Binding Site Information of Target
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T01003 | Target Info | |||
| Target Name | Endoplasmic reticulum to nucleus signaling 1 (ERN1) | ||||
| Synonyms | Serine/threonine-protein kinase/endoribonuclease IRE1; Ire1-alpha; IRE1a; IRE1; Inositol-requiring protein 1; hIRE1p; Endoplasmic reticulum-to-nucleus signaling 1 | ||||
| Target Type | Clinical trial Target | ||||
| Gene Name | ERN1 | ||||
| Biochemical Class | Kinase | ||||
| UniProt ID | |||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: L-serine-O-phosphate | Ligand Info | |||||
| Structure Description | Crystal structure of IRE1 in complex with G-3053 | PDB:6XDD | ||||
| Method | X-ray diffraction | Resolution | 2.40 Å | Mutation | No | [1] |
| PDB Sequence |
ETSVVIVGKI
569 SFCPKDVLGH579 GAEGTIVYRG589 MFDNRDVAVK599 RILPECFSFA609 DREVQLLRES 619 DEHPNVIRYF629 CTEKDRQFQY639 IAIELCAATL649 QEYVEQKDFA659 HLGLEPITLL 669 QQTTSGLAHL679 HSLNIVHRDL689 KPHNILISMP699 NAHGKIKAMI709 SDFGLCKKLA 719 VGRHFRRGVP732 GTEGWIAPEM742 LSEDCKENPT752 YTVDIFSAGC762 VFYYVISEGS 772 HPFGKSLQRQ782 ANILLGACSL792 DCLHPEKHED802 VIARELIEKM812 IAMDPQKRPS 822 AKHVLKHPFF832 WSLEKQLQFF842 QDVSDRIEKE852 SLDGPIVKQL862 ERGGRAVVKM 872 DWRENITVPL882 QTDLRKFRTY892 KGGSVRDLLR902 AMRNKKHHYR912 ELPAEVRETL 922 GSLPDDFVCY932 FTSRFPHLLA942 HTYRAMELCS952 HERLFQPYYF962 H |
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: adenosine diphosphate | Ligand Info | |||||
| Structure Description | Crystal structure of the Human kinase and RNase domains in complex with ADP | PDB:3P23 | ||||
| Method | X-ray diffraction | Resolution | 2.70 Å | Mutation | No | [2] |
| PDB Sequence |
VVIVGKISFC
572 PKDVLGHGAE582 GTIVYRGMFD592 NRDVAVKRIL602 PECFSFADRE612 VQLLRESDEH 622 PNVIRYFCTE632 KDRQFQYIAI642 ELCAATLQEY652 VEQKDFAHLG662 LEPITLLQQT 672 TSGLAHLHSL682 NIVHRDLKPH692 NILISMPNAH702 GKIKAMISDF712 GLCKKLVPGT 734 EGWIAPEMLS744 EDNPTYTVDI757 FSAGCVFYYV767 ISEGSHPFGK777 SLQRQANILL 787 GACSLDCLHP797 EKHEDVIARE807 LIEKMIAMDP817 QKRPSAKHVL827 KHPFFWSLEK 837 QLQFFQDVSD847 RIEKESLDGP857 IVKQLERGGR867 AVVKMDWREN877 ITVPLQTDLR 887 KFRTYKGGSV897 RDLLRAMRNK907 KHHYRELPAE917 VRETLGTLPD927 DFVCYFTSRF 937 PHLLAHTYRA947 MELCSHERLF957 QPYYFH
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LEU577
3.951
GLY578
3.837
HIS579
3.355
GLY580
3.030
ALA581
4.456
THR584
3.329
VAL586
3.709
ALA597
3.487
LYS599
2.690
ILE626
4.702
ILE642
3.617
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: Staurosporine | Ligand Info | |||||
| Structure Description | Crystal structure of pIRE1alpha in complex with staurosporine | PDB:4YZC | ||||
| Method | X-ray diffraction | Resolution | 2.49 Å | Mutation | No | [3] |
| PDB Sequence |
SVVIVGKISF
571 CPKDVLGHGA581 EGTIVYRGMF591 DNRDVAVKRI601 LPDREVQLLR617 ESDEHPNVIR 627 YFCTEKDRQF637 QYIAIELCAA647 TLQEYVEQEP665 ITLLQQTTSG675 LAHLHSLNIV 685 HRDLKPHNIL695 ISMPNAHGKI705 KAMISDFGLC715 KKLAVRHFRR728 GVPGTEGWIA 739 PEMLSCKENP751 TYTVDIFSAG761 CVFYYVISEG771 SHPFGKSLQR781 QANILLGACS 791 LDCLHPEKHE801 DVIARELIEK811 MIAMDPQKRP821 SAKHVLKHPF831 FWSLEKQLQF 841 FQDVSDRIEK851 ESLDGPIVKQ861 LERGGRAVVK871 MDWRENITVP881 LQTDLRKFRT 891 YKGGSVRDLL901 RAMRNKKHHY911 RELPAEVRET921 LGSLPDDFVC931 YFTSRFPHLL 941 AHTYRAMELC951 SHERLFQPYY961 FH
