lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cn1nc(-c2nccs2)cc1-c1ccc(C(=O)Nc2c(F)cncc2F)s1
InChIKey: ZAUMNKFDDVAMTI-UHFFFAOYSA-N
Target: ORAI1/STIM1 (PROTEIN COMPLEX), Rattus norvegicus
UniProt: Q5M848
Assay: Inhibition of STIM1/Orai1 in rat RBL2H3 cells assessed as inhibition of upslope incubated for 5 mins followed by thapsigargin addition for 25 mins measured for 7 secs by fluo4-AM dye-based FLIPR assay
Measurement: IC50 < 600 nM (pChEMBL 6.2220001220703125)
Descriptors: MW 403.44, ALogP 4.2, HBA 7, HBD 1, PSA 72.7, QED 0.55
Compound (SMILES): Cn1nc(-c2nccs2)cc1-c1ccc(C(=O)Nc2ccncc2F)s1
InChIKey: IRLDBYVLSNVEPT-UHFFFAOYSA-N
Target: ORAI1/STIM1 (PROTEIN COMPLEX), Rattus norvegicus
UniProt: Q5M848
Assay: Inhibition of STIM1/Orai1 in rat RBL2H3 cells assessed as inhibition of upslope incubated for 5 mins followed by thapsigargin addition for 25 mins measured for 7 secs by fluo4-AM dye-based FLIPR assay
Measurement: IC50 < 600 nM (pChEMBL 6.2220001220703125)
Descriptors: MW 385.45, ALogP 4.06, HBA 7, HBD 1, PSA 72.7, QED 0.57
Compound (SMILES): Cn1nc(-c2nccs2)cc1-c1ccc(C(=O)Nc2ncccc2F)s1
InChIKey: TUMHROIRXUWFRA-UHFFFAOYSA-N
Target: ORAI1/STIM1 (PROTEIN COMPLEX), Rattus norvegicus
UniProt: Q5M848
Assay: Inhibition of STIM1/Orai1 in rat RBL2H3 cells assessed as inhibition of upslope incubated for 5 mins followed by thapsigargin addition for 25 mins measured for 7 secs by fluo4-AM dye-based FLIPR assay
Measurement: IC50 = 600 nM (pChEMBL 6.21999979019165)
Descriptors: MW 385.45, ALogP 4.06, HBA 7, HBD 1, PSA 72.7, QED 0.57
Compound (SMILES): Cn1nc(-c2nccs2)cc1-c1ccc(C(=O)Nc2ncc(Cl)cc2F)s1
InChIKey: HLCWYVVFTZGONF-UHFFFAOYSA-N
Target: ORAI1/STIM1 (PROTEIN COMPLEX), Rattus norvegicus
UniProt: Q5M848
Assay: Inhibition of STIM1/Orai1 in rat RBL2H3 cells assessed as inhibition of upslope incubated for 5 mins followed by thapsigargin addition for 25 mins measured for 7 secs by fluo4-AM dye-based FLIPR assay
Measurement: IC50 < 600 nM (pChEMBL 6.2220001220703125)
Descriptors: MW 419.89, ALogP 4.71, HBA 7, HBD 1, PSA 72.7, QED 0.52
Compound (SMILES): COC(=O)c1cccc(NS(=O)(=O)c2sc3ccc(Cl)cc3c2C)c1
InChIKey: ZLBHXMKNUSHLCO-UHFFFAOYSA-N
Target: fructose-2,6-bisphosphatase 3/4 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q16875
Assay: Inhibition of PFKFB3/PFKFB4 in human Panc1 cells assessed as fructose -2,6-bisphosphate production preincubated for 1 hr followed by addition of D-glucose measured after 2 hrs by spectrophotometry
Measurement: IC50 = 3700 nM (pChEMBL 5.429999828338623)
Descriptors: MW 395.89, ALogP 4.45, HBA 5, HBD 1, PSA 72.47, QED 0.66
Compound (SMILES): COC(=O)c1cccc(NS(=O)(=O)c2ccc(-c3csc(C)n3)s2)c1
InChIKey: CGSUSMNJDUMENA-UHFFFAOYSA-N
Target: fructose-2,6-bisphosphatase 3/4 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q16875
Assay: Inhibition of PFKFB3/PFKFB4 in human Panc1 cells assessed as fructose -2,6-bisphosphate production preincubated for 1 hr followed by addition of D-glucose measured after 2 hrs by spectrophotometry
Measurement: IC50 = 5400 nM (pChEMBL 5.269999980926514)
Descriptors: MW 394.5, ALogP 3.77, HBA 7, HBD 1, PSA 85.36, QED 0.67
Compound (SMILES): COC(=O)c1cccc(NS(=O)(=O)c2sc3ccc(C(C)C)cc3c2C)c1
