Structure of PDB 8fy0 Chain D Binding Site BS01

Receptor Information
>8fy0 Chain D (length=144) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
MSQSNRELVVDFLSYKLSQKGYSWSQFSDPMAAVKQALREAGDEFELRYR
RAFSDLTSQLHITPGTAYQSFEQVVNELFRDGVNWGRIVAFFSFGGALCV
ESVDKEMQVLVSRIAAWMATYLNDHLEPWIQENGGWDTFVELYG
Ligand information
Ligand IDYF8
InChIInChI=1S/C82H105ClF3N11O11S4/c1-56(58-18-20-60(21-19-58)75-57(2)87-55-110-75)88-78(102)71-48-66(98)52-97(71)79(103)76(80(3,4)5)90-73(99)16-12-7-8-13-17-74(100)96-42-38-94(39-43-96)54-81(6)34-32-69(59-22-26-63(83)27-23-59)62(50-81)51-93-36-40-95(41-37-93)65-28-24-61(25-29-65)77(101)91-112(106,107)68-30-31-70(72(49-68)111(104,105)82(84,85)86)89-64(33-35-92-44-46-108-47-45-92)53-109-67-14-10-9-11-15-67/h9-11,14-15,18-31,49,55-56,64,66,71,76,89,98H,7-8,12-13,16-17,32-48,50-54H2,1-6H3,(H,88,102)(H,90,99)(H,91,101)/t56-,64+,66+,71-,76+,81+/m0/s1
InChIKeyKQEMZZJSHJCPSI-RYFXIQSLSA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 2.0.7Cc1c(scn1)c2ccc(cc2)C(C)NC(=O)C3CC(CN3C(=O)C(C(C)(C)C)NC(=O)CCCCCCC(=O)N4CCN(CC4)CC5(CCC(=C(C5)CN6CCN(CC6)c7ccc(cc7)C(=O)NS(=O)(=O)c8ccc(c(c8)S(=O)(=O)C(F)(F)F)NC(CCN9CCOCC9)CSc1ccccc1)c1ccc(cc1)Cl)C)[O]
CACTVS 3.385C[C@H](NC(=O)[C@@H]1C[C@@H]([O])CN1C(=O)[C@@H](NC(=O)CCCCCCC(=O)N2CCN(CC2)C[C@]3(C)CCC(=C(CN4CCN(CC4)c5ccc(cc5)C(=O)N[S](=O)(=O)c6ccc(N[C@H](CCN7CCOCC7)CSc8ccccc8)c(c6)[S](=O)(=O)C(F)(F)F)C3)c9ccc(Cl)cc9)C(C)(C)C)c%10ccc(cc%10)c%11scnc%11C
OpenEye OEToolkits 2.0.7Cc1c(scn1)c2ccc(cc2)[C@H](C)NC(=O)[C@@H]3C[C@H](CN3C(=O)[C@H](C(C)(C)C)NC(=O)CCCCCCC(=O)N4CCN(CC4)C[C@@]5(CCC(=C(C5)CN6CCN(CC6)c7ccc(cc7)C(=O)NS(=O)(=O)c8ccc(c(c8)S(=O)(=O)C(F)(F)F)N[C@H](CCN9CCOCC9)CSc1ccccc1)c1ccc(cc1)Cl)C)[O]
CACTVS 3.385C[CH](NC(=O)[CH]1C[CH]([O])CN1C(=O)[CH](NC(=O)CCCCCCC(=O)N2CCN(CC2)C[C]3(C)CCC(=C(CN4CCN(CC4)c5ccc(cc5)C(=O)N[S](=O)(=O)c6ccc(N[CH](CCN7CCOCC7)CSc8ccccc8)c(c6)[S](=O)(=O)C(F)(F)F)C3)c9ccc(Cl)cc9)C(C)(C)C)c%10ccc(cc%10)c%11scnc%11C
ACDLabs 12.01O=S(=O)(c1cc(ccc1NC(CSc1ccccc1)CCN1CCOCC1)S(=O)(=O)NC(=O)c1ccc(cc1)N1CCN(CC1)CC=1CC(C)(CCC=1c1ccc(Cl)cc1)CN1CCN(CC1)C(=O)CCCCCCC(=O)NC(C(=O)N1CC(O)CC1C(=O)NC(C)c1ccc(cc1)c1scnc1C)C(C)(C)C)C(F)(F)F
FormulaC82 H104 Cl F3 N11 O11 S4
NameN-[8-(4-{[(1R,3R,4S)-4-(4-chlorophenyl)-1-methyl-3-{[4-(4-{[4-{[(2R)-4-(morpholin-4-yl)-1-(phenylsulfanyl)butan-2-yl]amino}-3-(trifluoromethanesulfonyl)benzene-1-sulfonyl]carbamoyl}phenyl)piperazin-1-yl]methyl}cyclohexyl]methyl}piperazin-1-yl)-8-oxooctanoyl]-3-methyl-L-valyl-(4R)-4-hydroxy-N-{(1S)-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl}-L-prolinamide
ChEMBL
DrugBank
ZINC
PDB chain8fy0 Chain D Residue 301 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
Global viewLocal viewStructure summary

