ailab-bio/TACK huggingface dataset:
Compound (SMILES): CC(C)(O)C1=C(F)C2=NC(C3CCN(C4CN(C5CN(c6cc(F)c7c(c6)C(=O)N(C6CCC(=O)NC6=O)C7=O)C5)C4)CC3)CN2C=C1NC(=O)c1cccc(C2CC2(F)F)n1
Modality: PROteolysis-TArgeting Chimera (PROTAC)
Target protein (POI): IRAK4 (UniProt Q9NWZ3)
POI sequence: MNKPITPSTYVRCLNVGLIRKLSDFIDPQEGWKKLAVAIKKPSGDDRYNQFHIRRFEALLQTGKSPTSELLFDWGTTNCTVGDLVDLLIQNEFFAPASLLLPDAVPKTANTLPSKEAITVQQKQMPFCDKDRTLMTPVQNLEQSYMPPDSSSPENKSLEVSDTRFHSFSFYELKNVTNNFDERPISVGGNKMGEGGFGVVYKGYVNNTTVAVKKLAAMVDITTEELKQQFDQEIKVMAKCQHENLVELLGFSSDGDDLCLVYVYMPNGSLLDRLSCLDGTPPLSWHMRCKIAQGAANGINFLHENHHIHRDIKSANILLDEAFTAKISDFGLARASEKFAQTVMTSRIVGTTAYMAPEALRGEITPKSDIYSFGVVLLEIITGLPAVDEHREPQLLLDIKEEIEDEEKTIEDYIDKKMNDADSTSVEAMYSVASQCLHEKKNKRPDIKKVQQLLQEMTAS
E3 ligase: CRBN (UniProt Q96SW2)
Ligase sequence: MAGEGDQQDAAHNMGNHLPLLPAESEEEDEMEVEDQDSKEAKKPNIINFDTSLPTSHTYLGADMEEFHGRTLHDDDSCQVIPVLPQVMMILIPGQTLPLQLFHPQEVSMVRNLIQKDRTFAVLAYSNVQEREAQFGTTAEIYAYREEQDFGIEIVKVKAIGRQRFKVLELRTQSDGIQQAKVQILPECVLPSTMSAVQLESLNKCQIFPSKPVSREDQCSYKWWQKYQKRKFHCANLTSWPRWLYSLYDAETLMDRIKKQLREWDENLKDDSLPSNPIDFSYRVAACLPIDDVLRIQLLKIGSAIQRLRCELDIMNKCTSLCCKQCQETEITTKNEIFSLSLCGPMAAYVNPHGYVHETLTVYKACNLNLIGRPSTEHSWFPGYAWTVAQCKICASHIGWKFTATKKDMSPQKFWGLTRSALLPTIPDTEDEISPDKVILCL
Cell line: HEK293 (Homo sapiens)
Cell line description: Used for the production of the Gamaleya SARS-CoV-2 (COVID-19) vaccine (Trade name
A*02 A*03
In situ; Fetal kidney; 
Vaccine production cell line.
NCBI_TaxID; 28285; Human adenovirus C serotype 5.
Transformed cell line
Assay: Nano-Glo HiBiT Lytic
Dmax:  93 %
Assay description: 1) Cell culture. The culture medium for cell culture is DMEM medium containing inactivated 10% fetal bovine serum, 100U/ml penicillin and 100μg/ml streptomycin. HEK293-IRAK4-Hibit cells are cultured in an incubator at 37°C and 5% CO2 . When the cell confluence reaches 80-90%, the cells are subcultured. Cells in the logarithmic growth phase are used for plating. HEK293-IRAK4-Hibit cells are plated in a 96-well plate with 100μL culture medium, 20,000-30,000 cells per well, and cultured overnight.

2) Compound dilution. The compound was dissolved in DMSO to a concentration of 10 mM. The compound was then graded diluted in DMSO to concentrations of 2000 μM, 500 μM, 125 μM, 32.25 μM, 7.81 μM, 1.95 μM, 0.49 μM, 0.12 μM and 0.031 μM.

3) Adding drugs. Take 1 μL of the diluted compound and add it to 1 ml of complete medium. After mixing, take 100 μL and add it to a 96-well plate. The working concentrations reach 1000 nM, 250 nM, 62.5 nM, 15.6 nM, 3.91 nM, 0.98 nM, 0.24 nM, 0.061 nM, 0.015 nM and 0 nM.

4) Activity detection. The drug treatment was performed for 24 hours and the detection method was based on that of Promega HiBiT Lytic Detection System Instructions.

5) DC50 calculation. Relative IRAK4 (%) = (Lumninence experiment - Lumninence blank) / (Lumninence DMSO - Lumninence blank), calculated by fitting based on log (inhibitor) vs. response -- Variable slope (four parameters).

The experimental results are shown in Table 1, showing the data of the degradation of IRAK4 protein by the compounds of the present invention.
Reference: FLUOROIMIDAZOPYRIDINE COMPOUND AS IRAK4 DEGRADATION AGENT AND USE THEREOF (patent)
Source database: TPDdb
Compound (SMILES): CC(C)(O)c1c(NC(=O)c2ccc(F)c(C3CC3(F)F)n2)cn2cc(C3CCN(CC4(O)CN(c5cc6c(cc5F)C(=O)N(C5CCC(=O)NC5=O)C6=O)C4)CC3)nc2c1F
Modality: PROteolysis-TArgeting Chimera (PROTAC)
Target protein (POI): IRAK4 (UniProt Q9NWZ3)
POI sequence: MNKPITPSTYVRCLNVGLIRKLSDFIDPQEGWKKLAVAIKKPSGDDRYNQFHIRRFEALLQTGKSPTSELLFDWGTTNCTVGDLVDLLIQNEFFAPASLLLPDAVPKTANTLPSKEAITVQQKQMPFCDKDRTLMTPVQNLEQSYMPPDSSSPENKSLEVSDTRFHSFSFYELKNVTNNFDERPISVGGNKMGEGGFGVVYKGYVNNTTVAVKKLAAMVDITTEELKQQFDQEIKVMAKCQHENLVELLGFSSDGDDLCLVYVYMPNGSLLDRLSCLDGTPPLSWHMRCKIAQGAANGINFLHENHHIHRDIKSANILLDEAFTAKISDFGLARASEKFAQTVMTSRIVGTTAYMAPEALRGEITPKSDIYSFGVVLLEIITGLPAVDEHREPQLLLDIKEEIEDEEKTIEDYIDKKMNDADSTSVEAMYSVASQCLHEKKNKRPDIKKVQQLLQEMTAS
E3 ligase: CRBN (UniProt Q96SW2)
Ligase sequence: MAGEGDQQDAAHNMGNHLPLLPAESEEEDEMEVEDQDSKEAKKPNIINFDTSLPTSHTYLGADMEEFHGRTLHDDDSCQVIPVLPQVMMILIPGQTLPLQLFHPQEVSMVRNLIQKDRTFAVLAYSNVQEREAQFGTTAEIYAYREEQDFGIEIVKVKAIGRQRFKVLELRTQSDGIQQAKVQILPECVLPSTMSAVQLESLNKCQIFPSKPVSREDQCSYKWWQKYQKRKFHCANLTSWPRWLYSLYDAETLMDRIKKQLREWDENLKDDSLPSNPIDFSYRVAACLPIDDVLRIQLLKIGSAIQRLRCELDIMNKCTSLCCKQCQETEITTKNEIFSLSLCGPMAAYVNPHGYVHETLTVYKACNLNLIGRPSTEHSWFPGYAWTVAQCKICASHIGWKFTATKKDMSPQKFWGLTRSALLPTIPDTEDEISPDKVILCL
Cell line: HEK293 (Homo sapiens)
Cell line description: Used for the production of the Gamaleya SARS-CoV-2 (COVID-19) vaccine (Trade name
A*02 A*03
In situ; Fetal kidney; 
Vaccine production cell line.
NCBI_TaxID; 28285; Human adenovirus C serotype 5.
Transformed cell line
Assay: Nano-Glo HiBiT Lytic
DC50:  7.55 nM
Assay description: 1) Cell culture. The culture medium for cell culture is DMEM medium containing inactivated 10% fetal bovine serum, 100U/ml penicillin and 100μg/ml streptomycin. HEK293-IRAK4-Hibit cells are cultured in an incubator at 37°C and 5% CO2 . When the cell confluence reaches 80-90%, the cells are subcultured. Cells in the logarithmic growth phase are used for plating. HEK293-IRAK4-Hibit cells are plated in a 96-well plate with 100μL culture medium, 20,000-30,000 cells per well, and cultured overnight.

2) Compound dilution. The compound was dissolved in DMSO to a concentration of 10 mM. The compound was then graded diluted in DMSO to concentrations of 2000 μM, 500 μM, 125 μM, 32.25 μM, 7.81 μM, 1.95 μM, 0.49 μM, 0.12 μM and 0.031 μM.

3) Adding drugs. Take 1 μL of the diluted compound and add it to 1 ml of complete medium. After mixing, take 100 μL and add it to a 96-well plate. The working concentrations reach 1000 nM, 250 nM, 62.5 nM, 15.6 nM, 3.91 nM, 0.98 nM, 0.24 nM, 0.061 nM, 0.015 nM and 0 nM.