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .STU or .STU2 or .STU3 or :3STU;style chemicals stick;color identity;select .A:577 or .A:578 or .A:579 or .A:580 or .A:584 or .A:586 or .A:597 or .A:599 or .A:626 or .A:642 or .A:643 or .A:644 or .A:645 or .A:646 or .A:647 or .A:648 or .A:651 or .A:690 or .A:692 or .A:693 or .A:694 or .A:695 or .A:710 or .A:711 or .A:712 or .A:713; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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LEU577
2.390
GLY578
2.538
HIS579
3.161
GLY580
3.501
THR584
3.896
VAL586
2.758
ALA597
2.584
LYS599
2.115
ILE626
3.082
ILE642
2.195
GLU643
1.774
LEU644
2.633
CYS645
1.742
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| Ligand Name: N-{4-[(3-{2-[(Trans-4-Aminocyclohexyl)amino]pyrimidin-4-Yl}pyridin-2-Yl)oxy]-3-Methylnaphthalen-1-Yl}-2-Chlorobenzenesulfonamide | Ligand Info | |||||
| Structure Description | Crystal structure of human IRE1 cytoplasmic domains in complex with a sulfonamide inhibitor. | PDB:4U6R | ||||
| Method | X-ray diffraction | Resolution | 2.50 Å | Mutation | No | [4] |
| PDB Sequence |
TSVVIVGKIS
570 FCPKDVLGHG580 AEGTIVYRGM590 FDNRDVAVKR600 ILPECFSFAD610 REVQLLRESD 620 EHPNVIRYFC630 TEKDRQFQYI640 AIELCAATLQ650 EYVEQKDFAH660 LGLEPITLLQ 670 QTTSGLAHLH680 SLNIVHRDLK690 PHNILISMPN700 AHGKIKAMIS710 DFGLCKKLAV 720 GRHSFSRRSG730 VPGTEGWIAP740 EMLSEDCKEN750 PTYTVDIFSA760 GCVFYYVISE 770 GSHPFGKSLQ780 RQANILLGAC790 SLDCLHPEKH800 EDVIARELIE810 KMIAMDPQKR 820 PSAKHVLKHP830 FFWSLEKQLQ840 FFQDVSDRIE850 KESLDGPIVK860 QLERGGRAVV 870 KMDWRENITV880 PLQTDLRKFR890 TYKGGSVRDL900 LRAMRNKKHH910 YRELPAEVRE 920 TLGTLPDDFV930 CYFTSRFPHL940 LAHTYRAMEL950 CSHERLFQPY960 YFH |
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .3E4 or .3E42 or .3E43 or :33E4;style chemicals stick;color identity;select .A:577 or .A:578 or .A:579 or .A:580 or .A:586 or .A:597 or .A:598 or .A:599 or .A:609 or .A:612 or .A:613 or .A:616 or .A:626 or .A:628 or .A:640 or .A:642 or .A:643 or .A:644 or .A:645 or .A:646 or .A:647 or .A:648 or .A:651 or .A:693 or .A:695 or .A:710 or .A:711 or .A:712 or .A:713; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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LEU577
3.910
GLY578
4.187
HIS579
4.036
GLY580
4.511
VAL586
3.327
ALA597
3.555
VAL598
4.482
LYS599
3.220
ALA609
4.736
GLU612
3.199
VAL613
4.110
LEU616
3.226
ILE626
4.458
TYR628
3.828
ILE640
3.781
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| Ligand Name: 2,2,2-tris(fluoranyl)-~{N}-[4-[3-[2-[[(3~{S})-piperidin-3-yl]amino]pyrimidin-4-yl]pyridin-2-yl]oxynaphthalen-1-yl]ethanesulfonamide | Ligand Info | |||||
| Structure Description | ATP-Competitive Partial Antagonists-'PAIR's-Rheostatically Modulate IRE1alpha's Kinase Helix-alphaC to Segregate its RNase-Mediated Biological Outputs | PDB:7BMK | ||||
| Method | X-ray diffraction | Resolution | 1.85 Å | Mutation | No | [5] |
| PDB Sequence |
TSVVIVGKIS
570 FCPKDVLGHG580 AEGTIVYRGM590 FDNRDVAVKR600 ILPECFSFAD610 REVQLLRESD 620 EHPNVIRYFC630 TEKDRQFQYI640 AIELCAATLQ650 EYVEQKDFAH660 LGLEPITLLQ 670 QTTSGLAHLH680 SLNIVHRDLK690 PHNILISMPN700 AHGKIKAMIS710 DFGLCKKLAV 720 GRHSFSRRSG730 VPGTEGWIAP740 EMLSEDCKEN750 PTYTVDIFSA760 GCVFYYVISE 770 GSHPFGKSLQ780 RQANILLGAC790 SLDCLHPEKH800 EDVIARELIE810 KMIAMDPQKR 820 PSAKHVLKHP830 FFWSLEKQLQ840 FFQDVSDRIE850 KESLDGPIVK860 QLERGGRAVV 870 KMDWRENITV880 PLQTDLRKFR890 TYKGGSVRDL900 LRAMRNKKHH910 YRELPAEVRE 920 TLGSLPDDFV930 CYFTSRFPHL940 LAHTYRAMEL950 CSHERLFQPY960 YFHEPP |
