lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1cc2c(cc1-c1c(C)noc1C)[nH]c1ccnc(-c3c(C)nn(C)c3C)c12
InChIKey: SDJOVLUEILKTJF-UHFFFAOYSA-N
Target: Bromodomain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25440
Assay: FP Competitive Binding Assay (No.350): Fluorescence Polarization (FP) competitive binding studies (see above) were carried out using the FAM labeled fluorescent probe Cpd. No. 350 to determine binding affinities of representative compounds to both BD1 and BD2 of BRD2, BRD3, and BRD4 proteins. Equilibrium dissociation constants (Id) values of Cpd. No. 350 to these six proteins were determined from protein saturation experiments by monitoring the total fluorescence polarization of mixtures composed with the fluorescent probe at a fixed concentration and proteins with increasing concentrations up to full saturation. Serial dilutions of testing protein were mixed with Cpd. No. 350 to a final volume of 200 μl in the assay buffer. In order to achieve large dynamic rages, particularly for BD1 bromodomains, 100 mM phosphate buffer (pH=6.5, 0.01% Triton X-100 (Sigma, 282103) being added right before assays) was used as the assay buffer. Final Cpd. No. 350 concentration was 1.5 nM for all proteins. Plates were incubated at room temperature for 30 minutes with gentle shaking to assure equilibrium. FP values in millipolarization units (mP) were measured using the Infinite M-1000 plate reader (Tecan U.S., Research Triangle Park, N.C.) in Microfluor 1 96-well, black, round-bottom plates (Thermo Scientific, Waltham, Mass.) at an excitation wavelength of 485 nm and an emission wavelength of 530 nm. Kd values of Cpd. No. 350, which were calculated by fitting the sigmoidal dose-dependent FP increases as a function of protein concentrations using Graphpad Prism 6.0 software (Graphpad Software, San Diego, Calif.), are 2.0, 2.2, 6.5, 0.6, 5.5, and 3.0 nM to BRD2 BD1 and 2, BRD3 BD1 and 2, and BDR4 BD1 and 2, respectively.
Measurement: Ki = 134 nM (pChEMBL 6.869999885559082)
Descriptors: MW 401.47, ALogP 5.01, HBA 6, HBD 1, PSA 81.76, QED 0.46
Compound (SMILES): CCc1n[nH]c(CC)c1-c1nccc2[nH]c3cc(-c4c(C)noc4C)c(OC)cc3c12
InChIKey: XOEVAYXDSJABMS-UHFFFAOYSA-N
Target: Bromodomain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25440
Assay: Biolayer Interferometry (BLI) Binding Assay: Biotin labeled BRD proteins (10 μg/ml) in kinetic assay buffer (PBS, pH 7.4, 0.1% BSA and 0.01% Tween-20) were immobilized on Super Streptavidin (SSA) sensors for 15 minutes followed by washing in kinetic buffer for 10 minutes to eliminate any loose non-specific immobilization. In the same 96-well plate serial dilutions of testing compounds with concentrations typically ranging from 0.1-10 times of expected Kd values in the identical assay buffer were prepared. These protein coated sensors were then immersed into the testing compound solutions, starting from the one with the lowest concentration, where compound association occurs and then returned to the fresh buffer for the dissociation. The same operation was repeated for the next solution with higher concentration up to the one with the highest concentration. Identical procedure was performed again with control sensors that were immobilized with SAB4 inactive control protein prepared by following protocols from the manufacturer. Blank buffer controls were included in both BRD protein sensor and inactive protein sensor runs. For each kinetic cycle, kinetic curves for association and dissociation were obtained from raw sensorgrams by using the double reference subtraction protocol included in the analysis program (Data Analysis 7.0) provided by the manufacturer, in which nonspecific interaction and buffer drift were both corrected. The association and dissociation rate constants (kon and koff) were determined using the global fitting protocol in the analysis program based on a reversible 1:1 binding model. The equilibrium association constant (KA) was calculated thereafter. All binding data were collected at 30 degree. Assay plates were kept being shaken at 1000 RPM in the whole experiment time period to avoid mass transport effect.
Measurement: Kd = 34 nM (pChEMBL 7.46999979019165)
Descriptors: MW 415.5, ALogP 5.51, HBA 5, HBD 2, PSA 92.62, QED 0.39
Compound (SMILES): COc1cc2c(cc1-c1c(C)noc1C)[nH]c1ccnc(-c3c(C4CC4)n[nH]c3C)c12
InChIKey: WHDUHJYPRJXLGF-UHFFFAOYSA-N
Target: Bromodomain-containing protein 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15059
Assay: Binding affinity to biotinylated BRD3 BD1 (24 to 144 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells by bio-layer interferometry method
Measurement: Kd = 17.7 nM (pChEMBL 7.75)
Descriptors: MW 413.48, ALogP 5.57, HBA 5, HBD 2, PSA 92.62, QED 0.4
Compound (SMILES): CCNC(=O)NCCSC[C@H]1O[C@@H](n2cnc3c(N)ncnc32)[C@H](O)[C@@H]1O
InChIKey: CACMCLIHCDTJHL-IDTAVKCVSA-N
Target: Protein arginine N-methyltransferase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: O14744
Assay: Affinity Biochemical interaction: (Enzyme inhibition assay-SPA) EUB0002223a PRMT5
Measurement: IC50 = 5900 nM (pChEMBL 5.230000019073486)
Descriptors: MW 397.46, ALogP -0.92, HBA 10, HBD 5, PSA 160.44, QED 0.37
Compound (SMILES): C[C@H](c1ccc(F)cc1)N(Cc1cccc(C(=O)O)c1)C(=O)c1cnc2ccccc2c1
InChIKey: BXNMZRPTQFVRFA-QGZVFWFLSA-N
Target: Transient receptor potential cation channel subfamily M member 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q7Z2W7
Assay: Affinity Biochemical interaction (FLIPR assay) EUB0000304b TRPM8
Measurement: IC50 = 181 nM (pChEMBL 6.739999771118164)
Descriptors: MW 428.46, ALogP 5.48, HBA 3, HBD 1, PSA 70.5, QED 0.44
Compound (SMILES): C[C@@H]1NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]2CCCN2C(=O)[C@H]2CCCN2C(=O)[C@H](Cc2ccccc2)NC1=O
InChIKey: MTKQTEXYJKPBQD-GNDHHEKASA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P32245
Assay: Displacement of [125I]-NDP-MSH from human melanocortin receptor 4 expressed in HEK293 cell mebranes incubated for 1 hr by automatic gamma counting method
Measurement: IC50 = 70 nM (pChEMBL 7.159999847412109)
Descriptors: MW 977.14, ALogP -1.22, HBA 10, HBD 10, PSA 320.21, QED 0.06
Compound (SMILES): Cc1oc(=O)oc1COC(=O)[C@@H]1N2C(=O)[C@@H](NC(=O)[C@H](N)c3ccccc3)[C@H]2SC1(C)C
InChIKey: ZKUKMWMSYCIYRD-ZXFNITATSA-N
Target: Progesterone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06401