4) Activity detection. The drug treatment was performed for 24 hours and the detection method was based on that of Promega HiBiT Lytic Detection System Instructions.

5) DC50 calculation. Relative IRAK4 (%) = (Lumninence experiment - Lumninence blank) / (Lumninence DMSO - Lumninence blank), calculated by fitting based on log (inhibitor) vs. response -- Variable slope (four parameters).

The experimental results are shown in Table 1, showing the data of the degradation of IRAK4 protein by the compounds of the present invention.
Reference: FLUOROIMIDAZOPYRIDINE COMPOUND AS IRAK4 DEGRADATION AGENT AND USE THEREOF (patent)
Source database: TPDdb
Compound (SMILES): CC(C)(O)c1c(NC(=O)c2ccc(F)c(C3CC3(F)F)n2)cn2cc(C3CCN(CC4(O)CN(c5cc6c(cc5F)C(=O)N(C5CCC(=O)NC5=O)C6=O)C4)CC3)nc2c1F
Modality: PROteolysis-TArgeting Chimera (PROTAC)
Target protein (POI): IRAK4 (UniProt Q9NWZ3)
POI sequence: MNKPITPSTYVRCLNVGLIRKLSDFIDPQEGWKKLAVAIKKPSGDDRYNQFHIRRFEALLQTGKSPTSELLFDWGTTNCTVGDLVDLLIQNEFFAPASLLLPDAVPKTANTLPSKEAITVQQKQMPFCDKDRTLMTPVQNLEQSYMPPDSSSPENKSLEVSDTRFHSFSFYELKNVTNNFDERPISVGGNKMGEGGFGVVYKGYVNNTTVAVKKLAAMVDITTEELKQQFDQEIKVMAKCQHENLVELLGFSSDGDDLCLVYVYMPNGSLLDRLSCLDGTPPLSWHMRCKIAQGAANGINFLHENHHIHRDIKSANILLDEAFTAKISDFGLARASEKFAQTVMTSRIVGTTAYMAPEALRGEITPKSDIYSFGVVLLEIITGLPAVDEHREPQLLLDIKEEIEDEEKTIEDYIDKKMNDADSTSVEAMYSVASQCLHEKKNKRPDIKKVQQLLQEMTAS
E3 ligase: CRBN (UniProt Q96SW2)
Ligase sequence: MAGEGDQQDAAHNMGNHLPLLPAESEEEDEMEVEDQDSKEAKKPNIINFDTSLPTSHTYLGADMEEFHGRTLHDDDSCQVIPVLPQVMMILIPGQTLPLQLFHPQEVSMVRNLIQKDRTFAVLAYSNVQEREAQFGTTAEIYAYREEQDFGIEIVKVKAIGRQRFKVLELRTQSDGIQQAKVQILPECVLPSTMSAVQLESLNKCQIFPSKPVSREDQCSYKWWQKYQKRKFHCANLTSWPRWLYSLYDAETLMDRIKKQLREWDENLKDDSLPSNPIDFSYRVAACLPIDDVLRIQLLKIGSAIQRLRCELDIMNKCTSLCCKQCQETEITTKNEIFSLSLCGPMAAYVNPHGYVHETLTVYKACNLNLIGRPSTEHSWFPGYAWTVAQCKICASHIGWKFTATKKDMSPQKFWGLTRSALLPTIPDTEDEISPDKVILCL
Cell line: HEK293 (Homo sapiens)
Cell line description: Used for the production of the Gamaleya SARS-CoV-2 (COVID-19) vaccine (Trade name
A*02 A*03
In situ; Fetal kidney; 
Vaccine production cell line.
NCBI_TaxID; 28285; Human adenovirus C serotype 5.
Transformed cell line
Assay: Nano-Glo HiBiT Lytic
Dmax:  94 %
Assay description: 1) Cell culture. The culture medium for cell culture is DMEM medium containing inactivated 10% fetal bovine serum, 100U/ml penicillin and 100μg/ml streptomycin. HEK293-IRAK4-Hibit cells are cultured in an incubator at 37°C and 5% CO2 . When the cell confluence reaches 80-90%, the cells are subcultured. Cells in the logarithmic growth phase are used for plating. HEK293-IRAK4-Hibit cells are plated in a 96-well plate with 100μL culture medium, 20,000-30,000 cells per well, and cultured overnight.

2) Compound dilution. The compound was dissolved in DMSO to a concentration of 10 mM. The compound was then graded diluted in DMSO to concentrations of 2000 μM, 500 μM, 125 μM, 32.25 μM, 7.81 μM, 1.95 μM, 0.49 μM, 0.12 μM and 0.031 μM.

3) Adding drugs. Take 1 μL of the diluted compound and add it to 1 ml of complete medium. After mixing, take 100 μL and add it to a 96-well plate. The working concentrations reach 1000 nM, 250 nM, 62.5 nM, 15.6 nM, 3.91 nM, 0.98 nM, 0.24 nM, 0.061 nM, 0.015 nM and 0 nM.

4) Activity detection. The drug treatment was performed for 24 hours and the detection method was based on that of Promega HiBiT Lytic Detection System Instructions.

5) DC50 calculation. Relative IRAK4 (%) = (Lumninence experiment - Lumninence blank) / (Lumninence DMSO - Lumninence blank), calculated by fitting based on log (inhibitor) vs. response -- Variable slope (four parameters).

The experimental results are shown in Table 1, showing the data of the degradation of IRAK4 protein by the compounds of the present invention.
Reference: FLUOROIMIDAZOPYRIDINE COMPOUND AS IRAK4 DEGRADATION AGENT AND USE THEREOF (patent)
Source database: TPDdb
Compound (SMILES): CC(C)(O)c1c(NC(=O)c2cccc(C3CC3(F)F)n2)cn2cc(C3CCN(C(=O)CN4CCN(c5cc6c(cc5F)C(=O)N(C5CCC(=O)NC5=O)C6=O)CC4)CC3)nc2c1F
Modality: PROteolysis-TArgeting Chimera (PROTAC)
Target protein (POI): IRAK4 (UniProt Q9NWZ3)
POI sequence: MNKPITPSTYVRCLNVGLIRKLSDFIDPQEGWKKLAVAIKKPSGDDRYNQFHIRRFEALLQTGKSPTSELLFDWGTTNCTVGDLVDLLIQNEFFAPASLLLPDAVPKTANTLPSKEAITVQQKQMPFCDKDRTLMTPVQNLEQSYMPPDSSSPENKSLEVSDTRFHSFSFYELKNVTNNFDERPISVGGNKMGEGGFGVVYKGYVNNTTVAVKKLAAMVDITTEELKQQFDQEIKVMAKCQHENLVELLGFSSDGDDLCLVYVYMPNGSLLDRLSCLDGTPPLSWHMRCKIAQGAANGINFLHENHHIHRDIKSANILLDEAFTAKISDFGLARASEKFAQTVMTSRIVGTTAYMAPEALRGEITPKSDIYSFGVVLLEIITGLPAVDEHREPQLLLDIKEEIEDEEKTIEDYIDKKMNDADSTSVEAMYSVASQCLHEKKNKRPDIKKVQQLLQEMTAS
E3 ligase: CRBN (UniProt Q96SW2)
Ligase sequence: MAGEGDQQDAAHNMGNHLPLLPAESEEEDEMEVEDQDSKEAKKPNIINFDTSLPTSHTYLGADMEEFHGRTLHDDDSCQVIPVLPQVMMILIPGQTLPLQLFHPQEVSMVRNLIQKDRTFAVLAYSNVQEREAQFGTTAEIYAYREEQDFGIEIVKVKAIGRQRFKVLELRTQSDGIQQAKVQILPECVLPSTMSAVQLESLNKCQIFPSKPVSREDQCSYKWWQKYQKRKFHCANLTSWPRWLYSLYDAETLMDRIKKQLREWDENLKDDSLPSNPIDFSYRVAACLPIDDVLRIQLLKIGSAIQRLRCELDIMNKCTSLCCKQCQETEITTKNEIFSLSLCGPMAAYVNPHGYVHETLTVYKACNLNLIGRPSTEHSWFPGYAWTVAQCKICASHIGWKFTATKKDMSPQKFWGLTRSALLPTIPDTEDEISPDKVILCL
Cell line: HEK293 (Homo sapiens)
Cell line description: Used for the production of the Gamaleya SARS-CoV-2 (COVID-19) vaccine (Trade name
A*02 A*03
In situ; Fetal kidney; 
Vaccine production cell line.
NCBI_TaxID; 28285; Human adenovirus C serotype 5.
Transformed cell line
Assay: Nano-Glo HiBiT Lytic
DC50:  28.7 nM
Assay description: 1) Cell culture. The culture medium for cell culture is DMEM medium containing inactivated 10% fetal bovine serum, 100U/ml penicillin and 100μg/ml streptomycin. HEK293-IRAK4-Hibit cells are cultured in an incubator at 37°C and 5% CO2 . When the cell confluence reaches 80-90%, the cells are subcultured. Cells in the logarithmic growth phase are used for plating. HEK293-IRAK4-Hibit cells are plated in a 96-well plate with 100μL culture medium, 20,000-30,000 cells per well, and cultured overnight.

