Target Binding Site Detail
Target General Information | Top | ||||
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Target ID | T23172 | Target Info | |||
Target Name | Janus kinase 3 (JAK-3) | ||||
Synonyms | Tyrosine-protein kinase JAK3; Leukocyte janus kinase; L-JAK | ||||
Target Type | Successful Target | ||||
Gene Name | JAK3 | ||||
Biochemical Class | Kinase | ||||
UniProt ID |
Ligand General Information | Top | ||||
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Ligand Name | 1-Phenylurea | Ligand Info | |||
Canonical SMILES | C1=CC=C(C=C1)NC(=O)N | ||||
InChI | 1S/C7H8N2O/c8-7(10)9-6-4-2-1-3-5-6/h1-5H,(H3,8,9,10) | ||||
InChIKey | LUBJCRLGQSPQNN-UHFFFAOYSA-N | ||||
PubChem Compound ID | 6145 |
Drug Binding Sites of Target | Top | |||||
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PDB ID: 4HVD JAK3 kinase domain in complex with 2-Cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-1,2,2-trimethyl-propyl)-amide | ||||||
Method | X-ray diffraction | Resolution | 1.85 Å | Mutation | Yes | [1] |
PDB Sequence |
TIFEERHLKY
824 ISQLGKGNFG834 SVELCRYDPL844 GDNTGALVAV854 KQLQHSGPDQ864 QRDFQREIQI 874 LKALHSDFIV884 KYRGVSYLRL900 VMEYLPSGCL910 RDFLQRHRAR920 LDASRLLLYS 930 SQICKGMEYL940 GSRRCVHRDL950 AARNILVESE960 AHVKIADFGL970 AKLLPLDKDY 980 YVVREPGQSP990 IFWYAPESLS1000 DNIFSRQSDV1010 WSFGVVLYEL1020 FTYCDKSCSP 1030 SAEFLRMMVP1045 ALSRLLELLE1055 EGQRLPAPPA1065 CPAEVHELMK1075 LCWAPSPQDR 1085 PSFSALGPQL1095 DMLWSG
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PDB ID: 4I6Q JAK3 kinase domain in complex with 2-Phenoxy-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-1-cyclopropyl-ethyl)-amide | ||||||
Method | X-ray diffraction | Resolution | 1.85 Å | Mutation | Yes | [2] |
PDB Sequence |
TIFEERHLKY
824 ISQLGKGNFG834 SVELCRYDPL844 GDNTGALVAV854 KQLQHSGPDQ864 QRDFQREIQI 874 LKALHSDFIV884 KYRGVSYLRL900 VMEYLPSGCL910 RDFLQRHRAR920 LDASRLLLYS 930 SQICKGMEYL940 GSRRCVHRDL950 AARNILVESE960 AHVKIADFGL970 AKLLPLDKDY 980 YVVREPGQSP990 IFWYAPESLS1000 DNIFSRQSDV1010 WSFGVVLYEL1020 FTYCDKSCSP 1030 SAEFLRMMVP1045 ALSRLLELLE1055 EGQRLPAPPA1065 CPAEVHELMK1075 LCWAPSPQDR 1085 PSFSALGPQL1095 DMLWSGS
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PDB ID: 5LWM Crystal structure of JAK3 in complex with Compound 4 (FM381) | ||||||
Method | X-ray diffraction | Resolution | 1.55 Å | Mutation | No | [3] |
PDB Sequence |
PTIFEERHLK
823 YISQLGKGNF833 GSVELCRYDP843 LGDNTGALVA853 VKQLQHSGPD863 QQRDFQREIQ 873 ILKALHSDFI883 VKYRGVSYGP893 GRQSLRLVME903 YLPSGCLRDF913 LQRHRARLDA 923 SRLLLYSSQI933 CKGMEYLGSR943 RCVHRALAAR953 NILVESEAHV963 KIADFGLAKL 973 LPLDKDYYVV983 REPGQSPIFW993 YAPESLSDNI1003 FSRQSDVWSF1013 GVVLYELFTY 1023 CDKSCSPSAE1033 FLRMMGSERD1043 VPALSRLLEL1053 LEEGQRLPAP1063 PACPAEVHEL 1073 MKLCWAPSPQ1083 DRPSFSALGP1093 QLDMLWSGSR1103
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PDB ID: 5LWN Crystal structure of JAK3 in complex with Compound 5 (FM409) | ||||||
Method | X-ray diffraction | Resolution | 1.60 Å | Mutation | No | [3] |
PDB Sequence |
PTIFEERHLK
823 YISQLGKGNF833 GSVELCRYDP843 LGDNTGALVA853 VKQLQHSGPD863 QQRDFQREIQ 873 ILKALHSDFI883 VKYRGVSYGP893 GRQSLRLVME903 YLPSGCLRDF913 LQRHRARLDA 923 SRLLLYSSQI933 CKGMEYLGSR943 RCVHRALAAR953 NILVESEAHV963 KIADFGLAKL 973 LPLDKDYYVV983 REPGQSPIFW993 YAPESLSDNI1003 FSRQSDVWSF1013 GVVLYELFTY 1023 CDKSCSPSAE1033 FLRMMGSERD1043 VPALSRLLEL1053 LEEGQRLPAP1063 PACPAEVHEL 1073 MKLCWAPSPQ1083 DRPSFSALGP1093 QLDMLWSGSR1103