InChIKey: DQSMMMTWUVJPIV-UHFFFAOYSA-N
Target: fructose-2,6-bisphosphatase 3/4 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q16875
Assay: Inhibition of PFKFB3/PFKFB4 in human Panc1 cells assessed as fructose -2,6-bisphosphate production preincubated for 1 hr followed by addition of D-glucose measured after 2 hrs by spectrophotometry
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 403.53, ALogP 4.92, HBA 5, HBD 1, PSA 72.47, QED 0.61
Compound (SMILES): Cc1c(S(=O)(=O)Nc2cccc(C(=O)OC(C)C)c2)sc2ccc(Cl)cc12
InChIKey: KFDXVRMGIJGIIU-UHFFFAOYSA-N
Target: fructose-2,6-bisphosphatase 3/4 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q16875
Assay: Inhibition of PFKFB3/PFKFB4 in human Panc1 cells assessed as fructose -2,6-bisphosphate production preincubated for 1 hr followed by addition of D-glucose measured after 2 hrs by spectrophotometry
Measurement: IC50 = 3100 nM (pChEMBL 5.510000228881836)
Descriptors: MW 423.94, ALogP 5.23, HBA 5, HBD 1, PSA 72.47, QED 0.57
Compound (SMILES): CCN1C(=O)C(C)(C)C(=O)N(C)c2cc(OCCCN(CCn3ccc4ccccc4c3=O)S(=O)(=O)c3ccccc3)ccc21
InChIKey: CMPJAGCXBOHFAF-UHFFFAOYSA-N
Target: Kir3.1/Kir3.4 (PROTEIN COMPLEX), Homo sapiens
UniProt: P48549
Assay: Inhibition of full-length human GIRK1/4 expresssed in CHO-K1 cells under holding potential at -80 mV by patch clamp method
Measurement: IC50 = 490 nM (pChEMBL 6.309999942779541)
Descriptors: MW 630.77, ALogP 4.52, HBA 7, HBD 0, PSA 109.23, QED 0.18
Compound (SMILES): Cc1nc2cc(Cl)c(-c3ccc(C(=O)Nc4ccccc4Cl)s3)cc2o1
InChIKey: GOPUDJORJSHVES-UHFFFAOYSA-N
Target: ORAI1/STIM1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96D31
Assay: Inhibition of recombinant human STIM1/Orai1 expressed in HEK293 cells assessed as inhibition of peak basal signal after 30 mins by fluo4-AM dye-based FLIPR assay
Measurement: IC50 < 600 nM (pChEMBL 6.2220001220703125)
Descriptors: MW 403.29, ALogP 6.42, HBA 4, HBD 1, PSA 55.13, QED 0.43
Compound (SMILES): Cc1nc2cc(Cl)c(-c3ccc(C(=O)Nc4ccccc4F)s3)cc2o1
InChIKey: DKYBVDJELINRIP-UHFFFAOYSA-N
Target: ORAI1/STIM1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96D31
Assay: Inhibition of recombinant human STIM1/Orai1 expressed in HEK293 cells assessed as inhibition of peak basal signal after 30 mins by fluo4-AM dye-based FLIPR assay
Measurement: IC50 < 600 nM (pChEMBL 6.2220001220703125)
Descriptors: MW 386.84, ALogP 5.91, HBA 4, HBD 1, PSA 55.13, QED 0.48
Compound (SMILES): Cc1nc2cc(Cl)c(-c3ccc(C(=O)Nc4c(F)cccc4F)s3)cc2o1
InChIKey: DXOBPHUQIBOKHF-UHFFFAOYSA-N
Target: ORAI1/STIM1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96D31
Assay: Inhibition of recombinant human STIM1/Orai1 expressed in HEK293 cells assessed as inhibition of peak basal signal after 30 mins by fluo4-AM dye-based FLIPR assay
Measurement: IC50 < 600 nM (pChEMBL 6.2220001220703125)
Descriptors: MW 404.83, ALogP 6.05, HBA 4, HBD 1, PSA 55.13, QED 0.45
Compound (SMILES): Cc1cc2scnc2cc1-c1ccc(C(=O)Nc2c(F)cccc2F)s1
InChIKey: LWIUQSIQOBEIHH-UHFFFAOYSA-N
Target: ORAI1/STIM1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96D31
Assay: Inhibition of recombinant human STIM1/Orai1 expressed in HEK293 cells assessed as inhibition of peak basal signal after 30 mins by fluo4-AM dye-based FLIPR assay