2) Compound dilution. The compound was dissolved in DMSO to a concentration of 10 mM. The compound was then graded diluted in DMSO to concentrations of 2000 μM, 500 μM, 125 μM, 32.25 μM, 7.81 μM, 1.95 μM, 0.49 μM, 0.12 μM and 0.031 μM.

3) Adding drugs. Take 1 μL of the diluted compound and add it to 1 ml of complete medium. After mixing, take 100 μL and add it to a 96-well plate. The working concentrations reach 1000 nM, 250 nM, 62.5 nM, 15.6 nM, 3.91 nM, 0.98 nM, 0.24 nM, 0.061 nM, 0.015 nM and 0 nM.

4) Activity detection. The drug treatment was performed for 24 hours and the detection method was based on that of Promega HiBiT Lytic Detection System Instructions.

5) DC50 calculation. Relative IRAK4 (%) = (Lumninence experiment - Lumninence blank) / (Lumninence DMSO - Lumninence blank), calculated by fitting based on log (inhibitor) vs. response -- Variable slope (four parameters).

The experimental results are shown in Table 1, showing the data of the degradation of IRAK4 protein by the compounds of the present invention.
Reference: FLUOROIMIDAZOPYRIDINE COMPOUND AS IRAK4 DEGRADATION AGENT AND USE THEREOF (patent)
Source database: TPDdb
Compound (SMILES): CC(C)(O)c1c(NC(=O)c2cccc(C3CC3(F)F)n2)cn2cc(C3CCN(C(=O)CN4CCN(c5cc6c(cc5F)C(=O)N(C5CCC(=O)NC5=O)C6=O)CC4)CC3)nc2c1F
Modality: PROteolysis-TArgeting Chimera (PROTAC)
Target protein (POI): IRAK4 (UniProt Q9NWZ3)
POI sequence: MNKPITPSTYVRCLNVGLIRKLSDFIDPQEGWKKLAVAIKKPSGDDRYNQFHIRRFEALLQTGKSPTSELLFDWGTTNCTVGDLVDLLIQNEFFAPASLLLPDAVPKTANTLPSKEAITVQQKQMPFCDKDRTLMTPVQNLEQSYMPPDSSSPENKSLEVSDTRFHSFSFYELKNVTNNFDERPISVGGNKMGEGGFGVVYKGYVNNTTVAVKKLAAMVDITTEELKQQFDQEIKVMAKCQHENLVELLGFSSDGDDLCLVYVYMPNGSLLDRLSCLDGTPPLSWHMRCKIAQGAANGINFLHENHHIHRDIKSANILLDEAFTAKISDFGLARASEKFAQTVMTSRIVGTTAYMAPEALRGEITPKSDIYSFGVVLLEIITGLPAVDEHREPQLLLDIKEEIEDEEKTIEDYIDKKMNDADSTSVEAMYSVASQCLHEKKNKRPDIKKVQQLLQEMTAS
E3 ligase: CRBN (UniProt Q96SW2)
Ligase sequence: MAGEGDQQDAAHNMGNHLPLLPAESEEEDEMEVEDQDSKEAKKPNIINFDTSLPTSHTYLGADMEEFHGRTLHDDDSCQVIPVLPQVMMILIPGQTLPLQLFHPQEVSMVRNLIQKDRTFAVLAYSNVQEREAQFGTTAEIYAYREEQDFGIEIVKVKAIGRQRFKVLELRTQSDGIQQAKVQILPECVLPSTMSAVQLESLNKCQIFPSKPVSREDQCSYKWWQKYQKRKFHCANLTSWPRWLYSLYDAETLMDRIKKQLREWDENLKDDSLPSNPIDFSYRVAACLPIDDVLRIQLLKIGSAIQRLRCELDIMNKCTSLCCKQCQETEITTKNEIFSLSLCGPMAAYVNPHGYVHETLTVYKACNLNLIGRPSTEHSWFPGYAWTVAQCKICASHIGWKFTATKKDMSPQKFWGLTRSALLPTIPDTEDEISPDKVILCL
Cell line: HEK293 (Homo sapiens)
Cell line description: Used for the production of the Gamaleya SARS-CoV-2 (COVID-19) vaccine (Trade name
A*02 A*03
In situ; Fetal kidney; 
Vaccine production cell line.
NCBI_TaxID; 28285; Human adenovirus C serotype 5.
Transformed cell line
Assay: Nano-Glo HiBiT Lytic
Dmax:  93 %
Assay description: 1) Cell culture. The culture medium for cell culture is DMEM medium containing inactivated 10% fetal bovine serum, 100U/ml penicillin and 100μg/ml streptomycin. HEK293-IRAK4-Hibit cells are cultured in an incubator at 37°C and 5% CO2 . When the cell confluence reaches 80-90%, the cells are subcultured. Cells in the logarithmic growth phase are used for plating. HEK293-IRAK4-Hibit cells are plated in a 96-well plate with 100μL culture medium, 20,000-30,000 cells per well, and cultured overnight.

2) Compound dilution. The compound was dissolved in DMSO to a concentration of 10 mM. The compound was then graded diluted in DMSO to concentrations of 2000 μM, 500 μM, 125 μM, 32.25 μM, 7.81 μM, 1.95 μM, 0.49 μM, 0.12 μM and 0.031 μM.

3) Adding drugs. Take 1 μL of the diluted compound and add it to 1 ml of complete medium. After mixing, take 100 μL and add it to a 96-well plate. The working concentrations reach 1000 nM, 250 nM, 62.5 nM, 15.6 nM, 3.91 nM, 0.98 nM, 0.24 nM, 0.061 nM, 0.015 nM and 0 nM.

4) Activity detection. The drug treatment was performed for 24 hours and the detection method was based on that of Promega HiBiT Lytic Detection System Instructions.

5) DC50 calculation. Relative IRAK4 (%) = (Lumninence experiment - Lumninence blank) / (Lumninence DMSO - Lumninence blank), calculated by fitting based on log (inhibitor) vs. response -- Variable slope (four parameters).

The experimental results are shown in Table 1, showing the data of the degradation of IRAK4 protein by the compounds of the present invention.
Reference: FLUOROIMIDAZOPYRIDINE COMPOUND AS IRAK4 DEGRADATION AGENT AND USE THEREOF (patent)
Source database: TPDdb
Compound (SMILES): CC(C)(O)c1c(NC(=O)c2cccc(C3CC3(F)F)n2)cn2cc(C3CCN(CC(=O)N4CCN(c5cc6c(cc5F)C(=O)N(C5CCC(=O)NC5=O)C6=O)CC4)CC3)nc2c1F
Modality: PROteolysis-TArgeting Chimera (PROTAC)
Target protein (POI): IRAK4 (UniProt Q9NWZ3)
POI sequence: MNKPITPSTYVRCLNVGLIRKLSDFIDPQEGWKKLAVAIKKPSGDDRYNQFHIRRFEALLQTGKSPTSELLFDWGTTNCTVGDLVDLLIQNEFFAPASLLLPDAVPKTANTLPSKEAITVQQKQMPFCDKDRTLMTPVQNLEQSYMPPDSSSPENKSLEVSDTRFHSFSFYELKNVTNNFDERPISVGGNKMGEGGFGVVYKGYVNNTTVAVKKLAAMVDITTEELKQQFDQEIKVMAKCQHENLVELLGFSSDGDDLCLVYVYMPNGSLLDRLSCLDGTPPLSWHMRCKIAQGAANGINFLHENHHIHRDIKSANILLDEAFTAKISDFGLARASEKFAQTVMTSRIVGTTAYMAPEALRGEITPKSDIYSFGVVLLEIITGLPAVDEHREPQLLLDIKEEIEDEEKTIEDYIDKKMNDADSTSVEAMYSVASQCLHEKKNKRPDIKKVQQLLQEMTAS
E3 ligase: CRBN (UniProt Q96SW2)
Ligase sequence: MAGEGDQQDAAHNMGNHLPLLPAESEEEDEMEVEDQDSKEAKKPNIINFDTSLPTSHTYLGADMEEFHGRTLHDDDSCQVIPVLPQVMMILIPGQTLPLQLFHPQEVSMVRNLIQKDRTFAVLAYSNVQEREAQFGTTAEIYAYREEQDFGIEIVKVKAIGRQRFKVLELRTQSDGIQQAKVQILPECVLPSTMSAVQLESLNKCQIFPSKPVSREDQCSYKWWQKYQKRKFHCANLTSWPRWLYSLYDAETLMDRIKKQLREWDENLKDDSLPSNPIDFSYRVAACLPIDDVLRIQLLKIGSAIQRLRCELDIMNKCTSLCCKQCQETEITTKNEIFSLSLCGPMAAYVNPHGYVHETLTVYKACNLNLIGRPSTEHSWFPGYAWTVAQCKICASHIGWKFTATKKDMSPQKFWGLTRSALLPTIPDTEDEISPDKVILCL
Cell line: HEK293 (Homo sapiens)
Cell line description: Used for the production of the Gamaleya SARS-CoV-2 (COVID-19) vaccine (Trade name
A*02 A*03
In situ; Fetal kidney; 
Vaccine production cell line.
NCBI_TaxID; 28285; Human adenovirus C serotype 5.
Transformed cell line
Assay: Nano-Glo HiBiT Lytic
DC50:  32.7 nM
Assay description: 1) Cell culture. The culture medium for cell culture is DMEM medium containing inactivated 10% fetal bovine serum, 100U/ml penicillin and 100μg/ml streptomycin. HEK293-IRAK4-Hibit cells are cultured in an incubator at 37°C and 5% CO2 . When the cell confluence reaches 80-90%, the cells are subcultured. Cells in the logarithmic growth phase are used for plating. HEK293-IRAK4-Hibit cells are plated in a 96-well plate with 100μL culture medium, 20,000-30,000 cells per well, and cultured overnight.

