8cij

CRYSTAL STRUCTURE OF HUMAN HPK1 (MAP4K1) COMPLEX WITH 2-[8-Amino-7-fluoro-6-(8-methyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-7-yl)-isoquinolin-3-ylamino]-6-isopropyl-5,6-dihydro-4H-1,6,8a-triaza-azulen-7-oneCRYSTAL STRUCTURE OF HUMAN HPK1 (MAP4K1) COMPLEX WITH 2-[8-Amino-7-fluoro-6-(8-methyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-7-yl)-isoquinolin-3-ylamino]-6-isopropyl-5,6-dihydro-4H-1,6,8a-triaza-azulen-7-one

Structural highlights 8cij is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.821Å Ligands: Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function M4K1_HUMAN Serine/threonine-protein kinase, which may play a role in the response to environmental stress. Appears to act upstream of the JUN N-terminal pathway. May play a role in hematopoietic lineage decisions and growth regulation. Able to autophosphorylate. Publication Abstract from PubMed Hematopoietic progenitor kinase 1 (HPK1) is regarded as a highly validated target in pre-clinical immune oncology. HPK1 has been described as regulating multiple critical signaling pathway in both adaptive and innate cells. In support of this role, HPK1 KO T cells show enhanced sensitivity to TCR activation and HPK1 KO mice display enhanced anti-tumor activity. Taken together, inhibition of HPK1 has the potential to induce enhanced anti-tumor immune response. Herein, we described the discovery of highly potent HPK1 inhibitors starting form a weak HTS hit. Using a structure-based drug design, HPK1 inhibitors exhibiting excellent cellular single-digit nanomolar potency in both proximal (pSLP76) and distal (IL-2) biomarkers along with sustained elevation of IL-2 cytokine secretion were discovered. Discovery of quinazoline HPK1 inhibitors with high cellular potency.,Toure M, Johnson T, Li B, Schmidt R, Ma H, Neagu C, Lopez AU, Wang Y, Guler S, Xiao Y, Henkes R, Ho K, Zhang S, Chu CL, Gundra UM, Porichis F, Li L, Maurer CK, Fang Z, Musil D, DiPoto M, Friis E, Jones R, Jones C, Cummings J, Chekler E, Tanzer EM, Huck B, Sherer B Bioorg Med Chem. 2023 Jul 27;92:117423. doi: 10.1016/j.bmc.2023.117423. PMID:37531921 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

spinqualitylabelsall models 8cij, resolution 2.82Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image