Measurement: IC50 < 600 nM (pChEMBL 6.2220001220703125)
Descriptors: MW 386.45, ALogP 5.86, HBA 4, HBD 1, PSA 41.99, QED 0.48
Compound (SMILES): Cc1cc2scnc2cc1-c1ccc(C(=O)Nc2ccccc2F)s1
InChIKey: RDEJYXRFEBACJU-UHFFFAOYSA-N
Target: ORAI1/STIM1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96D31
Assay: Inhibition of recombinant human STIM1/Orai1 expressed in HEK293 cells assessed as inhibition of peak basal signal after 30 mins by fluo4-AM dye-based FLIPR assay
Measurement: IC50 < 600 nM (pChEMBL 6.2220001220703125)
Descriptors: MW 368.46, ALogP 5.72, HBA 4, HBD 1, PSA 41.99, QED 0.5
Compound (SMILES): Cc1cc2scnc2cc1-c1ccc(C(=O)Nc2ccccc2Cl)s1
InChIKey: FDNBETUOBSTQCR-UHFFFAOYSA-N
Target: ORAI1/STIM1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96D31
Assay: Inhibition of recombinant human STIM1/Orai1 expressed in HEK293 cells assessed as inhibition of peak basal signal after 30 mins by fluo4-AM dye-based FLIPR assay
Measurement: IC50 < 600 nM (pChEMBL 6.2220001220703125)
Descriptors: MW 384.91, ALogP 6.24, HBA 4, HBD 1, PSA 41.99, QED 0.45
Compound (SMILES): O=C(Nc1c(F)cccc1F)c1ccc(-c2cc3scnc3cc2Cl)s1
InChIKey: BPMPEFMAQOLROE-UHFFFAOYSA-N
Target: ORAI1/STIM1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96D31
Assay: Inhibition of recombinant human STIM1/Orai1 expressed in HEK293 cells assessed as inhibition of peak basal signal after 30 mins by fluo4-AM dye-based FLIPR assay
Measurement: IC50 < 600 nM (pChEMBL 6.2220001220703125)
Descriptors: MW 406.87, ALogP 6.21, HBA 4, HBD 1, PSA 41.99, QED 0.44
Compound (SMILES): O=C(Nc1ccccc1Cl)c1ccc(-c2cc3scnc3cc2Cl)s1
InChIKey: IZJNQHNFNWKYND-UHFFFAOYSA-N
Target: ORAI1/STIM1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96D31
Assay: Inhibition of recombinant human STIM1/Orai1 expressed in HEK293 cells assessed as inhibition of peak basal signal after 30 mins by fluo4-AM dye-based FLIPR assay
Measurement: IC50 = 600 nM (pChEMBL 6.21999979019165)
Descriptors: MW 405.33, ALogP 6.58, HBA 4, HBD 1, PSA 41.99, QED 0.42
Compound (SMILES): O=C(Nc1ccccc1F)c1ccc(-c2cc3scnc3cc2Cl)s1
InChIKey: GAWNHZKICVYPFO-UHFFFAOYSA-N
Target: ORAI1/STIM1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96D31
Assay: Inhibition of recombinant human STIM1/Orai1 expressed in HEK293 cells assessed as inhibition of peak basal signal after 30 mins by fluo4-AM dye-based FLIPR assay
Measurement: IC50 < 600 nM (pChEMBL 6.2220001220703125)
Descriptors: MW 388.88, ALogP 6.07, HBA 4, HBD 1, PSA 41.99, QED 0.46
Compound (SMILES): Cc1cc2c(C)noc2cc1-c1ccc(C(=O)Nc2c(F)cccc2F)s1
InChIKey: GFHBVTGLYOESLW-UHFFFAOYSA-N
Target: ORAI1/STIM1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96D31
Assay: Inhibition of recombinant human STIM1/Orai1 expressed in HEK293 cells assessed as inhibition of peak basal signal after 30 mins by fluo4-AM dye-based FLIPR assay
Measurement: IC50 < 600 nM (pChEMBL 6.2220001220703125)
Descriptors: MW 384.41, ALogP 5.7, HBA 4, HBD 1, PSA 55.13, QED 0.49
Compound (SMILES): Cc1cc2c(C)noc2cc1-c1ccc(C(=O)Nc2ccccc2F)s1
InChIKey: GEWKCEAVMAIXAJ-UHFFFAOYSA-N
Target: ORAI1/STIM1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96D31