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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 .PHU or .PHU2 or .PHU3 or :3PHU;style chemicals stick;color identity;select .A:992 or .A:1011 or .A:1015 or .A:1030 or .A:1033 or .A:1034 or .A:1037 or .A:1050 or .A:1054 or .A:1058 or .A:1059 or .A:1060 or .A:1078; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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PDB ID: 6GL9 Crystal structure of JAK3 in complex with Compound 10 (FM475) | ||||||
Method | X-ray diffraction | Resolution | 1.70 Å | Mutation | No | [4] |
PDB Sequence |
QDPTIFEERH
821 LKYISQLGKG831 NFGSVELCRY841 DPLGDNTGAL851 VAVKQLQHSG861 PDQQRDFQRE 871 IQILKALHSD881 FIVKYRGVSY891 GPGRQSLRLV901 MEYLPSGCLR911 DFLQRHRARL 921 DASRLLLYSS931 QICKGMEYLG941 SRRCVHRALA951 ARNILVESEA961 HVKIADFGLA 971 KLLPLDKDYY981 VVREPGQSPI991 FWYAPESLSD1001 NIFSRQSDVW1011 SFGVVLYELF 1021 TYCDKSCSPS1031 AEFLRMMGSE1041 RDVPALSRLL1051 ELLEEGQRLP1061 APPACPAEVH 1071 ELMKLCWAPS1081 PQDRPSFSAL1091 GPQLDMLWSG1101 SR
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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 .PHU or .PHU2 or .PHU3 or :3PHU;style chemicals stick;color identity;select .A:992 or .A:1011 or .A:1015 or .A:1030 or .A:1033 or .A:1034 or .A:1037 or .A:1050 or .A:1054 or .A:1058 or .A:1059 or .A:1060 or .A:1078; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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PDB ID: 6GLA Crystal structure of JAK3 in complex with Compound 11 (FM481) | ||||||
Method | X-ray diffraction | Resolution | 1.92 Å | Mutation | No | [4] |
PDB Sequence |
DPTIFEERHL
822 KYISQLGKGN832 FGSVELCRYD842 PLGDNTGALV852 AVKQLQHSGP862 DQQRDFQREI 872 QILKALHSDF882 IVKYRGVSYG892 PGRQSLRLVM902 EYLPSGCLRD912 FLQRHRARLD 922 ASRLLLYSSQ932 ICKGMEYLGS942 RRCVHRALAA952 RNILVESEAH962 VKIADFGLAK 972 LLPLDKDYYV982 VRQSPIFWYA995 PESLSDNIFS1005 RQSDVWSFGV1015 VLYELFTYCD 1025 KSCSPSAEFL1035 RMMGSERDVP1045 ALSRLLELLE1055 EGQRLPAPPA1065 CPAEVHELMK 1075 LCWAPSPQDR1085 PSFSALGPQL1095 DMLWSGSR
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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 .PHU or .PHU2 or .PHU3 or :3PHU;style chemicals stick;color identity;select .A:992 or .A:1011 or .A:1015 or .A:1030 or .A:1033 or .A:1034 or .A:1037 or .A:1050 or .A:1054 or .A:1058 or .A:1059 or .A:1060 or .A:1078; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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PDB ID: 7APF Crystal structure of JAK3 in complex with FM601 (compound 10a) | ||||||
Method | X-ray diffraction | Resolution | 1.95 Å | Mutation | No | [5] |
PDB Sequence |
PTIFEERHLK
823 YISQLGKGNF833 GSVELCRYDP843 LGDNTGALVA853 VKQLQHSGPD863 QQRDFQREIQ 873 ILKALHSDFI883 VKYRGVSYGP893 GRQSLRLVME903 YLPSGCLRDF913 LQRHRARLDA 923 SRLLLYSSQI933 CKGMEYLGSR943 RCVHRALAAR953 NILVESEAHV963 KIADFGLAKL 973 LPLDKDYYVV983 REPGQSPIFW993 YAPESLSDNI1003 FSRQSDVWSF1013 GVVLYELFTY 1023 CDKSCSPSAE1033 FLRMMGSERD1043 VPALSRLLEL1053 LEEGQRLPAP1063 PACPAEVHEL 1073 MKLCWAPSPQ1083 DRPSFSALGP1093 QLDMLWSGSR1103
