ailab-bio/TACK huggingface dataset:
Compound (SMILES): Cc1ncsc1-c1ccc([C@H](C)NC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)CCCCCCCN(C)CCOc2ccc(C(=O)c3c(-c4ccc(O)cc4)sc4cc(O)ccc34)cc2)C(C)(C)C)cc1
Modality: PROteolysis-TArgeting Chimera (PROTAC)
Target protein (POI): ESR1 (UniProt P03372)
POI sequence: MTMTLHTKASGMALLHQIQGNELEPLNRPQLKIPLERPLGEVYLDSSKPAVYNYPEGAAYEFNAAAAANAQVYGQTGLPYGPGSEAAAFGSNGLGGFPPLNSVSPSPLMLLHPPPQLSPFLQPHGQQVPYYLENEPSGYTVREAGPPAFYRPNSDNRRQGGRERLASTNDKGSMAMESAKETRYCAVCNDYASGYHYGVWSCEGCKAFFKRSIQGHNDYMCPATNQCTIDKNRRKSCQACRLRKCYEVGMMKGGIRKDRRGGRMLKHKRQRDDGEGRGEVGSAGDMRAANLWPSPLMIKRSKKNSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWLEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGMVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITDTLIHLMAKAGLTLQQQHQRLAQLLLILSHIRHMSNKGMEHLYSMKCKNVVPLYDLLLEMLDAHRLHAPTSRGGASVEETDQSHLATAGSTSSHSLQKYYITGEAEGFPATV
E3 ligase: VHL (UniProt P40337)
Ligase sequence: MPRRAENWDEAEVGAEEAGVEEYGPEEDGGEESGAEESGPEESGPEELGAEEEMEAGRPRPVLRSVNSREPSQVIFCNRSPRVVLPVWLNFDGEPQPYPTLPPGTGRRIHSYRGHLWLFRDAGTHDGLLVNQTELFVPSLNVDGQPIFANITLPVYTLKERCLQVVRSLVKPENYRRLDIVRSLYEDLEDHPNVQKDLERLTQERIAHQRMGD
Cell line: MCF-7 (Homo sapiens)
Cell line description: African=0.74%; Native American=0%; East Asian, North=4.2%; East Asian, South=0%; South Asian=0%; European, North=56.91%; European, South=38.15%.
Helen Marion Mallon (sister Catherine Frances), the patient from which this cell line is derived was a nun at the Immaculate Heart of Mary convent in Monroe, Michigan (CelloPub=CLPUB00336).
Gene deletion; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC
A*02 A*02 A*02
Stable (MSS).
Metastatic; Pleural effusion; 
Caucasian.
Space-flown cell line (cellonaut).
Cancer cell line
Assay time (hours): 4
Dmax:  73 %
Assay description: EC50 of ligand was measured in MCF7 cells. DCmax was measured in 1 nM (at 10 nM 0 %).
Reference: https://pubmed.ncbi.nlm.nih.gov/30990042/
Source database: PROTACpedia
Compound (SMILES): Cc1ncsc1-c1ccc([C@H](C)NC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)CCCCCCCN(CCOc2ccc(C(=O)c3c(-c4ccc(O)cc4)sc4cc(O)ccc34)cc2)C(C)(C)C)C(C)(C)C)cc1
Modality: PROteolysis-TArgeting Chimera (PROTAC)
Target protein (POI): ESR1 (UniProt P03372)
POI sequence: MTMTLHTKASGMALLHQIQGNELEPLNRPQLKIPLERPLGEVYLDSSKPAVYNYPEGAAYEFNAAAAANAQVYGQTGLPYGPGSEAAAFGSNGLGGFPPLNSVSPSPLMLLHPPPQLSPFLQPHGQQVPYYLENEPSGYTVREAGPPAFYRPNSDNRRQGGRERLASTNDKGSMAMESAKETRYCAVCNDYASGYHYGVWSCEGCKAFFKRSIQGHNDYMCPATNQCTIDKNRRKSCQACRLRKCYEVGMMKGGIRKDRRGGRMLKHKRQRDDGEGRGEVGSAGDMRAANLWPSPLMIKRSKKNSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWLEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGMVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITDTLIHLMAKAGLTLQQQHQRLAQLLLILSHIRHMSNKGMEHLYSMKCKNVVPLYDLLLEMLDAHRLHAPTSRGGASVEETDQSHLATAGSTSSHSLQKYYITGEAEGFPATV
E3 ligase: VHL (UniProt P40337)
Ligase sequence: MPRRAENWDEAEVGAEEAGVEEYGPEEDGGEESGAEESGPEESGPEELGAEEEMEAGRPRPVLRSVNSREPSQVIFCNRSPRVVLPVWLNFDGEPQPYPTLPPGTGRRIHSYRGHLWLFRDAGTHDGLLVNQTELFVPSLNVDGQPIFANITLPVYTLKERCLQVVRSLVKPENYRRLDIVRSLYEDLEDHPNVQKDLERLTQERIAHQRMGD
Cell line: MCF-7 (Homo sapiens)
Cell line description: African=0.74%; Native American=0%; East Asian, North=4.2%; East Asian, South=0%; South Asian=0%; European, North=56.91%; European, South=38.15%.
Helen Marion Mallon (sister Catherine Frances), the patient from which this cell line is derived was a nun at the Immaculate Heart of Mary convent in Monroe, Michigan (CelloPub=CLPUB00336).
Gene deletion; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC
A*02 A*02 A*02
Stable (MSS).
Metastatic; Pleural effusion; 
Caucasian.
Space-flown cell line (cellonaut).
Cancer cell line
Assay time (hours): 4
Dmax:  79 %
Assay description: EC50 of ligand was measured in MCF7 cells. DCmax was measured in 1 nM (at 10 nM > 99 %).
Reference: https://pubmed.ncbi.nlm.nih.gov/30990042/
Source database: PROTACpedia
Compound (SMILES): Cc1ncsc1-c1ccc([C@H](C)NC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)CCCCCCCN(CCOc2ccc(C(=O)c3c(-c4ccc(O)cc4)sc4cc(O)ccc34)cc2)C(C)C)C(C)(C)C)cc1
Modality: PROteolysis-TArgeting Chimera (PROTAC)
Target protein (POI): ESR1 (UniProt P03372)
POI sequence: MTMTLHTKASGMALLHQIQGNELEPLNRPQLKIPLERPLGEVYLDSSKPAVYNYPEGAAYEFNAAAAANAQVYGQTGLPYGPGSEAAAFGSNGLGGFPPLNSVSPSPLMLLHPPPQLSPFLQPHGQQVPYYLENEPSGYTVREAGPPAFYRPNSDNRRQGGRERLASTNDKGSMAMESAKETRYCAVCNDYASGYHYGVWSCEGCKAFFKRSIQGHNDYMCPATNQCTIDKNRRKSCQACRLRKCYEVGMMKGGIRKDRRGGRMLKHKRQRDDGEGRGEVGSAGDMRAANLWPSPLMIKRSKKNSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWLEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGMVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITDTLIHLMAKAGLTLQQQHQRLAQLLLILSHIRHMSNKGMEHLYSMKCKNVVPLYDLLLEMLDAHRLHAPTSRGGASVEETDQSHLATAGSTSSHSLQKYYITGEAEGFPATV
E3 ligase: VHL (UniProt P40337)
Ligase sequence: MPRRAENWDEAEVGAEEAGVEEYGPEEDGGEESGAEESGPEESGPEELGAEEEMEAGRPRPVLRSVNSREPSQVIFCNRSPRVVLPVWLNFDGEPQPYPTLPPGTGRRIHSYRGHLWLFRDAGTHDGLLVNQTELFVPSLNVDGQPIFANITLPVYTLKERCLQVVRSLVKPENYRRLDIVRSLYEDLEDHPNVQKDLERLTQERIAHQRMGD
Cell line: MCF-7 (Homo sapiens)
Cell line description: African=0.74%; Native American=0%; East Asian, North=4.2%; East Asian, South=0%; South Asian=0%; European, North=56.91%; European, South=38.15%.
Helen Marion Mallon (sister Catherine Frances), the patient from which this cell line is derived was a nun at the Immaculate Heart of Mary convent in Monroe, Michigan (CelloPub=CLPUB00336).
Gene deletion; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC
A*02 A*02 A*02
Stable (MSS).