Assay: Binding affinity towards human PGR in an in vitro assay with cellular components measured by scintillation counting
Measurement: AC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 461.5, ALogP 0.83, HBA 9, HBD 2, PSA 145.08, QED 0.47
Compound (SMILES): CN1CCN(C(=O)C[C@H](NC(=O)/C=C/c2cc(Cl)ccc2-n2cnnn2)c2nc(-c3ccc4[nH]c(=O)cc(O)c4c3)c(Cl)[nH]2)CC1
InChIKey: NBMJTOOHXJGJNZ-RJOTYRNVSA-N
Target: Coagulation factor IX (SINGLE PROTEIN), Homo sapiens
UniProt: P00740
Assay: Inhibition of coagulation factor 9a (unknown origin)
Measurement: Ki > 60000 nM (pChEMBL 4.2220001220703125)
Descriptors: MW 663.53, ALogP 2.94, HBA 10, HBD 4, PSA 178.02, QED 0.18
Compound (SMILES): N=C(N)NCCC[C@@H]1NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccc(O)cc2)NC(=O)[C@@H]2CCCN2C(=O)[C@H](Cc2ccc3ccccc3c2)NC1=O
InChIKey: AVNDVFCGYOONJV-LUKCZKMGSA-N
Target: Atypical chemokine receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P25106
Assay: Agonist activity at CXCR7 D179N mutant (unknown origin) expressed in HEK293E cells co-transfected with receptor-eYFP construct and beta-arrestin2-Rluc assessed as induction of receptor-mediated beta-arrestin recruitment by BRET assay
Measurement: EC50 = 3981.07 nM (pChEMBL 5.400000095367432)
Descriptors: MW 769.91, ALogP -0.2, HBA 8, HBD 11, PSA 280.74, QED 0.07
Compound (SMILES): CN1C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccc(O)cc2)NC(=O)[C@@H]2CCCN2C(=O)[C@H](Cc2ccc3ccccc3c2)NC(=O)[C@@H]1CCCNC(=N)N
InChIKey: LTTCRTAQQFHLPF-WUXKFAKNSA-N
Target: Atypical chemokine receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P25106
Assay: Agonist activity at CXCR7 D179N mutant (unknown origin) expressed in HEK293E cells co-transfected with receptor-eYFP construct and beta-arrestin2-Rluc assessed as induction of receptor-mediated beta-arrestin recruitment by BRET assay
Measurement: EC50 = 1995.26 nM (pChEMBL 5.699999809265137)
Descriptors: MW 783.94, ALogP 0.14, HBA 8, HBD 10, PSA 271.95, QED 0.07
Compound (SMILES): Cc1sc2c(c1C)C(c1ccc(Cl)cc1)=N[C@@H](CC(=O)Nc1ccc(O)cc1)c1nnc(C)n1-2
InChIKey: GNMUEVRJHCWKTO-FQEVSTJZSA-N
Target: Bromodomain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25440
Assay: Inhibition of acetylated H4 binding to BRD2 (unknown origin)
Measurement: IC50 = 92 nM (pChEMBL 7.039999961853027)
Descriptors: MW 492, ALogP 5.53, HBA 7, HBD 2, PSA 92.4, QED 0.37
Compound (SMILES): COc1cc2c(cc1-c1c(C)noc1C)[nH]c1ccncc12
InChIKey: NCPRCNJIGPDNGS-UHFFFAOYSA-N
Target: Bromodomain-containing protein 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15059
Assay: FP Competitive Binding Assay (No.350): Fluorescence Polarization (FP) competitive binding studies (see above) were carried out using the FAM labeled fluorescent probe Cpd. No. 350 to determine binding affinities of representative compounds to both BD1 and BD2 of BRD2, BRD3, and BRD4 proteins. Equilibrium dissociation constants (Id) values of Cpd. No. 350 to these six proteins were determined from protein saturation experiments by monitoring the total fluorescence polarization of mixtures composed with the fluorescent probe at a fixed concentration and proteins with increasing concentrations up to full saturation. Serial dilutions of testing protein were mixed with Cpd. No. 350 to a final volume of 200 μl in the assay buffer. In order to achieve large dynamic rages, particularly for BD1 bromodomains, 100 mM phosphate buffer (pH=6.5, 0.01% Triton X-100 (Sigma, 282103) being added right before assays) was used as the assay buffer. Final Cpd. No. 350 concentration was 1.5 nM for all proteins. Plates were incubated at room temperature for 30 minutes with gentle shaking to assure equilibrium. FP values in millipolarization units (mP) were measured using the Infinite M-1000 plate reader (Tecan U.S., Research Triangle Park, N.C.) in Microfluor 1 96-well, black, round-bottom plates (Thermo Scientific, Waltham, Mass.) at an excitation wavelength of 485 nm and an emission wavelength of 530 nm. Kd values of Cpd. No. 350, which were calculated by fitting the sigmoidal dose-dependent FP increases as a function of protein concentrations using Graphpad Prism 6.0 software (Graphpad Software, San Diego, Calif.), are 2.0, 2.2, 6.5, 0.6, 5.5, and 3.0 nM to BRD2 BD1 and 2, BRD3 BD1 and 2, and BDR4 BD1 and 2, respectively.
Measurement: Ki = 730 nM (pChEMBL 6.139999866485596)
Descriptors: MW 293.33, ALogP 4, HBA 4, HBD 1, PSA 63.94, QED 0.61
Compound (SMILES): COc1cc2c(cc1-c1c(C)noc1C)[nH]c1ccnc(-c3c(C)n[nH]c3C)c12
InChIKey: VVRZMYLMDPVHTL-UHFFFAOYSA-N
Target: Bromodomain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25440
Assay: FP Competitive Binding Assay (No.350): Fluorescence Polarization (FP) competitive binding studies (see above) were carried out using the FAM labeled fluorescent probe Cpd. No. 350 to determine binding affinities of representative compounds to both BD1 and BD2 of BRD2, BRD3, and BRD4 proteins. Equilibrium dissociation constants (Id) values of Cpd. No. 350 to these six proteins were determined from protein saturation experiments by monitoring the total fluorescence polarization of mixtures composed with the fluorescent probe at a fixed concentration and proteins with increasing concentrations up to full saturation. Serial dilutions of testing protein were mixed with Cpd. No. 350 to a final volume of 200 μl in the assay buffer. In order to achieve large dynamic rages, particularly for BD1 bromodomains, 100 mM phosphate buffer (pH=6.5, 0.01% Triton X-100 (Sigma, 282103) being added right before assays) was used as the assay buffer. Final Cpd. No. 350 concentration was 1.5 nM for all proteins. Plates were incubated at room temperature for 30 minutes with gentle shaking to assure equilibrium. FP values in millipolarization units (mP) were measured using the Infinite M-1000 plate reader (Tecan U.S., Research Triangle Park, N.C.) in Microfluor 1 96-well, black, round-bottom plates (Thermo Scientific, Waltham, Mass.) at an excitation wavelength of 485 nm and an emission wavelength of 530 nm. Kd values of Cpd. No. 350, which were calculated by fitting the sigmoidal dose-dependent FP increases as a function of protein concentrations using Graphpad Prism 6.0 software (Graphpad Software, San Diego, Calif.), are 2.0, 2.2, 6.5, 0.6, 5.5, and 3.0 nM to BRD2 BD1 and 2, BRD3 BD1 and 2, and BDR4 BD1 and 2, respectively.