2) Compound dilution. The compound was dissolved in DMSO to a concentration of 10 mM. The compound was then graded diluted in DMSO to concentrations of 2000 μM, 500 μM, 125 μM, 32.25 μM, 7.81 μM, 1.95 μM, 0.49 μM, 0.12 μM and 0.031 μM.

3) Adding drugs. Take 1 μL of the diluted compound and add it to 1 ml of complete medium. After mixing, take 100 μL and add it to a 96-well plate. The working concentrations reach 1000 nM, 250 nM, 62.5 nM, 15.6 nM, 3.91 nM, 0.98 nM, 0.24 nM, 0.061 nM, 0.015 nM and 0 nM.

4) Activity detection. The drug treatment was performed for 24 hours and the detection method was based on that of Promega HiBiT Lytic Detection System Instructions.

5) DC50 calculation. Relative IRAK4 (%) = (Lumninence experiment - Lumninence blank) / (Lumninence DMSO - Lumninence blank), calculated by fitting based on log (inhibitor) vs. response -- Variable slope (four parameters).

The experimental results are shown in Table 1, showing the data of the degradation of IRAK4 protein by the compounds of the present invention.
Reference: FLUOROIMIDAZOPYRIDINE COMPOUND AS IRAK4 DEGRADATION AGENT AND USE THEREOF (patent)
Source database: TPDdb
Compound (SMILES): CC(C)(O)c1c(NC(=O)c2cccc(C3CC3(F)F)n2)cn2cc(C3CCN(CC(=O)N4CCN(c5cc6c(cc5F)C(=O)N(C5CCC(=O)NC5=O)C6=O)CC4)CC3)nc2c1F
Modality: PROteolysis-TArgeting Chimera (PROTAC)
Target protein (POI): IRAK4 (UniProt Q9NWZ3)
POI sequence: MNKPITPSTYVRCLNVGLIRKLSDFIDPQEGWKKLAVAIKKPSGDDRYNQFHIRRFEALLQTGKSPTSELLFDWGTTNCTVGDLVDLLIQNEFFAPASLLLPDAVPKTANTLPSKEAITVQQKQMPFCDKDRTLMTPVQNLEQSYMPPDSSSPENKSLEVSDTRFHSFSFYELKNVTNNFDERPISVGGNKMGEGGFGVVYKGYVNNTTVAVKKLAAMVDITTEELKQQFDQEIKVMAKCQHENLVELLGFSSDGDDLCLVYVYMPNGSLLDRLSCLDGTPPLSWHMRCKIAQGAANGINFLHENHHIHRDIKSANILLDEAFTAKISDFGLARASEKFAQTVMTSRIVGTTAYMAPEALRGEITPKSDIYSFGVVLLEIITGLPAVDEHREPQLLLDIKEEIEDEEKTIEDYIDKKMNDADSTSVEAMYSVASQCLHEKKNKRPDIKKVQQLLQEMTAS
E3 ligase: CRBN (UniProt Q96SW2)
Ligase sequence: MAGEGDQQDAAHNMGNHLPLLPAESEEEDEMEVEDQDSKEAKKPNIINFDTSLPTSHTYLGADMEEFHGRTLHDDDSCQVIPVLPQVMMILIPGQTLPLQLFHPQEVSMVRNLIQKDRTFAVLAYSNVQEREAQFGTTAEIYAYREEQDFGIEIVKVKAIGRQRFKVLELRTQSDGIQQAKVQILPECVLPSTMSAVQLESLNKCQIFPSKPVSREDQCSYKWWQKYQKRKFHCANLTSWPRWLYSLYDAETLMDRIKKQLREWDENLKDDSLPSNPIDFSYRVAACLPIDDVLRIQLLKIGSAIQRLRCELDIMNKCTSLCCKQCQETEITTKNEIFSLSLCGPMAAYVNPHGYVHETLTVYKACNLNLIGRPSTEHSWFPGYAWTVAQCKICASHIGWKFTATKKDMSPQKFWGLTRSALLPTIPDTEDEISPDKVILCL
Cell line: HEK293 (Homo sapiens)
Cell line description: Used for the production of the Gamaleya SARS-CoV-2 (COVID-19) vaccine (Trade name
A*02 A*03
In situ; Fetal kidney; 
Vaccine production cell line.
NCBI_TaxID; 28285; Human adenovirus C serotype 5.
Transformed cell line
Assay: Nano-Glo HiBiT Lytic
Dmax:  94 %
Assay description: 1) Cell culture. The culture medium for cell culture is DMEM medium containing inactivated 10% fetal bovine serum, 100U/ml penicillin and 100μg/ml streptomycin. HEK293-IRAK4-Hibit cells are cultured in an incubator at 37°C and 5% CO2 . When the cell confluence reaches 80-90%, the cells are subcultured. Cells in the logarithmic growth phase are used for plating. HEK293-IRAK4-Hibit cells are plated in a 96-well plate with 100μL culture medium, 20,000-30,000 cells per well, and cultured overnight.

2) Compound dilution. The compound was dissolved in DMSO to a concentration of 10 mM. The compound was then graded diluted in DMSO to concentrations of 2000 μM, 500 μM, 125 μM, 32.25 μM, 7.81 μM, 1.95 μM, 0.49 μM, 0.12 μM and 0.031 μM.

3) Adding drugs. Take 1 μL of the diluted compound and add it to 1 ml of complete medium. After mixing, take 100 μL and add it to a 96-well plate. The working concentrations reach 1000 nM, 250 nM, 62.5 nM, 15.6 nM, 3.91 nM, 0.98 nM, 0.24 nM, 0.061 nM, 0.015 nM and 0 nM.

4) Activity detection. The drug treatment was performed for 24 hours and the detection method was based on that of Promega HiBiT Lytic Detection System Instructions.

5) DC50 calculation. Relative IRAK4 (%) = (Lumninence experiment - Lumninence blank) / (Lumninence DMSO - Lumninence blank), calculated by fitting based on log (inhibitor) vs. response -- Variable slope (four parameters).

The experimental results are shown in Table 1, showing the data of the degradation of IRAK4 protein by the compounds of the present invention.
Reference: FLUOROIMIDAZOPYRIDINE COMPOUND AS IRAK4 DEGRADATION AGENT AND USE THEREOF (patent)
Source database: TPDdb
Compound (SMILES): CC(C)(O)c1c(NC(=O)c2cccc(C3CC3(F)F)n2)cn2cc(C3CCN(CC4(O)CN(c5cc6c(cc5F)C(=O)N(C5CCC(=O)NC5=O)C6)C4)CC3)nc2c1F
Modality: PROteolysis-TArgeting Chimera (PROTAC)
Target protein (POI): IRAK4 (UniProt Q9NWZ3)
POI sequence: MNKPITPSTYVRCLNVGLIRKLSDFIDPQEGWKKLAVAIKKPSGDDRYNQFHIRRFEALLQTGKSPTSELLFDWGTTNCTVGDLVDLLIQNEFFAPASLLLPDAVPKTANTLPSKEAITVQQKQMPFCDKDRTLMTPVQNLEQSYMPPDSSSPENKSLEVSDTRFHSFSFYELKNVTNNFDERPISVGGNKMGEGGFGVVYKGYVNNTTVAVKKLAAMVDITTEELKQQFDQEIKVMAKCQHENLVELLGFSSDGDDLCLVYVYMPNGSLLDRLSCLDGTPPLSWHMRCKIAQGAANGINFLHENHHIHRDIKSANILLDEAFTAKISDFGLARASEKFAQTVMTSRIVGTTAYMAPEALRGEITPKSDIYSFGVVLLEIITGLPAVDEHREPQLLLDIKEEIEDEEKTIEDYIDKKMNDADSTSVEAMYSVASQCLHEKKNKRPDIKKVQQLLQEMTAS
E3 ligase: CRBN (UniProt Q96SW2)
Ligase sequence: MAGEGDQQDAAHNMGNHLPLLPAESEEEDEMEVEDQDSKEAKKPNIINFDTSLPTSHTYLGADMEEFHGRTLHDDDSCQVIPVLPQVMMILIPGQTLPLQLFHPQEVSMVRNLIQKDRTFAVLAYSNVQEREAQFGTTAEIYAYREEQDFGIEIVKVKAIGRQRFKVLELRTQSDGIQQAKVQILPECVLPSTMSAVQLESLNKCQIFPSKPVSREDQCSYKWWQKYQKRKFHCANLTSWPRWLYSLYDAETLMDRIKKQLREWDENLKDDSLPSNPIDFSYRVAACLPIDDVLRIQLLKIGSAIQRLRCELDIMNKCTSLCCKQCQETEITTKNEIFSLSLCGPMAAYVNPHGYVHETLTVYKACNLNLIGRPSTEHSWFPGYAWTVAQCKICASHIGWKFTATKKDMSPQKFWGLTRSALLPTIPDTEDEISPDKVILCL
Cell line: HEK293 (Homo sapiens)
Cell line description: Used for the production of the Gamaleya SARS-CoV-2 (COVID-19) vaccine (Trade name
A*02 A*03
In situ; Fetal kidney; 
Vaccine production cell line.
NCBI_TaxID; 28285; Human adenovirus C serotype 5.
Transformed cell line
Assay: Nano-Glo HiBiT Lytic
DC50:  7.41 nM
Assay description: 1) Cell culture. The culture medium for cell culture is DMEM medium containing inactivated 10% fetal bovine serum, 100U/ml penicillin and 100μg/ml streptomycin. HEK293-IRAK4-Hibit cells are cultured in an incubator at 37°C and 5% CO2 . When the cell confluence reaches 80-90%, the cells are subcultured. Cells in the logarithmic growth phase are used for plating. HEK293-IRAK4-Hibit cells are plated in a 96-well plate with 100μL culture medium, 20,000-30,000 cells per well, and cultured overnight.