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .U4N or .U4N2 or .U4N3 or :3U4N;style chemicals stick;color identity;select .A:577 or .A:578 or .A:586 or .A:597 or .A:598 or .A:599 or .A:612 or .A:613 or .A:616 or .A:626 or .A:628 or .A:640 or .A:641 or .A:642 or .A:643 or .A:644 or .A:645 or .A:646 or .A:647 or .A:648 or .A:651 or .A:692 or .A:695 or .A:710 or .A:711 or .A:712 or .A:713; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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LEU577
3.738
GLY578
4.233
VAL586
3.770
ALA597
3.558
VAL598
4.158
LYS599
3.389
GLU612
3.422
VAL613
3.745
LEU616
3.523
ILE626
3.877
TYR628
3.621
ILE640
3.310
ALA641
4.791
ILE642
3.445
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| Ligand Name: 4-[5-[2,6-bis(fluoranyl)phenyl]-2~{H}-pyrazolo[3,4-b]pyridin-3-yl]-2-(4-oxidanylpiperidin-1-yl)-1~{H}-pyrimidin-6-one | Ligand Info | |||||
| Structure Description | Structure of unphosphorylated human IRE1 bound to G-9807 | PDB:6W3K | ||||
| Method | X-ray diffraction | Resolution | 2.08 Å | Mutation | No | [6] |
| PDB Sequence |
SVVIVGKISF
571 CPKDVLGHGA581 EGTIVYRGMF591 DNRDVAVKRI601 LPECFSFADR611 EVQLLRESDE 621 HPNVIRYFCT631 EKDRQFQYIA641 IELCAATLQE651 YVEQKDFAHL661 GLEPITLLQQ 671 TTSGLAHLHS681 LNIVHRDLKP691 HNILISMPNA701 HGKIKAMISD711 FGLCKKLAVG 721 RHSFSRPGTE735 GWIAPEMLSE745 DCKENPTYTV755 DIFSAGCVFY765 YVISEGSHPF 775 GKSLQRQANI785 LLGACSLDCL795 HPEKHEDVIA805 RELIEKMIAM815 DPQKRPSAKH 825 VLKHPFFWSL835 EKQLQFFQDV845 SDRIEKESLD855 GPIVKQLERG865 GRAVVKMDWR 875 ENITVPLQTD885 LRKFRTYKGG895 SVRDLLRAMR905 NKKHHYRELP915 AEVRETLGSL 925 PDDFVCYFTS935 RFPHLLAHTY945 RAMELCSHER955 LFQPYYFH
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .SJS or .SJS2 or .SJS3 or :3SJS;style chemicals stick;color identity;select .A:577 or .A:578 or .A:579 or .A:580 or .A:586 or .A:597 or .A:599 or .A:612 or .A:626 or .A:642 or .A:643 or .A:644 or .A:645 or .A:646 or .A:647 or .A:648 or .A:651 or .A:692 or .A:693 or .A:695 or .A:710 or .A:711 or .A:712; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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LEU577
3.166
GLY578
3.706
HIS579
3.843
GLY580
4.431
VAL586
3.811
ALA597
3.198
LYS599
2.579
GLU612
3.696
ILE626
3.408
ILE642
3.235
GLU643
2.803
LEU644
3.909
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| Ligand Name: (S)-2-Chloro-N-(6-methyl-5-((3-(2-(piperidin-3-ylamino)pyrimidin-4-yl)pyridin-2-yl)oxy)naphthalen-1-yl)benzenesulfonamide | Ligand Info | |||||
| Structure Description | Crystal structure of IRE1a in complex with compound 18 | PDB:6URC | ||||
| Method | X-ray diffraction | Resolution | 2.20 Å | Mutation | No | [7] |
| PDB Sequence |
ETSVVIVGKI
569 SFCPKDVLGH579 GAEGTIVYRG589 MFDNRDVAVK599 RILPECFSFA609 DREVQLLRES 619 DEHPNVIRYF629 CTEKDRQFQY639 IAIELCAATL649 QEYVEQKDFA659 HLGLEPITLL 669 QQTTSGLAHL679 HSLNIVHRDL689 KPHNILISMP699 NAHGKIKAMI709 SDFGLCKKLA 719 VGRHSFSRRS729 GVPGTEGWIA739 PEMLSEDCKE749 NPTYTVDIFS759 AGCVFYYVIS 769 EGSHPFGKSL779 QRQANILLGA789 CSLDCLHPEK799 HEDVIARELI809 EKMIAMDPQK 819 RPSAKHVLKH829 PFFWSLEKQL839 QFFQDVSDRI849 EKESLDGPIV859 KQLERGGRAV 869 VKMDWRENIT879 VPLQTDLTYK893 GGSVRDLLRA903 MRNKKHHYRE913 LPAEVRETLG 923 SLPDDFVCYF933 TSRFPHLLAH943 TYRAMELCSH953 ERLFQPYYFH963 |
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .QFV or .QFV2 or .QFV3 or :3QFV;style chemicals stick;color identity;select .A:577 or .A:578 or .A:579 or .A:586 or .A:597 or .A:599 or .A:609 or .A:612 or .A:613 or .A:616 or .A:626 or .A:627 or .A:628 or .A:640 or .A:642 or .A:643 or .A:644 or .A:645 or .A:646 or .A:647 or .A:648 or .A:651 or .A:692 or .A:693 or .A:695 or .A:710 or .A:711 or .A:712 or .A:713; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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LEU577