Measurement: Ki = 58 nM (pChEMBL 7.239999771118164)
Descriptors: MW 387.44, ALogP 5, HBA 5, HBD 2, PSA 92.62, QED 0.45
Compound (SMILES): COc1cc2c(cc1-c1c(C)noc1C)[nH]c1ccnc(-c3cn[nH]c3)c12
InChIKey: XJIIOIPLGWEZJR-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of FAM-labeled ZBA248 from BRD4 BD2 (333 to 460 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells after 30 mins by fluorescence polarization assay
Measurement: Ki = 201 nM (pChEMBL 6.699999809265137)
Descriptors: MW 359.39, ALogP 4.39, HBA 5, HBD 2, PSA 92.62, QED 0.5
Compound (SMILES): CCc1n[nH]c(CC)c1-c1nccc2[nH]c3cc(-c4c(C)noc4C)c(OC)cc3c12
InChIKey: XOEVAYXDSJABMS-UHFFFAOYSA-N
Target: Bromodomain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25440
Assay: Biolayer Interferometry (BLI) Binding Assay: Biotin labeled BRD proteins (10 μg/ml) in kinetic assay buffer (PBS, pH 7.4, 0.1% BSA and 0.01% Tween-20) were immobilized on Super Streptavidin (SSA) sensors for 15 minutes followed by washing in kinetic buffer for 10 minutes to eliminate any loose non-specific immobilization. In the same 96-well plate serial dilutions of testing compounds with concentrations typically ranging from 0.1-10 times of expected Kd values in the identical assay buffer were prepared. These protein coated sensors were then immersed into the testing compound solutions, starting from the one with the lowest concentration, where compound association occurs and then returned to the fresh buffer for the dissociation. The same operation was repeated for the next solution with higher concentration up to the one with the highest concentration. Identical procedure was performed again with control sensors that were immobilized with SAB4 inactive control protein prepared by following protocols from the manufacturer. Blank buffer controls were included in both BRD protein sensor and inactive protein sensor runs. For each kinetic cycle, kinetic curves for association and dissociation were obtained from raw sensorgrams by using the double reference subtraction protocol included in the analysis program (Data Analysis 7.0) provided by the manufacturer, in which nonspecific interaction and buffer drift were both corrected. The association and dissociation rate constants (kon and koff) were determined using the global fitting protocol in the analysis program based on a reversible 1:1 binding model. The equilibrium association constant (KA) was calculated thereafter. All binding data were collected at 30 degree. Assay plates were kept being shaken at 1000 RPM in the whole experiment time period to avoid mass transport effect.
Measurement: Kd = 24 nM (pChEMBL 7.619999885559082)
Descriptors: MW 415.5, ALogP 5.51, HBA 5, HBD 2, PSA 92.62, QED 0.39
Compound (SMILES): COc1cc2c(cc1-c1c(C)noc1C)[nH]c1ccnc(-c3c(C4CC4)n[nH]c3C)c12
InChIKey: WHDUHJYPRJXLGF-UHFFFAOYSA-N
Target: Bromodomain-containing protein 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15059
Assay: Binding affinity to biotinylated BRD3 BD2 (306 to 417 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells by bio-layer interferometry method
Measurement: Kd = 16.3 nM (pChEMBL 7.789999961853027)
Descriptors: MW 413.48, ALogP 5.57, HBA 5, HBD 2, PSA 92.62, QED 0.4
Compound (SMILES): CCNC(=O)NCCSC[C@H]1O[C@@H](n2cnc3c(N)ncnc32)[C@H](O)[C@@H]1O
InChIKey: CACMCLIHCDTJHL-IDTAVKCVSA-N
Target: Protein arginine N-methyltransferase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: O14744
Assay: Affinity Biochemical interaction: (SPR) EUB0002223a PRMT5
Measurement: IC50 = 25000 nM (pChEMBL 4.599999904632568)
Descriptors: MW 397.46, ALogP -0.92, HBA 10, HBD 5, PSA 160.44, QED 0.37
Compound (SMILES): C[C@H](c1ccc(F)cc1)N(Cc1cccc(C(=O)O)c1)C(=O)c1cnc2ccccc2c1
InChIKey: BXNMZRPTQFVRFA-QGZVFWFLSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14867
Assay: Selectivity interaction (GPCR panel (PDSP screen)) EUB0000304b GABRA1
Measurement: Ki = 1022.12 nM (pChEMBL 5.989999771118164)
Descriptors: MW 428.46, ALogP 5.48, HBA 3, HBD 1, PSA 70.5, QED 0.44
Compound (SMILES): C[C@@H]1NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]2CCCN2C(=O)[C@H]2CCCN2C(=O)[C@H](Cc2ccccc2)NC1=O
InChIKey: MTKQTEXYJKPBQD-GNDHHEKASA-N
Target: Melanocortin receptor 3 (SINGLE PROTEIN), Mus musculus
UniProt: P33033
Assay: Antagonist activity at mouse melanocortin receptor 3 expressed in HEK293 cells assessed as inhibition of NDP-MSH-induced cAMP accumulation after 2 hrs by AlphaScreen assay
Measurement: Kd = 501.19 nM (pChEMBL 6.300000190734863)
Descriptors: MW 977.14, ALogP -1.22, HBA 10, HBD 10, PSA 320.21, QED 0.06
Compound (SMILES): Cc1oc(=O)oc1COC(=O)[C@@H]1N2C(=O)[C@@H](NC(=O)[C@H](N)c3ccccc3)[C@H]2SC1(C)C
InChIKey: ZKUKMWMSYCIYRD-ZXFNITATSA-N
Target: Prostaglandin G/H synthase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23219
Assay: Compound was evaluated for inhibition of human PTGS1 in an in vitro cell free assay measured by time-resolved fluorescence resonance energy transfer method
Measurement: AC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 461.5, ALogP 0.83, HBA 9, HBD 2, PSA 145.08, QED 0.47
Compound (SMILES): CN1CCN(C(=O)C[C@H](NC(=O)/C=C/c2cc(Cl)ccc2-n2cnnn2)c2nc(-c3ccc4[nH]c(=O)cc(O)c4c3)c(Cl)[nH]2)CC1
InChIKey: NBMJTOOHXJGJNZ-RJOTYRNVSA-N
Target: Coagulation factor X (SINGLE PROTEIN), Homo sapiens
UniProt: P00742
Assay: Inhibition of coagulation factor 10a (unknown origin)
Measurement: Ki > 9000 nM (pChEMBL 5.046000003814697)
Descriptors: MW 663.53, ALogP 2.94, HBA 10, HBD 4, PSA 178.02, QED 0.18
Compound (SMILES): N=C(N)NCCC[C@@H]1NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccc(O)cc2)NC(=O)[C@@H]2CCCN2C(=O)[C@H](Cc2ccc3ccccc3c2)NC1=O