2) Compound dilution. The compound was dissolved in DMSO to a concentration of 10 mM. The compound was then graded diluted in DMSO to concentrations of 2000 μM, 500 μM, 125 μM, 32.25 μM, 7.81 μM, 1.95 μM, 0.49 μM, 0.12 μM and 0.031 μM.

3) Adding drugs. Take 1 μL of the diluted compound and add it to 1 ml of complete medium. After mixing, take 100 μL and add it to a 96-well plate. The working concentrations reach 1000 nM, 250 nM, 62.5 nM, 15.6 nM, 3.91 nM, 0.98 nM, 0.24 nM, 0.061 nM, 0.015 nM and 0 nM.

4) Activity detection. The drug treatment was performed for 24 hours and the detection method was based on that of Promega HiBiT Lytic Detection System Instructions.

5) DC50 calculation. Relative IRAK4 (%) = (Lumninence experiment - Lumninence blank) / (Lumninence DMSO - Lumninence blank), calculated by fitting based on log (inhibitor) vs. response -- Variable slope (four parameters).

The experimental results are shown in Table 1, showing the data of the degradation of IRAK4 protein by the compounds of the present invention.
Reference: FLUOROIMIDAZOPYRIDINE COMPOUND AS IRAK4 DEGRADATION AGENT AND USE THEREOF (patent)
Source database: TPDdb
Compound (SMILES): CC(C)(O)c1c(NC(=O)c2cccc(C3CC3(F)F)n2)cn2cc(C3CCN(CC4(O)CN(c5cc6c(cc5F)C(=O)N(C5CCC(=O)NC5=O)C6)C4)CC3)nc2c1F
Modality: PROteolysis-TArgeting Chimera (PROTAC)
Target protein (POI): IRAK4 (UniProt Q9NWZ3)
POI sequence: MNKPITPSTYVRCLNVGLIRKLSDFIDPQEGWKKLAVAIKKPSGDDRYNQFHIRRFEALLQTGKSPTSELLFDWGTTNCTVGDLVDLLIQNEFFAPASLLLPDAVPKTANTLPSKEAITVQQKQMPFCDKDRTLMTPVQNLEQSYMPPDSSSPENKSLEVSDTRFHSFSFYELKNVTNNFDERPISVGGNKMGEGGFGVVYKGYVNNTTVAVKKLAAMVDITTEELKQQFDQEIKVMAKCQHENLVELLGFSSDGDDLCLVYVYMPNGSLLDRLSCLDGTPPLSWHMRCKIAQGAANGINFLHENHHIHRDIKSANILLDEAFTAKISDFGLARASEKFAQTVMTSRIVGTTAYMAPEALRGEITPKSDIYSFGVVLLEIITGLPAVDEHREPQLLLDIKEEIEDEEKTIEDYIDKKMNDADSTSVEAMYSVASQCLHEKKNKRPDIKKVQQLLQEMTAS
E3 ligase: CRBN (UniProt Q96SW2)
Ligase sequence: MAGEGDQQDAAHNMGNHLPLLPAESEEEDEMEVEDQDSKEAKKPNIINFDTSLPTSHTYLGADMEEFHGRTLHDDDSCQVIPVLPQVMMILIPGQTLPLQLFHPQEVSMVRNLIQKDRTFAVLAYSNVQEREAQFGTTAEIYAYREEQDFGIEIVKVKAIGRQRFKVLELRTQSDGIQQAKVQILPECVLPSTMSAVQLESLNKCQIFPSKPVSREDQCSYKWWQKYQKRKFHCANLTSWPRWLYSLYDAETLMDRIKKQLREWDENLKDDSLPSNPIDFSYRVAACLPIDDVLRIQLLKIGSAIQRLRCELDIMNKCTSLCCKQCQETEITTKNEIFSLSLCGPMAAYVNPHGYVHETLTVYKACNLNLIGRPSTEHSWFPGYAWTVAQCKICASHIGWKFTATKKDMSPQKFWGLTRSALLPTIPDTEDEISPDKVILCL
Cell line: HEK293 (Homo sapiens)
Cell line description: Used for the production of the Gamaleya SARS-CoV-2 (COVID-19) vaccine (Trade name
A*02 A*03
In situ; Fetal kidney; 
Vaccine production cell line.
NCBI_TaxID; 28285; Human adenovirus C serotype 5.
Transformed cell line
Assay: Nano-Glo HiBiT Lytic
Dmax:  95 %
Assay description: 1) Cell culture. The culture medium for cell culture is DMEM medium containing inactivated 10% fetal bovine serum, 100U/ml penicillin and 100μg/ml streptomycin. HEK293-IRAK4-Hibit cells are cultured in an incubator at 37°C and 5% CO2 . When the cell confluence reaches 80-90%, the cells are subcultured. Cells in the logarithmic growth phase are used for plating. HEK293-IRAK4-Hibit cells are plated in a 96-well plate with 100μL culture medium, 20,000-30,000 cells per well, and cultured overnight.

2) Compound dilution. The compound was dissolved in DMSO to a concentration of 10 mM. The compound was then graded diluted in DMSO to concentrations of 2000 μM, 500 μM, 125 μM, 32.25 μM, 7.81 μM, 1.95 μM, 0.49 μM, 0.12 μM and 0.031 μM.

3) Adding drugs. Take 1 μL of the diluted compound and add it to 1 ml of complete medium. After mixing, take 100 μL and add it to a 96-well plate. The working concentrations reach 1000 nM, 250 nM, 62.5 nM, 15.6 nM, 3.91 nM, 0.98 nM, 0.24 nM, 0.061 nM, 0.015 nM and 0 nM.

4) Activity detection. The drug treatment was performed for 24 hours and the detection method was based on that of Promega HiBiT Lytic Detection System Instructions.

5) DC50 calculation. Relative IRAK4 (%) = (Lumninence experiment - Lumninence blank) / (Lumninence DMSO - Lumninence blank), calculated by fitting based on log (inhibitor) vs. response -- Variable slope (four parameters).

The experimental results are shown in Table 1, showing the data of the degradation of IRAK4 protein by the compounds of the present invention.
Reference: FLUOROIMIDAZOPYRIDINE COMPOUND AS IRAK4 DEGRADATION AGENT AND USE THEREOF (patent)
Source database: TPDdb
Compound (SMILES): CC(C)(O)c1c(NC(=O)c2cccc(C3CC3(F)F)n2)cn2cc(C3CCN(CC4(O)CN(c5cc6c(cc5F)C(=O)N(C5CCC(=O)NC5=O)C6=O)C4)CC3)nc2c1F
Modality: PROteolysis-TArgeting Chimera (PROTAC)
Target protein (POI): IRAK4 (UniProt Q9NWZ3)
POI sequence: MNKPITPSTYVRCLNVGLIRKLSDFIDPQEGWKKLAVAIKKPSGDDRYNQFHIRRFEALLQTGKSPTSELLFDWGTTNCTVGDLVDLLIQNEFFAPASLLLPDAVPKTANTLPSKEAITVQQKQMPFCDKDRTLMTPVQNLEQSYMPPDSSSPENKSLEVSDTRFHSFSFYELKNVTNNFDERPISVGGNKMGEGGFGVVYKGYVNNTTVAVKKLAAMVDITTEELKQQFDQEIKVMAKCQHENLVELLGFSSDGDDLCLVYVYMPNGSLLDRLSCLDGTPPLSWHMRCKIAQGAANGINFLHENHHIHRDIKSANILLDEAFTAKISDFGLARASEKFAQTVMTSRIVGTTAYMAPEALRGEITPKSDIYSFGVVLLEIITGLPAVDEHREPQLLLDIKEEIEDEEKTIEDYIDKKMNDADSTSVEAMYSVASQCLHEKKNKRPDIKKVQQLLQEMTAS
E3 ligase: CRBN (UniProt Q96SW2)
Ligase sequence: MAGEGDQQDAAHNMGNHLPLLPAESEEEDEMEVEDQDSKEAKKPNIINFDTSLPTSHTYLGADMEEFHGRTLHDDDSCQVIPVLPQVMMILIPGQTLPLQLFHPQEVSMVRNLIQKDRTFAVLAYSNVQEREAQFGTTAEIYAYREEQDFGIEIVKVKAIGRQRFKVLELRTQSDGIQQAKVQILPECVLPSTMSAVQLESLNKCQIFPSKPVSREDQCSYKWWQKYQKRKFHCANLTSWPRWLYSLYDAETLMDRIKKQLREWDENLKDDSLPSNPIDFSYRVAACLPIDDVLRIQLLKIGSAIQRLRCELDIMNKCTSLCCKQCQETEITTKNEIFSLSLCGPMAAYVNPHGYVHETLTVYKACNLNLIGRPSTEHSWFPGYAWTVAQCKICASHIGWKFTATKKDMSPQKFWGLTRSALLPTIPDTEDEISPDKVILCL
Cell line: HEK293 (Homo sapiens)
Cell line description: Used for the production of the Gamaleya SARS-CoV-2 (COVID-19) vaccine (Trade name
A*02 A*03
In situ; Fetal kidney; 
Vaccine production cell line.
NCBI_TaxID; 28285; Human adenovirus C serotype 5.
Transformed cell line
Assay: Nano-Glo HiBiT Lytic
DC50:  4.49 nM
Assay description: 1) Cell culture. The culture medium for cell culture is DMEM medium containing inactivated 10% fetal bovine serum, 100U/ml penicillin and 100μg/ml streptomycin. HEK293-IRAK4-Hibit cells are cultured in an incubator at 37°C and 5% CO2 . When the cell confluence reaches 80-90%, the cells are subcultured. Cells in the logarithmic growth phase are used for plating. HEK293-IRAK4-Hibit cells are plated in a 96-well plate with 100μL culture medium, 20,000-30,000 cells per well, and cultured overnight.

