ailab-bio/TACK huggingface dataset:
Compound (SMILES): O=C1CCC(Nc2ccc3c(c2)OCC32CCN(C[C@H]3CC[C@@H](OC4CCN(c5ccc([C@@H]6c7ccc(O)cc7CCC6c6ccccc6)cc5)CC4)CC3)CC2)C(=O)N1
Modality: PROteolysis-TArgeting Chimera (PROTAC)
Target protein (POI): ESR1 (UniProt P03372)
POI sequence: MTMTLHTKASGMALLHQIQGNELEPLNRPQLKIPLERPLGEVYLDSSKPAVYNYPEGAAYEFNAAAAANAQVYGQTGLPYGPGSEAAAFGSNGLGGFPPLNSVSPSPLMLLHPPPQLSPFLQPHGQQVPYYLENEPSGYTVREAGPPAFYRPNSDNRRQGGRERLASTNDKGSMAMESAKETRYCAVCNDYASGYHYGVWSCEGCKAFFKRSIQGHNDYMCPATNQCTIDKNRRKSCQACRLRKCYEVGMMKGGIRKDRRGGRMLKHKRQRDDGEGRGEVGSAGDMRAANLWPSPLMIKRSKKNSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWLEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGMVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITDTLIHLMAKAGLTLQQQHQRLAQLLLILSHIRHMSNKGMEHLYSMKCKNVVPLYDLLLEMLDAHRLHAPTSRGGASVEETDQSHLATAGSTSSHSLQKYYITGEAEGFPATV
E3 ligase: CRBN (UniProt Q96SW2)
Ligase sequence: MAGEGDQQDAAHNMGNHLPLLPAESEEEDEMEVEDQDSKEAKKPNIINFDTSLPTSHTYLGADMEEFHGRTLHDDDSCQVIPVLPQVMMILIPGQTLPLQLFHPQEVSMVRNLIQKDRTFAVLAYSNVQEREAQFGTTAEIYAYREEQDFGIEIVKVKAIGRQRFKVLELRTQSDGIQQAKVQILPECVLPSTMSAVQLESLNKCQIFPSKPVSREDQCSYKWWQKYQKRKFHCANLTSWPRWLYSLYDAETLMDRIKKQLREWDENLKDDSLPSNPIDFSYRVAACLPIDDVLRIQLLKIGSAIQRLRCELDIMNKCTSLCCKQCQETEITTKNEIFSLSLCGPMAAYVNPHGYVHETLTVYKACNLNLIGRPSTEHSWFPGYAWTVAQCKICASHIGWKFTATKKDMSPQKFWGLTRSALLPTIPDTEDEISPDKVILCL
Cell line: T-47D (Homo sapiens)
Cell line description: African=0.86%; Native American=1.2%; East Asian, North=3.03%; East Asian, South=1.59%; South Asian=8.04%; European, North=22.59%; European, South=62.69%.
Mutation; HGNC; HGNC Mutation; HGNC; HGNC
A*33 A*33 A*33
Stable (MSS).
CVCL_3945 ! T-47
Metastatic; Pleural effusion; 
Caucasian.
Cancer cell line
Assay: Western Blot
Dmax:  52.5 %
Treatment concentration: 10 nM
Assay description: PROTAC compounds disclosed in this invention degrade ERα in T-47D cells. T-47D cells were cultured in PRMI-1640 medium supplemented with 10% FBS at 37°C and 5% CO2 until they entered the logarithmic growth phase. T-47D cells were seeded at a density of 3×105 cells/well in 6-well plates and incubated at 37°C and 5% CO2 for 24 hours. After the cells adhered, 1 μL of compound solution in dimethyl sulfoxide (DMSO) (final concentration 0.15-1000 nM) was added and incubated for another 4 hours at 37°C and 5% CO2. After 4 hours, the medium was discarded, and each well was washed once with 1 mL of pre-chilled 1× DPBS. The cells were then lysed with 50 μL of RIPA lysis buffer and 1× protease inhibitor cocktail, incubated on ice for 20 minutes, and centrifuged at 14,000g at 4°C for 30 minutes. The supernatant was carefully removed and analyzed for ERα protein levels by immunoblotting.
Reference: CEREBELLAR PROTEIN E3 UBIQUITIN LIGASE INHIBITOR AND CHIMERIC COMPOUND TARGETING PROTEIN DEGRADATION (patent)
Source database: TPDdb
Compound (SMILES): O=C1CCC(Nc2ccc3c(c2)OC[C@@H]2CN(C4CC5(CCN(c6ccc([C@@H]7c8ccc(O)cc8CC[C@@H]7c7ccccc7)cc6)CC5)C4)CCN32)C(=O)N1
Modality: PROteolysis-TArgeting Chimera (PROTAC)
Target protein (POI): ESR1 (UniProt P03372)
POI sequence: MTMTLHTKASGMALLHQIQGNELEPLNRPQLKIPLERPLGEVYLDSSKPAVYNYPEGAAYEFNAAAAANAQVYGQTGLPYGPGSEAAAFGSNGLGGFPPLNSVSPSPLMLLHPPPQLSPFLQPHGQQVPYYLENEPSGYTVREAGPPAFYRPNSDNRRQGGRERLASTNDKGSMAMESAKETRYCAVCNDYASGYHYGVWSCEGCKAFFKRSIQGHNDYMCPATNQCTIDKNRRKSCQACRLRKCYEVGMMKGGIRKDRRGGRMLKHKRQRDDGEGRGEVGSAGDMRAANLWPSPLMIKRSKKNSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWLEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGMVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITDTLIHLMAKAGLTLQQQHQRLAQLLLILSHIRHMSNKGMEHLYSMKCKNVVPLYDLLLEMLDAHRLHAPTSRGGASVEETDQSHLATAGSTSSHSLQKYYITGEAEGFPATV
E3 ligase: CRBN (UniProt Q96SW2)
Ligase sequence: MAGEGDQQDAAHNMGNHLPLLPAESEEEDEMEVEDQDSKEAKKPNIINFDTSLPTSHTYLGADMEEFHGRTLHDDDSCQVIPVLPQVMMILIPGQTLPLQLFHPQEVSMVRNLIQKDRTFAVLAYSNVQEREAQFGTTAEIYAYREEQDFGIEIVKVKAIGRQRFKVLELRTQSDGIQQAKVQILPECVLPSTMSAVQLESLNKCQIFPSKPVSREDQCSYKWWQKYQKRKFHCANLTSWPRWLYSLYDAETLMDRIKKQLREWDENLKDDSLPSNPIDFSYRVAACLPIDDVLRIQLLKIGSAIQRLRCELDIMNKCTSLCCKQCQETEITTKNEIFSLSLCGPMAAYVNPHGYVHETLTVYKACNLNLIGRPSTEHSWFPGYAWTVAQCKICASHIGWKFTATKKDMSPQKFWGLTRSALLPTIPDTEDEISPDKVILCL
Cell line: T-47D (Homo sapiens)
Cell line description: African=0.86%; Native American=1.2%; East Asian, North=3.03%; East Asian, South=1.59%; South Asian=8.04%; European, North=22.59%; European, South=62.69%.
Mutation; HGNC; HGNC Mutation; HGNC; HGNC
A*33 A*33 A*33
Stable (MSS).
CVCL_3945 ! T-47
Metastatic; Pleural effusion; 
Caucasian.
Cancer cell line
Assay: Western Blot
Dmax:  21 %
Treatment concentration: 10 nM
Assay description: PROTAC compounds disclosed in this invention degrade ERα in T-47D cells. T-47D cells were cultured in PRMI-1640 medium supplemented with 10% FBS at 37°C and 5% CO2 until they entered the logarithmic growth phase. T-47D cells were seeded at a density of 3×105 cells/well in 6-well plates and incubated at 37°C and 5% CO2 for 24 hours. After the cells adhered, 1 μL of compound solution in dimethyl sulfoxide (DMSO) (final concentration 0.15-1000 nM) was added and incubated for another 4 hours at 37°C and 5% CO2. After 4 hours, the medium was discarded, and each well was washed once with 1 mL of pre-chilled 1× DPBS. The cells were then lysed with 50 μL of RIPA lysis buffer and 1× protease inhibitor cocktail, incubated on ice for 20 minutes, and centrifuged at 14,000g at 4°C for 30 minutes. The supernatant was carefully removed and analyzed for ERα protein levels by immunoblotting.
