Target Binding Site Detail
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T99089 | Target Info | |||
| Target Name | Serine/threonine-protein kinase B-raf (BRAF) | ||||
| Synonyms | V-Raf murine sarcoma viral oncogene homolog B1; RAFB1; Proto-oncogene B-Raf; P94; BRAF1; BRAF(V599E); BRAF serine/threonine kinase; B-raf protein; B-Raf | ||||
| Target Type | Successful Target | ||||
| Gene Name | BRAF | ||||
| Biochemical Class | Kinase | ||||
| UniProt ID | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | AZ-628 | Ligand Info | |||
| Canonical SMILES | CC1=C(C=C(C=C1)NC(=O)C2=CC(=CC=C2)C(C)(C)C#N)NC3=CC4=C(C=C3)N=CN(C4=O)C | ||||
| InChI | 1S/C27H25N5O2/c1-17-8-9-21(31-25(33)18-6-5-7-19(12-18)27(2,3)15-28)14-24(17)30-20-10-11-23-22(13-20)26(34)32(4)16-29-23/h5-14,16,30H,1-4H3,(H,31,33) | ||||
| InChIKey | ZGBGPEDJXCYQPH-UHFFFAOYSA-N | ||||
| PubChem Compound ID | 11676786 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 4G9R B-Raf V600E Kinase Domain Bound to a Type II Dihydroquinazoline Inhibitor | ||||||
| Method | X-ray diffraction | Resolution | 3.20 Å | Mutation | Yes | [1] |
| PDB Sequence |
DDWEIPDGQI
457 TVGQRIGSGS467 FGTVYKGKWH477 GDVAVKMLNV487 TAPTPQQLQA497 FKNEVGVLRK 507 TRHVNILLFM517 GYSTKPQLAI527 VTQWCEGSSL537 YHHLHIIETK547 FEMIKLIDIA 557 RQTAQGMDYL567 HAKSIIHRDL577 KSNNIFLHED587 LTVKIGDFGL597 ATEKSGSILW 619 MAPEVIRMQD629 KNPYSFQSDV639 YAFGIVLYEL649 MTGQLPYSNI659 NNRDQIIFMV 669 GRGYLSPDLS679 KVRSNCPKAM689 KRLMAECLKK699 KRDERPLFPQ709 ILASIELLAR 719 SL
|
|||||
|
|
ILE463
3.740
VAL471
3.972
ALA481
3.334
VAL482
3.965
LYS483
3.337
GLU501
3.006
VAL504
3.771
LEU505
3.820
THR508
4.523
LEU514
3.493
ILE527
3.667
THR529
3.165
GLN530
3.595
|
|||||
| PDB ID: 5HID BRAF Kinase domain b3aC loop deletion mutant in complex with AZ628 | ||||||
| Method | X-ray diffraction | Resolution | 2.50 Å | Mutation | Yes | [2] |
| PDB Sequence |
DWEIPDGQIT
458 VGQRIGSGSF468 GTVYKGKWHG478 DVAVKMLTPQ493 QLQAFKNEVG503 VLRKTRHVNI 513 LLFMGYSTKP523 QLAIVTQWCE533 GSSLYHHLHA543 SETKFEMKKL553 IDIARQTARG 563 MDYLHAKSII573 HRDLKSNNIF583 LHEDNTVKIG593 DFGLAEQLSG615 SILWMAPEVI 625 RMQDSNPYSF635 QSDVYAFGIV645 LYELMTGQLP655 YSNINNRDQI665 IEMVGRGSLS 675 PDLSKVRSNC685 PKRMKRLMAE695 CLKKKRDERP705 SFPRILAEIE715 ELARELS |
|||||
|
|
ILE463
3.665
VAL471
3.860
ALA481
3.414
VAL482
3.943
LYS483
3.600
GLU501
2.756
VAL504
3.696
LEU505
3.783
THR508
4.691
ILE513
4.383
LEU514
3.628
ILE527
3.766
THR529
3.244
|
|||||
| PDB ID: 4RZW Crystal structure of BRAF (R509H) kinase domain bound to AZ628 | ||||||
| Method | X-ray diffraction | Resolution | 3.49 Å | Mutation | Yes | [3] |
| PDB Sequence |
DDWEIPDGQI
457 TVGQRIGSGS467 FGTVYKGKWH477 GDVAVKMLNV487 TAPTPQQLQA497 FKNEVGVLRK 507 THHVNILLFM517 GYSTKPQLAI527 VTQWCEGSSL537 YHHLHASETK547 FEMKKLIDIA 557 RQTARGMDYL567 HAKSIIHRDL577 KSNNIFLHED587 NTVKIGDFGG615 SILWMAPEVI 625 RNPYSFQSDV639 YAFGIVLYEL649 MTGQLPYSNI659 NNRDQIIEMV669 GRGSLSPDLS 679 KVRSNCPKRM689 KRLMAECLKK699 KRDERPSFPR709 ILAEIEELAR719 E |
|||||
|
|
ILE463
4.273
VAL471
4.365
ALA481
3.567
VAL482
4.022
LYS483
3.555
GLU501
3.358
VAL504
4.240
LEU505
4.274
THR508
4.538
LEU514
3.490
ILE527
4.033
THR529
3.233
|
|||||
| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Pyrazolopyridine inhibitors of B-Raf(V600E). Part 4: rational design and kinase selectivity profile of cell potent type II inhibitors. Bioorg Med Chem Lett. 2012 Oct 1;22(19):6237-41. | ||||
| REF 2 | Activation Mechanism of Oncogenic Deletion Mutations in BRAF, EGFR, and HER2. Cancer Cell. 2016 Apr 11;29(4):477-493. | ||||
| REF 3 | An integrated model of RAF inhibitor action predicts | ||||
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.