2) Compound dilution. The compound was dissolved in DMSO to a concentration of 10 mM. The compound was then graded diluted in DMSO to concentrations of 2000 μM, 500 μM, 125 μM, 32.25 μM, 7.81 μM, 1.95 μM, 0.49 μM, 0.12 μM and 0.031 μM.

3) Adding drugs. Take 1 μL of the diluted compound and add it to 1 ml of complete medium. After mixing, take 100 μL and add it to a 96-well plate. The working concentrations reach 1000 nM, 250 nM, 62.5 nM, 15.6 nM, 3.91 nM, 0.98 nM, 0.24 nM, 0.061 nM, 0.015 nM and 0 nM.

4) Activity detection. The drug treatment was performed for 24 hours and the detection method was based on that of Promega HiBiT Lytic Detection System Instructions.

5) DC50 calculation. Relative IRAK4 (%) = (Lumninence experiment - Lumninence blank) / (Lumninence DMSO - Lumninence blank), calculated by fitting based on log (inhibitor) vs. response -- Variable slope (four parameters).

The experimental results are shown in Table 1, showing the data of the degradation of IRAK4 protein by the compounds of the present invention.
Reference: FLUOROIMIDAZOPYRIDINE COMPOUND AS IRAK4 DEGRADATION AGENT AND USE THEREOF (patent)
Source database: TPDdb
Compound (SMILES): CC(C)(O)c1c(NC(=O)c2cccc(C3CC3(F)F)n2)cn2cc(C3CCN(CC4(O)CN(c5cc6c(cc5F)C(=O)N(C5CCC(=O)NC5=O)C6=O)C4)CC3)nc2c1F
Modality: PROteolysis-TArgeting Chimera (PROTAC)
Target protein (POI): IRAK4 (UniProt Q9NWZ3)
POI sequence: MNKPITPSTYVRCLNVGLIRKLSDFIDPQEGWKKLAVAIKKPSGDDRYNQFHIRRFEALLQTGKSPTSELLFDWGTTNCTVGDLVDLLIQNEFFAPASLLLPDAVPKTANTLPSKEAITVQQKQMPFCDKDRTLMTPVQNLEQSYMPPDSSSPENKSLEVSDTRFHSFSFYELKNVTNNFDERPISVGGNKMGEGGFGVVYKGYVNNTTVAVKKLAAMVDITTEELKQQFDQEIKVMAKCQHENLVELLGFSSDGDDLCLVYVYMPNGSLLDRLSCLDGTPPLSWHMRCKIAQGAANGINFLHENHHIHRDIKSANILLDEAFTAKISDFGLARASEKFAQTVMTSRIVGTTAYMAPEALRGEITPKSDIYSFGVVLLEIITGLPAVDEHREPQLLLDIKEEIEDEEKTIEDYIDKKMNDADSTSVEAMYSVASQCLHEKKNKRPDIKKVQQLLQEMTAS
E3 ligase: CRBN (UniProt Q96SW2)
Ligase sequence: MAGEGDQQDAAHNMGNHLPLLPAESEEEDEMEVEDQDSKEAKKPNIINFDTSLPTSHTYLGADMEEFHGRTLHDDDSCQVIPVLPQVMMILIPGQTLPLQLFHPQEVSMVRNLIQKDRTFAVLAYSNVQEREAQFGTTAEIYAYREEQDFGIEIVKVKAIGRQRFKVLELRTQSDGIQQAKVQILPECVLPSTMSAVQLESLNKCQIFPSKPVSREDQCSYKWWQKYQKRKFHCANLTSWPRWLYSLYDAETLMDRIKKQLREWDENLKDDSLPSNPIDFSYRVAACLPIDDVLRIQLLKIGSAIQRLRCELDIMNKCTSLCCKQCQETEITTKNEIFSLSLCGPMAAYVNPHGYVHETLTVYKACNLNLIGRPSTEHSWFPGYAWTVAQCKICASHIGWKFTATKKDMSPQKFWGLTRSALLPTIPDTEDEISPDKVILCL
Cell line: HEK293 (Homo sapiens)
Cell line description: Used for the production of the Gamaleya SARS-CoV-2 (COVID-19) vaccine (Trade name
A*02 A*03
In situ; Fetal kidney; 
Vaccine production cell line.
NCBI_TaxID; 28285; Human adenovirus C serotype 5.
Transformed cell line
Assay: Nano-Glo HiBiT Lytic
Dmax:  95 %
Assay description: 1) Cell culture. The culture medium for cell culture is DMEM medium containing inactivated 10% fetal bovine serum, 100U/ml penicillin and 100μg/ml streptomycin. HEK293-IRAK4-Hibit cells are cultured in an incubator at 37°C and 5% CO2 . When the cell confluence reaches 80-90%, the cells are subcultured. Cells in the logarithmic growth phase are used for plating. HEK293-IRAK4-Hibit cells are plated in a 96-well plate with 100μL culture medium, 20,000-30,000 cells per well, and cultured overnight.

2) Compound dilution. The compound was dissolved in DMSO to a concentration of 10 mM. The compound was then graded diluted in DMSO to concentrations of 2000 μM, 500 μM, 125 μM, 32.25 μM, 7.81 μM, 1.95 μM, 0.49 μM, 0.12 μM and 0.031 μM.

3) Adding drugs. Take 1 μL of the diluted compound and add it to 1 ml of complete medium. After mixing, take 100 μL and add it to a 96-well plate. The working concentrations reach 1000 nM, 250 nM, 62.5 nM, 15.6 nM, 3.91 nM, 0.98 nM, 0.24 nM, 0.061 nM, 0.015 nM and 0 nM.

4) Activity detection. The drug treatment was performed for 24 hours and the detection method was based on that of Promega HiBiT Lytic Detection System Instructions.

5) DC50 calculation. Relative IRAK4 (%) = (Lumninence experiment - Lumninence blank) / (Lumninence DMSO - Lumninence blank), calculated by fitting based on log (inhibitor) vs. response -- Variable slope (four parameters).