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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 .PHU or .PHU2 or .PHU3 or :3PHU;style chemicals stick;color identity;select .A:992 or .A:1011 or .A:1015 or .A:1030 or .A:1033 or .A:1034 or .A:1037 or .A:1050 or .A:1053 or .A:1054 or .A:1058 or .A:1059 or .A:1060 or .A:1078; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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PDB ID: 6GLB Crystal structure of JAK3 in complex with Compound 20 (FM484) | ||||||
Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | No | [4] |
PDB Sequence |
DPTIFEERHL
822 KYISQLGKGN832 FGSVELCRYD842 PLGDNTGALV852 AVKQLQHSGP862 DQQRDFQREI 872 QILKALHSDF882 IVKYRGVSYG892 PGRQSLRLVM902 EYLPSGCLRD912 FLQRHRARLD 922 ASRLLLYSSQ932 ICKGMEYLGS942 RRCVHRALAA952 RNILVESEAH962 VKIADFGLAK 972 LLPLDKDYYV982 VRQSPIFWYA995 PESLSDNIFS1005 RQSDVWSFGV1015 VLYELFTYCD 1025 KSCSPSAEFL1035 RMMGSERDVP1045 ALSRLLELLE1055 EGQRLPAPPA1065 CPAEVHELMK 1075 LCWAPSPQDR1085 PSFSALGPQL1095 DMLWSGSR
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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 .PHU or .PHU2 or .PHU3 or :3PHU;style chemicals stick;color identity;select .A:992 or .A:1011 or .A:1015 or .A:1030 or .A:1033 or .A:1034 or .A:1037 or .A:1050 or .A:1054 or .A:1058 or .A:1059 or .A:1060 or .A:1078; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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PDB ID: 7APG Crystal structure of JAK3 in complex with FM587 (compound 9a) | ||||||
Method | X-ray diffraction | Resolution | 2.40 Å | Mutation | No | [5] |
PDB Sequence |
DPTIFEERHL
822 KYISQLGKGN832 FGSVELCRYD842 PLGDNTGALV852 AVKQLQHSGP862 DQQRDFQREI 872 QILKALHSDF882 IVKYRGVSYS897 LRLVMEYLPS907 GCLRDFLQRH917 RARLDASRLL 927 LYSSQICKGM937 EYLGSRRCVH947 RALAARNILV957 ESEAHVKIAD967 FGLAKLLPLD 977 KDYYVVREPG987 QSPIFWYAPE997 SLSDNIFSRQ1007 SDVWSFGVVL1017 YELFTYCDKS 1027 CSPSAEFLRM1037 MALSRLLELL1054 EEGQRLPAPP1064 ACPAEVHELM1074 KLCWAPSPQD 1084 RPSFSALGPQ1094 LDMLWSGSR
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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 .PHU or .PHU2 or .PHU3 or :3PHU;style chemicals stick;color identity;select .A:992 or .A:1011 or .A:1015 or .A:1030 or .A:1033 or .A:1034 or .A:1037 or .A:1050 or .A:1053 or .A:1054 or .A:1058 or .A:1059 or .A:1060 or .A:1078; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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References | Top | ||||
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REF 1 | 3-Amido pyrrolopyrazine JAK kinase inhibitors: development of a JAK3 vs JAK1 selective inhibitor and evaluation in cellular and in vivo models. J Med Chem. 2013 Jan 10;56(1):345-56. | ||||
REF 2 | Discovery of a series of novel 5H-pyrrolo[2,3-b]pyrazine-2-phenyl ethers, as potent JAK3 kinase inhibitors. Bioorg Med Chem Lett. 2013 May 1;23(9):2522-6. | ||||
REF 3 | Selective JAK3 Inhibitors with a Covalent Reversible Binding Mode Targeting a New Induced Fit Binding Pocket. Cell Chem Biol. 2016 Nov 17;23(11):1335-1340. | ||||
REF 4 | Development, Optimization, and Structure-Activity Relationships of Covalent-Reversible JAK3 Inhibitors Based on a Tricyclic Imidazo[5,4- d]pyrrolo[2,3- b]pyridine Scaffold. J Med Chem. 2018 Jun 28;61(12):5350-5366. | ||||
REF 5 | Discovery of a Novel Class of Covalent Dual Inhibitors Targeting the Protein Kinases BMX and BTK. Int J Mol Sci. 2020 Dec 4;21(23):9269. |
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