8FLV
Bruton's tyrosine kinase in complex with compound 34
Summary for 8FLV
| Entry DOI | 10.2210/pdb8flv/pdb |
| Related | 8FLG 8FLH |
| Descriptor | Tyrosine-protein kinase BTK, 2-(3,5-dichloroanilino)-1-{(3R)-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]piperidin-1-yl}ethan-1-one, DIMETHYL SULFOXIDE, ... (5 entities in total) |
| Functional Keywords | tyrosine protein kinase btk, ligase, transferase-inhibitor complex, transferase/inhibitor |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 33454.32 |
| Authors | Metrick, C.M.,Marcotte, D.J. (deposition date: 2022-12-22, release date: 2023-04-05, Last modification date: 2024-05-22) |
| Primary citation | Vandeveer, G.H.,Arduini, R.M.,Baker, D.P.,Barry, K.,Bohnert, T.,Bowden-Verhoek, J.K.,Conlon, P.,Cullen, P.F.,Guan, B.,Jenkins, T.J.,Liao, S.Y.,Lin, L.,Liu, Y.T.,Marcotte, D.,Mertsching, E.,Metrick, C.M.,Negrou, E.,Powell, N.,Scott, D.,Silvian, L.F.,Hopkins, B.T. Discovery of structural diverse reversible BTK inhibitors utilized to develop a novel in vivo CD69 and CD86 PK/PD mouse model. Bioorg.Med.Chem.Lett., 80:129108-129108, 2023 Cited by PubMed Abstract: For the past two decades, BTK a tyrosine kinase and member of the Tec family has been a drug target of significant interest due to its potential to selectively treat various B cell-mediated diseases such as CLL, MCL, RA, and MS. Owning to the challenges encountered in identifying drug candidates exhibiting the potency block B cell activation via BTK inhibition, the pharmaceutical industry has relied on the use of covalent/irreversible inhibitors to address this unmet medical need. Herein, we describe a medicinal chemistry campaign to identify structurally diverse reversible BTK inhibitors originating from HITS identified using a fragment base screen. The leads were optimized to improve the potency and in vivo ADME properties resulting in a structurally distinct chemical series used to develop and validate a novel in vivo CD69 and CD86 PD assay in rodents. PubMed: 36538993DOI: 10.1016/j.bmcl.2022.129108 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.3 Å) |
Structure validation
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