Defoin-Platel, C.,Deret, S.,Forissier, M.,Harris, C.S.,Isabet, T.,Lamy, L.,Luzy, A.P.,Pascau, J.,Soulet, C.,Taddei, A.,Taquet, N.,Tomas, L.,Thoreau, E.,Varvier, E.,Vial, E.,Hennequin, L.F. (deposition date: 2018-06-21, release date: 2019-10-02, Last modification date: 2024-05-15)

Primary citation

Ouvry, G.,Clary, L.,Tomas, L.,Aurelly, M.,Bonnary, L.,Borde, E.,Bouix-Peter, C.,Chantalat, L.,Defoin-Platel, C.,Deret, S.,Forissier, M.,Harris, C.S.,Isabet, T.,Lamy, L.,Luzy, A.P.,Pascau, J.,Soulet, C.,Taddei, A.,Taquet, N.,Thoreau, E.,Varvier, E.,Vial, E.,Hennequin, L.F.
Impact of Minor Structural Modifications on Properties of a Series of mTOR Inhibitors.
Acs Med.Chem.Lett., 10:1561-1567, 2019

PubMed Abstract: Minor structural modifications-sometimes single atom changes-can have a dramatic impact on the properties of compounds. This is illustrated here on structures related to known mTOR inhibitor Sapanisertib. Subtle changes in the hinge binder lead to strikingly different overall profiles with changes in physical properties, metabolism, and kinase selectivity.

PubMed: 31749911
DOI: 10.1021/acsmedchemlett.9b00401

Experimental method

X-RAY DIFFRACTION (2.74 Å)