Assay: Inhibition of recombinant human STIM1/Orai1 expressed in HEK293 cells assessed as inhibition of peak basal signal after 30 mins by fluo4-AM dye-based FLIPR assay
Measurement: IC50 < 600 nM (pChEMBL 6.2220001220703125)
Descriptors: MW 366.42, ALogP 5.56, HBA 4, HBD 1, PSA 55.13, QED 0.52
Compound (SMILES): Cc1cc2cnn(C)c2cc1-c1ccc(C(=O)Nc2ccccc2F)s1
InChIKey: ZNPKKPWHPIOPCQ-UHFFFAOYSA-N
Target: ORAI1/STIM1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96D31
Assay: Inhibition of recombinant human STIM1/Orai1 expressed in HEK293 cells assessed as inhibition of peak basal signal after 30 mins by fluo4-AM dye-based FLIPR assay
Measurement: IC50 = 600 nM (pChEMBL 6.21999979019165)
Descriptors: MW 365.43, ALogP 5, HBA 4, HBD 1, PSA 46.92, QED 0.56
Compound (SMILES): Cc1cc2cn(C)nc2cc1-c1ccc(C(=O)Nc2ccccc2F)s1
InChIKey: WLQSDYBZGDXMQL-UHFFFAOYSA-N
Target: ORAI1/STIM1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96D31
Assay: Inhibition of recombinant human STIM1/Orai1 expressed in HEK293 cells assessed as inhibition of peak basal signal after 30 mins by fluo4-AM dye-based FLIPR assay
Measurement: IC50 < 600 nM (pChEMBL 6.2220001220703125)
Descriptors: MW 365.43, ALogP 5, HBA 4, HBD 1, PSA 46.92, QED 0.56
Compound (SMILES): Cc1cc2cn(C)nc2cc1-c1ccc(C(=O)Nc2ccccc2Cl)s1
InChIKey: QMHJZOAUIUNANF-UHFFFAOYSA-N
Target: ORAI1/STIM1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96D31
Assay: Inhibition of recombinant human STIM1/Orai1 expressed in HEK293 cells assessed as inhibition of peak basal signal after 30 mins by fluo4-AM dye-based FLIPR assay
Measurement: IC50 = 600 nM (pChEMBL 6.21999979019165)
Descriptors: MW 381.89, ALogP 5.52, HBA 4, HBD 1, PSA 46.92, QED 0.51
Compound (SMILES): Cc1nc(-c2cc(-c3ccc(C(=O)Nc4ccccc4F)s3)n(C)n2)no1
InChIKey: XUVJIRAOAVAXRJ-UHFFFAOYSA-N
Target: ORAI1/STIM1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96D31
Assay: Inhibition of recombinant human STIM1/Orai1 expressed in HEK293 cells assessed as inhibition of peak basal signal after 30 mins by fluo4-AM dye-based FLIPR assay
Measurement: IC50 = 600 nM (pChEMBL 6.21999979019165)
Descriptors: MW 383.41, ALogP 3.9, HBA 7, HBD 1, PSA 85.84, QED 0.58
Compound (SMILES): Cc1nc2cc(Cl)c(-c3cnc(NC(=O)c4ccccc4Cl)s3)cc2o1
InChIKey: IHGGCZBQXGPQNY-UHFFFAOYSA-N
Target: ORAI1/STIM1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96D31
Assay: Inhibition of recombinant human STIM1/Orai1 expressed in HEK293 cells assessed as inhibition of peak basal signal after 30 mins by fluo4-AM dye-based FLIPR assay
Measurement: IC50 < 600 nM (pChEMBL 6.2220001220703125)
Descriptors: MW 404.28, ALogP 5.82, HBA 5, HBD 1, PSA 68.02, QED 0.47
Compound (SMILES): Cc1cc2scnc2cc1-c1cnc(NC(=O)c2c(F)cccc2F)s1
InChIKey: OOAARYDDNHOJTD-UHFFFAOYSA-N
Target: ORAI1/STIM1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96D31
Assay: Inhibition of recombinant human STIM1/Orai1 expressed in HEK293 cells assessed as inhibition of peak basal signal after 30 mins by fluo4-AM dye-based FLIPR assay
Measurement: IC50 = 600 nM (pChEMBL 6.21999979019165)
Descriptors: MW 387.44, ALogP 5.26, HBA 5, HBD 1, PSA 54.88, QED 0.52
Compound (SMILES): Cn1c(-c2cnc(NC(=O)c3ccccc3Cl)s2)cc2ccccc21