The experimental results are shown in Table 1, showing the data of the degradation of IRAK4 protein by the compounds of the present invention.
Reference: FLUOROIMIDAZOPYRIDINE COMPOUND AS IRAK4 DEGRADATION AGENT AND USE THEREOF (patent)
Source database: TPDdb
Compound (SMILES): CC(C)(O)c1c(NC(=O)c2cccc(C3CC3(F)F)n2)cn2cc(C3CCN(CC4CN(c5cc6c(cc5F)C(=O)N(C5CCC(=O)NC5=O)C6=O)C4)CC3)nc2c1F
Modality: PROteolysis-TArgeting Chimera (PROTAC)
Target protein (POI): IRAK4 (UniProt Q9NWZ3)
POI sequence: MNKPITPSTYVRCLNVGLIRKLSDFIDPQEGWKKLAVAIKKPSGDDRYNQFHIRRFEALLQTGKSPTSELLFDWGTTNCTVGDLVDLLIQNEFFAPASLLLPDAVPKTANTLPSKEAITVQQKQMPFCDKDRTLMTPVQNLEQSYMPPDSSSPENKSLEVSDTRFHSFSFYELKNVTNNFDERPISVGGNKMGEGGFGVVYKGYVNNTTVAVKKLAAMVDITTEELKQQFDQEIKVMAKCQHENLVELLGFSSDGDDLCLVYVYMPNGSLLDRLSCLDGTPPLSWHMRCKIAQGAANGINFLHENHHIHRDIKSANILLDEAFTAKISDFGLARASEKFAQTVMTSRIVGTTAYMAPEALRGEITPKSDIYSFGVVLLEIITGLPAVDEHREPQLLLDIKEEIEDEEKTIEDYIDKKMNDADSTSVEAMYSVASQCLHEKKNKRPDIKKVQQLLQEMTAS
E3 ligase: CRBN (UniProt Q96SW2)
Ligase sequence: MAGEGDQQDAAHNMGNHLPLLPAESEEEDEMEVEDQDSKEAKKPNIINFDTSLPTSHTYLGADMEEFHGRTLHDDDSCQVIPVLPQVMMILIPGQTLPLQLFHPQEVSMVRNLIQKDRTFAVLAYSNVQEREAQFGTTAEIYAYREEQDFGIEIVKVKAIGRQRFKVLELRTQSDGIQQAKVQILPECVLPSTMSAVQLESLNKCQIFPSKPVSREDQCSYKWWQKYQKRKFHCANLTSWPRWLYSLYDAETLMDRIKKQLREWDENLKDDSLPSNPIDFSYRVAACLPIDDVLRIQLLKIGSAIQRLRCELDIMNKCTSLCCKQCQETEITTKNEIFSLSLCGPMAAYVNPHGYVHETLTVYKACNLNLIGRPSTEHSWFPGYAWTVAQCKICASHIGWKFTATKKDMSPQKFWGLTRSALLPTIPDTEDEISPDKVILCL
Cell line: HEK293 (Homo sapiens)
Cell line description: Used for the production of the Gamaleya SARS-CoV-2 (COVID-19) vaccine (Trade name
A*02 A*03
In situ; Fetal kidney; 
Vaccine production cell line.
NCBI_TaxID; 28285; Human adenovirus C serotype 5.
Transformed cell line
Assay: Nano-Glo HiBiT Lytic
DC50:  5 nM
Assay description: 1) Cell culture. The culture medium for cell culture is DMEM medium containing inactivated 10% fetal bovine serum, 100U/ml penicillin and 100μg/ml streptomycin. HEK293-IRAK4-Hibit cells are cultured in an incubator at 37°C and 5% CO2 . When the cell confluence reaches 80-90%, the cells are subcultured. Cells in the logarithmic growth phase are used for plating. HEK293-IRAK4-Hibit cells are plated in a 96-well plate with 100μL culture medium, 20,000-30,000 cells per well, and cultured overnight.

2) Compound dilution. The compound was dissolved in DMSO to a concentration of 10 mM. The compound was then graded diluted in DMSO to concentrations of 2000 μM, 500 μM, 125 μM, 32.25 μM, 7.81 μM, 1.95 μM, 0.49 μM, 0.12 μM and 0.031 μM.

3) Adding drugs. Take 1 μL of the diluted compound and add it to 1 ml of complete medium. After mixing, take 100 μL and add it to a 96-well plate. The working concentrations reach 1000 nM, 250 nM, 62.5 nM, 15.6 nM, 3.91 nM, 0.98 nM, 0.24 nM, 0.061 nM, 0.015 nM and 0 nM.

4) Activity detection. The drug treatment was performed for 24 hours and the detection method was based on that of Promega HiBiT Lytic Detection System Instructions.

5) DC50 calculation. Relative IRAK4 (%) = (Lumninence experiment - Lumninence blank) / (Lumninence DMSO - Lumninence blank), calculated by fitting based on log (inhibitor) vs. response -- Variable slope (four parameters).

The experimental results are shown in Table 1, showing the data of the degradation of IRAK4 protein by the compounds of the present invention.
Reference: FLUOROIMIDAZOPYRIDINE COMPOUND AS IRAK4 DEGRADATION AGENT AND USE THEREOF (patent)
Source database: TPDdb
Compound (SMILES): CC(C)(O)c1c(NC(=O)c2cccc(C3CC3(F)F)n2)cn2cc(C3CCN(CC4CN(c5cc6c(cc5F)C(=O)N(C5CCC(=O)NC5=O)C6=O)C4)CC3)nc2c1F
Modality: PROteolysis-TArgeting Chimera (PROTAC)
Target protein (POI): IRAK4 (UniProt Q9NWZ3)
POI sequence: MNKPITPSTYVRCLNVGLIRKLSDFIDPQEGWKKLAVAIKKPSGDDRYNQFHIRRFEALLQTGKSPTSELLFDWGTTNCTVGDLVDLLIQNEFFAPASLLLPDAVPKTANTLPSKEAITVQQKQMPFCDKDRTLMTPVQNLEQSYMPPDSSSPENKSLEVSDTRFHSFSFYELKNVTNNFDERPISVGGNKMGEGGFGVVYKGYVNNTTVAVKKLAAMVDITTEELKQQFDQEIKVMAKCQHENLVELLGFSSDGDDLCLVYVYMPNGSLLDRLSCLDGTPPLSWHMRCKIAQGAANGINFLHENHHIHRDIKSANILLDEAFTAKISDFGLARASEKFAQTVMTSRIVGTTAYMAPEALRGEITPKSDIYSFGVVLLEIITGLPAVDEHREPQLLLDIKEEIEDEEKTIEDYIDKKMNDADSTSVEAMYSVASQCLHEKKNKRPDIKKVQQLLQEMTAS
E3 ligase: CRBN (UniProt Q96SW2)
Ligase sequence: MAGEGDQQDAAHNMGNHLPLLPAESEEEDEMEVEDQDSKEAKKPNIINFDTSLPTSHTYLGADMEEFHGRTLHDDDSCQVIPVLPQVMMILIPGQTLPLQLFHPQEVSMVRNLIQKDRTFAVLAYSNVQEREAQFGTTAEIYAYREEQDFGIEIVKVKAIGRQRFKVLELRTQSDGIQQAKVQILPECVLPSTMSAVQLESLNKCQIFPSKPVSREDQCSYKWWQKYQKRKFHCANLTSWPRWLYSLYDAETLMDRIKKQLREWDENLKDDSLPSNPIDFSYRVAACLPIDDVLRIQLLKIGSAIQRLRCELDIMNKCTSLCCKQCQETEITTKNEIFSLSLCGPMAAYVNPHGYVHETLTVYKACNLNLIGRPSTEHSWFPGYAWTVAQCKICASHIGWKFTATKKDMSPQKFWGLTRSALLPTIPDTEDEISPDKVILCL
Cell line: HEK293 (Homo sapiens)
Cell line description: Used for the production of the Gamaleya SARS-CoV-2 (COVID-19) vaccine (Trade name
A*02 A*03
In situ; Fetal kidney; 
Vaccine production cell line.
NCBI_TaxID; 28285; Human adenovirus C serotype 5.
Transformed cell line
Assay: Nano-Glo HiBiT Lytic
Dmax:  96 %
Assay description: 1) Cell culture. The culture medium for cell culture is DMEM medium containing inactivated 10% fetal bovine serum, 100U/ml penicillin and 100μg/ml streptomycin. HEK293-IRAK4-Hibit cells are cultured in an incubator at 37°C and 5% CO2 . When the cell confluence reaches 80-90%, the cells are subcultured. Cells in the logarithmic growth phase are used for plating. HEK293-IRAK4-Hibit cells are plated in a 96-well plate with 100μL culture medium, 20,000-30,000 cells per well, and cultured overnight.

2) Compound dilution. The compound was dissolved in DMSO to a concentration of 10 mM. The compound was then graded diluted in DMSO to concentrations of 2000 μM, 500 μM, 125 μM, 32.25 μM, 7.81 μM, 1.95 μM, 0.49 μM, 0.12 μM and 0.031 μM.

3) Adding drugs. Take 1 μL of the diluted compound and add it to 1 ml of complete medium. After mixing, take 100 μL and add it to a 96-well plate. The working concentrations reach 1000 nM, 250 nM, 62.5 nM, 15.6 nM, 3.91 nM, 0.98 nM, 0.24 nM, 0.061 nM, 0.015 nM and 0 nM.

4) Activity detection. The drug treatment was performed for 24 hours and the detection method was based on that of Promega HiBiT Lytic Detection System Instructions.

5) DC50 calculation. Relative IRAK4 (%) = (Lumninence experiment - Lumninence blank) / (Lumninence DMSO - Lumninence blank), calculated by fitting based on log (inhibitor) vs. response -- Variable slope (four parameters).