InChIKey: AVNDVFCGYOONJV-LUKCZKMGSA-N
Target: Atypical chemokine receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P25106
Assay: Agonist activity at CXCR7 S198R mutant (unknown origin) expressed in HEK293E cells co-transfected with receptor-eYFP construct and beta-arrestin2-Rluc assessed as induction of receptor-mediated beta-arrestin recruitment by BRET assay
Measurement: EC50 = 398.11 nM (pChEMBL 6.400000095367432)
Descriptors: MW 769.91, ALogP -0.2, HBA 8, HBD 11, PSA 280.74, QED 0.07
Compound (SMILES): CN1C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccc(O)cc2)NC(=O)[C@@H]2CCCN2C(=O)[C@H](Cc2ccc3ccccc3c2)NC(=O)[C@@H]1CCCNC(=N)N
InChIKey: LTTCRTAQQFHLPF-WUXKFAKNSA-N
Target: Atypical chemokine receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P25106
Assay: Agonist activity at CXCR7 S198R mutant (unknown origin) expressed in HEK293E cells co-transfected with receptor-eYFP construct and beta-arrestin2-Rluc assessed as induction of receptor-mediated beta-arrestin recruitment by BRET assay
Measurement: EC50 = 398.11 nM (pChEMBL 6.400000095367432)
Descriptors: MW 783.94, ALogP 0.14, HBA 8, HBD 10, PSA 271.95, QED 0.07
Compound (SMILES): Cc1sc2c(c1C)C(c1ccc(Cl)cc1)=N[C@@H](CC(=O)Nc1ccc(O)cc1)c1nnc(C)n1-2
InChIKey: GNMUEVRJHCWKTO-FQEVSTJZSA-N
Target: Bromodomain-containing protein 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15059
Assay: Inhibition of acetylated H4 binding to BRD3 (unknown origin)
Measurement: IC50 = 92 nM (pChEMBL 7.039999961853027)
Descriptors: MW 492, ALogP 5.53, HBA 7, HBD 2, PSA 92.4, QED 0.37
Compound (SMILES): COc1cc2c(cc1-c1c(C)noc1C)[nH]c1ccncc12
InChIKey: NCPRCNJIGPDNGS-UHFFFAOYSA-N
Target: Bromodomain-containing protein 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15059
Assay: FP Competitive Binding Assay (No.350): Fluorescence Polarization (FP) competitive binding studies (see above) were carried out using the FAM labeled fluorescent probe Cpd. No. 350 to determine binding affinities of representative compounds to both BD1 and BD2 of BRD2, BRD3, and BRD4 proteins. Equilibrium dissociation constants (Id) values of Cpd. No. 350 to these six proteins were determined from protein saturation experiments by monitoring the total fluorescence polarization of mixtures composed with the fluorescent probe at a fixed concentration and proteins with increasing concentrations up to full saturation. Serial dilutions of testing protein were mixed with Cpd. No. 350 to a final volume of 200 μl in the assay buffer. In order to achieve large dynamic rages, particularly for BD1 bromodomains, 100 mM phosphate buffer (pH=6.5, 0.01% Triton X-100 (Sigma, 282103) being added right before assays) was used as the assay buffer. Final Cpd. No. 350 concentration was 1.5 nM for all proteins. Plates were incubated at room temperature for 30 minutes with gentle shaking to assure equilibrium. FP values in millipolarization units (mP) were measured using the Infinite M-1000 plate reader (Tecan U.S., Research Triangle Park, N.C.) in Microfluor 1 96-well, black, round-bottom plates (Thermo Scientific, Waltham, Mass.) at an excitation wavelength of 485 nm and an emission wavelength of 530 nm. Kd values of Cpd. No. 350, which were calculated by fitting the sigmoidal dose-dependent FP increases as a function of protein concentrations using Graphpad Prism 6.0 software (Graphpad Software, San Diego, Calif.), are 2.0, 2.2, 6.5, 0.6, 5.5, and 3.0 nM to BRD2 BD1 and 2, BRD3 BD1 and 2, and BDR4 BD1 and 2, respectively.
Measurement: Ki = 241 nM (pChEMBL 6.619999885559082)
Descriptors: MW 293.33, ALogP 4, HBA 4, HBD 1, PSA 63.94, QED 0.61
Compound (SMILES): COc1cc2c(cc1-c1c(C)noc1C)[nH]c1ccnc(-c3c(C)n[nH]c3C)c12
InChIKey: VVRZMYLMDPVHTL-UHFFFAOYSA-N
Target: Bromodomain-containing protein 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15059
Assay: FP Competitive Binding Assay (No.350): Fluorescence Polarization (FP) competitive binding studies (see above) were carried out using the FAM labeled fluorescent probe Cpd. No. 350 to determine binding affinities of representative compounds to both BD1 and BD2 of BRD2, BRD3, and BRD4 proteins. Equilibrium dissociation constants (Id) values of Cpd. No. 350 to these six proteins were determined from protein saturation experiments by monitoring the total fluorescence polarization of mixtures composed with the fluorescent probe at a fixed concentration and proteins with increasing concentrations up to full saturation. Serial dilutions of testing protein were mixed with Cpd. No. 350 to a final volume of 200 μl in the assay buffer. In order to achieve large dynamic rages, particularly for BD1 bromodomains, 100 mM phosphate buffer (pH=6.5, 0.01% Triton X-100 (Sigma, 282103) being added right before assays) was used as the assay buffer. Final Cpd. No. 350 concentration was 1.5 nM for all proteins. Plates were incubated at room temperature for 30 minutes with gentle shaking to assure equilibrium. FP values in millipolarization units (mP) were measured using the Infinite M-1000 plate reader (Tecan U.S., Research Triangle Park, N.C.) in Microfluor 1 96-well, black, round-bottom plates (Thermo Scientific, Waltham, Mass.) at an excitation wavelength of 485 nm and an emission wavelength of 530 nm. Kd values of Cpd. No. 350, which were calculated by fitting the sigmoidal dose-dependent FP increases as a function of protein concentrations using Graphpad Prism 6.0 software (Graphpad Software, San Diego, Calif.), are 2.0, 2.2, 6.5, 0.6, 5.5, and 3.0 nM to BRD2 BD1 and 2, BRD3 BD1 and 2, and BDR4 BD1 and 2, respectively.
