2025-01-18_00000217|ligand|9E5D

Discovery of an Orally Biovailable KRAS G12D Inhibitor; X-ray diffraction 1.36Å

Protein #1 170 residues (99% resolved)

Raw Sequence ...

GMTEYKLVVVGADGVGKSALTIQLIQNHFVDEYDPTIEDSYRKQVVIDGETCLLDILDTAGQEEYSAMRDQYMRTGEGFLCVFAINNTKSFEDIHHYREQIKRVKDSEDVPMVLVGNKCDLPSRTVDTKQAQDLARSYGIPFIETSAKTRQGVDDAFYTLVREIRKHKEK

Canonical Sequence ...

GMTEYKLVVVGADGVGKSALTIQLIQNHFVDEYDPTIEDSYRKQVVIDGETCLLDILDTAGQEEYSAMRDQYMRTGEGFLCVFAINNTKSFEDIHHYREQIKRVKDSEDVPMVLVGNKCDLPSRTVDTKQAQDLARSYGIPFIETSAKTRQGVDDAFYTLVREIRKHKEK

Non polymer #2 A1BEI

InChI=1S/C37H38FN7O3/c1-43(2)23-18-44(19-23)37-34-36(45(35-22-15-28(35)40-17-22)29(41-34)10-11-30(47)48-3)27-14-21(8-6-12-39)31(32(38)33(27)42-37)26-16-24(46)13-20-7-4-5-9-25(20)26/h4-5,7,9,13-14,16,22-23,28,35,40,46H,6,8,10-11,15,17-19H2,1-3H3/t22-,28-,35+/m1/s1

InChI=1S/C37H38FN7O3/c1-43(2)23-18-44(19-23)37-34-36(45(35-22-15-28(35)40-17-22)29(41-34)10-11-30(47)48-3)27-14-21(8-6-12-39)31(32(38)33(27)42-37)26-16-24(46)13-20-7-4-5-9-25(20)26/h4-5,7,9,13-14,16,22-23,28,35,40,46H,6,8,10-11,15,17-19H2,1-3H3/t22-,28-,35+/m1/s1

SMILES: CN(C)C1CN(C1)c2c3c(c4cc(c(c(c4n2)F)c5cc(cc6c5cccc6)O)CCC#N)n(c(n3)CCC(=O)OC)[C@H]7[C@@H]8C[C@H]7NC8

CN(C)C1CN(C1)c2c3c(c4cc(c(c(c4n2)F)c5cc(cc6c5cccc6)O)CCC#N)n(c(n3)CCC(=O)OC)[C@H]7[C@@H]8C[C@H]7NC8

Non polymer #3 GDP

InChI=1S/C10H15N5O11P2/c11-10-13-7-4(8(18)14-10)12-2-15(7)9-6(17)5(16)3(25-9)1-24-28(22,23)26-27(19,20)21/h2-3,5-6,9,16-17H,1H2,(H,22,23)(H2,19,20,21)(H3,11,13,14,18)/t3-,5-,6-,9-/m1/s1

SMILES: c1nc2c(n1[C@H]3[C@@H]([C@@H]([C@H](O3)CO[P@](=O)(O)OP(=O)(O)O)O)O)N=C(NC2=O)N

c1nc2c(n1[C@H]3[C@@H]([C@@H]([C@H](O3)CO[P@](=O)(O)OP(=O)(O)O)O)O)N=C(NC2=O)N

Non polymer #4 MG

InChI=1S/Mg/q+2

SMILES: [Mg+2]

[Mg+2]

Biounit #1 monomer

Reference