3.573
GLY578
3.940
HIS579
4.947
VAL586
3.732
ALA597
3.481
LYS599
2.881
ALA609
4.965
GLU612
3.049
VAL613
3.752
LEU616
3.278
ILE626
3.933
ARG627
4.977
TYR628
3.712
ILE640
3.621
ILE642
3.544
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| Ligand Name: 4-[(trans-4-aminocyclohexyl)amino]-N-(6-chloro-3-{[(2,5-difluorophenyl)sulfonyl]amino}-2-fluorophenyl)thieno[3,2-d]pyrimidine-7-carboxamide | Ligand Info | |||||
| Structure Description | Crystal structure of IRE1 in complex with G-3053 | PDB:6XDD | ||||
| Method | X-ray diffraction | Resolution | 2.40 Å | Mutation | No | [1] |
| PDB Sequence |
ETSVVIVGKI
569 SFCPKDVLGH579 GAEGTIVYRG589 MFDNRDVAVK599 RILPECFSFA609 DREVQLLRES 619 DEHPNVIRYF629 CTEKDRQFQY639 IAIELCAATL649 QEYVEQKDFA659 HLGLEPITLL 669 QQTTSGLAHL679 HSLNIVHRDL689 KPHNILISMP699 NAHGKIKAMI709 SDFGLCKKLA 719 VGRHFRRGVP732 GTEGWIAPEM742 LSEDCKENPT752 YTVDIFSAGC762 VFYYVISEGS 772 HPFGKSLQRQ782 ANILLGACSL792 DCLHPEKHED802 VIARELIEKM812 IAMDPQKRPS 822 AKHVLKHPFF832 WSLEKQLQFF842 QDVSDRIEKE852 SLDGPIVKQL862 ERGGRAVVKM 872 DWRENITVPL882 QTDLRKFRTY892 KGGSVRDLLR902 AMRNKKHHYR912 ELPAEVRETL 922 GSLPDDFVCY932 FTSRFPHLLA942 HTYRAMELCS952 HERLFQPYYF962 H |
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .N97 or .N972 or .N973 or :3N97;style chemicals stick;color identity;select .A:577 or .A:586 or .A:597 or .A:598 or .A:599 or .A:601 or .A:605 or .A:608 or .A:609 or .A:612 or .A:613 or .A:616 or .A:640 or .A:642 or .A:643 or .A:644 or .A:645 or .A:646 or .A:647 or .A:648 or .A:651 or .A:695 or .A:710 or .A:711 or .A:712 or .A:713; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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LEU577
3.787
VAL586
3.812
ALA597
3.389
VAL598
3.907
LYS599
3.111
ILE601
3.704
CYS605
4.907
PHE608
4.525
ALA609
3.096
GLU612
3.422
VAL613
3.955
LEU616
4.062
ILE640
3.640
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| Ligand Name: 4-amino-N-(6-chloro-2-fluoro-3-{[(2-fluorophenyl)sulfonyl]amino}phenyl)-6-(1,3-dimethyl-1H-pyrazol-4-yl)quinazoline-8-carboxamide | Ligand Info | |||||
| Structure Description | Crystal structure of IRE1a in complex with G-6904 | PDB:6XDB | ||||
| Method | X-ray diffraction | Resolution | 2.45 Å | Mutation | No | [1] |
| PDB Sequence |
TSVVIVGKIS
570 FCPKDVLGHG580 AEGTIVYRGM590 FDNRDVAVKR600 ILPECFSFAD610 REVQLLRESD 620 EHPNVIRYFC630 TEKDRQFQYI640 AIELCAATLQ650 EYVEQKDFAH660 LGLEPITLLQ 670 QTTSGLAHLH680 SLNIVHRNLK690 PHNILISMPN700 AHGKIKAMIS710 DFGLCKKLAV 720 GRHSFSRRSG730 VPGTEGWIAP740 EMLSEDCKEN750 PTYTVDIFSA760 GCVFYYVISE 770 GSHPFGKSLQ780 RQANILLGAC790 SLDCLHPEKH800 EDVIARELIE810 KMIAMDPQKR 820 PSAKHVLKHP830 FFWSLEKQLQ840 FFQDVSDRIE850 KESLDGPIVK860 QLERGGRAVV 870 KMDWRENITV880 PLQTDLRKFR890 TYKGGSVRDL900 LRAMRNKKHH910 YRELPAEVRE 920 TLGSLPDDFV930 CYFTSRFPHL940 LAHTYRAMEL950 CSHERLFQPY960 YFHE |
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .N8S or .N8S2 or .N8S3 or :3N8S;style chemicals stick;color identity;select .A:577 or .A:578 or .A:579 or .A:586 or .A:597 or .A:598 or .A:599 or .A:612 or .A:613 or .A:616 or .A:626 or .A:628 or .A:640 or .A:642 or .A:643 or .A:644 or .A:645 or .A:646 or .A:647 or .A:648 or .A:651 or .A:692 or .A:695 or .A:710 or .A:711 or .A:712 or .A:713; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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LEU577
3.399
GLY578
3.670
HIS579
3.640
VAL586
3.772