The experimental results are shown in Table 1, showing the data of the degradation of IRAK4 protein by the compounds of the present invention.
Reference: FLUOROIMIDAZOPYRIDINE COMPOUND AS IRAK4 DEGRADATION AGENT AND USE THEREOF (patent)
Source database: TPDdb
Compound (SMILES): CC(C)(O)c1c(NC(=O)c2cccc(C3CC3(F)F)n2)cn2cc(C3CCN(S(=O)(=O)C4CCN(c5cc6c(cc5F)C(=O)N(C5CCC(=O)NC5=O)C6=O)CC4)CC3)nc2c1F
Modality: PROteolysis-TArgeting Chimera (PROTAC)
Target protein (POI): IRAK4 (UniProt Q9NWZ3)
POI sequence: MNKPITPSTYVRCLNVGLIRKLSDFIDPQEGWKKLAVAIKKPSGDDRYNQFHIRRFEALLQTGKSPTSELLFDWGTTNCTVGDLVDLLIQNEFFAPASLLLPDAVPKTANTLPSKEAITVQQKQMPFCDKDRTLMTPVQNLEQSYMPPDSSSPENKSLEVSDTRFHSFSFYELKNVTNNFDERPISVGGNKMGEGGFGVVYKGYVNNTTVAVKKLAAMVDITTEELKQQFDQEIKVMAKCQHENLVELLGFSSDGDDLCLVYVYMPNGSLLDRLSCLDGTPPLSWHMRCKIAQGAANGINFLHENHHIHRDIKSANILLDEAFTAKISDFGLARASEKFAQTVMTSRIVGTTAYMAPEALRGEITPKSDIYSFGVVLLEIITGLPAVDEHREPQLLLDIKEEIEDEEKTIEDYIDKKMNDADSTSVEAMYSVASQCLHEKKNKRPDIKKVQQLLQEMTAS
E3 ligase: CRBN (UniProt Q96SW2)
Ligase sequence: MAGEGDQQDAAHNMGNHLPLLPAESEEEDEMEVEDQDSKEAKKPNIINFDTSLPTSHTYLGADMEEFHGRTLHDDDSCQVIPVLPQVMMILIPGQTLPLQLFHPQEVSMVRNLIQKDRTFAVLAYSNVQEREAQFGTTAEIYAYREEQDFGIEIVKVKAIGRQRFKVLELRTQSDGIQQAKVQILPECVLPSTMSAVQLESLNKCQIFPSKPVSREDQCSYKWWQKYQKRKFHCANLTSWPRWLYSLYDAETLMDRIKKQLREWDENLKDDSLPSNPIDFSYRVAACLPIDDVLRIQLLKIGSAIQRLRCELDIMNKCTSLCCKQCQETEITTKNEIFSLSLCGPMAAYVNPHGYVHETLTVYKACNLNLIGRPSTEHSWFPGYAWTVAQCKICASHIGWKFTATKKDMSPQKFWGLTRSALLPTIPDTEDEISPDKVILCL
Cell line: HEK293 (Homo sapiens)
Cell line description: Used for the production of the Gamaleya SARS-CoV-2 (COVID-19) vaccine (Trade name
A*02 A*03
In situ; Fetal kidney; 
Vaccine production cell line.
NCBI_TaxID; 28285; Human adenovirus C serotype 5.
Transformed cell line
Assay: Nano-Glo HiBiT Lytic
DC50:  10.4 nM
Assay description: 1) Cell culture. The culture medium for cell culture is DMEM medium containing inactivated 10% fetal bovine serum, 100U/ml penicillin and 100μg/ml streptomycin. HEK293-IRAK4-Hibit cells are cultured in an incubator at 37°C and 5% CO2 . When the cell confluence reaches 80-90%, the cells are subcultured. Cells in the logarithmic growth phase are used for plating. HEK293-IRAK4-Hibit cells are plated in a 96-well plate with 100μL culture medium, 20,000-30,000 cells per well, and cultured overnight.

2) Compound dilution. The compound was dissolved in DMSO to a concentration of 10 mM. The compound was then graded diluted in DMSO to concentrations of 2000 μM, 500 μM, 125 μM, 32.25 μM, 7.81 μM, 1.95 μM, 0.49 μM, 0.12 μM and 0.031 μM.

3) Adding drugs. Take 1 μL of the diluted compound and add it to 1 ml of complete medium. After mixing, take 100 μL and add it to a 96-well plate. The working concentrations reach 1000 nM, 250 nM, 62.5 nM, 15.6 nM, 3.91 nM, 0.98 nM, 0.24 nM, 0.061 nM, 0.015 nM and 0 nM.

4) Activity detection. The drug treatment was performed for 24 hours and the detection method was based on that of Promega HiBiT Lytic Detection System Instructions.

5) DC50 calculation. Relative IRAK4 (%) = (Lumninence experiment - Lumninence blank) / (Lumninence DMSO - Lumninence blank), calculated by fitting based on log (inhibitor) vs. response -- Variable slope (four parameters).

The experimental results are shown in Table 1, showing the data of the degradation of IRAK4 protein by the compounds of the present invention.
Reference: FLUOROIMIDAZOPYRIDINE COMPOUND AS IRAK4 DEGRADATION AGENT AND USE THEREOF (patent)
Source database: TPDdb
Compound (SMILES): CC(C)(O)c1c(NC(=O)c2cccc(C3CC3(F)F)n2)cn2cc(C3CCN(S(=O)(=O)C4CCN(c5cc6c(cc5F)C(=O)N(C5CCC(=O)NC5=O)C6=O)CC4)CC3)nc2c1F
Modality: PROteolysis-TArgeting Chimera (PROTAC)
Target protein (POI): IRAK4 (UniProt Q9NWZ3)
POI sequence: MNKPITPSTYVRCLNVGLIRKLSDFIDPQEGWKKLAVAIKKPSGDDRYNQFHIRRFEALLQTGKSPTSELLFDWGTTNCTVGDLVDLLIQNEFFAPASLLLPDAVPKTANTLPSKEAITVQQKQMPFCDKDRTLMTPVQNLEQSYMPPDSSSPENKSLEVSDTRFHSFSFYELKNVTNNFDERPISVGGNKMGEGGFGVVYKGYVNNTTVAVKKLAAMVDITTEELKQQFDQEIKVMAKCQHENLVELLGFSSDGDDLCLVYVYMPNGSLLDRLSCLDGTPPLSWHMRCKIAQGAANGINFLHENHHIHRDIKSANILLDEAFTAKISDFGLARASEKFAQTVMTSRIVGTTAYMAPEALRGEITPKSDIYSFGVVLLEIITGLPAVDEHREPQLLLDIKEEIEDEEKTIEDYIDKKMNDADSTSVEAMYSVASQCLHEKKNKRPDIKKVQQLLQEMTAS
E3 ligase: CRBN (UniProt Q96SW2)
Ligase sequence: MAGEGDQQDAAHNMGNHLPLLPAESEEEDEMEVEDQDSKEAKKPNIINFDTSLPTSHTYLGADMEEFHGRTLHDDDSCQVIPVLPQVMMILIPGQTLPLQLFHPQEVSMVRNLIQKDRTFAVLAYSNVQEREAQFGTTAEIYAYREEQDFGIEIVKVKAIGRQRFKVLELRTQSDGIQQAKVQILPECVLPSTMSAVQLESLNKCQIFPSKPVSREDQCSYKWWQKYQKRKFHCANLTSWPRWLYSLYDAETLMDRIKKQLREWDENLKDDSLPSNPIDFSYRVAACLPIDDVLRIQLLKIGSAIQRLRCELDIMNKCTSLCCKQCQETEITTKNEIFSLSLCGPMAAYVNPHGYVHETLTVYKACNLNLIGRPSTEHSWFPGYAWTVAQCKICASHIGWKFTATKKDMSPQKFWGLTRSALLPTIPDTEDEISPDKVILCL
Cell line: HEK293 (Homo sapiens)
Cell line description: Used for the production of the Gamaleya SARS-CoV-2 (COVID-19) vaccine (Trade name
A*02 A*03
In situ; Fetal kidney; 
Vaccine production cell line.
NCBI_TaxID; 28285; Human adenovirus C serotype 5.
Transformed cell line
Assay: Nano-Glo HiBiT Lytic
Dmax:  94 %
Assay description: 1) Cell culture. The culture medium for cell culture is DMEM medium containing inactivated 10% fetal bovine serum, 100U/ml penicillin and 100μg/ml streptomycin. HEK293-IRAK4-Hibit cells are cultured in an incubator at 37°C and 5% CO2 . When the cell confluence reaches 80-90%, the cells are subcultured. Cells in the logarithmic growth phase are used for plating. HEK293-IRAK4-Hibit cells are plated in a 96-well plate with 100μL culture medium, 20,000-30,000 cells per well, and cultured overnight.

2) Compound dilution. The compound was dissolved in DMSO to a concentration of 10 mM. The compound was then graded diluted in DMSO to concentrations of 2000 μM, 500 μM, 125 μM, 32.25 μM, 7.81 μM, 1.95 μM, 0.49 μM, 0.12 μM and 0.031 μM.

3) Adding drugs. Take 1 μL of the diluted compound and add it to 1 ml of complete medium. After mixing, take 100 μL and add it to a 96-well plate. The working concentrations reach 1000 nM, 250 nM, 62.5 nM, 15.6 nM, 3.91 nM, 0.98 nM, 0.24 nM, 0.061 nM, 0.015 nM and 0 nM.

4) Activity detection. The drug treatment was performed for 24 hours and the detection method was based on that of Promega HiBiT Lytic Detection System Instructions.

5) DC50 calculation. Relative IRAK4 (%) = (Lumninence experiment - Lumninence blank) / (Lumninence DMSO - Lumninence blank), calculated by fitting based on log (inhibitor) vs. response -- Variable slope (four parameters).

The experimental results are shown in Table 1, showing the data of the degradation of IRAK4 protein by the compounds of the present invention.
Reference: FLUOROIMIDAZOPYRIDINE COMPOUND AS IRAK4 DEGRADATION AGENT AND USE THEREOF (patent)
Source database: TPDdb