Measurement: Ki = 32 nM (pChEMBL 7.5)
Descriptors: MW 387.44, ALogP 5, HBA 5, HBD 2, PSA 92.62, QED 0.45
Compound (SMILES): COc1cc2c(cc1-c1c(C)noc1C)[nH]c1ccnc(-c3cn[nH]c3)c12
InChIKey: XJIIOIPLGWEZJR-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of FAM-labeled ZBA248 from BRD4 BD1 (44 to 168 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells after 30 mins by fluorescence polarization assay
Measurement: Ki = 247 nM (pChEMBL 6.610000133514404)
Descriptors: MW 359.39, ALogP 4.39, HBA 5, HBD 2, PSA 92.62, QED 0.5
Compound (SMILES): CCc1n[nH]c(CC)c1-c1nccc2[nH]c3cc(-c4c(C)noc4C)c(OC)cc3c12
InChIKey: XOEVAYXDSJABMS-UHFFFAOYSA-N
Target: Bromodomain-containing protein 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15059
Assay: Biolayer Interferometry (BLI) Binding Assay: Biotin labeled BRD proteins (10 μg/ml) in kinetic assay buffer (PBS, pH 7.4, 0.1% BSA and 0.01% Tween-20) were immobilized on Super Streptavidin (SSA) sensors for 15 minutes followed by washing in kinetic buffer for 10 minutes to eliminate any loose non-specific immobilization. In the same 96-well plate serial dilutions of testing compounds with concentrations typically ranging from 0.1-10 times of expected Kd values in the identical assay buffer were prepared. These protein coated sensors were then immersed into the testing compound solutions, starting from the one with the lowest concentration, where compound association occurs and then returned to the fresh buffer for the dissociation. The same operation was repeated for the next solution with higher concentration up to the one with the highest concentration. Identical procedure was performed again with control sensors that were immobilized with SAB4 inactive control protein prepared by following protocols from the manufacturer. Blank buffer controls were included in both BRD protein sensor and inactive protein sensor runs. For each kinetic cycle, kinetic curves for association and dissociation were obtained from raw sensorgrams by using the double reference subtraction protocol included in the analysis program (Data Analysis 7.0) provided by the manufacturer, in which nonspecific interaction and buffer drift were both corrected. The association and dissociation rate constants (kon and koff) were determined using the global fitting protocol in the analysis program based on a reversible 1:1 binding model. The equilibrium association constant (KA) was calculated thereafter. All binding data were collected at 30 degree. Assay plates were kept being shaken at 1000 RPM in the whole experiment time period to avoid mass transport effect.
Measurement: Kd = 18 nM (pChEMBL 7.75)
Descriptors: MW 415.5, ALogP 5.51, HBA 5, HBD 2, PSA 92.62, QED 0.39
Compound (SMILES): COc1cc2c(cc1-c1c(C)noc1C)[nH]c1ccnc(-c3c(C4CC4)n[nH]c3C)c12
InChIKey: WHDUHJYPRJXLGF-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Binding affinity to biotinylated BRD4 BD1 (44 to 168 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells by bio-layer interferometry method
Measurement: Kd = 47 nM (pChEMBL 7.329999923706055)
Descriptors: MW 413.48, ALogP 5.57, HBA 5, HBD 2, PSA 92.62, QED 0.4
Compound (SMILES): CCNC(=O)NCCSC[C@H]1O[C@@H](n2cnc3c(N)ncnc32)[C@H](O)[C@@H]1O
InChIKey: CACMCLIHCDTJHL-IDTAVKCVSA-N
Target: Protein arginine N-methyltransferase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NVM4
Assay: Affinity Biochemical interaction: (Enzyme inhibition assay-SPA) EUB0002223a PRMT7
Measurement: IC50 = 6000 nM (pChEMBL 5.21999979019165)
Descriptors: MW 397.46, ALogP -0.92, HBA 10, HBD 5, PSA 160.44, QED 0.37
Compound (SMILES): C[C@H](c1ccc(F)cc1)N(Cc1cccc(C(=O)O)c1)C(=O)c1cnc2ccccc2c1
InChIKey: BXNMZRPTQFVRFA-QGZVFWFLSA-N
Target: Transient receptor potential cation channel subfamily M member 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q7Z2W7
Assay: Selectivity interaction (Voltage activation assay (using HEK-293 cells at 12°C)) EUB0000304b TRPM8
Measurement: IC50 = 13.8 nM (pChEMBL 7.860000133514404)
Descriptors: MW 428.46, ALogP 5.48, HBA 3, HBD 1, PSA 70.5, QED 0.44
Compound (SMILES): C[C@@H]1NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]2CCCN2C(=O)[C@H]2CCCN2C(=O)[C@H](Cc2ccccc2)NC1=O
InChIKey: MTKQTEXYJKPBQD-GNDHHEKASA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Mus musculus
UniProt: P56450
Assay: Antagonist activity at mouse melanocortin receptor 4 expressed in HEK293 cells assessed as inhibition of NDP-MSH-induced cAMP accumulation after 2 hrs by AlphaScreen assay
Measurement: Kd = 6.31 nM (pChEMBL 8.199999809265137)
Descriptors: MW 977.14, ALogP -1.22, HBA 10, HBD 10, PSA 320.21, QED 0.06
Compound (SMILES): Cc1oc(=O)oc1COC(=O)[C@@H]1N2C(=O)[C@@H](NC(=O)[C@H](N)c3ccccc3)[C@H]2SC1(C)C
InChIKey: ZKUKMWMSYCIYRD-ZXFNITATSA-N
Target: Prostaglandin G/H synthase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23219
Assay: Compound was evaluated for inhibition of human PTGS1 in an in vitro cell free assay measured by fluorescence method
Measurement: AC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 461.5, ALogP 0.83, HBA 9, HBD 2, PSA 145.08, QED 0.47
Compound (SMILES): CN1CCN(C(=O)C[C@H](NC(=O)/C=C/c2cc(Cl)ccc2-n2cnnn2)c2nc(-c3ccc4[nH]c(=O)cc(O)c4c3)c(Cl)[nH]2)CC1
InChIKey: NBMJTOOHXJGJNZ-RJOTYRNVSA-N
Target: Coagulation factor VII (SINGLE PROTEIN), Homo sapiens
UniProt: P08709
Assay: Inhibition of coagulation factor 7a (unknown origin)
Measurement: Ki > 13330 nM (pChEMBL 4.875)
Descriptors: MW 663.53, ALogP 2.94, HBA 10, HBD 4, PSA 178.02, QED 0.18
Compound (SMILES): N=C(N)NCCC[C@@H]1NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccc(O)cc2)NC(=O)[C@@H]2CCCN2C(=O)[C@H](Cc2ccc3ccccc3c2)NC1=O