ALA597
3.363
VAL598
3.807
LYS599
2.848
GLU612
3.562
VAL613
3.487
LEU616
3.318
ILE626
3.052
TYR628
3.541
ILE640
3.849
ILE642
3.400
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| Ligand Name: N-[6-methyl-5-[3-[2-[[(3S)-piperidin-3-yl]amino]pyrimidin-4-yl]pyridin-2-yl]oxynaphthalen-1-yl]but-2-ynamide | Ligand Info | |||||
| Structure Description | Structure of unphosphorylated IRE1 in complex with G-7658 | PDB:6W3A | ||||
| Method | X-ray diffraction | Resolution | 2.61 Å | Mutation | No | [6] |
| PDB Sequence |
SVVIVGKISF
571 CPKDVLGHEG583 TIVYRGMFDN593 RDVAVKRILP603 ECFSFADREV613 QLLRESDEHP 623 NVIRYFCTEK633 DRQFQYIAIE643 LCAATLQEYV653 EQLEPITLLQ670 QTTSGLAHLH 680 SLNIVHRDLK690 PHNILISMPN700 AHGKIKAMIS710 DFGLGTEGWI738 APEMLENPTY 753 TVDIFSAGCV763 FYYVISEGSH773 PFGKSLQRQA783 NILLGACSLD793 CLHPEKHEDV 803 IARELIEKMI813 AMDPQKRPSA823 KHVLKHPFFW833 SLEKQLQFFQ843 DVSDRIEKES 853 LDGPIVKQLE863 RGGRAVVKMD873 WRENIVPLQT884 DLKGGSVRDL900 LRAMRNKKHH 910 YRELPAEVRE920 TLSLPDDFVC931 YFTSRFPHLL941 AHTYRAMELC951 SHERLFQPYY 961 FHE
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .SJM or .SJM2 or .SJM3 or :3SJM;style chemicals stick;color identity;select .A:577 or .A:578 or .A:579 or .A:586 or .A:597 or .A:599 or .A:612 or .A:615 or .A:616 or .A:626 or .A:640 or .A:642 or .A:643 or .A:644 or .A:645 or .A:646 or .A:647 or .A:648 or .A:651 or .A:692 or .A:693 or .A:695 or .A:710 or .A:711 or .A:712 or .A:714; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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LEU577
2.258
GLY578
3.145
HIS579
4.439
VAL586
3.055
ALA597
2.865
LYS599
2.936
GLU612
2.565
LEU615
3.135
LEU616
2.768
ILE626
3.162
ILE640
3.726
ILE642
2.751
GLU643
3.547
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| Ligand Name: (S)-Ethyl (6-methyl-5-((3-(2-(piperidin-3-ylamino)pyrimidin-4-yl)pyridin-2-yl)oxy)naphthalen-1-yl)carbamate | Ligand Info | |||||
| Structure Description | Structure of unphosphorylated IRE1 in complex with G-1749 | PDB:6W39 | ||||
| Method | X-ray diffraction | Resolution | 1.74 Å | Mutation | No | [6] |
| PDB Sequence |
VVIVGKISFC
572 PKDVLGHAEG583 TIVYRGMFDN593 RDVAVKRILP603 ECFSFADREV613 QLLRESDEHP 623 NVIRYFCTEK633 DRQFQYIAIE643 LCAATLQEYV653 EQKDFAHLGL663 EPITLLQQTT 673 SGLAHLHSLN683 IVHRDLKPHN693 ILISMPNAHG703 KIKAMISDFG713 LTEGWIAPEM 742 LSENPTYTVD756 IFSAGCVFYY766 VISEGSHPFG776 KSLQRQANIL786 LGACSLDCLH 796 PEKHEDVIAR806 ELIEKMIAMD816 PQKRPSAKHV826 LKHPFFWSLE836 KQLQFFQDVS 846 DRIEKESLDG856 PIVKQLERGG866 RAVVKMDWRE876 NITVPLQTDL886 RTYKGGSVRD 899 LLRAMRNKKH909 HYRELPAEVR919 ETLGSLPDDF929 VCYFTSRFPH939 LLAHTYRAME 949 LCSHERLFQP959 YYFH
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .SJG or .SJG2 or .SJG3 or :3SJG;style chemicals stick;color identity;select .A:577 or .A:578 or .A:579 or .A:586 or .A:597 or .A:599 or .A:612 or .A:615 or .A:616 or .A:626 or .A:640 or .A:642 or .A:643 or .A:644 or .A:645 or .A:646 or .A:647 or .A:648 or .A:651 or .A:658 or .A:692 or .A:693 or .A:695 or .A:710 or .A:711 or .A:712 or .A:714; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
LEU577
2.734
GLY578
3.296
HIS579
4.501
VAL586
2.640
ALA597
2.932
LYS599
2.950
GLU612
2.410
LEU615
3.361
LEU616
2.861
ILE626
3.468
ILE640
3.635
ILE642
2.887
GLU643
3.502
LEU644
2.916
|
|||||
| Ligand Name: 4-amino-N-(6-chloro-2-fluoro-3-{[(pyrrolidin-1-yl)sulfonyl]amino}phenyl)quinazoline-8-carboxamide | Ligand Info | |||||
| Structure Description | Crystal structure of IRE1a in complex with G-4100 | PDB:6XDF | ||||