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PDB8fy0 Development and crystal structures of a potent second-generation dual degrader of BCL-2 and BCL-xL.
Resolution2.94 Å
Binding residue
(original residue number in PDB)		E96 F97 Y101 A104 F105 L108 Q111 E129 L130 N136 W137 G138 R139 V141 S145 F146 F191 L194 Y195
Binding residue
(residue number reindexed from 1)		E44 F45 Y49 A52 F53 L56 Q59 E77 L78 N84 W85 G86 R87 V89 S93 F94 F139 L142 Y143
Annotation score1
Enzymatic activity
Enzyme Commision number ?
Gene Ontology
Molecular Function
GO:0005515 protein binding
GO:0019901 protein kinase binding
GO:0042802 identical protein binding
GO:0051400 BH domain binding
GO:0051434 BH3 domain binding
Biological Process
GO:0001541 ovarian follicle development
GO:0001701 in utero embryonic development
GO:0001836 release of cytochrome c from mitochondria
GO:0006897 endocytosis
GO:0006915 apoptotic process
GO:0007005 mitochondrion organization
GO:0007281 germ cell development
GO:0007283 spermatogenesis
GO:0008584 male gonad development
GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage
GO:0008637 apoptotic mitochondrial changes
GO:0009314 response to radiation
GO:0009566 fertilization
GO:0009615 response to virus
GO:0032465 regulation of cytokinesis
GO:0032946 positive regulation of mononuclear cell proliferation
GO:0034097 response to cytokine
GO:0035234 ectopic germ cell programmed cell death
GO:0040008 regulation of growth
GO:0042981 regulation of apoptotic process
GO:0043066 negative regulation of apoptotic process
GO:0043524 negative regulation of neuron apoptotic process
GO:0044565 dendritic cell proliferation
GO:0046898 response to cycloheximide
GO:0046902 regulation of mitochondrial membrane permeability
GO:0050673 epithelial cell proliferation
GO:0051093 negative regulation of developmental process
GO:0051402 neuron apoptotic process
GO:0051607 defense response to virus
GO:0051881 regulation of mitochondrial membrane potential
GO:0071230 cellular response to amino acid stimulus
GO:0071312 cellular response to alkaloid
GO:0071480 cellular response to gamma radiation
GO:0071839 apoptotic process in bone marrow cell
GO:0090201 negative regulation of release of cytochrome c from mitochondria
GO:0097048 dendritic cell apoptotic process
GO:0097192 extrinsic apoptotic signaling pathway in absence of ligand
GO:0097284 hepatocyte apoptotic process
GO:1900118 negative regulation of execution phase of apoptosis
GO:1902042 negative regulation of extrinsic apoptotic signaling pathway via death domain receptors
GO:1902230 negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage
GO:1902236 negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway
GO:1903077 negative regulation of protein localization to plasma membrane
GO:2000242 negative regulation of reproductive process
GO:2000669 negative regulation of dendritic cell apoptotic process
GO:2001233 regulation of apoptotic signaling pathway
GO:2001240 negative regulation of extrinsic apoptotic signaling pathway in absence of ligand
GO:2001243 negative regulation of intrinsic apoptotic signaling pathway
Cellular Component
GO:0005634 nucleus
GO:0005737 cytoplasm
GO:0005739 mitochondrion
GO:0005741 mitochondrial outer membrane
GO:0005743 mitochondrial inner membrane
GO:0005759 mitochondrial matrix
GO:0005783 endoplasmic reticulum
GO:0005813 centrosome
GO:0005829 cytosol
GO:0005856 cytoskeleton
GO:0016020 membrane
GO:0030672 synaptic vesicle membrane
GO:0031410 cytoplasmic vesicle
GO:0031965 nuclear membrane
GO:0031966 mitochondrial membrane
GO:0045202 synapse
GO:0097136 Bcl-2 family protein complex

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Molecular Function
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Biological Process
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Cellular Component
External links
PDB RCSB:8fy0, PDBe:8fy0, PDBj:8fy0
PDBsum8fy0
PubMed38548768
UniProtQ07817|B2CL1_HUMAN Bcl-2-like protein 1 (Gene Name=BCL2L1)

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