Metastatic; Pleural effusion; 
Caucasian.
Space-flown cell line (cellonaut).
Cancer cell line
Assay time (hours): 4
Dmax:  72 %
Assay description: EC50 of ligand was measured in MCF7 cells. DCmax was measured in 1 nM (at 10 nM > 99 %).
Reference: https://pubmed.ncbi.nlm.nih.gov/30990042/
Source database: PROTACpedia
Compound (SMILES): Cc1ncsc1-c1ccc([C@H](C)NC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)CCCCCCCN(CCOc2ccc(C(=O)c3c(-c4ccc(O)cc4)sc4cc(O)ccc34)cc2)C2CC2)C(C)(C)C)cc1
Modality: PROteolysis-TArgeting Chimera (PROTAC)
Target protein (POI): ESR1 (UniProt P03372)
POI sequence: MTMTLHTKASGMALLHQIQGNELEPLNRPQLKIPLERPLGEVYLDSSKPAVYNYPEGAAYEFNAAAAANAQVYGQTGLPYGPGSEAAAFGSNGLGGFPPLNSVSPSPLMLLHPPPQLSPFLQPHGQQVPYYLENEPSGYTVREAGPPAFYRPNSDNRRQGGRERLASTNDKGSMAMESAKETRYCAVCNDYASGYHYGVWSCEGCKAFFKRSIQGHNDYMCPATNQCTIDKNRRKSCQACRLRKCYEVGMMKGGIRKDRRGGRMLKHKRQRDDGEGRGEVGSAGDMRAANLWPSPLMIKRSKKNSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWLEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGMVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITDTLIHLMAKAGLTLQQQHQRLAQLLLILSHIRHMSNKGMEHLYSMKCKNVVPLYDLLLEMLDAHRLHAPTSRGGASVEETDQSHLATAGSTSSHSLQKYYITGEAEGFPATV
E3 ligase: VHL (UniProt P40337)
Ligase sequence: MPRRAENWDEAEVGAEEAGVEEYGPEEDGGEESGAEESGPEESGPEELGAEEEMEAGRPRPVLRSVNSREPSQVIFCNRSPRVVLPVWLNFDGEPQPYPTLPPGTGRRIHSYRGHLWLFRDAGTHDGLLVNQTELFVPSLNVDGQPIFANITLPVYTLKERCLQVVRSLVKPENYRRLDIVRSLYEDLEDHPNVQKDLERLTQERIAHQRMGD
Cell line: MCF-7 (Homo sapiens)
Cell line description: African=0.74%; Native American=0%; East Asian, North=4.2%; East Asian, South=0%; South Asian=0%; European, North=56.91%; European, South=38.15%.
Helen Marion Mallon (sister Catherine Frances), the patient from which this cell line is derived was a nun at the Immaculate Heart of Mary convent in Monroe, Michigan (CelloPub=CLPUB00336).
Gene deletion; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC
A*02 A*02 A*02
Stable (MSS).
Metastatic; Pleural effusion; 
Caucasian.
Space-flown cell line (cellonaut).
Cancer cell line
Assay time (hours): 4
Dmax:  80 %
Assay description: EC50 of ligand was measured in MCF7 cells. DCmax was measured in 1 nM (at 10 nM > 99 %).
Reference: https://pubmed.ncbi.nlm.nih.gov/30990042/
Source database: PROTACpedia
Compound (SMILES): Cc1ncsc1-c1ccc([C@H](C)NC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)CCCCCCCN(CCOc2ccc(C(=O)c3c(-c4ccc(O)cc4)sc4cc(O)ccc34)cc2)C2CCC2)C(C)(C)C)cc1
Modality: PROteolysis-TArgeting Chimera (PROTAC)
Target protein (POI): ESR1 (UniProt P03372)
POI sequence: MTMTLHTKASGMALLHQIQGNELEPLNRPQLKIPLERPLGEVYLDSSKPAVYNYPEGAAYEFNAAAAANAQVYGQTGLPYGPGSEAAAFGSNGLGGFPPLNSVSPSPLMLLHPPPQLSPFLQPHGQQVPYYLENEPSGYTVREAGPPAFYRPNSDNRRQGGRERLASTNDKGSMAMESAKETRYCAVCNDYASGYHYGVWSCEGCKAFFKRSIQGHNDYMCPATNQCTIDKNRRKSCQACRLRKCYEVGMMKGGIRKDRRGGRMLKHKRQRDDGEGRGEVGSAGDMRAANLWPSPLMIKRSKKNSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWLEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGMVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITDTLIHLMAKAGLTLQQQHQRLAQLLLILSHIRHMSNKGMEHLYSMKCKNVVPLYDLLLEMLDAHRLHAPTSRGGASVEETDQSHLATAGSTSSHSLQKYYITGEAEGFPATV
E3 ligase: VHL (UniProt P40337)
Ligase sequence: MPRRAENWDEAEVGAEEAGVEEYGPEEDGGEESGAEESGPEESGPEELGAEEEMEAGRPRPVLRSVNSREPSQVIFCNRSPRVVLPVWLNFDGEPQPYPTLPPGTGRRIHSYRGHLWLFRDAGTHDGLLVNQTELFVPSLNVDGQPIFANITLPVYTLKERCLQVVRSLVKPENYRRLDIVRSLYEDLEDHPNVQKDLERLTQERIAHQRMGD
Cell line: MCF-7 (Homo sapiens)
Cell line description: African=0.74%; Native American=0%; East Asian, North=4.2%; East Asian, South=0%; South Asian=0%; European, North=56.91%; European, South=38.15%.
Helen Marion Mallon (sister Catherine Frances), the patient from which this cell line is derived was a nun at the Immaculate Heart of Mary convent in Monroe, Michigan (CelloPub=CLPUB00336).
Gene deletion; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC
A*02 A*02 A*02
Stable (MSS).
Metastatic; Pleural effusion; 
Caucasian.
Space-flown cell line (cellonaut).
Cancer cell line
Assay time (hours): 4
Dmax:  85 %
Assay description: EC50 of ligand was measured in MCF7 cells. DCmax was measured in 1 nM (at 10 nM > 99 %).
Reference: https://pubmed.ncbi.nlm.nih.gov/30990042/
Source database: PROTACpedia
Compound (SMILES): Cc1ncsc1-c1ccc([C@H](C)NC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)CCCCCCCN(CCOc2ccc(C(=O)c3c(-c4ccc(O)cc4)sc4cc(O)ccc34)cc2)C2CCCC2)C(C)(C)C)cc1
Modality: PROteolysis-TArgeting Chimera (PROTAC)
Target protein (POI): ESR1 (UniProt P03372)
POI sequence: MTMTLHTKASGMALLHQIQGNELEPLNRPQLKIPLERPLGEVYLDSSKPAVYNYPEGAAYEFNAAAAANAQVYGQTGLPYGPGSEAAAFGSNGLGGFPPLNSVSPSPLMLLHPPPQLSPFLQPHGQQVPYYLENEPSGYTVREAGPPAFYRPNSDNRRQGGRERLASTNDKGSMAMESAKETRYCAVCNDYASGYHYGVWSCEGCKAFFKRSIQGHNDYMCPATNQCTIDKNRRKSCQACRLRKCYEVGMMKGGIRKDRRGGRMLKHKRQRDDGEGRGEVGSAGDMRAANLWPSPLMIKRSKKNSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWLEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGMVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITDTLIHLMAKAGLTLQQQHQRLAQLLLILSHIRHMSNKGMEHLYSMKCKNVVPLYDLLLEMLDAHRLHAPTSRGGASVEETDQSHLATAGSTSSHSLQKYYITGEAEGFPATV
E3 ligase: VHL (UniProt P40337)
Ligase sequence: MPRRAENWDEAEVGAEEAGVEEYGPEEDGGEESGAEESGPEESGPEELGAEEEMEAGRPRPVLRSVNSREPSQVIFCNRSPRVVLPVWLNFDGEPQPYPTLPPGTGRRIHSYRGHLWLFRDAGTHDGLLVNQTELFVPSLNVDGQPIFANITLPVYTLKERCLQVVRSLVKPENYRRLDIVRSLYEDLEDHPNVQKDLERLTQERIAHQRMGD
Cell line: MCF-7 (Homo sapiens)
Cell line description: African=0.74%; Native American=0%; East Asian, North=4.2%; East Asian, South=0%; South Asian=0%; European, North=56.91%; European, South=38.15%.