| Method | X-ray diffraction | Resolution | 2.54 Å | Mutation | No | [1] |
| PDB Sequence |
ETSVVIVGKI
569 SFCPKDVLGH579 GAETIVYRGM590 FDNRDVAVKR600 ILPECFSFAD610 REVQLLRESD 620 EHPNVIRYFC630 TEKDRQFQYI640 AIELCAATLQ650 EYVEQKDGLE664 PITLLQQTTS 674 GLAHLHSLNI684 VHRDLKPHNI694 LISMPNAHGK704 IKAMISDFGL714 CKKLAVGRHS 724 FSRRSGVPGT734 EGWIAPEMLS744 EDCKENPTYT754 VDIFSAGCVF764 YYVISEGSHP 774 FGKSLQRQAN784 ILLGACSLDC794 LHPEKHEDVI804 ARELIEKMIA814 MDPQKRPSAK 824 HVLKHPFFWS834 LEKQLQFFQD844 VSDRIEKESL854 DGPIVKQLER864 GGRAVVKMDW 874 RENITVPLQT884 DLRKFRTYKG894 GSVRDLLRAM904 RNKKHHYREL914 PAEVRETLGS 924 LPDDFVCYFT934 SRFPHLLAHT944 YRAMELCSHE954 RLFQPYYFHE964 PP |
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|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .N94 or .N942 or .N943 or :3N94;style chemicals stick;color identity;select .A:577 or .A:578 or .A:579 or .A:580 or .A:586 or .A:597 or .A:598 or .A:599 or .A:609 or .A:612 or .A:613 or .A:616 or .A:626 or .A:628 or .A:640 or .A:642 or .A:643 or .A:644 or .A:645 or .A:646 or .A:647 or .A:648 or .A:692 or .A:695 or .A:710 or .A:711 or .A:712 or .A:713; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
LEU577
4.162
GLY578
4.643
HIS579
3.505
GLY580
4.017
VAL586
3.518
ALA597
3.281
VAL598
3.577
LYS599
3.338
ALA609
4.875
GLU612
3.601
VAL613
3.501
LEU616
3.710
ILE626
3.815
TYR628
3.661
|
|||||
| Ligand Name: methyl ~{N}-[6-methyl-5-[3-[2-[[(3~{S})-piperidin-3-yl]amino]pyrimidin-4-yl]pyridin-2-yl]oxy-naphthalen-1-yl]carbamate | Ligand Info | |||||
| Structure Description | Structure of phosphorylated IRE1 in complex with G-0701 | PDB:6W3E | ||||
| Method | X-ray diffraction | Resolution | 2.74 Å | Mutation | No | [6] |
| PDB Sequence |
SVVIVGKISF
571 CPKDVLGHGA581 EGTIVYRGMF591 DNRDVAVKRI601 LPECFSFADR611 EVQLLRESDE 621 HPNVIRYFCT631 EKDRQFQYIA641 IELCAATLQE651 YVEQKDFAHL661 GLEPITLLQQ 671 TTSGLAHLHS681 LNIVHRDLKP691 HNILISMPNA701 HGKIKAMISD711 FGEGWIAPET 752 YTVDIFSAGC762 VFYYVISEGS772 HPFGKSLQRQ782 ANILLGACSL792 DCLHPEKHED 802 VIARELIEKM812 IAMDPQKRPS822 AKHVLKHPFF832 WSLEKQLQFF842 QDVSDRIEKE 852 SLDGPIVKQL862 ERGGRAVVKM872 DWRENITVPL882 QTDLTYKGGS896 VRDLLRAMRN 906 KKHHYRELPA916 EVRETLGSLP926 DDFVCYFTSR936 FPHLLAHTYR946 AMELCSHERL 956 FQPYYF
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .SJV or .SJV2 or .SJV3 or :3SJV;style chemicals stick;color identity;select .A:577 or .A:578 or .A:586 or .A:597 or .A:599 or .A:601 or .A:609 or .A:612 or .A:613 or .A:616 or .A:640 or .A:642 or .A:643 or .A:644 or .A:645 or .A:646 or .A:647 or .A:648 or .A:651 or .A:692 or .A:693 or .A:695 or .A:710 or .A:711; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
LEU577
2.570
GLY578
3.100
VAL586
2.957
ALA597
2.888
LYS599
2.731
ILE601
4.541
ALA609
3.316
GLU612
3.328
VAL613
2.974
LEU616
4.149
ILE640
2.716
ILE642
2.702
|
|||||
| Ligand Name: 6-chloro-3-(1H-indazol-5-yl)-N-propan-2-ylimidazo[1,2-b]pyridazin-8-amine | Ligand Info | |||||
| Structure Description | IRE1 kinase/RNase in complex with imidazo[1,2-b]pyridazin-8-amine compound 33 | PDB:6HV0 | ||||
| Method | X-ray diffraction | Resolution | 2.73 Å | Mutation | No | [8] |
| PDB Sequence |
SVVIVGKISF
571 CPKDVLGHGA581 EGTIVYRGMF591 DNRDVAVKRI601 LPECSDEHPN624 VIRYFCTEKD 634 RQFQYIAIEL644 CAATLQEYVE654 QKDFGLEPIT667 LLQQTTSGLA677 HLHSLNIVHR 687 DLKPHNILIS697 MPNAHGKIKA707 MISDFGLCKK717 LAVGRHSFSR727 RSGVPGTEGW 737 IAPEMNPTYT754 VDIFSAGCVF764 YYVISEGSHP774 FGKSLQRQAN784 ILLGACSLDC 794 LHPEKHEDVI804 ARELIEKMIA814 MDPQKRPSAK824 HVLKHPFFWS834 LEKQLQFFQD 844 VSDRIEKESL854 DGPIVKQLER864 GGRAVVKMDW874 RENITVPLQT884 DLRRTYKGGS 896 VRDLLRAMRN906 KKHHYRELPA916 EVRETLGSLP926 DDFVCYFTSR936 FPHLLAHTYR 946 AMELCSHERL956 FQPYYFH