InChIKey: AVNDVFCGYOONJV-LUKCZKMGSA-N
Target: Atypical chemokine receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P25106
Assay: Agonist activity at CXCR7 D275N mutant (unknown origin) expressed in HEK293E cells co-transfected with receptor-eYFP construct and beta-arrestin2-Rluc assessed as induction of receptor-mediated beta-arrestin recruitment by BRET assay
Measurement: EC50 = 1584.89 nM (pChEMBL 5.800000190734863)
Descriptors: MW 769.91, ALogP -0.2, HBA 8, HBD 11, PSA 280.74, QED 0.07
Compound (SMILES): CN1C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccc(O)cc2)NC(=O)[C@@H]2CCCN2C(=O)[C@H](Cc2ccc3ccccc3c2)NC(=O)[C@@H]1CCCNC(=N)N
InChIKey: LTTCRTAQQFHLPF-WUXKFAKNSA-N
Target: Atypical chemokine receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P25106
Assay: Agonist activity at CXCR7 D275N mutant (unknown origin) expressed in HEK293E cells co-transfected with receptor-eYFP construct and beta-arrestin2-Rluc assessed as induction of receptor-mediated beta-arrestin recruitment by BRET assay
Measurement: EC50 = 630.96 nM (pChEMBL 6.199999809265137)
Descriptors: MW 783.94, ALogP 0.14, HBA 8, HBD 10, PSA 271.95, QED 0.07
Compound (SMILES): Cc1sc2c(c1C)C(c1ccc(Cl)cc1)=N[C@@H](CC(=O)Nc1ccc(O)cc1)c1nnc(C)n1-2
InChIKey: GNMUEVRJHCWKTO-FQEVSTJZSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Binding affinity to human BRD4 BD1 (44 to 168 residues) by fluorescence polarization assay
Measurement: IC50 = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 492, ALogP 5.53, HBA 7, HBD 2, PSA 92.4, QED 0.37
Compound (SMILES): COc1cc2c(cc1-c1c(C)noc1C)[nH]c1ccncc12
InChIKey: NCPRCNJIGPDNGS-UHFFFAOYSA-N
Target: Bromodomain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25440
Assay: FP Competitive Binding Assay (No.350): Fluorescence Polarization (FP) competitive binding studies (see above) were carried out using the FAM labeled fluorescent probe Cpd. No. 350 to determine binding affinities of representative compounds to both BD1 and BD2 of BRD2, BRD3, and BRD4 proteins. Equilibrium dissociation constants (Id) values of Cpd. No. 350 to these six proteins were determined from protein saturation experiments by monitoring the total fluorescence polarization of mixtures composed with the fluorescent probe at a fixed concentration and proteins with increasing concentrations up to full saturation. Serial dilutions of testing protein were mixed with Cpd. No. 350 to a final volume of 200 μl in the assay buffer. In order to achieve large dynamic rages, particularly for BD1 bromodomains, 100 mM phosphate buffer (pH=6.5, 0.01% Triton X-100 (Sigma, 282103) being added right before assays) was used as the assay buffer. Final Cpd. No. 350 concentration was 1.5 nM for all proteins. Plates were incubated at room temperature for 30 minutes with gentle shaking to assure equilibrium. FP values in millipolarization units (mP) were measured using the Infinite M-1000 plate reader (Tecan U.S., Research Triangle Park, N.C.) in Microfluor 1 96-well, black, round-bottom plates (Thermo Scientific, Waltham, Mass.) at an excitation wavelength of 485 nm and an emission wavelength of 530 nm. Kd values of Cpd. No. 350, which were calculated by fitting the sigmoidal dose-dependent FP increases as a function of protein concentrations using Graphpad Prism 6.0 software (Graphpad Software, San Diego, Calif.), are 2.0, 2.2, 6.5, 0.6, 5.5, and 3.0 nM to BRD2 BD1 and 2, BRD3 BD1 and 2, and BDR4 BD1 and 2, respectively.
Measurement: Ki = 824 nM (pChEMBL 6.079999923706055)
Descriptors: MW 293.33, ALogP 4, HBA 4, HBD 1, PSA 63.94, QED 0.61
Compound (SMILES): COc1cc2c(cc1-c1c(C)noc1C)[nH]c1ccnc(-c3c(C)n[nH]c3C)c12
InChIKey: VVRZMYLMDPVHTL-UHFFFAOYSA-N
Target: Bromodomain-containing protein 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15059
Assay: FP Competitive Binding Assay (No.350): Fluorescence Polarization (FP) competitive binding studies (see above) were carried out using the FAM labeled fluorescent probe Cpd. No. 350 to determine binding affinities of representative compounds to both BD1 and BD2 of BRD2, BRD3, and BRD4 proteins. Equilibrium dissociation constants (Id) values of Cpd. No. 350 to these six proteins were determined from protein saturation experiments by monitoring the total fluorescence polarization of mixtures composed with the fluorescent probe at a fixed concentration and proteins with increasing concentrations up to full saturation. Serial dilutions of testing protein were mixed with Cpd. No. 350 to a final volume of 200 μl in the assay buffer. In order to achieve large dynamic rages, particularly for BD1 bromodomains, 100 mM phosphate buffer (pH=6.5, 0.01% Triton X-100 (Sigma, 282103) being added right before assays) was used as the assay buffer. Final Cpd. No. 350 concentration was 1.5 nM for all proteins. Plates were incubated at room temperature for 30 minutes with gentle shaking to assure equilibrium. FP values in millipolarization units (mP) were measured using the Infinite M-1000 plate reader (Tecan U.S., Research Triangle Park, N.C.) in Microfluor 1 96-well, black, round-bottom plates (Thermo Scientific, Waltham, Mass.) at an excitation wavelength of 485 nm and an emission wavelength of 530 nm. Kd values of Cpd. No. 350, which were calculated by fitting the sigmoidal dose-dependent FP increases as a function of protein concentrations using Graphpad Prism 6.0 software (Graphpad Software, San Diego, Calif.), are 2.0, 2.2, 6.5, 0.6, 5.5, and 3.0 nM to BRD2 BD1 and 2, BRD3 BD1 and 2, and BDR4 BD1 and 2, respectively.