Reference: CEREBELLAR PROTEIN E3 UBIQUITIN LIGASE INHIBITOR AND CHIMERIC COMPOUND TARGETING PROTEIN DEGRADATION (patent)
Source database: TPDdb
Compound (SMILES): O=C1CCC(Nc2ccc3c(c2)OC[C@@H]2CN(C4CCC5(CC4)CN(c4ccc([C@@H]6c7ccc(O)cc7CC[C@@H]6c6ccccc6)cc4)C5)CCN32)C(=O)N1
Modality: PROteolysis-TArgeting Chimera (PROTAC)
Target protein (POI): ESR1 (UniProt P03372)
POI sequence: MTMTLHTKASGMALLHQIQGNELEPLNRPQLKIPLERPLGEVYLDSSKPAVYNYPEGAAYEFNAAAAANAQVYGQTGLPYGPGSEAAAFGSNGLGGFPPLNSVSPSPLMLLHPPPQLSPFLQPHGQQVPYYLENEPSGYTVREAGPPAFYRPNSDNRRQGGRERLASTNDKGSMAMESAKETRYCAVCNDYASGYHYGVWSCEGCKAFFKRSIQGHNDYMCPATNQCTIDKNRRKSCQACRLRKCYEVGMMKGGIRKDRRGGRMLKHKRQRDDGEGRGEVGSAGDMRAANLWPSPLMIKRSKKNSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWLEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGMVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITDTLIHLMAKAGLTLQQQHQRLAQLLLILSHIRHMSNKGMEHLYSMKCKNVVPLYDLLLEMLDAHRLHAPTSRGGASVEETDQSHLATAGSTSSHSLQKYYITGEAEGFPATV
E3 ligase: CRBN (UniProt Q96SW2)
Ligase sequence: MAGEGDQQDAAHNMGNHLPLLPAESEEEDEMEVEDQDSKEAKKPNIINFDTSLPTSHTYLGADMEEFHGRTLHDDDSCQVIPVLPQVMMILIPGQTLPLQLFHPQEVSMVRNLIQKDRTFAVLAYSNVQEREAQFGTTAEIYAYREEQDFGIEIVKVKAIGRQRFKVLELRTQSDGIQQAKVQILPECVLPSTMSAVQLESLNKCQIFPSKPVSREDQCSYKWWQKYQKRKFHCANLTSWPRWLYSLYDAETLMDRIKKQLREWDENLKDDSLPSNPIDFSYRVAACLPIDDVLRIQLLKIGSAIQRLRCELDIMNKCTSLCCKQCQETEITTKNEIFSLSLCGPMAAYVNPHGYVHETLTVYKACNLNLIGRPSTEHSWFPGYAWTVAQCKICASHIGWKFTATKKDMSPQKFWGLTRSALLPTIPDTEDEISPDKVILCL
Cell line: T-47D (Homo sapiens)
Cell line description: African=0.86%; Native American=1.2%; East Asian, North=3.03%; East Asian, South=1.59%; South Asian=8.04%; European, North=22.59%; European, South=62.69%.
Mutation; HGNC; HGNC Mutation; HGNC; HGNC
A*33 A*33 A*33
Stable (MSS).
CVCL_3945 ! T-47
Metastatic; Pleural effusion; 
Caucasian.
Cancer cell line
Assay: Western Blot
Dmax:  0.5 %
Treatment concentration: 10 nM
Assay description: PROTAC compounds disclosed in this invention degrade ERα in T-47D cells. T-47D cells were cultured in PRMI-1640 medium supplemented with 10% FBS at 37°C and 5% CO2 until they entered the logarithmic growth phase. T-47D cells were seeded at a density of 3×105 cells/well in 6-well plates and incubated at 37°C and 5% CO2 for 24 hours. After the cells adhered, 1 μL of compound solution in dimethyl sulfoxide (DMSO) (final concentration 0.15-1000 nM) was added and incubated for another 4 hours at 37°C and 5% CO2. After 4 hours, the medium was discarded, and each well was washed once with 1 mL of pre-chilled 1× DPBS. The cells were then lysed with 50 μL of RIPA lysis buffer and 1× protease inhibitor cocktail, incubated on ice for 20 minutes, and centrifuged at 14,000g at 4°C for 30 minutes. The supernatant was carefully removed and analyzed for ERα protein levels by immunoblotting.
Reference: CEREBELLAR PROTEIN E3 UBIQUITIN LIGASE INHIBITOR AND CHIMERIC COMPOUND TARGETING PROTEIN DEGRADATION (patent)
Source database: TPDdb
Compound (SMILES): O=C1CCC(n2c(=O)n3c4c(cccc42)N(C[C@H]2CC[C@@H](OC4CCN(c5ccc([C@@H]6c7ccc(O)cc7CC[C@@H]6c6ccccc6)cc5)CC4)CC2)CC3)C(=O)N1
Modality: PROteolysis-TArgeting Chimera (PROTAC)
Target protein (POI): ESR1 (UniProt P03372)
POI sequence: MTMTLHTKASGMALLHQIQGNELEPLNRPQLKIPLERPLGEVYLDSSKPAVYNYPEGAAYEFNAAAAANAQVYGQTGLPYGPGSEAAAFGSNGLGGFPPLNSVSPSPLMLLHPPPQLSPFLQPHGQQVPYYLENEPSGYTVREAGPPAFYRPNSDNRRQGGRERLASTNDKGSMAMESAKETRYCAVCNDYASGYHYGVWSCEGCKAFFKRSIQGHNDYMCPATNQCTIDKNRRKSCQACRLRKCYEVGMMKGGIRKDRRGGRMLKHKRQRDDGEGRGEVGSAGDMRAANLWPSPLMIKRSKKNSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWLEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGMVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITDTLIHLMAKAGLTLQQQHQRLAQLLLILSHIRHMSNKGMEHLYSMKCKNVVPLYDLLLEMLDAHRLHAPTSRGGASVEETDQSHLATAGSTSSHSLQKYYITGEAEGFPATV
E3 ligase: CRBN (UniProt Q96SW2)
Ligase sequence: MAGEGDQQDAAHNMGNHLPLLPAESEEEDEMEVEDQDSKEAKKPNIINFDTSLPTSHTYLGADMEEFHGRTLHDDDSCQVIPVLPQVMMILIPGQTLPLQLFHPQEVSMVRNLIQKDRTFAVLAYSNVQEREAQFGTTAEIYAYREEQDFGIEIVKVKAIGRQRFKVLELRTQSDGIQQAKVQILPECVLPSTMSAVQLESLNKCQIFPSKPVSREDQCSYKWWQKYQKRKFHCANLTSWPRWLYSLYDAETLMDRIKKQLREWDENLKDDSLPSNPIDFSYRVAACLPIDDVLRIQLLKIGSAIQRLRCELDIMNKCTSLCCKQCQETEITTKNEIFSLSLCGPMAAYVNPHGYVHETLTVYKACNLNLIGRPSTEHSWFPGYAWTVAQCKICASHIGWKFTATKKDMSPQKFWGLTRSALLPTIPDTEDEISPDKVILCL
Cell line: T-47D (Homo sapiens)
Cell line description: African=0.86%; Native American=1.2%; East Asian, North=3.03%; East Asian, South=1.59%; South Asian=8.04%; European, North=22.59%; European, South=62.69%.
Mutation; HGNC; HGNC Mutation; HGNC; HGNC
A*33 A*33 A*33
Stable (MSS).
CVCL_3945 ! T-47
Metastatic; Pleural effusion; 
Caucasian.
Cancer cell line
Assay: Western Blot
Dmax:  23 %
Treatment concentration: 10 nM
Assay description: PROTAC compounds disclosed in this invention degrade ERα in T-47D cells. T-47D cells were cultured in PRMI-1640 medium supplemented with 10% FBS at 37°C and 5% CO2 until they entered the logarithmic growth phase. T-47D cells were seeded at a density of 3×105 cells/well in 6-well plates and incubated at 37°C and 5% CO2 for 24 hours. After the cells adhered, 1 μL of compound solution in dimethyl sulfoxide (DMSO) (final concentration 0.15-1000 nM) was added and incubated for another 4 hours at 37°C and 5% CO2. After 4 hours, the medium was discarded, and each well was washed once with 1 mL of pre-chilled 1× DPBS. The cells were then lysed with 50 μL of RIPA lysis buffer and 1× protease inhibitor cocktail, incubated on ice for 20 minutes, and centrifuged at 14,000g at 4°C for 30 minutes. The supernatant was carefully removed and analyzed for ERα protein levels by immunoblotting.