Helen Marion Mallon (sister Catherine Frances), the patient from which this cell line is derived was a nun at the Immaculate Heart of Mary convent in Monroe, Michigan (CelloPub=CLPUB00336).
Gene deletion; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC
A*02 A*02 A*02
Stable (MSS).
Metastatic; Pleural effusion; 
Caucasian.
Space-flown cell line (cellonaut).
Cancer cell line
Assay time (hours): 4
Dmax:  25 %
Assay description: EC50 of ligand was measured in MCF7 cells. DCmax was measured in 1 nM (at 10 nM > 99 %).
Reference: https://pubmed.ncbi.nlm.nih.gov/30990042/
Source database: PROTACpedia
Compound (SMILES): Cc1ncsc1-c1ccc([C@H](C)NC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)CCCCCCCN(CCOc2ccc(C(=O)c3c(-c4ccc(O)cc4)sc4cc(O)ccc34)cc2)C2CCCCC2)C(C)(C)C)cc1
Modality: PROteolysis-TArgeting Chimera (PROTAC)
Target protein (POI): ESR1 (UniProt P03372)
POI sequence: MTMTLHTKASGMALLHQIQGNELEPLNRPQLKIPLERPLGEVYLDSSKPAVYNYPEGAAYEFNAAAAANAQVYGQTGLPYGPGSEAAAFGSNGLGGFPPLNSVSPSPLMLLHPPPQLSPFLQPHGQQVPYYLENEPSGYTVREAGPPAFYRPNSDNRRQGGRERLASTNDKGSMAMESAKETRYCAVCNDYASGYHYGVWSCEGCKAFFKRSIQGHNDYMCPATNQCTIDKNRRKSCQACRLRKCYEVGMMKGGIRKDRRGGRMLKHKRQRDDGEGRGEVGSAGDMRAANLWPSPLMIKRSKKNSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWLEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGMVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITDTLIHLMAKAGLTLQQQHQRLAQLLLILSHIRHMSNKGMEHLYSMKCKNVVPLYDLLLEMLDAHRLHAPTSRGGASVEETDQSHLATAGSTSSHSLQKYYITGEAEGFPATV
E3 ligase: VHL (UniProt P40337)
Ligase sequence: MPRRAENWDEAEVGAEEAGVEEYGPEEDGGEESGAEESGPEESGPEELGAEEEMEAGRPRPVLRSVNSREPSQVIFCNRSPRVVLPVWLNFDGEPQPYPTLPPGTGRRIHSYRGHLWLFRDAGTHDGLLVNQTELFVPSLNVDGQPIFANITLPVYTLKERCLQVVRSLVKPENYRRLDIVRSLYEDLEDHPNVQKDLERLTQERIAHQRMGD
Cell line: MCF-7 (Homo sapiens)
Cell line description: African=0.74%; Native American=0%; East Asian, North=4.2%; East Asian, South=0%; South Asian=0%; European, North=56.91%; European, South=38.15%.
Helen Marion Mallon (sister Catherine Frances), the patient from which this cell line is derived was a nun at the Immaculate Heart of Mary convent in Monroe, Michigan (CelloPub=CLPUB00336).
Gene deletion; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC
A*02 A*02 A*02
Stable (MSS).
Metastatic; Pleural effusion; 
Caucasian.
Space-flown cell line (cellonaut).
Cancer cell line
Assay time (hours): 4
Dmax:  32 %
Assay description: EC50 of ligand was measured in MCF7 cells. DCmax was measured in 1 nM (at 10 nM > 99 %).
Reference: https://pubmed.ncbi.nlm.nih.gov/30990042/
Source database: PROTACpedia
Compound (SMILES): Cc1ncsc1-c1ccc([C@H](C)NC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)CCCCCCCN(CCOc2ccc(C(=O)c3c(-c4ccc(O)cc4)sc4cc(O)ccc34)cc2)CC2CCC2)C(C)(C)C)cc1
Modality: PROteolysis-TArgeting Chimera (PROTAC)
Target protein (POI): ESR1 (UniProt P03372)
POI sequence: MTMTLHTKASGMALLHQIQGNELEPLNRPQLKIPLERPLGEVYLDSSKPAVYNYPEGAAYEFNAAAAANAQVYGQTGLPYGPGSEAAAFGSNGLGGFPPLNSVSPSPLMLLHPPPQLSPFLQPHGQQVPYYLENEPSGYTVREAGPPAFYRPNSDNRRQGGRERLASTNDKGSMAMESAKETRYCAVCNDYASGYHYGVWSCEGCKAFFKRSIQGHNDYMCPATNQCTIDKNRRKSCQACRLRKCYEVGMMKGGIRKDRRGGRMLKHKRQRDDGEGRGEVGSAGDMRAANLWPSPLMIKRSKKNSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWLEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGMVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITDTLIHLMAKAGLTLQQQHQRLAQLLLILSHIRHMSNKGMEHLYSMKCKNVVPLYDLLLEMLDAHRLHAPTSRGGASVEETDQSHLATAGSTSSHSLQKYYITGEAEGFPATV
E3 ligase: VHL (UniProt P40337)
Ligase sequence: MPRRAENWDEAEVGAEEAGVEEYGPEEDGGEESGAEESGPEESGPEELGAEEEMEAGRPRPVLRSVNSREPSQVIFCNRSPRVVLPVWLNFDGEPQPYPTLPPGTGRRIHSYRGHLWLFRDAGTHDGLLVNQTELFVPSLNVDGQPIFANITLPVYTLKERCLQVVRSLVKPENYRRLDIVRSLYEDLEDHPNVQKDLERLTQERIAHQRMGD
Cell line: MCF-7 (Homo sapiens)
Cell line description: African=0.74%; Native American=0%; East Asian, North=4.2%; East Asian, South=0%; South Asian=0%; European, North=56.91%; European, South=38.15%.
Helen Marion Mallon (sister Catherine Frances), the patient from which this cell line is derived was a nun at the Immaculate Heart of Mary convent in Monroe, Michigan (CelloPub=CLPUB00336).
Gene deletion; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC
A*02 A*02 A*02
Stable (MSS).
Metastatic; Pleural effusion; 
Caucasian.
Space-flown cell line (cellonaut).
Cancer cell line
Assay time (hours): 4
Dmax:  24 %
Assay description: EC50 of ligand was measured in MCF7 cells. DCmax was measured in 1 nM (at 10 nM > 99 %).
Reference: https://pubmed.ncbi.nlm.nih.gov/30990042/
Source database: PROTACpedia
Compound (SMILES): Cc1ncsc1-c1ccc([C@H](C)NC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)CCCCCCCNC(=O)C[C@@H]2CCN(CCc3cc(O)c(N4CC(=O)NS4(=O)=O)c(F)c3)C2)C(C)(C)C)cc1
Modality: PROteolysis-TArgeting Chimera (PROTAC)
Target protein (POI): PTPN1 (UniProt P18031)
POI sequence: MEMEKEFEQIDKSGSWAAIYQDIRHEASDFPCRVAKLPKNKNRNRYRDVSPFDHSRIKLHQEDNDYINASLIKMEEAQRSYILTQGPLPNTCGHFWEMVWEQKSRGVVMLNRVMEKGSLKCAQYWPQKEEKEMIFEDTNLKLTLISEDIKSYYTVRQLELENLTTQETREILHFHYTTWPDFGVPESPASFLNFLFKVRESGSLSPEHGPVVVHCSAGIGRSGTFCLADTCLLLMDKRKDPSSVDIKKVLLEMRKFRMGLIQTADQLRFSYLAVIEGAKFIMGDSSVQDQWKELSHEDLEPPPEHIPPPPRPPKRILEPHNGKCREFFPNHQWVKEETQEDKDCPIKEEKGSPLNAAPYGIESMSQDTEVRSRVVGGSLRGAQAASPAKGEPSLPEKDEDHALSYWKPFLVNMCVATVLTAGAYLCYRFLFNSNT
E3 ligase: VHL (UniProt P40337)
Ligase sequence: MPRRAENWDEAEVGAEEAGVEEYGPEEDGGEESGAEESGPEESGPEELGAEEEMEAGRPRPVLRSVNSREPSQVIFCNRSPRVVLPVWLNFDGEPQPYPTLPPGTGRRIHSYRGHLWLFRDAGTHDGLLVNQTELFVPSLNVDGQPIFANITLPVYTLKERCLQVVRSLVKPENYRRLDIVRSLYEDLEDHPNVQKDLERLTQERIAHQRMGD
Cell line: Jurkat (Homo sapiens)
Cell line description: African=0.4%; Native American=0%; East Asian, North=0.13%; East Asian, South=1.21%; South Asian=1.08%; European, North=70.73%; European, South=26.45%.
Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC
A*03
Instable (MSI-high).
In situ; Peripheral blood; 
Caucasian.
Space-flown cell line (cellonaut).
T-cell; CL=CL_0000084.
Cancer cell line
Assay: HiBiT
DC50:  3830 nM
Assay description: Parental Jurkat cells (ATCC, TIB-152) were grown in complete RPMI medium consisting of RPMI 1640 Medium (Gibco, 61870036) supplemented with 10% fetal bovine serum (Gibco, 10082147) and 1x Pen Strep (Gibco, 15140122). The sequence encoding the HiBiT tag (Promega) was integrated into the 5' end of the coding sequence on both alleles of the PTPN2 gene in Jurkat cells by CRISPR to create the Jurkat-PTPN2-N-HiBiT cell line. The sequence for the HiBiT tag was integrated into the 3' end of the coding sequence on both alleles of the PTPN1 gene in Jurkat cells by CRISPR to create the Jurkat-PTPN1-C-HiBiT cell line.
Degradation of HiBiT-tagged proteins was monitored by luminescence using the Nano-Glo HiBiT Lytic Detection System (Promega, N3040). Five thousand cells per well of either Jurkat-PTPN2-N-HiBit or Jurkat-PTPN1-C-HiBiT were plated into white opaque OptiPlate-384 microplates (Perkin-Elmer, 6007290) in 25 μL complete RPMI medium. Compounds were added to the cells using a Tecan D300e Digital Dispenser. Cells were incubated for 24 hours in a humidified incubator at 37°C and 5% CO2. Following the 24 hour incubation, Nano-Glo HiBiT Lytic Reagent was added to cells and luminescence levels were read on a CLARIOstar Microplate Reader (BMG LABTECH). Each plate included a vehicle control (0.1% DMSO) from which % degradation for test compounds was calculated. A four-parameter curve fit was used to determine DC50 and Dmax values.
Reference: PROTEIN TYROSINE PHOSPHATASE DEGRADERS AND USES THEREOF (patent)
Source database: TPDdb
Compound (SMILES): Cc1ncsc1-c1ccc([C@H](C)NC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)CCCCCCCNC(=O)C[C@@H]2CCN(CCc3cc(O)c(N4CC(=O)NS4(=O)=O)c(F)c3)C2)C(C)(C)C)cc1
Modality: PROteolysis-TArgeting Chimera (PROTAC)
Target protein (POI): PTPN1 (UniProt P18031)
POI sequence: MEMEKEFEQIDKSGSWAAIYQDIRHEASDFPCRVAKLPKNKNRNRYRDVSPFDHSRIKLHQEDNDYINASLIKMEEAQRSYILTQGPLPNTCGHFWEMVWEQKSRGVVMLNRVMEKGSLKCAQYWPQKEEKEMIFEDTNLKLTLISEDIKSYYTVRQLELENLTTQETREILHFHYTTWPDFGVPESPASFLNFLFKVRESGSLSPEHGPVVVHCSAGIGRSGTFCLADTCLLLMDKRKDPSSVDIKKVLLEMRKFRMGLIQTADQLRFSYLAVIEGAKFIMGDSSVQDQWKELSHEDLEPPPEHIPPPPRPPKRILEPHNGKCREFFPNHQWVKEETQEDKDCPIKEEKGSPLNAAPYGIESMSQDTEVRSRVVGGSLRGAQAASPAKGEPSLPEKDEDHALSYWKPFLVNMCVATVLTAGAYLCYRFLFNSNT
E3 ligase: VHL (UniProt P40337)
Ligase sequence: MPRRAENWDEAEVGAEEAGVEEYGPEEDGGEESGAEESGPEESGPEELGAEEEMEAGRPRPVLRSVNSREPSQVIFCNRSPRVVLPVWLNFDGEPQPYPTLPPGTGRRIHSYRGHLWLFRDAGTHDGLLVNQTELFVPSLNVDGQPIFANITLPVYTLKERCLQVVRSLVKPENYRRLDIVRSLYEDLEDHPNVQKDLERLTQERIAHQRMGD
Cell line: Jurkat (Homo sapiens)
Cell line description: African=0.4%; Native American=0%; East Asian, North=0.13%; East Asian, South=1.21%; South Asian=1.08%; European, North=70.73%; European, South=26.45%.
Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC
A*03
Instable (MSI-high).
In situ; Peripheral blood; 
Caucasian.
Space-flown cell line (cellonaut).
T-cell; CL=CL_0000084.
Cancer cell line
Assay: HiBiT
Dmax:  78 %
Assay description: Parental Jurkat cells (ATCC, TIB-152) were grown in complete RPMI medium consisting of RPMI 1640 Medium (Gibco, 61870036) supplemented with 10% fetal bovine serum (Gibco, 10082147) and 1x Pen Strep (Gibco, 15140122). The sequence encoding the HiBiT tag (Promega) was integrated into the 5' end of the coding sequence on both alleles of the PTPN2 gene in Jurkat cells by CRISPR to create the Jurkat-PTPN2-N-HiBiT cell line. The sequence for the HiBiT tag was integrated into the 3' end of the coding sequence on both alleles of the PTPN1 gene in Jurkat cells by CRISPR to create the Jurkat-PTPN1-C-HiBiT cell line.
Degradation of HiBiT-tagged proteins was monitored by luminescence using the Nano-Glo HiBiT Lytic Detection System (Promega, N3040). Five thousand cells per well of either Jurkat-PTPN2-N-HiBit or Jurkat-PTPN1-C-HiBiT were plated into white opaque OptiPlate-384 microplates (Perkin-Elmer, 6007290) in 25 μL complete RPMI medium. Compounds were added to the cells using a Tecan D300e Digital Dispenser. Cells were incubated for 24 hours in a humidified incubator at 37°C and 5% CO2. Following the 24 hour incubation, Nano-Glo HiBiT Lytic Reagent was added to cells and luminescence levels were read on a CLARIOstar Microplate Reader (BMG LABTECH). Each plate included a vehicle control (0.1% DMSO) from which % degradation for test compounds was calculated. A four-parameter curve fit was used to determine DC50 and Dmax values.
Reference: PROTEIN TYROSINE PHOSPHATASE DEGRADERS AND USES THEREOF (patent)
Source database: TPDdb
Compound (SMILES): Cc1ncsc1-c1ccc([C@H](C)NC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)CCCCCCCNC(=O)C[C@@H]2CCN(CCc3cc(O)c(N4CC(=O)NS4(=O)=O)c(F)c3)C2)C(C)(C)C)cc1
Modality: PROteolysis-TArgeting Chimera (PROTAC)
Target protein (POI): PTPN2 (UniProt P17706)
POI sequence: MPTTIEREFEELDTQRRWQPLYLEIRNESHDYPHRVAKFPENRNRNRYRDVSPYDHSRVKLQNAENDYINASLVDIEEAQRSYILTQGPLPNTCCHFWLMVWQQKTKAVVMLNRIVEKESVKCAQYWPTDDQEMLFKETGFSVKLLSEDVKSYYTVHLLQLENINSGETRTISHFHYTTWPDFGVPESPASFLNFLFKVRESGSLNPDHGPAVIHCSAGIGRSGTFSLVDTCLVLMEKGDDINIKQVLLNMRKYRMGLIQTPDQLRFSYMAIIEGAKCIKGDSSIQKRWKELSKEDLSPAFDHSPNKIMTEKYNGNRIGLEEEKLTGDRCTGLSSKMQDTMEENSESALRKRIREDRKATTAQKVQQMKQRLNENERKRKRWLYWQPILTKMGFMSVILVGAFVGWTLFFQQNAL
E3 ligase: VHL (UniProt P40337)
Ligase sequence: MPRRAENWDEAEVGAEEAGVEEYGPEEDGGEESGAEESGPEESGPEELGAEEEMEAGRPRPVLRSVNSREPSQVIFCNRSPRVVLPVWLNFDGEPQPYPTLPPGTGRRIHSYRGHLWLFRDAGTHDGLLVNQTELFVPSLNVDGQPIFANITLPVYTLKERCLQVVRSLVKPENYRRLDIVRSLYEDLEDHPNVQKDLERLTQERIAHQRMGD
Cell line: Jurkat (Homo sapiens)
Cell line description: African=0.4%; Native American=0%; East Asian, North=0.13%; East Asian, South=1.21%; South Asian=1.08%; European, North=70.73%; European, South=26.45%.
Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC
A*03
Instable (MSI-high).
In situ; Peripheral blood; 
Caucasian.
Space-flown cell line (cellonaut).
T-cell; CL=CL_0000084.
Cancer cell line
Assay: HiBiT
DC50:  146 nM
Assay description: Parental Jurkat cells (ATCC, TIB-152) were grown in complete RPMI medium consisting of RPMI 1640 Medium (Gibco, 61870036) supplemented with 10% fetal bovine serum (Gibco, 10082147) and 1x Pen Strep (Gibco, 15140122). The sequence encoding the HiBiT tag (Promega) was integrated into the 5' end of the coding sequence on both alleles of the PTPN2 gene in Jurkat cells by CRISPR to create the Jurkat-PTPN2-N-HiBiT cell line. The sequence for the HiBiT tag was integrated into the 3' end of the coding sequence on both alleles of the PTPN1 gene in Jurkat cells by CRISPR to create the Jurkat-PTPN1-C-HiBiT cell line.
Degradation of HiBiT-tagged proteins was monitored by luminescence using the Nano-Glo HiBiT Lytic Detection System (Promega, N3040). Five thousand cells per well of either Jurkat-PTPN2-N-HiBit or Jurkat-PTPN1-C-HiBiT were plated into white opaque OptiPlate-384 microplates (Perkin-Elmer, 6007290) in 25 μL complete RPMI medium. Compounds were added to the cells using a Tecan D300e Digital Dispenser. Cells were incubated for 24 hours in a humidified incubator at 37°C and 5% CO2. Following the 24 hour incubation, Nano-Glo HiBiT Lytic Reagent was added to cells and luminescence levels were read on a CLARIOstar Microplate Reader (BMG LABTECH). Each plate included a vehicle control (0.1% DMSO) from which % degradation for test compounds was calculated. A four-parameter curve fit was used to determine DC50 and Dmax values.
Reference: PROTEIN TYROSINE PHOSPHATASE DEGRADERS AND USES THEREOF (patent)
Source database: TPDdb
Compound (SMILES): Cc1ncsc1-c1ccc([C@H](C)NC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)CCCCCCCNC(=O)C[C@@H]2CCN(CCc3cc(O)c(N4CC(=O)NS4(=O)=O)c(F)c3)C2)C(C)(C)C)cc1
Modality: PROteolysis-TArgeting Chimera (PROTAC)
Target protein (POI): PTPN2 (UniProt P17706)
POI sequence: MPTTIEREFEELDTQRRWQPLYLEIRNESHDYPHRVAKFPENRNRNRYRDVSPYDHSRVKLQNAENDYINASLVDIEEAQRSYILTQGPLPNTCCHFWLMVWQQKTKAVVMLNRIVEKESVKCAQYWPTDDQEMLFKETGFSVKLLSEDVKSYYTVHLLQLENINSGETRTISHFHYTTWPDFGVPESPASFLNFLFKVRESGSLNPDHGPAVIHCSAGIGRSGTFSLVDTCLVLMEKGDDINIKQVLLNMRKYRMGLIQTPDQLRFSYMAIIEGAKCIKGDSSIQKRWKELSKEDLSPAFDHSPNKIMTEKYNGNRIGLEEEKLTGDRCTGLSSKMQDTMEENSESALRKRIREDRKATTAQKVQQMKQRLNENERKRKRWLYWQPILTKMGFMSVILVGAFVGWTLFFQQNAL
E3 ligase: VHL (UniProt P40337)
Ligase sequence: MPRRAENWDEAEVGAEEAGVEEYGPEEDGGEESGAEESGPEESGPEELGAEEEMEAGRPRPVLRSVNSREPSQVIFCNRSPRVVLPVWLNFDGEPQPYPTLPPGTGRRIHSYRGHLWLFRDAGTHDGLLVNQTELFVPSLNVDGQPIFANITLPVYTLKERCLQVVRSLVKPENYRRLDIVRSLYEDLEDHPNVQKDLERLTQERIAHQRMGD
Cell line: Jurkat (Homo sapiens)
Cell line description: African=0.4%; Native American=0%; East Asian, North=0.13%; East Asian, South=1.21%; South Asian=1.08%; European, North=70.73%; European, South=26.45%.
Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC
A*03
Instable (MSI-high).
In situ; Peripheral blood; 
Caucasian.
Space-flown cell line (cellonaut).
T-cell; CL=CL_0000084.
Cancer cell line
Assay: HiBiT
Dmax:  98 %
Assay description: Parental Jurkat cells (ATCC, TIB-152) were grown in complete RPMI medium consisting of RPMI 1640 Medium (Gibco, 61870036) supplemented with 10% fetal bovine serum (Gibco, 10082147) and 1x Pen Strep (Gibco, 15140122). The sequence encoding the HiBiT tag (Promega) was integrated into the 5' end of the coding sequence on both alleles of the PTPN2 gene in Jurkat cells by CRISPR to create the Jurkat-PTPN2-N-HiBiT cell line. The sequence for the HiBiT tag was integrated into the 3' end of the coding sequence on both alleles of the PTPN1 gene in Jurkat cells by CRISPR to create the Jurkat-PTPN1-C-HiBiT cell line.
Degradation of HiBiT-tagged proteins was monitored by luminescence using the Nano-Glo HiBiT Lytic Detection System (Promega, N3040). Five thousand cells per well of either Jurkat-PTPN2-N-HiBit or Jurkat-PTPN1-C-HiBiT were plated into white opaque OptiPlate-384 microplates (Perkin-Elmer, 6007290) in 25 μL complete RPMI medium. Compounds were added to the cells using a Tecan D300e Digital Dispenser. Cells were incubated for 24 hours in a humidified incubator at 37°C and 5% CO2. Following the 24 hour incubation, Nano-Glo HiBiT Lytic Reagent was added to cells and luminescence levels were read on a CLARIOstar Microplate Reader (BMG LABTECH). Each plate included a vehicle control (0.1% DMSO) from which % degradation for test compounds was calculated. A four-parameter curve fit was used to determine DC50 and Dmax values.
Reference: PROTEIN TYROSINE PHOSPHATASE DEGRADERS AND USES THEREOF (patent)
Source database: TPDdb
Compound (SMILES): Cc1ncsc1-c1ccc([C@H](C)NC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)CCCCCCCc2ccc(-c3ccc(OCCCc4sc(N5CCc6cccc(C(=O)Nc7nc8ccccc8s7)c6C5)nc4C(=O)O)cc3)nc2)C(C)(C)C)cc1
Modality: PROteolysis-TArgeting Chimera (PROTAC)
Target protein (POI): BCL2L1 (UniProt Q07817)
POI sequence: MSQSNRELVVDFLSYKLSQKGYSWSQFSDVEENRTEAPEGTESEMETPSAINGNPSWHLADSPAVNGATGHSSSLDAREVIPMAAVKQALREAGDEFELRYRRAFSDLTSQLHITPGTAYQSFEQVVNELFRDGVNWGRIVAFFSFGGALCVESVDKEMQVLVSRIAAWMATYLNDHLEPWIQENGGWDTFVELYGNNAAAESRKGQERFNRWFLTGMTVAGVVLLGSLFSRK
E3 ligase: VHL (UniProt P40337)
Ligase sequence: MPRRAENWDEAEVGAEEAGVEEYGPEEDGGEESGAEESGPEESGPEELGAEEEMEAGRPRPVLRSVNSREPSQVIFCNRSPRVVLPVWLNFDGEPQPYPTLPPGTGRRIHSYRGHLWLFRDAGTHDGLLVNQTELFVPSLNVDGQPIFANITLPVYTLKERCLQVVRSLVKPENYRRLDIVRSLYEDLEDHPNVQKDLERLTQERIAHQRMGD
Cell line: MOLT-4 (Homo sapiens)
Cell line description: African=0.38%; Native American=0%; East Asian, North=1.74%; East Asian, South=0%; South Asian=0.94%; European, North=68.08%; European, South=28.87%.
Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC
A*01 A*01 A*01
Instable (MSI-high).
In situ; Peripheral blood; 
Caucasian.
T-cell; CL=CL_0000084.
Cancer cell line
Assay: Western Blot/CellTiterGlo
DC50:  3 nM
Assay description: BCL-XL Degradation Assay
Cell Culture
Human T lymphoblast MOLT-4 were cultured in RPMI 1640 media, supplemented with 10%FBS. All cell lines were maintained at 37 °C in an atmosphere of 5%CO2.
Protein extraction and Western blotting
Whole cell lysates were prepared using cell Lysis Buffer supplemented with Protease inhibitor, phosphatase inhibitor and PMSF solution. The concentration of protein was quantified using a Pierce Bicinchoninic Acid (BCA) Protein Concentration Kit. Equal amounts of protein were loaded for PAGE and transfer samples onto a PVDF membrane using Bio-Rad's Trans blot. The blots were incubated with a primary antibody followed by HRP conjugated to an appropriate secondary antibody.
Cell viability assay
Cell viability was measured using a CellTiter-Glo Assay kit according to the manufacturer's protocol. MOLT-4 were seeded into 384-well plates and treated with various increasing doses of compound for 72 hours. Cell plates were taken from the incubator and equilibrated withThe plates were read on an Envision 2104 Multi-plate reader using a luminescence detector.
Representative degradation activity and cell viability from exemplary compounds is presented in Table 8.
Reference: BCL-XL DEGRADING COMPOUNDS (patent)
Source database: TPDdb
Compound (SMILES): Cc1ncsc1-c1ccc([C@H](C)NC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)CCCCCCCc2cnc(-c3ccc(OCCCc4sc(N5CCc6cccc(C(=O)Nc7nc8ccccc8s7)c6C5)nc4C(=O)O)cc3)c(F)c2)C(C)(C)C)cc1
Modality: PROteolysis-TArgeting Chimera (PROTAC)
Target protein (POI): BCL2L1 (UniProt Q07817)
POI sequence: MSQSNRELVVDFLSYKLSQKGYSWSQFSDVEENRTEAPEGTESEMETPSAINGNPSWHLADSPAVNGATGHSSSLDAREVIPMAAVKQALREAGDEFELRYRRAFSDLTSQLHITPGTAYQSFEQVVNELFRDGVNWGRIVAFFSFGGALCVESVDKEMQVLVSRIAAWMATYLNDHLEPWIQENGGWDTFVELYGNNAAAESRKGQERFNRWFLTGMTVAGVVLLGSLFSRK
E3 ligase: VHL (UniProt P40337)
Ligase sequence: MPRRAENWDEAEVGAEEAGVEEYGPEEDGGEESGAEESGPEESGPEELGAEEEMEAGRPRPVLRSVNSREPSQVIFCNRSPRVVLPVWLNFDGEPQPYPTLPPGTGRRIHSYRGHLWLFRDAGTHDGLLVNQTELFVPSLNVDGQPIFANITLPVYTLKERCLQVVRSLVKPENYRRLDIVRSLYEDLEDHPNVQKDLERLTQERIAHQRMGD
Cell line: MOLT-4 (Homo sapiens)
Cell line description: African=0.38%; Native American=0%; East Asian, North=1.74%; East Asian, South=0%; South Asian=0.94%; European, North=68.08%; European, South=28.87%.
Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC
A*01 A*01 A*01
Instable (MSI-high).
In situ; Peripheral blood; 
Caucasian.
T-cell; CL=CL_0000084.
Cancer cell line
Assay: Western Blot/CellTiterGlo
DC50:  2 nM
Assay description: BCL-XL Degradation Assay
Cell Culture
Human T lymphoblast MOLT-4 were cultured in RPMI 1640 media, supplemented with 10%FBS. All cell lines were maintained at 37 °C in an atmosphere of 5%CO2.
Protein extraction and Western blotting
Whole cell lysates were prepared using cell Lysis Buffer supplemented with Protease inhibitor, phosphatase inhibitor and PMSF solution. The concentration of protein was quantified using a Pierce Bicinchoninic Acid (BCA) Protein Concentration Kit. Equal amounts of protein were loaded for PAGE and transfer samples onto a PVDF membrane using Bio-Rad's Trans blot. The blots were incubated with a primary antibody followed by HRP conjugated to an appropriate secondary antibody.
Cell viability assay
Cell viability was measured using a CellTiter-Glo Assay kit according to the manufacturer's protocol. MOLT-4 were seeded into 384-well plates and treated with various increasing doses of compound for 72 hours. Cell plates were taken from the incubator and equilibrated withThe plates were read on an Envision 2104 Multi-plate reader using a luminescence detector.
Representative degradation activity and cell viability from exemplary compounds is presented in Table 8.
Reference: BCL-XL DEGRADING COMPOUNDS (patent)
Source database: TPDdb
Compound (SMILES): Cc1ncsc1-c1ccc([C@H](C)NC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)CCCCCCN(C)CC[C@H](CSc2ccccc2)Nc2ccc(S(=O)(=O)NC(=O)c3ccc(N4CCN(CC5=C(c6ccc(Cl)cc6)CCC(C)(C)C5)CC4)cc3)cc2S(=O)(=O)C(F)(F)F)C(C)(C)C)cc1
Modality: PROteolysis-TArgeting Chimera (PROTAC)
Target protein (POI): BCL-XL (UniProt Q07817)
POI sequence: MSQSNRELVVDFLSYKLSQKGYSWSQFSDVEENRTEAPEGTESEMETPSAINGNPSWHLADSPAVNGATGHSSSLDAREVIPMAAVKQALREAGDEFELRYRRAFSDLTSQLHITPGTAYQSFEQVVNELFRDGVNWGRIVAFFSFGGALCVESVDKEMQVLVSRIAAWMATYLNDHLEPWIQENGGWDTFVELYGNNAAAESRKGQERFNRWFLTGMTVAGVVLLGSLFSRK
E3 ligase: VHL (UniProt P40337)
Ligase sequence: MPRRAENWDEAEVGAEEAGVEEYGPEEDGGEESGAEESGPEESGPEELGAEEEMEAGRPRPVLRSVNSREPSQVIFCNRSPRVVLPVWLNFDGEPQPYPTLPPGTGRRIHSYRGHLWLFRDAGTHDGLLVNQTELFVPSLNVDGQPIFANITLPVYTLKERCLQVVRSLVKPENYRRLDIVRSLYEDLEDHPNVQKDLERLTQERIAHQRMGD
Cell line: MOLT-4 (Homo sapiens)
Cell line description: African=0.38%; Native American=0%; East Asian, North=1.74%; East Asian, South=0%; South Asian=0.94%; European, North=68.08%; European, South=28.87%.
Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC
A*01 A*01 A*01
Instable (MSI-high).
In situ; Peripheral blood; 
Caucasian.
T-cell; CL=CL_0000084.
Cancer cell line
Assay time (hours): 16
DC50:  71 nM
Assay description: Degradation of BCL-xL in MOLT-4 cells after 16 h treatment
Reference: 10.1016/j.ejmech.2020.112186
Source database: PROTAC-DB
Compound (SMILES): Cc1ncsc1-c1ccc([C@H](C)NC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)CCCCCCN(C)CC[C@H](CSc2ccccc2)Nc2ccc(S(=O)(=O)NC(=O)c3ccc(N4CCN(CC5=C(c6ccc(Cl)cc6)CCC(C)(C)C5)CC4)cc3)cc2S(=O)(=O)C(F)(F)F)C(C)(C)C)cc1
Modality: PROteolysis-TArgeting Chimera (PROTAC)
Target protein (POI): BCL2L1 (UniProt Q07817)
POI sequence: MSQSNRELVVDFLSYKLSQKGYSWSQFSDVEENRTEAPEGTESEMETPSAINGNPSWHLADSPAVNGATGHSSSLDAREVIPMAAVKQALREAGDEFELRYRRAFSDLTSQLHITPGTAYQSFEQVVNELFRDGVNWGRIVAFFSFGGALCVESVDKEMQVLVSRIAAWMATYLNDHLEPWIQENGGWDTFVELYGNNAAAESRKGQERFNRWFLTGMTVAGVVLLGSLFSRK
E3 ligase: VHL (UniProt P40337)
Ligase sequence: MPRRAENWDEAEVGAEEAGVEEYGPEEDGGEESGAEESGPEESGPEELGAEEEMEAGRPRPVLRSVNSREPSQVIFCNRSPRVVLPVWLNFDGEPQPYPTLPPGTGRRIHSYRGHLWLFRDAGTHDGLLVNQTELFVPSLNVDGQPIFANITLPVYTLKERCLQVVRSLVKPENYRRLDIVRSLYEDLEDHPNVQKDLERLTQERIAHQRMGD
Cell line: MOLT-4 (Homo sapiens)
Cell line description: African=0.38%; Native American=0%; East Asian, North=1.74%; East Asian, South=0%; South Asian=0.94%; European, North=68.08%; European, South=28.87%.
Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC
A*01 A*01 A*01
Instable (MSI-high).
In situ; Peripheral blood; 
Caucasian.
T-cell; CL=CL_0000084.
Cancer cell line
Assay time (hours): 48
DC50:  71 nM
Assay description: IC50's are for cell viability assays
Reference: https://pubmed.ncbi.nlm.nih.gov/32145645/
Source database: PROTACpedia
Compound (SMILES): Cc1ncsc1-c1ccc([C@H](C)NC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)CCCCCN2CCN(CC[C@H](CSc3ccccc3)Nc3ccc(S(=O)(=O)NC(=O)c4ccc(N5CCN(CC6=C(c7ccc(Cl)cc7)CCC(C)(C)C6)CC5)cc4)cc3S(=O)(=O)C(F)(F)F)CC2)C(C)(C)C)cc1
Modality: PROteolysis-TArgeting Chimera (PROTAC)
Target protein (POI): BCL-XL (UniProt Q07817)
POI sequence: MSQSNRELVVDFLSYKLSQKGYSWSQFSDVEENRTEAPEGTESEMETPSAINGNPSWHLADSPAVNGATGHSSSLDAREVIPMAAVKQALREAGDEFELRYRRAFSDLTSQLHITPGTAYQSFEQVVNELFRDGVNWGRIVAFFSFGGALCVESVDKEMQVLVSRIAAWMATYLNDHLEPWIQENGGWDTFVELYGNNAAAESRKGQERFNRWFLTGMTVAGVVLLGSLFSRK
E3 ligase: VHL (UniProt P40337)
Ligase sequence: MPRRAENWDEAEVGAEEAGVEEYGPEEDGGEESGAEESGPEESGPEELGAEEEMEAGRPRPVLRSVNSREPSQVIFCNRSPRVVLPVWLNFDGEPQPYPTLPPGTGRRIHSYRGHLWLFRDAGTHDGLLVNQTELFVPSLNVDGQPIFANITLPVYTLKERCLQVVRSLVKPENYRRLDIVRSLYEDLEDHPNVQKDLERLTQERIAHQRMGD
Cell line: MOLT-4 (Homo sapiens)
Cell line description: African=0.38%; Native American=0%; East Asian, North=1.74%; East Asian, South=0%; South Asian=0.94%; European, North=68.08%; European, South=28.87%.
Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC
A*01 A*01 A*01
Instable (MSI-high).
In situ; Peripheral blood; 
Caucasian.
T-cell; CL=CL_0000084.
Cancer cell line
Assay time (hours): 16
DC50:  93 nM
Assay description: Degradation of BCL-xL in MOLT-4 cells after 16 h treatment
Reference: 10.1016/j.ejmech.2020.112186
Source database: PROTAC-DB
Compound (SMILES): Cc1ncsc1-c1ccc([C@H](C)NC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)CCCCCN2CCN(CC[C@H](CSc3ccccc3)Nc3ccc(S(=O)(=O)NC(=O)c4ccc(N5CCN(CC6=C(c7ccc(Cl)cc7)CCC(C)(C)C6)CC5)cc4)cc3S(=O)(=O)C(F)(F)F)CC2)C(C)(C)C)cc1
Modality: PROteolysis-TArgeting Chimera (PROTAC)
Target protein (POI): BCL2L1 (UniProt Q07817)
POI sequence: MSQSNRELVVDFLSYKLSQKGYSWSQFSDVEENRTEAPEGTESEMETPSAINGNPSWHLADSPAVNGATGHSSSLDAREVIPMAAVKQALREAGDEFELRYRRAFSDLTSQLHITPGTAYQSFEQVVNELFRDGVNWGRIVAFFSFGGALCVESVDKEMQVLVSRIAAWMATYLNDHLEPWIQENGGWDTFVELYGNNAAAESRKGQERFNRWFLTGMTVAGVVLLGSLFSRK
E3 ligase: VHL (UniProt P40337)
Ligase sequence: MPRRAENWDEAEVGAEEAGVEEYGPEEDGGEESGAEESGPEESGPEELGAEEEMEAGRPRPVLRSVNSREPSQVIFCNRSPRVVLPVWLNFDGEPQPYPTLPPGTGRRIHSYRGHLWLFRDAGTHDGLLVNQTELFVPSLNVDGQPIFANITLPVYTLKERCLQVVRSLVKPENYRRLDIVRSLYEDLEDHPNVQKDLERLTQERIAHQRMGD
Cell line: MOLT-4 (Homo sapiens)
Cell line description: African=0.38%; Native American=0%; East Asian, North=1.74%; East Asian, South=0%; South Asian=0.94%; European, North=68.08%; European, South=28.87%.
Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC
A*01 A*01 A*01
Instable (MSI-high).
In situ; Peripheral blood; 
Caucasian.
T-cell; CL=CL_0000084.
Cancer cell line
Assay time (hours): 48
DC50:  93 nM
Assay description: IC50's are for cell viability assays
Reference: https://pubmed.ncbi.nlm.nih.gov/32145645/
Source database: PROTACpedia
Compound (SMILES): Cc1ncsc1-c1ccc([C@H](C)NC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)CCCCCN2CCN(CC[C@H](CSc3ccccc3)Nc3ccc(S(=O)(=O)NC(=O)c4ccc(N5CCN(CC6=C(c7ccc(Cl)cc7)CCC(C)(C)C6)CC5)cc4)cc3S(=O)(=O)C(F)(F)F)CC2)C(C)(C)C)cc1
Modality: PROteolysis-TArgeting Chimera (PROTAC)
Target protein (POI): BCL2L1 (UniProt Q07817)
POI sequence: MSQSNRELVVDFLSYKLSQKGYSWSQFSDVEENRTEAPEGTESEMETPSAINGNPSWHLADSPAVNGATGHSSSLDAREVIPMAAVKQALREAGDEFELRYRRAFSDLTSQLHITPGTAYQSFEQVVNELFRDGVNWGRIVAFFSFGGALCVESVDKEMQVLVSRIAAWMATYLNDHLEPWIQENGGWDTFVELYGNNAAAESRKGQERFNRWFLTGMTVAGVVLLGSLFSRK
E3 ligase: VHL (UniProt P40337)
Ligase sequence: MPRRAENWDEAEVGAEEAGVEEYGPEEDGGEESGAEESGPEESGPEELGAEEEMEAGRPRPVLRSVNSREPSQVIFCNRSPRVVLPVWLNFDGEPQPYPTLPPGTGRRIHSYRGHLWLFRDAGTHDGLLVNQTELFVPSLNVDGQPIFANITLPVYTLKERCLQVVRSLVKPENYRRLDIVRSLYEDLEDHPNVQKDLERLTQERIAHQRMGD
Cell line: MOLT-4 (Homo sapiens)
Cell line description: African=0.38%; Native American=0%; East Asian, North=1.74%; East Asian, South=0%; South Asian=0.94%; European, North=68.08%; European, South=28.87%.
Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC
A*01 A*01 A*01
Instable (MSI-high).
In situ; Peripheral blood; 
Caucasian.
T-cell; CL=CL_0000084.