Measurement: Ki = 26 nM (pChEMBL 7.579999923706055)
Descriptors: MW 387.44, ALogP 5, HBA 5, HBD 2, PSA 92.62, QED 0.45
Compound (SMILES): COc1cc2c(cc1-c1c(C)noc1C)[nH]c1ccnc(-c3cn[nH]c3)c12
InChIKey: XJIIOIPLGWEZJR-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of FAM-labeled ZBA248 from BRD4 BD2 (333 to 460 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells after 30 mins by fluorescence polarization assay
Measurement: IC50 = 658 nM (pChEMBL 6.179999828338623)
Descriptors: MW 359.39, ALogP 4.39, HBA 5, HBD 2, PSA 92.62, QED 0.5
Compound (SMILES): CCc1n[nH]c(CC)c1-c1nccc2[nH]c3cc(-c4c(C)noc4C)c(OC)cc3c12
InChIKey: XOEVAYXDSJABMS-UHFFFAOYSA-N
Target: Bromodomain-containing protein 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15059
Assay: Biolayer Interferometry (BLI) Binding Assay: Biotin labeled BRD proteins (10 μg/ml) in kinetic assay buffer (PBS, pH 7.4, 0.1% BSA and 0.01% Tween-20) were immobilized on Super Streptavidin (SSA) sensors for 15 minutes followed by washing in kinetic buffer for 10 minutes to eliminate any loose non-specific immobilization. In the same 96-well plate serial dilutions of testing compounds with concentrations typically ranging from 0.1-10 times of expected Kd values in the identical assay buffer were prepared. These protein coated sensors were then immersed into the testing compound solutions, starting from the one with the lowest concentration, where compound association occurs and then returned to the fresh buffer for the dissociation. The same operation was repeated for the next solution with higher concentration up to the one with the highest concentration. Identical procedure was performed again with control sensors that were immobilized with SAB4 inactive control protein prepared by following protocols from the manufacturer. Blank buffer controls were included in both BRD protein sensor and inactive protein sensor runs. For each kinetic cycle, kinetic curves for association and dissociation were obtained from raw sensorgrams by using the double reference subtraction protocol included in the analysis program (Data Analysis 7.0) provided by the manufacturer, in which nonspecific interaction and buffer drift were both corrected. The association and dissociation rate constants (kon and koff) were determined using the global fitting protocol in the analysis program based on a reversible 1:1 binding model. The equilibrium association constant (KA) was calculated thereafter. All binding data were collected at 30 degree. Assay plates were kept being shaken at 1000 RPM in the whole experiment time period to avoid mass transport effect.
Measurement: Kd = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 415.5, ALogP 5.51, HBA 5, HBD 2, PSA 92.62, QED 0.39
Compound (SMILES): COc1cc2c(cc1-c1c(C)noc1C)[nH]c1ccnc(-c3c(C4CC4)n[nH]c3C)c12
InChIKey: WHDUHJYPRJXLGF-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Binding affinity to biotinylated BRD4 BD2 (333 to 460 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells by bio-layer interferometry method
Measurement: Kd = 44.6 nM (pChEMBL 7.349999904632568)
Descriptors: MW 413.48, ALogP 5.57, HBA 5, HBD 2, PSA 92.62, QED 0.4
Compound (SMILES): CCNC(=O)NCCSC[C@H]1O[C@@H](n2cnc3c(N)ncnc32)[C@H](O)[C@@H]1O
InChIKey: CACMCLIHCDTJHL-IDTAVKCVSA-N
Target: Protein arginine N-methyltransferase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NVM4
Assay: Affinity Biochemical interaction: (SPR) EUB0002223a PRMT7
Measurement: IC50 = 37000 nM (pChEMBL 4.429999828338623)
Descriptors: MW 397.46, ALogP -0.92, HBA 10, HBD 5, PSA 160.44, QED 0.37
Compound (SMILES): C[C@@H]1NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]2CCCN2C(=O)[C@H]2CCCN2C(=O)[C@H](Cc2ccccc2)NC1=O
InChIKey: MTKQTEXYJKPBQD-GNDHHEKASA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Mus musculus
UniProt: P56450
Assay: Agonist activity at mouse melanocortin receptor 4 expressed in HEK293 cells assessed as increase in cAMP accumulation after 2 hrs by AlphaScreen assay
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 977.14, ALogP -1.22, HBA 10, HBD 10, PSA 320.21, QED 0.06
Compound (SMILES): Cc1oc(=O)oc1COC(=O)[C@@H]1N2C(=O)[C@@H](NC(=O)[C@H](N)c3ccccc3)[C@H]2SC1(C)C
InChIKey: ZKUKMWMSYCIYRD-ZXFNITATSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4A (SINGLE PROTEIN), Homo sapiens
UniProt: P27815
Assay: Compound was evaluated for inhibition of human PDE4A in an in vitro cell free assay measured by time-resolved fluorescence resonance energy transfer method
Measurement: AC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 461.5, ALogP 0.83, HBA 9, HBD 2, PSA 145.08, QED 0.47
Compound (SMILES): CN1C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccc(O)cc2)NC(=O)[C@@H]2CCCN2C(=O)[C@H](Cc2ccc3ccccc3c2)NC(=O)[C@@H]1CCCNC(=N)N
InChIKey: LTTCRTAQQFHLPF-WUXKFAKNSA-N
Target: Atypical chemokine receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P25106
Assay: Displacement of [125I]SDF-1alpha from ACKR3 (unknown origin) expressed in CHO cells after 1 hr by scintillation counting method
Measurement: IC50 = 860 nM (pChEMBL 6.070000171661377)
Descriptors: MW 783.94, ALogP 0.14, HBA 8, HBD 10, PSA 271.95, QED 0.07
Compound (SMILES): Cc1sc2c(c1C)C(c1ccc(Cl)cc1)=N[C@@H](CC(=O)Nc1ccc(O)cc1)c1nnc(C)n1-2
InChIKey: GNMUEVRJHCWKTO-FQEVSTJZSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Binding affinity to human BRD4 BD1 (44 to 168 residues) by fluorescence polarization assay
Measurement: Ki = 5.7 nM (pChEMBL 8.239999771118164)
Descriptors: MW 492, ALogP 5.53, HBA 7, HBD 2, PSA 92.4, QED 0.37
Compound (SMILES): COc1cc2c(cc1-c1c(C)noc1C)[nH]c1ccnc(-c3c(C)n[nH]c3C)c12
InChIKey: VVRZMYLMDPVHTL-UHFFFAOYSA-N
Target: Bromodomain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25440
Assay: FP Competitive Binding Assay (No.350): Fluorescence Polarization (FP) competitive binding studies (see above) were carried out using the FAM labeled fluorescent probe Cpd. No. 350 to determine binding affinities of representative compounds to both BD1 and BD2 of BRD2, BRD3, and BRD4 proteins. Equilibrium dissociation constants (Id) values of Cpd. No. 350 to these six proteins were determined from protein saturation experiments by monitoring the total fluorescence polarization of mixtures composed with the fluorescent probe at a fixed concentration and proteins with increasing concentrations up to full saturation. Serial dilutions of testing protein were mixed with Cpd. No. 350 to a final volume of 200 μl in the assay buffer. In order to achieve large dynamic rages, particularly for BD1 bromodomains, 100 mM phosphate buffer (pH=6.5, 0.01% Triton X-100 (Sigma, 282103) being added right before assays) was used as the assay buffer. Final Cpd. No. 350 concentration was 1.5 nM for all proteins. Plates were incubated at room temperature for 30 minutes with gentle shaking to assure equilibrium. FP values in millipolarization units (mP) were measured using the Infinite M-1000 plate reader (Tecan U.S., Research Triangle Park, N.C.) in Microfluor 1 96-well, black, round-bottom plates (Thermo Scientific, Waltham, Mass.) at an excitation wavelength of 485 nm and an emission wavelength of 530 nm. Kd values of Cpd. No. 350, which were calculated by fitting the sigmoidal dose-dependent FP increases as a function of protein concentrations using Graphpad Prism 6.0 software (Graphpad Software, San Diego, Calif.), are 2.0, 2.2, 6.5, 0.6, 5.5, and 3.0 nM to BRD2 BD1 and 2, BRD3 BD1 and 2, and BDR4 BD1 and 2, respectively.