Reference: CEREBELLAR PROTEIN E3 UBIQUITIN LIGASE INHIBITOR AND CHIMERIC COMPOUND TARGETING PROTEIN DEGRADATION (patent)
Source database: TPDdb
Compound (SMILES): O=C1CC[C@H](N2Cc3cc(N4CCN(CC5CCN(c6ccc([C@@H]7c8ccc(O)cc8CC[C@@H]7c7ccccc7)cc6)CC5)CC4)ccc3C2=O)C(=O)N1
Modality: PROteolysis-TArgeting Chimera (PROTAC)
Target protein (POI): ER (UniProt P03372)
POI sequence: MTMTLHTKASGMALLHQIQGNELEPLNRPQLKIPLERPLGEVYLDSSKPAVYNYPEGAAYEFNAAAAANAQVYGQTGLPYGPGSEAAAFGSNGLGGFPPLNSVSPSPLMLLHPPPQLSPFLQPHGQQVPYYLENEPSGYTVREAGPPAFYRPNSDNRRQGGRERLASTNDKGSMAMESAKETRYCAVCNDYASGYHYGVWSCEGCKAFFKRSIQGHNDYMCPATNQCTIDKNRRKSCQACRLRKCYEVGMMKGGIRKDRRGGRMLKHKRQRDDGEGRGEVGSAGDMRAANLWPSPLMIKRSKKNSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWLEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGMVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITDTLIHLMAKAGLTLQQQHQRLAQLLLILSHIRHMSNKGMEHLYSMKCKNVVPLYDLLLEMLDAHRLHAPTSRGGASVEETDQSHLATAGSTSSHSLQKYYITGEAEGFPATV
E3 ligase: CRBN (UniProt Q96SW2)
Ligase sequence: MAGEGDQQDAAHNMGNHLPLLPAESEEEDEMEVEDQDSKEAKKPNIINFDTSLPTSHTYLGADMEEFHGRTLHDDDSCQVIPVLPQVMMILIPGQTLPLQLFHPQEVSMVRNLIQKDRTFAVLAYSNVQEREAQFGTTAEIYAYREEQDFGIEIVKVKAIGRQRFKVLELRTQSDGIQQAKVQILPECVLPSTMSAVQLESLNKCQIFPSKPVSREDQCSYKWWQKYQKRKFHCANLTSWPRWLYSLYDAETLMDRIKKQLREWDENLKDDSLPSNPIDFSYRVAACLPIDDVLRIQLLKIGSAIQRLRCELDIMNKCTSLCCKQCQETEITTKNEIFSLSLCGPMAAYVNPHGYVHETLTVYKACNLNLIGRPSTEHSWFPGYAWTVAQCKICASHIGWKFTATKKDMSPQKFWGLTRSALLPTIPDTEDEISPDKVILCL
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
DC50:  2 nM
Assay description: Degradation of ER in ER-positive breast cancer cell lines
Reference: 10.1158/1538-7445.SABCS18-P5-04-18
Source database: PROTAC-DB
Compound (SMILES): O=C1CC[C@H](NC(=O)c2cc3c(cc2F)N2CCN(C[C@H]4CC[C@@H](OC5CCN(c6ccc([C@@H]7c8ccc(O)cc8CC[C@@H]7c7ccccc7)cc6)CC5)CC4)C[C@@H]2CO3)C(=O)N1
Modality: PROteolysis-TArgeting Chimera (PROTAC)
Target protein (POI): ESR1 (UniProt P03372)
POI sequence: MTMTLHTKASGMALLHQIQGNELEPLNRPQLKIPLERPLGEVYLDSSKPAVYNYPEGAAYEFNAAAAANAQVYGQTGLPYGPGSEAAAFGSNGLGGFPPLNSVSPSPLMLLHPPPQLSPFLQPHGQQVPYYLENEPSGYTVREAGPPAFYRPNSDNRRQGGRERLASTNDKGSMAMESAKETRYCAVCNDYASGYHYGVWSCEGCKAFFKRSIQGHNDYMCPATNQCTIDKNRRKSCQACRLRKCYEVGMMKGGIRKDRRGGRMLKHKRQRDDGEGRGEVGSAGDMRAANLWPSPLMIKRSKKNSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWLEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGMVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITDTLIHLMAKAGLTLQQQHQRLAQLLLILSHIRHMSNKGMEHLYSMKCKNVVPLYDLLLEMLDAHRLHAPTSRGGASVEETDQSHLATAGSTSSHSLQKYYITGEAEGFPATV
E3 ligase: CRBN (UniProt Q96SW2)
Ligase sequence: MAGEGDQQDAAHNMGNHLPLLPAESEEEDEMEVEDQDSKEAKKPNIINFDTSLPTSHTYLGADMEEFHGRTLHDDDSCQVIPVLPQVMMILIPGQTLPLQLFHPQEVSMVRNLIQKDRTFAVLAYSNVQEREAQFGTTAEIYAYREEQDFGIEIVKVKAIGRQRFKVLELRTQSDGIQQAKVQILPECVLPSTMSAVQLESLNKCQIFPSKPVSREDQCSYKWWQKYQKRKFHCANLTSWPRWLYSLYDAETLMDRIKKQLREWDENLKDDSLPSNPIDFSYRVAACLPIDDVLRIQLLKIGSAIQRLRCELDIMNKCTSLCCKQCQETEITTKNEIFSLSLCGPMAAYVNPHGYVHETLTVYKACNLNLIGRPSTEHSWFPGYAWTVAQCKICASHIGWKFTATKKDMSPQKFWGLTRSALLPTIPDTEDEISPDKVILCL
Cell line: T-47D (Homo sapiens)
Cell line description: African=0.86%; Native American=1.2%; East Asian, North=3.03%; East Asian, South=1.59%; South Asian=8.04%; European, North=22.59%; European, South=62.69%.
Mutation; HGNC; HGNC Mutation; HGNC; HGNC
A*33 A*33 A*33
Stable (MSS).
CVCL_3945 ! T-47
Metastatic; Pleural effusion; 
Caucasian.
Cancer cell line
Assay: Western Blot
Dmax:  13 %
Treatment concentration: 10 nM
Assay description: PROTAC compounds disclosed in this invention degrade ERα in T-47D cells. T-47D cells were cultured in PRMI-1640 medium supplemented with 10% FBS at 37°C and 5% CO2 until they entered the logarithmic growth phase. T-47D cells were seeded at a density of 3×105 cells/well in 6-well plates and incubated at 37°C and 5% CO2 for 24 hours. After the cells adhered, 1 μL of compound solution in dimethyl sulfoxide (DMSO) (final concentration 0.15-1000 nM) was added and incubated for another 4 hours at 37°C and 5% CO2. After 4 hours, the medium was discarded, and each well was washed once with 1 mL of pre-chilled 1× DPBS. The cells were then lysed with 50 μL of RIPA lysis buffer and 1× protease inhibitor cocktail, incubated on ice for 20 minutes, and centrifuged at 14,000g at 4°C for 30 minutes. The supernatant was carefully removed and analyzed for ERα protein levels by immunoblotting.