Cancer cell line
Assay time (hours): 48
Dmax: ~ 90 %
Assay description: IC50's are for cell viability assays
Reference: https://pubmed.ncbi.nlm.nih.gov/32145645/
Source database: PROTACpedia
Compound (SMILES): Cc1ncsc1-c1ccc([C@H](C)NC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)CCCCCN2CCc3cc(O)c(N4CC(=O)NS4(=O)=O)c(F)c3CC2)C(C)(C)C)cc1
Modality: PROteolysis-TArgeting Chimera (PROTAC)
Target protein (POI): PTPN1 (UniProt P18031)
POI sequence: MEMEKEFEQIDKSGSWAAIYQDIRHEASDFPCRVAKLPKNKNRNRYRDVSPFDHSRIKLHQEDNDYINASLIKMEEAQRSYILTQGPLPNTCGHFWEMVWEQKSRGVVMLNRVMEKGSLKCAQYWPQKEEKEMIFEDTNLKLTLISEDIKSYYTVRQLELENLTTQETREILHFHYTTWPDFGVPESPASFLNFLFKVRESGSLSPEHGPVVVHCSAGIGRSGTFCLADTCLLLMDKRKDPSSVDIKKVLLEMRKFRMGLIQTADQLRFSYLAVIEGAKFIMGDSSVQDQWKELSHEDLEPPPEHIPPPPRPPKRILEPHNGKCREFFPNHQWVKEETQEDKDCPIKEEKGSPLNAAPYGIESMSQDTEVRSRVVGGSLRGAQAASPAKGEPSLPEKDEDHALSYWKPFLVNMCVATVLTAGAYLCYRFLFNSNT
E3 ligase: VHL (UniProt P40337)
Ligase sequence: MPRRAENWDEAEVGAEEAGVEEYGPEEDGGEESGAEESGPEESGPEELGAEEEMEAGRPRPVLRSVNSREPSQVIFCNRSPRVVLPVWLNFDGEPQPYPTLPPGTGRRIHSYRGHLWLFRDAGTHDGLLVNQTELFVPSLNVDGQPIFANITLPVYTLKERCLQVVRSLVKPENYRRLDIVRSLYEDLEDHPNVQKDLERLTQERIAHQRMGD
Cell line: Jurkat (Homo sapiens)
Cell line description: African=0.4%; Native American=0%; East Asian, North=0.13%; East Asian, South=1.21%; South Asian=1.08%; European, North=70.73%; European, South=26.45%.
Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC
A*03
Instable (MSI-high).
In situ; Peripheral blood; 
Caucasian.
Space-flown cell line (cellonaut).
T-cell; CL=CL_0000084.
Cancer cell line
Assay: HiBiT
DC50:  1640 nM
Assay description: Parental Jurkat cells (ATCC, TIB-152) were grown in complete RPMI medium consisting of RPMI 1640 Medium (Gibco, 61870036) supplemented with 10% fetal bovine serum (Gibco, 10082147) and 1x Pen Strep (Gibco, 15140122). The sequence encoding the HiBiT tag (Promega) was integrated into the 5' end of the coding sequence on both alleles of the PTPN2 gene in Jurkat cells by CRISPR to create the Jurkat-PTPN2-N-HiBiT cell line. The sequence for the HiBiT tag was integrated into the 3' end of the coding sequence on both alleles of the PTPN1 gene in Jurkat cells by CRISPR to create the Jurkat-PTPN1-C-HiBiT cell line.
Degradation of HiBiT-tagged proteins was monitored by luminescence using the Nano-Glo HiBiT Lytic Detection System (Promega, N3040). Five thousand cells per well of either Jurkat-PTPN2-N-HiBit or Jurkat-PTPN1-C-HiBiT were plated into white opaque OptiPlate-384 microplates (Perkin-Elmer, 6007290) in 25 μL complete RPMI medium. Compounds were added to the cells using a Tecan D300e Digital Dispenser. Cells were incubated for 24 hours in a humidified incubator at 37°C and 5% CO2. Following the 24 hour incubation, Nano-Glo HiBiT Lytic Reagent was added to cells and luminescence levels were read on a CLARIOstar Microplate Reader (BMG LABTECH). Each plate included a vehicle control (0.1% DMSO) from which % degradation for test compounds was calculated. A four-parameter curve fit was used to determine DC50 and Dmax values.
Reference: PROTEIN TYROSINE PHOSPHATASE DEGRADERS AND USES THEREOF (patent)
Source database: TPDdb
Compound (SMILES): Cc1ncsc1-c1ccc([C@H](C)NC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)CCCCCN2CCc3cc(O)c(N4CC(=O)NS4(=O)=O)c(F)c3CC2)C(C)(C)C)cc1
Modality: PROteolysis-TArgeting Chimera (PROTAC)
Target protein (POI): PTPN1 (UniProt P18031)
POI sequence: MEMEKEFEQIDKSGSWAAIYQDIRHEASDFPCRVAKLPKNKNRNRYRDVSPFDHSRIKLHQEDNDYINASLIKMEEAQRSYILTQGPLPNTCGHFWEMVWEQKSRGVVMLNRVMEKGSLKCAQYWPQKEEKEMIFEDTNLKLTLISEDIKSYYTVRQLELENLTTQETREILHFHYTTWPDFGVPESPASFLNFLFKVRESGSLSPEHGPVVVHCSAGIGRSGTFCLADTCLLLMDKRKDPSSVDIKKVLLEMRKFRMGLIQTADQLRFSYLAVIEGAKFIMGDSSVQDQWKELSHEDLEPPPEHIPPPPRPPKRILEPHNGKCREFFPNHQWVKEETQEDKDCPIKEEKGSPLNAAPYGIESMSQDTEVRSRVVGGSLRGAQAASPAKGEPSLPEKDEDHALSYWKPFLVNMCVATVLTAGAYLCYRFLFNSNT
E3 ligase: VHL (UniProt P40337)
Ligase sequence: MPRRAENWDEAEVGAEEAGVEEYGPEEDGGEESGAEESGPEESGPEELGAEEEMEAGRPRPVLRSVNSREPSQVIFCNRSPRVVLPVWLNFDGEPQPYPTLPPGTGRRIHSYRGHLWLFRDAGTHDGLLVNQTELFVPSLNVDGQPIFANITLPVYTLKERCLQVVRSLVKPENYRRLDIVRSLYEDLEDHPNVQKDLERLTQERIAHQRMGD
Cell line: Jurkat (Homo sapiens)
Cell line description: African=0.4%; Native American=0%; East Asian, North=0.13%; East Asian, South=1.21%; South Asian=1.08%; European, North=70.73%; European, South=26.45%.
Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC
A*03
Instable (MSI-high).
In situ; Peripheral blood; 
Caucasian.
Space-flown cell line (cellonaut).
T-cell; CL=CL_0000084.
Cancer cell line
Assay: HiBiT
Dmax:  68 %
Assay description: Parental Jurkat cells (ATCC, TIB-152) were grown in complete RPMI medium consisting of RPMI 1640 Medium (Gibco, 61870036) supplemented with 10% fetal bovine serum (Gibco, 10082147) and 1x Pen Strep (Gibco, 15140122). The sequence encoding the HiBiT tag (Promega) was integrated into the 5' end of the coding sequence on both alleles of the PTPN2 gene in Jurkat cells by CRISPR to create the Jurkat-PTPN2-N-HiBiT cell line. The sequence for the HiBiT tag was integrated into the 3' end of the coding sequence on both alleles of the PTPN1 gene in Jurkat cells by CRISPR to create the Jurkat-PTPN1-C-HiBiT cell line.
Degradation of HiBiT-tagged proteins was monitored by luminescence using the Nano-Glo HiBiT Lytic Detection System (Promega, N3040). Five thousand cells per well of either Jurkat-PTPN2-N-HiBit or Jurkat-PTPN1-C-HiBiT were plated into white opaque OptiPlate-384 microplates (Perkin-Elmer, 6007290) in 25 μL complete RPMI medium. Compounds were added to the cells using a Tecan D300e Digital Dispenser. Cells were incubated for 24 hours in a humidified incubator at 37°C and 5% CO2. Following the 24 hour incubation, Nano-Glo HiBiT Lytic Reagent was added to cells and luminescence levels were read on a CLARIOstar Microplate Reader (BMG LABTECH). Each plate included a vehicle control (0.1% DMSO) from which % degradation for test compounds was calculated. A four-parameter curve fit was used to determine DC50 and Dmax values.
Reference: PROTEIN TYROSINE PHOSPHATASE DEGRADERS AND USES THEREOF (patent)
Source database: TPDdb