|
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|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GUK or .GUK2 or .GUK3 or :3GUK;style chemicals stick;color identity;select .A:577 or .A:578 or .A:586 or .A:588 or .A:597 or .A:599 or .A:626 or .A:628 or .A:642 or .A:643 or .A:644 or .A:645 or .A:646 or .A:647 or .A:695 or .A:710 or .A:711 or .A:712 or .A:714 or .A:723 or .A:725; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
LEU577
3.106
GLY578
3.896
VAL586
3.286
ARG588
3.589
ALA597
3.986
LYS599
3.253
ILE626
3.485
TYR628
3.271
ILE642
3.488
GLU643
3.544
LEU644
3.533
|
|||||
| Ligand Name: 2-Methoxy-4-[6-(Propan-2-Ylamino)imidazo[1,2-B]pyridazin-3-Yl]benzamide | Ligand Info | |||||
| Structure Description | Crystal structure of human IRE1 cytoplasmic kinase-RNase region - complex with imidazopyridine compound 3 | PDB:4Z7H | ||||
| Method | X-ray diffraction | Resolution | 2.90 Å | Mutation | No | [9] |
| PDB Sequence |
SVVIVGKISF
571 CPKDVLGHGA581 EGTIVYRGMF591 DNRDVAVKRI601 LPECFSFADR611 EVQLLRESDE 621 HPNVIRYFCT631 EKDRQFQYIA641 IELCAATLQE651 YVEQKDFAHL661 GLEPITLLQQ 671 TTSGLAHLHS681 LNIVHRDLKP691 HNILISMPNA701 HGKIKAMISD711 FGLCKKLAVG 721 RHSFSPGTEG736 WIAPEMLSNP751 TYTVDIFSAG761 CVFYYVISEG771 SHPFGKSLQR 781 QANILLGACS791 LDCLHPEKHE801 DVIARELIEK811 MIAMDPQKRP821 SAKHVLKHPF 831 FWSLEKQLQF841 FQDVSDRIEK851 ESLDGPIVKQ861 LERGGRAVVK871 MDWRENITVP 881 LQTDKGGSVR898 DLLRAMRNKK908 HHYRELPAEV918 RETLGSLPDD928 FVCYFTSRFP 938 HLLAHTYRAM948 ELCSHERLFQ958 PYYFH
|
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|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .4L5 or .4L52 or .4L53 or :34L5;style chemicals stick;color identity;select .A:577 or .A:578 or .A:579 or .A:586 or .A:597 or .A:599 or .A:612 or .A:626 or .A:642 or .A:643 or .A:644 or .A:645 or .A:646 or .A:647 or .A:648 or .A:651 or .A:692 or .A:693 or .A:695 or .A:710 or .A:711; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
LEU577
2.766
GLY578
3.003
HIS579
3.682
VAL586
2.823
ALA597
3.261
LYS599
2.713
GLU612
3.483
ILE626
3.142
ILE642
2.922
GLU643
2.482
LEU644
3.769
|
|||||
| Ligand Name: (5r)-2-(3,4-Dichlorobenzyl)-N-(4-Methylbenzyl)-2,7-Diazaspiro[4.5]decane-7-Carboxamide | Ligand Info | |||||
| Structure Description | Crystal Structure of human phosphorylated IRE1alpha in complex with a type III kinase inhibitor (GSK2850163A) | PDB:4YZ9 | ||||
| Method | X-ray diffraction | Resolution | 2.46 Å | Mutation | No | [3] |
| PDB Sequence |
SVVIVGKISF
571 CPKDVLGHGA581 EGTIVYRGMF591 DNRDVAVKRI601 LPECFSFADR611 EVQLLRESDE 621 HPNVIRYFCT631 EKDRQFQYIA641 IELCAATLQE651 YVEQKDFAHL661 GLEPITLLQQ 671 TTSGLAHLHS681 LNIVHRDLKP691 HNILISMPNA701 HGKIKAMISD711 FGLCGTEGWI 738 APEMLENPTY753 TVDIFSAGCV763 FYYVISEGSH773 PFGKSLQRQA783 NILLGACSLD 793 CLHPEKHEDV803 IARELIEKMI813 AMDPQKRPSA823 KHVLKHPFFW833 SLEKQLQFFQ 843 DVSDRIEKES853 LDGPIVKQLE863 RGGRAVVKMD873 WRENITVPLQ883 TDLRKFRTYK 893 GGSVRDLLRA903 MRNKKHHYRE913 LPAEVRETLG923 SLPDDFVCYF933 TSRFPHLLAH 943 TYRAMELCSH953 ERLFQPYYFH963 E
|