Reference: CEREBELLAR PROTEIN E3 UBIQUITIN LIGASE INHIBITOR AND CHIMERIC COMPOUND TARGETING PROTEIN DEGRADATION (patent)
Source database: TPDdb
Compound (SMILES): O=C1CC[C@H](NC(=O)c2ccc3c(c2)OCC[C@H]2CN(CC4CCC(OC5CCN(c6ccc([C@@H]7c8ccc(O)cc8CC[C@@H]7c7ccccc7)cc6)CC5)CC4)CCN32)C(=O)N1
Modality: PROteolysis-TArgeting Chimera (PROTAC)
Target protein (POI): ESR1 (UniProt P03372)
POI sequence: MTMTLHTKASGMALLHQIQGNELEPLNRPQLKIPLERPLGEVYLDSSKPAVYNYPEGAAYEFNAAAAANAQVYGQTGLPYGPGSEAAAFGSNGLGGFPPLNSVSPSPLMLLHPPPQLSPFLQPHGQQVPYYLENEPSGYTVREAGPPAFYRPNSDNRRQGGRERLASTNDKGSMAMESAKETRYCAVCNDYASGYHYGVWSCEGCKAFFKRSIQGHNDYMCPATNQCTIDKNRRKSCQACRLRKCYEVGMMKGGIRKDRRGGRMLKHKRQRDDGEGRGEVGSAGDMRAANLWPSPLMIKRSKKNSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWLEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGMVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITDTLIHLMAKAGLTLQQQHQRLAQLLLILSHIRHMSNKGMEHLYSMKCKNVVPLYDLLLEMLDAHRLHAPTSRGGASVEETDQSHLATAGSTSSHSLQKYYITGEAEGFPATV
E3 ligase: CRBN (UniProt Q96SW2)
Ligase sequence: MAGEGDQQDAAHNMGNHLPLLPAESEEEDEMEVEDQDSKEAKKPNIINFDTSLPTSHTYLGADMEEFHGRTLHDDDSCQVIPVLPQVMMILIPGQTLPLQLFHPQEVSMVRNLIQKDRTFAVLAYSNVQEREAQFGTTAEIYAYREEQDFGIEIVKVKAIGRQRFKVLELRTQSDGIQQAKVQILPECVLPSTMSAVQLESLNKCQIFPSKPVSREDQCSYKWWQKYQKRKFHCANLTSWPRWLYSLYDAETLMDRIKKQLREWDENLKDDSLPSNPIDFSYRVAACLPIDDVLRIQLLKIGSAIQRLRCELDIMNKCTSLCCKQCQETEITTKNEIFSLSLCGPMAAYVNPHGYVHETLTVYKACNLNLIGRPSTEHSWFPGYAWTVAQCKICASHIGWKFTATKKDMSPQKFWGLTRSALLPTIPDTEDEISPDKVILCL
Cell line: T-47D (Homo sapiens)
Cell line description: African=0.86%; Native American=1.2%; East Asian, North=3.03%; East Asian, South=1.59%; South Asian=8.04%; European, North=22.59%; European, South=62.69%.
Mutation; HGNC; HGNC Mutation; HGNC; HGNC
A*33 A*33 A*33
Stable (MSS).
CVCL_3945 ! T-47
Metastatic; Pleural effusion; 
Caucasian.
Cancer cell line
Assay: Western Blot
Dmax:  -4 %
Treatment concentration: 10 nM
Assay description: PROTAC compounds disclosed in this invention degrade ERα in T-47D cells. T-47D cells were cultured in PRMI-1640 medium supplemented with 10% FBS at 37°C and 5% CO2 until they entered the logarithmic growth phase. T-47D cells were seeded at a density of 3×105 cells/well in 6-well plates and incubated at 37°C and 5% CO2 for 24 hours. After the cells adhered, 1 μL of compound solution in dimethyl sulfoxide (DMSO) (final concentration 0.15-1000 nM) was added and incubated for another 4 hours at 37°C and 5% CO2. After 4 hours, the medium was discarded, and each well was washed once with 1 mL of pre-chilled 1× DPBS. The cells were then lysed with 50 μL of RIPA lysis buffer and 1× protease inhibitor cocktail, incubated on ice for 20 minutes, and centrifuged at 14,000g at 4°C for 30 minutes. The supernatant was carefully removed and analyzed for ERα protein levels by immunoblotting.
Reference: CEREBELLAR PROTEIN E3 UBIQUITIN LIGASE INHIBITOR AND CHIMERIC COMPOUND TARGETING PROTEIN DEGRADATION (patent)
Source database: TPDdb
Compound (SMILES): O=C1CC[C@H](NC(=O)c2ccc3c(c2)OC[C@@H]2CN(C[C@H]4CC[C@@H](OC5CCN(c6ccc([C@@H]7c8ccc(O)cc8CC[C@@H]7c7ccccc7)cc6)CC5)CC4)CCN32)C(=O)N1
Modality: PROteolysis-TArgeting Chimera (PROTAC)
Target protein (POI): ESR1 (UniProt P03372)
POI sequence: MTMTLHTKASGMALLHQIQGNELEPLNRPQLKIPLERPLGEVYLDSSKPAVYNYPEGAAYEFNAAAAANAQVYGQTGLPYGPGSEAAAFGSNGLGGFPPLNSVSPSPLMLLHPPPQLSPFLQPHGQQVPYYLENEPSGYTVREAGPPAFYRPNSDNRRQGGRERLASTNDKGSMAMESAKETRYCAVCNDYASGYHYGVWSCEGCKAFFKRSIQGHNDYMCPATNQCTIDKNRRKSCQACRLRKCYEVGMMKGGIRKDRRGGRMLKHKRQRDDGEGRGEVGSAGDMRAANLWPSPLMIKRSKKNSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWLEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGMVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITDTLIHLMAKAGLTLQQQHQRLAQLLLILSHIRHMSNKGMEHLYSMKCKNVVPLYDLLLEMLDAHRLHAPTSRGGASVEETDQSHLATAGSTSSHSLQKYYITGEAEGFPATV
E3 ligase: CRBN (UniProt Q96SW2)
Ligase sequence: MAGEGDQQDAAHNMGNHLPLLPAESEEEDEMEVEDQDSKEAKKPNIINFDTSLPTSHTYLGADMEEFHGRTLHDDDSCQVIPVLPQVMMILIPGQTLPLQLFHPQEVSMVRNLIQKDRTFAVLAYSNVQEREAQFGTTAEIYAYREEQDFGIEIVKVKAIGRQRFKVLELRTQSDGIQQAKVQILPECVLPSTMSAVQLESLNKCQIFPSKPVSREDQCSYKWWQKYQKRKFHCANLTSWPRWLYSLYDAETLMDRIKKQLREWDENLKDDSLPSNPIDFSYRVAACLPIDDVLRIQLLKIGSAIQRLRCELDIMNKCTSLCCKQCQETEITTKNEIFSLSLCGPMAAYVNPHGYVHETLTVYKACNLNLIGRPSTEHSWFPGYAWTVAQCKICASHIGWKFTATKKDMSPQKFWGLTRSALLPTIPDTEDEISPDKVILCL
Cell line: T-47D (Homo sapiens)
Cell line description: African=0.86%; Native American=1.2%; East Asian, North=3.03%; East Asian, South=1.59%; South Asian=8.04%; European, North=22.59%; European, South=62.69%.
Mutation; HGNC; HGNC Mutation; HGNC; HGNC
A*33 A*33 A*33
Stable (MSS).
CVCL_3945 ! T-47
Metastatic; Pleural effusion; 
Caucasian.
Cancer cell line
Assay: Western Blot
Dmax:  5.5 %
Treatment concentration: 10 nM
Assay description: PROTAC compounds disclosed in this invention degrade ERα in T-47D cells. T-47D cells were cultured in PRMI-1640 medium supplemented with 10% FBS at 37°C and 5% CO2 until they entered the logarithmic growth phase. T-47D cells were seeded at a density of 3×105 cells/well in 6-well plates and incubated at 37°C and 5% CO2 for 24 hours. After the cells adhered, 1 μL of compound solution in dimethyl sulfoxide (DMSO) (final concentration 0.15-1000 nM) was added and incubated for another 4 hours at 37°C and 5% CO2. After 4 hours, the medium was discarded, and each well was washed once with 1 mL of pre-chilled 1× DPBS. The cells were then lysed with 50 μL of RIPA lysis buffer and 1× protease inhibitor cocktail, incubated on ice for 20 minutes, and centrifuged at 14,000g at 4°C for 30 minutes. The supernatant was carefully removed and analyzed for ERα protein levels by immunoblotting.