Measurement: Ki = 100 nM (pChEMBL 7)
Descriptors: MW 387.44, ALogP 5, HBA 5, HBD 2, PSA 92.62, QED 0.45
Compound (SMILES): COc1cc2c(cc1-c1c(C)noc1C)[nH]c1ccnc(-c3cn[nH]c3)c12
InChIKey: XJIIOIPLGWEZJR-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of FAM-labeled ZBA248 from BRD4 BD1 (44 to 168 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells after 30 mins by fluorescence polarization assay
Measurement: IC50 = 702 nM (pChEMBL 6.150000095367432)
Descriptors: MW 359.39, ALogP 4.39, HBA 5, HBD 2, PSA 92.62, QED 0.5
Compound (SMILES): CCc1n[nH]c(CC)c1-c1nccc2[nH]c3cc(-c4c(C)noc4C)c(OC)cc3c12
InChIKey: XOEVAYXDSJABMS-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Biolayer Interferometry (BLI) Binding Assay: Biotin labeled BRD proteins (10 μg/ml) in kinetic assay buffer (PBS, pH 7.4, 0.1% BSA and 0.01% Tween-20) were immobilized on Super Streptavidin (SSA) sensors for 15 minutes followed by washing in kinetic buffer for 10 minutes to eliminate any loose non-specific immobilization. In the same 96-well plate serial dilutions of testing compounds with concentrations typically ranging from 0.1-10 times of expected Kd values in the identical assay buffer were prepared. These protein coated sensors were then immersed into the testing compound solutions, starting from the one with the lowest concentration, where compound association occurs and then returned to the fresh buffer for the dissociation. The same operation was repeated for the next solution with higher concentration up to the one with the highest concentration. Identical procedure was performed again with control sensors that were immobilized with SAB4 inactive control protein prepared by following protocols from the manufacturer. Blank buffer controls were included in both BRD protein sensor and inactive protein sensor runs. For each kinetic cycle, kinetic curves for association and dissociation were obtained from raw sensorgrams by using the double reference subtraction protocol included in the analysis program (Data Analysis 7.0) provided by the manufacturer, in which nonspecific interaction and buffer drift were both corrected. The association and dissociation rate constants (kon and koff) were determined using the global fitting protocol in the analysis program based on a reversible 1:1 binding model. The equilibrium association constant (KA) was calculated thereafter. All binding data were collected at 30 degree. Assay plates were kept being shaken at 1000 RPM in the whole experiment time period to avoid mass transport effect.
Measurement: Kd = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 415.5, ALogP 5.51, HBA 5, HBD 2, PSA 92.62, QED 0.39
Compound (SMILES): COc1cc2c(cc1-c1c(C)noc1C)[nH]c1ccnc(-c3c(C4CC4)n[nH]c3C)c12
InChIKey: WHDUHJYPRJXLGF-UHFFFAOYSA-N
Target: CREB-binding protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q92793
Assay: Binding affinity to biotinylated CREBBP (1043 to 1159 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells by bio-layer interferometry method
Measurement: Kd = 670 nM (pChEMBL 6.170000076293945)
Descriptors: MW 413.48, ALogP 5.57, HBA 5, HBD 2, PSA 92.62, QED 0.4
Compound (SMILES): C[C@@H]1NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]2CCCN2C(=O)[C@H]2CCCN2C(=O)[C@H](Cc2ccccc2)NC1=O
InChIKey: MTKQTEXYJKPBQD-GNDHHEKASA-N
Target: Melanocortin receptor 3 (SINGLE PROTEIN), Mus musculus
UniProt: P33033
Assay: Agonist activity at mouse melanocortin receptor 3 expressed in HEK293 cells assessed as increase in cAMP accumulation after 2 hrs by AlphaScreen assay
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 977.14, ALogP -1.22, HBA 10, HBD 10, PSA 320.21, QED 0.06
Compound (SMILES): Cc1oc(=O)oc1COC(=O)[C@@H]1N2C(=O)[C@@H](NC(=O)[C@H](N)c3ccccc3)[C@H]2SC1(C)C
InChIKey: ZKUKMWMSYCIYRD-ZXFNITATSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P62813
Assay: Binding affinity towards rat Gabra1 in an in vitro assay with cellular components measured by scintillation counting
Measurement: AC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 461.5, ALogP 0.83, HBA 9, HBD 2, PSA 145.08, QED 0.47
Compound (SMILES): CN1C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccc(O)cc2)NC(=O)[C@@H]2CCCN2C(=O)[C@H](Cc2ccc3ccccc3c2)NC(=O)[C@@H]1CCCNC(=N)N
InChIKey: LTTCRTAQQFHLPF-WUXKFAKNSA-N
Target: Atypical chemokine receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P25106
Assay: Activation of YFP-tagged ACKR3 (unknown origin) expressed in HEK293E cells assessed as induction of Rluc-tagged beta-arrestin-2 recruitment after 30 mins by BRET assay
Measurement: EC50 = 91 nM (pChEMBL 7.039999961853027)
Descriptors: MW 783.94, ALogP 0.14, HBA 8, HBD 10, PSA 271.95, QED 0.07
Compound (SMILES): Cc1sc2c(c1C)C(c1ccc(Cl)cc1)=N[C@@H](CC(=O)Nc1ccc(O)cc1)c1nnc(C)n1-2
InChIKey: GNMUEVRJHCWKTO-FQEVSTJZSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Binding affinity to human BRD4 BD1 expressed in Escherichia coli BL21 (DE3) assessed as dissociation constant by bromodomain analysis
Measurement: Kd = 37 nM (pChEMBL 7.429999828338623)
Descriptors: MW 492, ALogP 5.53, HBA 7, HBD 2, PSA 92.4, QED 0.37