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|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .4K7 or .4K72 or .4K73 or :34K7;style chemicals stick;color identity;select .A:580 or .A:581 or .A:582 or .A:584 or .A:599 or .A:601 or .A:605 or .A:608 or .A:609 or .A:610 or .A:612 or .A:613 or .A:616 or .A:625 or .A:626 or .A:627 or .A:628 or .A:640 or .A:642 or .A:643 or .A:679 or .A:684 or .A:685 or .A:686 or .A:687 or .A:688 or .A:709 or .A:710 or .A:711; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
GLY580
4.372
ALA581
2.326
GLU582
2.930
THR584
2.698
LYS599
2.150
ILE601
2.786
CYS605
2.275
PHE608
2.138
ALA609
2.219
ASP610
4.877
GLU612
2.271
VAL613
2.134
LEU616
2.753
VAL625
3.401
ILE626
2.168
|
|||||
| Ligand Name: 6-chloro-N-(cyclopropylmethyl)-3-(1H-indazol-5-yl)imidazo[1,2-b]pyridazin-8-amine | Ligand Info | |||||
| Structure Description | IRE1 ALPHA IN COMPLEX WITH imidazo[1,2-b]pyridazin-8-amine compound 2 | PDB:6HX1 | ||||
| Method | X-ray diffraction | Resolution | 2.14 Å | Mutation | No | [8] |
| PDB Sequence |
SVVIVGKISF
571 CPKDVLGHGA581 EGTIVYRGMF591 DNRDVAVKRI601 LPECFRESDE621 HPNVIRYFCT 631 EKDRQFQYIA641 IELCAATLQE651 YVEQKDFAHL661 GLEPITLLQQ671 TTSGLAHLHS 681 LNIVHRDLKP691 HNILISMPNA701 HGKIKAMISD711 FGLCKKVGRH723 SFSRRSGVPG 733 TEGWIAPEML743 SENPTYTVDI757 FSAGCVFYYV767 ISEGSHPFGK777 SLQRQANILL 787 GACSLDCLHP797 EKHEDVIARE807 LIEKMIAMDP817 QKRPSAKHVL827 KHPFFWSLEK 837 QLQFFQDVSD847 RIEKESLDGP857 IVKQLERGGR867 AVVKMDWREN877 ITVPLQTDLR 887 KFRTYKGGSV897 RDLLRAMRNK907 KHHYRELPAE917 VRETLGSLPD927 DFVCYFTSRF 937 PHLLAHTYRA947 MELCSHERLF957 QPYYFHE
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GXK or .GXK2 or .GXK3 or :3GXK;style chemicals stick;color identity;select .A:577 or .A:578 or .A:586 or .A:597 or .A:599 or .A:626 or .A:628 or .A:642 or .A:643 or .A:644 or .A:645 or .A:646 or .A:647 or .A:651 or .A:695 or .A:710 or .A:711 or .A:712 or .A:714 or .A:723 or .A:725; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
LEU577
3.382
GLY578
3.726
VAL586
3.946
ALA597
4.022
LYS599
3.595
ILE626
3.660
TYR628
2.816
ILE642
3.590
GLU643
3.660
LEU644
3.907
CYS645
2.979
|
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Identification of BRaf-Sparing Amino-Thienopyrimidines with Potent IRE1Alpha Inhibitory Activity. ACS Med Chem Lett. 2020 Oct 16;11(12):2389-2396. | ||||
| REF 2 | Structure of the Ire1 autophosphorylation complex and implications for the unfolded protein response. EMBO J. 2011 Mar 2;30(5):894-905. | ||||
| REF 3 | Long-Range Inhibitor-Induced Conformational Regulation of Human IRE1Alpha Endoribonuclease Activity. Mol Pharmacol. 2015 Dec;88(6):1011-23. | ||||
| REF 4 | Unfolded Protein Response in Cancer: IRE1alpha Inhibition by Selective Kinase Ligands Does Not Impair Tumor Cell Viability. ACS Med Chem Lett. 2014 Sep 24;6(1):68-72. | ||||
| REF 5 | ATP-competitive partial antagonists of the IRE1Alpha RNase segregate outputs of the UPR. Nat Chem Biol. 2021 Nov;17(11):1148-1156. | ||||
| REF 6 | Activation of the IRE1 RNase through remodeling of the kinase front pocket by ATP-competitive ligands. Nat Commun. 2020 Dec 14;11(1):6387. | ||||
| REF 7 | Disruption of IRE1Alpha through its kinase domain attenuates multiple myeloma. Proc Natl Acad Sci U S A. 2019 Aug 13;116(33):16420-16429. | ||||
| REF 8 | Binding to an Unusual Inactive Kinase Conformation by Highly Selective Inhibitors of Inositol-Requiring Enzyme 1Alpha Kinase-Endoribonuclease. J Med Chem. 2019 Mar 14;62(5):2447-2465. | ||||
| REF 9 | Molecular mechanisms of human IRE1 activation through dimerization and ligand binding. Oncotarget. 2015 May 30;6(15):13019-35. | ||||
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