Reference: CEREBELLAR PROTEIN E3 UBIQUITIN LIGASE INHIBITOR AND CHIMERIC COMPOUND TARGETING PROTEIN DEGRADATION (patent)
Source database: TPDdb
Compound (SMILES): O=C1CC[C@H](NC(=O)c2ccc3c(c2F)OCC32CCN(C3CC4(CCN(c5ccc([C@@H]6c7ccc(O)cc7CC[C@@H]6c6ccccc6)cc5)CC4)C3)CC2)C(=O)N1
Modality: PROteolysis-TArgeting Chimera (PROTAC)
Target protein (POI): ESR1 (UniProt P03372)
POI sequence: MTMTLHTKASGMALLHQIQGNELEPLNRPQLKIPLERPLGEVYLDSSKPAVYNYPEGAAYEFNAAAAANAQVYGQTGLPYGPGSEAAAFGSNGLGGFPPLNSVSPSPLMLLHPPPQLSPFLQPHGQQVPYYLENEPSGYTVREAGPPAFYRPNSDNRRQGGRERLASTNDKGSMAMESAKETRYCAVCNDYASGYHYGVWSCEGCKAFFKRSIQGHNDYMCPATNQCTIDKNRRKSCQACRLRKCYEVGMMKGGIRKDRRGGRMLKHKRQRDDGEGRGEVGSAGDMRAANLWPSPLMIKRSKKNSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWLEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGMVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITDTLIHLMAKAGLTLQQQHQRLAQLLLILSHIRHMSNKGMEHLYSMKCKNVVPLYDLLLEMLDAHRLHAPTSRGGASVEETDQSHLATAGSTSSHSLQKYYITGEAEGFPATV
E3 ligase: CRBN (UniProt Q96SW2)
Ligase sequence: MAGEGDQQDAAHNMGNHLPLLPAESEEEDEMEVEDQDSKEAKKPNIINFDTSLPTSHTYLGADMEEFHGRTLHDDDSCQVIPVLPQVMMILIPGQTLPLQLFHPQEVSMVRNLIQKDRTFAVLAYSNVQEREAQFGTTAEIYAYREEQDFGIEIVKVKAIGRQRFKVLELRTQSDGIQQAKVQILPECVLPSTMSAVQLESLNKCQIFPSKPVSREDQCSYKWWQKYQKRKFHCANLTSWPRWLYSLYDAETLMDRIKKQLREWDENLKDDSLPSNPIDFSYRVAACLPIDDVLRIQLLKIGSAIQRLRCELDIMNKCTSLCCKQCQETEITTKNEIFSLSLCGPMAAYVNPHGYVHETLTVYKACNLNLIGRPSTEHSWFPGYAWTVAQCKICASHIGWKFTATKKDMSPQKFWGLTRSALLPTIPDTEDEISPDKVILCL
Cell line: T-47D (Homo sapiens)
Cell line description: African=0.86%; Native American=1.2%; East Asian, North=3.03%; East Asian, South=1.59%; South Asian=8.04%; European, North=22.59%; European, South=62.69%.
Mutation; HGNC; HGNC Mutation; HGNC; HGNC
A*33 A*33 A*33
Stable (MSS).
CVCL_3945 ! T-47
Metastatic; Pleural effusion; 
Caucasian.
Cancer cell line
Assay: Western Blot
Dmax:  5 %
Treatment concentration: 10 nM
Assay description: PROTAC compounds disclosed in this invention degrade ERα in T-47D cells. T-47D cells were cultured in PRMI-1640 medium supplemented with 10% FBS at 37°C and 5% CO2 until they entered the logarithmic growth phase. T-47D cells were seeded at a density of 3×105 cells/well in 6-well plates and incubated at 37°C and 5% CO2 for 24 hours. After the cells adhered, 1 μL of compound solution in dimethyl sulfoxide (DMSO) (final concentration 0.15-1000 nM) was added and incubated for another 4 hours at 37°C and 5% CO2. After 4 hours, the medium was discarded, and each well was washed once with 1 mL of pre-chilled 1× DPBS. The cells were then lysed with 50 μL of RIPA lysis buffer and 1× protease inhibitor cocktail, incubated on ice for 20 minutes, and centrifuged at 14,000g at 4°C for 30 minutes. The supernatant was carefully removed and analyzed for ERα protein levels by immunoblotting.
Reference: CEREBELLAR PROTEIN E3 UBIQUITIN LIGASE INHIBITOR AND CHIMERIC COMPOUND TARGETING PROTEIN DEGRADATION (patent)
Source database: TPDdb
Compound (SMILES): O=C1CC[C@H](NC(=O)c2ccc3c(c2F)OCC32CCN(C3CCC4(CC3)CCN(c3ccc([C@@H]5c6ccc(O)cc6CC[C@@H]5c5ccccc5)cc3)CC4)CC2)C(=O)N1
Modality: PROteolysis-TArgeting Chimera (PROTAC)
Target protein (POI): ESR1 (UniProt P03372)
POI sequence: MTMTLHTKASGMALLHQIQGNELEPLNRPQLKIPLERPLGEVYLDSSKPAVYNYPEGAAYEFNAAAAANAQVYGQTGLPYGPGSEAAAFGSNGLGGFPPLNSVSPSPLMLLHPPPQLSPFLQPHGQQVPYYLENEPSGYTVREAGPPAFYRPNSDNRRQGGRERLASTNDKGSMAMESAKETRYCAVCNDYASGYHYGVWSCEGCKAFFKRSIQGHNDYMCPATNQCTIDKNRRKSCQACRLRKCYEVGMMKGGIRKDRRGGRMLKHKRQRDDGEGRGEVGSAGDMRAANLWPSPLMIKRSKKNSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWLEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGMVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITDTLIHLMAKAGLTLQQQHQRLAQLLLILSHIRHMSNKGMEHLYSMKCKNVVPLYDLLLEMLDAHRLHAPTSRGGASVEETDQSHLATAGSTSSHSLQKYYITGEAEGFPATV
E3 ligase: CRBN (UniProt Q96SW2)
Ligase sequence: MAGEGDQQDAAHNMGNHLPLLPAESEEEDEMEVEDQDSKEAKKPNIINFDTSLPTSHTYLGADMEEFHGRTLHDDDSCQVIPVLPQVMMILIPGQTLPLQLFHPQEVSMVRNLIQKDRTFAVLAYSNVQEREAQFGTTAEIYAYREEQDFGIEIVKVKAIGRQRFKVLELRTQSDGIQQAKVQILPECVLPSTMSAVQLESLNKCQIFPSKPVSREDQCSYKWWQKYQKRKFHCANLTSWPRWLYSLYDAETLMDRIKKQLREWDENLKDDSLPSNPIDFSYRVAACLPIDDVLRIQLLKIGSAIQRLRCELDIMNKCTSLCCKQCQETEITTKNEIFSLSLCGPMAAYVNPHGYVHETLTVYKACNLNLIGRPSTEHSWFPGYAWTVAQCKICASHIGWKFTATKKDMSPQKFWGLTRSALLPTIPDTEDEISPDKVILCL
Cell line: T-47D (Homo sapiens)
Cell line description: African=0.86%; Native American=1.2%; East Asian, North=3.03%; East Asian, South=1.59%; South Asian=8.04%; European, North=22.59%; European, South=62.69%.
Mutation; HGNC; HGNC Mutation; HGNC; HGNC
A*33 A*33 A*33
Stable (MSS).
CVCL_3945 ! T-47
Metastatic; Pleural effusion; 
Caucasian.
Cancer cell line
Assay: Western Blot
Dmax:  -5 %
Treatment concentration: 10 nM
Assay description: PROTAC compounds disclosed in this invention degrade ERα in T-47D cells. T-47D cells were cultured in PRMI-1640 medium supplemented with 10% FBS at 37°C and 5% CO2 until they entered the logarithmic growth phase. T-47D cells were seeded at a density of 3×105 cells/well in 6-well plates and incubated at 37°C and 5% CO2 for 24 hours. After the cells adhered, 1 μL of compound solution in dimethyl sulfoxide (DMSO) (final concentration 0.15-1000 nM) was added and incubated for another 4 hours at 37°C and 5% CO2. After 4 hours, the medium was discarded, and each well was washed once with 1 mL of pre-chilled 1× DPBS. The cells were then lysed with 50 μL of RIPA lysis buffer and 1× protease inhibitor cocktail, incubated on ice for 20 minutes, and centrifuged at 14,000g at 4°C for 30 minutes. The supernatant was carefully removed and analyzed for ERα protein levels by immunoblotting.
