2024-06-01_00000091|ligand|8PO4

Discovery and Optimisation of Potent, Efficacious and Selective Inhibitors Targeting EGFR Exon20 Insertion Mutations. Compound 33 bound to EGFR[V948R]; X-ray diffraction 1.62Å

Protein #1 328 residues (94% resolved)

Raw Sequence ...

SGEAPNQALLRILKETEFKKIKVLGSGAFGTVYKGLWIPEGEKVKIPVAIKELREATSPKANKEILDEAYVMASVDNPHVCRLLGICLTSTVQLITQLMPFGCLLDYVREHKDNIGSQYLLNWCVQIAKGMNYLEDRRLVHRDLAARNVLVKTPQHVKITDFGLAKLLGAEEKEYHAEGGKVPIKWMALESILHRIYTHQSDVWSYGVTVWELMTFGSKPYDGIPASEISSILEKGERLPQPPICTIDVYMIMRKCWMIDADSRPKFRELIIEFSKMARDPQRYLVIQGDERMHLPSPTDSNFYRALMDEEDMDDVVDADEYLIPQQG

Canonical Sequence ...

Non polymer #2 26X

InChI=1S/C27H27N7O2/c1-2-25(35)32-13-22(14-32)34-15-23(18-8-10-28-11-9-18)26(31-34)19-4-3-5-20(12-19)30-27(36)24-16-33(17-29-24)21-6-7-21/h3-5,8-12,15-17,21-22H,2,6-7,13-14H2,1H3,(H,30,36)

SMILES: CCC(=O)N1CC(C1)n2cc(c(n2)c3cccc(c3)NC(=O)c4cn(cn4)C5CC5)c6ccncc6

CCC(=O)N1CC(C1)n2cc(c(n2)c3cccc(c3)NC(=O)c4cn(cn4)C5CC5)c6ccncc6

Non polymer #3 ATP

InChI=1S/C10H16N5O13P3/c11-8-5-9(13-2-12-8)15(3-14-5)10-7(17)6(16)4(26-10)1-25-30(21,22)28-31(23,24)27-29(18,19)20/h2-4,6-7,10,16-17H,1H2,(H,21,22)(H,23,24)(H2,11,12,13)(H2,18,19,20)/t4-,6-,7-,10-/m1/s1

InChI=1S/C10H16N5O13P3/c11-8-5-9(13-2-12-8)15(3-14-5)10-7(17)6(16)4(26-10)1-25-30(21,22)28-31(23,24)27-29(18,19)20/h2-4,6-7,10,16-17H,1H2,(H,21,22)(H,23,24)(H2,11,12,13)(H2,18,19,20)/t4-,6-,7-,10-/m1/s1

SMILES: c1nc(c2c(n1)n(cn2)[C@H]3[C@@H]([C@@H]([C@H](O3)CO[P@@](=O)(O)O[P@](=O)(O)OP(=O)(O)O)O)O)N

c1nc(c2c(n1)n(cn2)[C@H]3[C@@H]([C@@H]([C@H](O3)CO[P@@](=O)(O)O[P@](=O)(O)OP(=O)(O)O)O)O)N

Non polymer #4 MG

InChI=1S/Mg/q+2

SMILES: [Mg+2]

[Mg+2]

Biounit #1 monomer

Biounit #2 monomer

Reference