Reference: CEREBELLAR PROTEIN E3 UBIQUITIN LIGASE INHIBITOR AND CHIMERIC COMPOUND TARGETING PROTEIN DEGRADATION (patent)
Source database: TPDdb
Compound (SMILES): O=C1CC[C@H](NC(=O)c2ccc3c(c2F)OCC32CCN(C3CCC4(CC3)CN(c3ccc([C@@H]5c6ccc(O)cc6CC[C@@H]5c5ccccc5)cc3)C4)CC2)C(=O)N1
Modality: PROteolysis-TArgeting Chimera (PROTAC)
Target protein (POI): ESR1 (UniProt P03372)
POI sequence: MTMTLHTKASGMALLHQIQGNELEPLNRPQLKIPLERPLGEVYLDSSKPAVYNYPEGAAYEFNAAAAANAQVYGQTGLPYGPGSEAAAFGSNGLGGFPPLNSVSPSPLMLLHPPPQLSPFLQPHGQQVPYYLENEPSGYTVREAGPPAFYRPNSDNRRQGGRERLASTNDKGSMAMESAKETRYCAVCNDYASGYHYGVWSCEGCKAFFKRSIQGHNDYMCPATNQCTIDKNRRKSCQACRLRKCYEVGMMKGGIRKDRRGGRMLKHKRQRDDGEGRGEVGSAGDMRAANLWPSPLMIKRSKKNSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWLEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGMVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITDTLIHLMAKAGLTLQQQHQRLAQLLLILSHIRHMSNKGMEHLYSMKCKNVVPLYDLLLEMLDAHRLHAPTSRGGASVEETDQSHLATAGSTSSHSLQKYYITGEAEGFPATV
E3 ligase: CRBN (UniProt Q96SW2)
Ligase sequence: MAGEGDQQDAAHNMGNHLPLLPAESEEEDEMEVEDQDSKEAKKPNIINFDTSLPTSHTYLGADMEEFHGRTLHDDDSCQVIPVLPQVMMILIPGQTLPLQLFHPQEVSMVRNLIQKDRTFAVLAYSNVQEREAQFGTTAEIYAYREEQDFGIEIVKVKAIGRQRFKVLELRTQSDGIQQAKVQILPECVLPSTMSAVQLESLNKCQIFPSKPVSREDQCSYKWWQKYQKRKFHCANLTSWPRWLYSLYDAETLMDRIKKQLREWDENLKDDSLPSNPIDFSYRVAACLPIDDVLRIQLLKIGSAIQRLRCELDIMNKCTSLCCKQCQETEITTKNEIFSLSLCGPMAAYVNPHGYVHETLTVYKACNLNLIGRPSTEHSWFPGYAWTVAQCKICASHIGWKFTATKKDMSPQKFWGLTRSALLPTIPDTEDEISPDKVILCL
Cell line: T-47D (Homo sapiens)
Cell line description: African=0.86%; Native American=1.2%; East Asian, North=3.03%; East Asian, South=1.59%; South Asian=8.04%; European, North=22.59%; European, South=62.69%.
Mutation; HGNC; HGNC Mutation; HGNC; HGNC
A*33 A*33 A*33
Stable (MSS).
CVCL_3945 ! T-47
Metastatic; Pleural effusion; 
Caucasian.
Cancer cell line
Assay: Western Blot
Dmax:  2 %
Treatment concentration: 10 nM
Assay description: PROTAC compounds disclosed in this invention degrade ERα in T-47D cells. T-47D cells were cultured in PRMI-1640 medium supplemented with 10% FBS at 37°C and 5% CO2 until they entered the logarithmic growth phase. T-47D cells were seeded at a density of 3×105 cells/well in 6-well plates and incubated at 37°C and 5% CO2 for 24 hours. After the cells adhered, 1 μL of compound solution in dimethyl sulfoxide (DMSO) (final concentration 0.15-1000 nM) was added and incubated for another 4 hours at 37°C and 5% CO2. After 4 hours, the medium was discarded, and each well was washed once with 1 mL of pre-chilled 1× DPBS. The cells were then lysed with 50 μL of RIPA lysis buffer and 1× protease inhibitor cocktail, incubated on ice for 20 minutes, and centrifuged at 14,000g at 4°C for 30 minutes. The supernatant was carefully removed and analyzed for ERα protein levels by immunoblotting.
Reference: CEREBELLAR PROTEIN E3 UBIQUITIN LIGASE INHIBITOR AND CHIMERIC COMPOUND TARGETING PROTEIN DEGRADATION (patent)
Source database: TPDdb
Compound (SMILES): O=C1CC[C@H](NC(=O)c2ccc3c(c2F)OCC32CCN(CC3CCN(c4ccc([C@@H]5c6ccc(O)cc6CC[C@@H]5c5ccccc5)cc4)CC3)CC2)C(=O)N1
Modality: PROteolysis-TArgeting Chimera (PROTAC)
Target protein (POI): ESR1 (UniProt P03372)
POI sequence: MTMTLHTKASGMALLHQIQGNELEPLNRPQLKIPLERPLGEVYLDSSKPAVYNYPEGAAYEFNAAAAANAQVYGQTGLPYGPGSEAAAFGSNGLGGFPPLNSVSPSPLMLLHPPPQLSPFLQPHGQQVPYYLENEPSGYTVREAGPPAFYRPNSDNRRQGGRERLASTNDKGSMAMESAKETRYCAVCNDYASGYHYGVWSCEGCKAFFKRSIQGHNDYMCPATNQCTIDKNRRKSCQACRLRKCYEVGMMKGGIRKDRRGGRMLKHKRQRDDGEGRGEVGSAGDMRAANLWPSPLMIKRSKKNSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWLEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGMVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITDTLIHLMAKAGLTLQQQHQRLAQLLLILSHIRHMSNKGMEHLYSMKCKNVVPLYDLLLEMLDAHRLHAPTSRGGASVEETDQSHLATAGSTSSHSLQKYYITGEAEGFPATV
E3 ligase: CRBN (UniProt Q96SW2)
Ligase sequence: MAGEGDQQDAAHNMGNHLPLLPAESEEEDEMEVEDQDSKEAKKPNIINFDTSLPTSHTYLGADMEEFHGRTLHDDDSCQVIPVLPQVMMILIPGQTLPLQLFHPQEVSMVRNLIQKDRTFAVLAYSNVQEREAQFGTTAEIYAYREEQDFGIEIVKVKAIGRQRFKVLELRTQSDGIQQAKVQILPECVLPSTMSAVQLESLNKCQIFPSKPVSREDQCSYKWWQKYQKRKFHCANLTSWPRWLYSLYDAETLMDRIKKQLREWDENLKDDSLPSNPIDFSYRVAACLPIDDVLRIQLLKIGSAIQRLRCELDIMNKCTSLCCKQCQETEITTKNEIFSLSLCGPMAAYVNPHGYVHETLTVYKACNLNLIGRPSTEHSWFPGYAWTVAQCKICASHIGWKFTATKKDMSPQKFWGLTRSALLPTIPDTEDEISPDKVILCL
Cell line: T-47D (Homo sapiens)
Cell line description: African=0.86%; Native American=1.2%; East Asian, North=3.03%; East Asian, South=1.59%; South Asian=8.04%; European, North=22.59%; European, South=62.69%.
Mutation; HGNC; HGNC Mutation; HGNC; HGNC
A*33 A*33 A*33
Stable (MSS).
CVCL_3945 ! T-47
Metastatic; Pleural effusion; 
Caucasian.
Cancer cell line
Assay: Western Blot
Dmax:  -27.5 %
Treatment concentration: 10 nM
Assay description: PROTAC compounds disclosed in this invention degrade ERα in T-47D cells. T-47D cells were cultured in PRMI-1640 medium supplemented with 10% FBS at 37°C and 5% CO2 until they entered the logarithmic growth phase. T-47D cells were seeded at a density of 3×105 cells/well in 6-well plates and incubated at 37°C and 5% CO2 for 24 hours. After the cells adhered, 1 μL of compound solution in dimethyl sulfoxide (DMSO) (final concentration 0.15-1000 nM) was added and incubated for another 4 hours at 37°C and 5% CO2. After 4 hours, the medium was discarded, and each well was washed once with 1 mL of pre-chilled 1× DPBS. The cells were then lysed with 50 μL of RIPA lysis buffer and 1× protease inhibitor cocktail, incubated on ice for 20 minutes, and centrifuged at 14,000g at 4°C for 30 minutes. The supernatant was carefully removed and analyzed for ERα protein levels by immunoblotting.
Reference: CEREBELLAR PROTEIN E3 UBIQUITIN LIGASE INHIBITOR AND CHIMERIC COMPOUND TARGETING PROTEIN DEGRADATION (patent)
Source database: TPDdb
Compound (SMILES): O=C1NC(O)CCC1N1Cc2c(ccc3c2OCC32CCC3(CC2)CN(C2CCC4(CC2)CCN(c2ccc([C@@H]5c6ccc(O)cc6CC[C@@H]5c5ccccc5)cc2)CC4)C3)C1=O
Modality: PROteolysis-TArgeting Chimera (PROTAC)
Target protein (POI): ESR1 (UniProt P03372)
POI sequence: MTMTLHTKASGMALLHQIQGNELEPLNRPQLKIPLERPLGEVYLDSSKPAVYNYPEGAAYEFNAAAAANAQVYGQTGLPYGPGSEAAAFGSNGLGGFPPLNSVSPSPLMLLHPPPQLSPFLQPHGQQVPYYLENEPSGYTVREAGPPAFYRPNSDNRRQGGRERLASTNDKGSMAMESAKETRYCAVCNDYASGYHYGVWSCEGCKAFFKRSIQGHNDYMCPATNQCTIDKNRRKSCQACRLRKCYEVGMMKGGIRKDRRGGRMLKHKRQRDDGEGRGEVGSAGDMRAANLWPSPLMIKRSKKNSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWLEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGMVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITDTLIHLMAKAGLTLQQQHQRLAQLLLILSHIRHMSNKGMEHLYSMKCKNVVPLYDLLLEMLDAHRLHAPTSRGGASVEETDQSHLATAGSTSSHSLQKYYITGEAEGFPATV
E3 ligase: CRBN (UniProt Q96SW2)
Ligase sequence: MAGEGDQQDAAHNMGNHLPLLPAESEEEDEMEVEDQDSKEAKKPNIINFDTSLPTSHTYLGADMEEFHGRTLHDDDSCQVIPVLPQVMMILIPGQTLPLQLFHPQEVSMVRNLIQKDRTFAVLAYSNVQEREAQFGTTAEIYAYREEQDFGIEIVKVKAIGRQRFKVLELRTQSDGIQQAKVQILPECVLPSTMSAVQLESLNKCQIFPSKPVSREDQCSYKWWQKYQKRKFHCANLTSWPRWLYSLYDAETLMDRIKKQLREWDENLKDDSLPSNPIDFSYRVAACLPIDDVLRIQLLKIGSAIQRLRCELDIMNKCTSLCCKQCQETEITTKNEIFSLSLCGPMAAYVNPHGYVHETLTVYKACNLNLIGRPSTEHSWFPGYAWTVAQCKICASHIGWKFTATKKDMSPQKFWGLTRSALLPTIPDTEDEISPDKVILCL
Cell line: T-47D (Homo sapiens)
Cell line description: African=0.86%; Native American=1.2%; East Asian, North=3.03%; East Asian, South=1.59%; South Asian=8.04%; European, North=22.59%; European, South=62.69%.
Mutation; HGNC; HGNC Mutation; HGNC; HGNC
A*33 A*33 A*33
Stable (MSS).
CVCL_3945 ! T-47
Metastatic; Pleural effusion; 
Caucasian.
Cancer cell line
Assay: Western Blot
Dmax:  64.5 %
Treatment concentration: 10 nM
Assay description: PROTAC compounds disclosed in this invention degrade ERα in T-47D cells. T-47D cells were cultured in PRMI-1640 medium supplemented with 10% FBS at 37°C and 5% CO2 until they entered the logarithmic growth phase. T-47D cells were seeded at a density of 3×105 cells/well in 6-well plates and incubated at 37°C and 5% CO2 for 24 hours. After the cells adhered, 1 μL of compound solution in dimethyl sulfoxide (DMSO) (final concentration 0.15-1000 nM) was added and incubated for another 4 hours at 37°C and 5% CO2. After 4 hours, the medium was discarded, and each well was washed once with 1 mL of pre-chilled 1× DPBS. The cells were then lysed with 50 μL of RIPA lysis buffer and 1× protease inhibitor cocktail, incubated on ice for 20 minutes, and centrifuged at 14,000g at 4°C for 30 minutes. The supernatant was carefully removed and analyzed for ERα protein levels by immunoblotting.
Reference: CEREBELLAR PROTEIN E3 UBIQUITIN LIGASE INHIBITOR AND CHIMERIC COMPOUND TARGETING PROTEIN DEGRADATION (patent)
Source database: TPDdb
Compound (SMILES): [C-]#[N+]c1cc(S(=O)(=O)Nc2ccc(N3CCN(c4cc(F)cc(-c5c(C(=O)N6CCC(C)(C#N)C6)c(C)n(CC)c5-c5ccc(F)cc5)c4)CC3)cc2)ccc1N[C@@H](CCN1CCN(C(=O)CCCCCC(=O)N[C@H](C(=O)N2C[C@H](O)C[C@H]2C(=O)N[C@@H](C)c2ccc(-c3scnc3C)cc2)C(C)(C)C)CC1)CSc1ccccc1
Modality: PROteolysis-TArgeting Chimera (PROTAC)
Target protein (POI): BCL2L1 (UniProt Q07817)
POI sequence: MSQSNRELVVDFLSYKLSQKGYSWSQFSDVEENRTEAPEGTESEMETPSAINGNPSWHLADSPAVNGATGHSSSLDAREVIPMAAVKQALREAGDEFELRYRRAFSDLTSQLHITPGTAYQSFEQVVNELFRDGVNWGRIVAFFSFGGALCVESVDKEMQVLVSRIAAWMATYLNDHLEPWIQENGGWDTFVELYGNNAAAESRKGQERFNRWFLTGMTVAGVVLLGSLFSRK
E3 ligase: VHL (UniProt P40337)
Ligase sequence: MPRRAENWDEAEVGAEEAGVEEYGPEEDGGEESGAEESGPEESGPEELGAEEEMEAGRPRPVLRSVNSREPSQVIFCNRSPRVVLPVWLNFDGEPQPYPTLPPGTGRRIHSYRGHLWLFRDAGTHDGLLVNQTELFVPSLNVDGQPIFANITLPVYTLKERCLQVVRSLVKPENYRRLDIVRSLYEDLEDHPNVQKDLERLTQERIAHQRMGD
Cell line: MDA-MB-231 (Homo sapiens)
Cell line description: African=1.95%; Native American=0%; East Asian, North=2.44%; East Asian, South=0%; South Asian=7.42%; European, North=28.16%; European, South=60.03%.
Gene deletion; HGNC; HGNC Gene deletion; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC
A*02/28; B*07,08; C*w02,w06. A*02 A*02 A*02
Stable (MSS).
Metastatic; Pleural effusion; 
Caucasian.
Triple negative breast cancer (TNBC) cell line.
Cancer cell line
Assay: Western Blot
DC50:  31 nM
Assay description: Cells were collected and lysed in a lysis buffer (Cat. No. BP-115DG, Boston Bio Products, Ashland, MA, USA) containing protease and phosphatase inhibitor cocktails (Cat. No. PPC1010, Sigma-Aldrich, St. Louis, MO, USA) . An equal amount of protein lysates was separated on precasted 4-20%Tris-glycine gels (Mini-PROTEAN TGX, Cat. No. 456-1094, Bio-Rad, Hercules, CA, USA) . Thereafter, the proteins were transferred to PVDF membranes (Cat. No. LC2002, MilliporeSigma, Billerica, MA, USA) . The membranes were blocked with 5%w/v nonfat dry milk in TBS + Tween-20 (0.1%v/v) and then probed with primary antibodies overnight at 4 °C. Next day, the membranes were washed and incubated with appropriate horseradish peroxidase (HRP) -conjugated secondary antibodies. Primary antibodies against BCL-XL (Cat. No. 2762) and βactin (Cat. No. 4970) and the secondary HRP-linked antibody (Cat. No. 7074) were purchased from Cell Signaling Technology (Danvers, MA, USA) . The signal was detected using the ECL substrate (Cat. No. WBKLS0500, MilliporeSigma, Billerica, MA, USA) and captured on the ChemiDoc MP Imaging System (Bio-Rad, Hercules, CA, USA) . The band intensities were calculated on the ImageJ software and normalized to equal loading control β-actin.
Reference: BCL-2/BCL-XL PROTEIN DEGRADER AND USE THEREOF (patent)
Source database: TPDdb
Compound (SMILES): [C-]#[N+]c1cc(S(=O)(=O)Nc2ccc(N3CCN(c4cc(F)cc(-c5c(S(C)(=O)=O)c(C)n(CC)c5-c5ccc(F)cc5)c4)CC3)cc2)ccc1N[C@H](CCN1CC[C@H](NC(=O)CCCCCC(=O)N[C@H](C(=O)N2C[C@H](O)C[C@H]2C(=O)N[C@@H](C)c2ccc(-c3scnc3C)cc2)C(C)(C)C)C1)CSc1ccccc1
Modality: PROteolysis-TArgeting Chimera (PROTAC)
Target protein (POI): BCL2L1 (UniProt Q07817)
POI sequence: MSQSNRELVVDFLSYKLSQKGYSWSQFSDVEENRTEAPEGTESEMETPSAINGNPSWHLADSPAVNGATGHSSSLDAREVIPMAAVKQALREAGDEFELRYRRAFSDLTSQLHITPGTAYQSFEQVVNELFRDGVNWGRIVAFFSFGGALCVESVDKEMQVLVSRIAAWMATYLNDHLEPWIQENGGWDTFVELYGNNAAAESRKGQERFNRWFLTGMTVAGVVLLGSLFSRK
E3 ligase: VHL (UniProt P40337)
Ligase sequence: MPRRAENWDEAEVGAEEAGVEEYGPEEDGGEESGAEESGPEESGPEELGAEEEMEAGRPRPVLRSVNSREPSQVIFCNRSPRVVLPVWLNFDGEPQPYPTLPPGTGRRIHSYRGHLWLFRDAGTHDGLLVNQTELFVPSLNVDGQPIFANITLPVYTLKERCLQVVRSLVKPENYRRLDIVRSLYEDLEDHPNVQKDLERLTQERIAHQRMGD
Cell line: MDA-MB-231 (Homo sapiens)
Cell line description: African=1.95%; Native American=0%; East Asian, North=2.44%; East Asian, South=0%; South Asian=7.42%; European, North=28.16%; European, South=60.03%.
Gene deletion; HGNC; HGNC Gene deletion; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC
A*02/28; B*07,08; C*w02,w06. A*02 A*02 A*02
Stable (MSS).
Metastatic; Pleural effusion; 
Caucasian.
Triple negative breast cancer (TNBC) cell line.
Cancer cell line
Assay: Western Blot
DC50:  22 nM
Assay description: Cells were collected and lysed in a lysis buffer (Cat. No. BP-115DG, Boston Bio Products, Ashland, MA, USA) containing protease and phosphatase inhibitor cocktails (Cat. No. PPC1010, Sigma-Aldrich, St. Louis, MO, USA) . An equal amount of protein lysates was separated on precasted 4-20%Tris-glycine gels (Mini-PROTEAN TGX, Cat. No. 456-1094, Bio-Rad, Hercules, CA, USA) . Thereafter, the proteins were transferred to PVDF membranes (Cat. No. LC2002, MilliporeSigma, Billerica, MA, USA) . The membranes were blocked with 5%w/v nonfat dry milk in TBS + Tween-20 (0.1%v/v) and then probed with primary antibodies overnight at 4 °C. Next day, the membranes were washed and incubated with appropriate horseradish peroxidase (HRP) -conjugated secondary antibodies. Primary antibodies against BCL-XL (Cat. No. 2762) and βactin (Cat. No. 4970) and the secondary HRP-linked antibody (Cat. No. 7074) were purchased from Cell Signaling Technology (Danvers, MA, USA) . The signal was detected using the ECL substrate (Cat. No. WBKLS0500, MilliporeSigma, Billerica, MA, USA) and captured on the ChemiDoc MP Imaging System (Bio-Rad, Hercules, CA, USA) . The band intensities were calculated on the ImageJ software and normalized to equal loading control β-actin.
Reference: BCL-2/BCL-XL PROTEIN DEGRADER AND USE THEREOF (patent)
Source database: TPDdb
Compound (SMILES): [C-]#[N+]c1cc(S(=O)(=O)Nc2ccc(N3CCN(c4ccc(Cc5c(C(=O)N6CC[C@@H](NS(C)(=O)=O)C6)c(C)n(CC)c5-c5ccc(F)cc5)cc4)CC3)cc2)ccc1N[C@H](CCN1CCN(C(=O)CCCCCC(=O)N[C@H](C(=O)N2C[C@H](O)C[C@H]2C(=O)N[C@@H](C)c2ccc(-c3scnc3C)cc2)C(C)C)CC1)CSc1ccccc1
Modality: PROteolysis-TArgeting Chimera (PROTAC)
Target protein (POI): BCL2L1 (UniProt Q07817)
POI sequence: MSQSNRELVVDFLSYKLSQKGYSWSQFSDVEENRTEAPEGTESEMETPSAINGNPSWHLADSPAVNGATGHSSSLDAREVIPMAAVKQALREAGDEFELRYRRAFSDLTSQLHITPGTAYQSFEQVVNELFRDGVNWGRIVAFFSFGGALCVESVDKEMQVLVSRIAAWMATYLNDHLEPWIQENGGWDTFVELYGNNAAAESRKGQERFNRWFLTGMTVAGVVLLGSLFSRK
E3 ligase: VHL (UniProt P40337)
Ligase sequence: MPRRAENWDEAEVGAEEAGVEEYGPEEDGGEESGAEESGPEESGPEELGAEEEMEAGRPRPVLRSVNSREPSQVIFCNRSPRVVLPVWLNFDGEPQPYPTLPPGTGRRIHSYRGHLWLFRDAGTHDGLLVNQTELFVPSLNVDGQPIFANITLPVYTLKERCLQVVRSLVKPENYRRLDIVRSLYEDLEDHPNVQKDLERLTQERIAHQRMGD
Cell line: MDA-MB-231 (Homo sapiens)
Cell line description: African=1.95%; Native American=0%; East Asian, North=2.44%; East Asian, South=0%; South Asian=7.42%; European, North=28.16%; European, South=60.03%.
Gene deletion; HGNC; HGNC Gene deletion; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC Mutation; HGNC; HGNC
A*02/28; B*07,08; C*w02,w06. A*02 A*02 A*02
Stable (MSS).
Metastatic; Pleural effusion; 
Caucasian.
Triple negative breast cancer (TNBC) cell line.
Cancer cell line
Assay: Western Blot
DC50:  6 nM
Assay description: Cells were collected and lysed in a lysis buffer (Cat. No. BP-115DG, Boston Bio Products, Ashland, MA, USA) containing protease and phosphatase inhibitor cocktails (Cat. No. PPC1010, Sigma-Aldrich, St. Louis, MO, USA) . An equal amount of protein lysates was separated on precasted 4-20%Tris-glycine gels (Mini-PROTEAN TGX, Cat. No. 456-1094, Bio-Rad, Hercules, CA, USA) . Thereafter, the proteins were transferred to PVDF membranes (Cat. No. LC2002, MilliporeSigma, Billerica, MA, USA) . The membranes were blocked with 5%w/v nonfat dry milk in TBS + Tween-20 (0.1%v/v) and then probed with primary antibodies overnight at 4 °C. Next day, the membranes were washed and incubated with appropriate horseradish peroxidase (HRP) -conjugated secondary antibodies. Primary antibodies against BCL-XL (Cat. No. 2762) and βactin (Cat. No. 4970) and the secondary HRP-linked antibody (Cat. No. 7074) were purchased from Cell Signaling Technology (Danvers, MA, USA) . The signal was detected using the ECL substrate (Cat. No. WBKLS0500, MilliporeSigma, Billerica, MA, USA) and captured on the ChemiDoc MP Imaging System (Bio-Rad, Hercules, CA, USA) . The band intensities were calculated on the ImageJ software and normalized to equal loading control β-actin.
Reference: BCL-2/BCL-XL PROTEIN DEGRADER AND USE THEREOF (patent)
Source database: TPDdb