InChIKey: AKZPSPKIPWUYBC-UHFFFAOYSA-N
Target: ORAI1/STIM1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96D31
Assay: Inhibition of recombinant human STIM1/Orai1 expressed in HEK293 cells assessed as inhibition of peak basal signal after 30 mins by fluo4-AM dye-based FLIPR assay
Measurement: IC50 > 1200 nM (pChEMBL 5.921000003814697)
Descriptors: MW 367.86, ALogP 5.21, HBA 4, HBD 1, PSA 46.92, QED 0.54
Compound (SMILES): CCn1nc(C(F)(F)F)cc1-c1cnc(NC(=O)c2ccccc2Cl)s1
InChIKey: MURDVKZEODMGPZ-UHFFFAOYSA-N
Target: ORAI1/STIM1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96D31
Assay: Inhibition of recombinant human STIM1/Orai1 expressed in HEK293 cells assessed as inhibition of peak basal signal after 30 mins by fluo4-AM dye-based FLIPR assay
Measurement: IC50 = 600 nM (pChEMBL 6.21999979019165)
Descriptors: MW 400.81, ALogP 4.95, HBA 5, HBD 1, PSA 59.81, QED 0.67
Compound (SMILES): CC(C)n1nc(C(F)(F)F)cc1-c1cnc(NC(=O)c2ccccc2Cl)s1
InChIKey: BTEBBJDACLZGME-UHFFFAOYSA-N
Target: ORAI1/STIM1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96D31
Assay: Inhibition of recombinant human STIM1/Orai1 expressed in HEK293 cells assessed as inhibition of peak basal signal after 30 mins by fluo4-AM dye-based FLIPR assay
Measurement: IC50 > 1200 nM (pChEMBL 5.921000003814697)
Descriptors: MW 414.84, ALogP 5.51, HBA 5, HBD 1, PSA 59.81, QED 0.61
Compound (SMILES): Cn1nc(C(F)(F)F)cc1-c1cnc(NC(=O)c2ccccc2Cl)s1
InChIKey: WBPIRBLCLZUSKQ-UHFFFAOYSA-N
Target: ORAI1/STIM1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96D31
Assay: Inhibition of recombinant human STIM1/Orai1 expressed in HEK293 cells assessed as inhibition of peak basal signal after 30 mins by fluo4-AM dye-based FLIPR assay
Measurement: IC50 < 600 nM (pChEMBL 6.2220001220703125)
Descriptors: MW 386.79, ALogP 4.47, HBA 5, HBD 1, PSA 59.81, QED 0.72
Compound (SMILES): Cn1nc(C(F)(F)F)cc1-c1cnc(NC(=O)c2c(F)cccc2F)s1
InChIKey: AUYRYTZDJKXZCJ-UHFFFAOYSA-N
Target: ORAI1/STIM1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96D31
Assay: Inhibition of recombinant human STIM1/Orai1 expressed in HEK293 cells assessed as inhibition of peak basal signal after 30 mins by fluo4-AM dye-based FLIPR assay
Measurement: IC50 < 600 nM (pChEMBL 6.2220001220703125)
Descriptors: MW 388.32, ALogP 4.09, HBA 5, HBD 1, PSA 59.81, QED 0.69
Compound (SMILES): Cn1nc(C(F)(F)F)cc1-c1ncc(NC(=O)c2ccccc2Cl)s1
InChIKey: BOGAABAGZRMKTO-UHFFFAOYSA-N
Target: ORAI1/STIM1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96D31
Assay: Inhibition of recombinant human STIM1/Orai1 expressed in HEK293 cells assessed as inhibition of peak basal signal after 30 mins by fluo4-AM dye-based FLIPR assay
Measurement: IC50 > 1200 nM (pChEMBL 5.921000003814697)
Descriptors: MW 386.79, ALogP 4.47, HBA 5, HBD 1, PSA 59.81, QED 0.72
Compound (SMILES): Cn1nc(C(F)(F)F)cc1-c1sc(C(=O)Nc2ccccc2F)cc1N
InChIKey: HRRGZRVYQOLKBI-UHFFFAOYSA-N
Target: ORAI1/STIM1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96D31
Assay: Inhibition of recombinant human STIM1/Orai1 expressed in HEK293 cells assessed as inhibition of peak basal signal after 30 mins by fluo4-AM dye-based FLIPR assay
Measurement: IC50 > 1200 nM (pChEMBL 5.921000003814697)
Descriptors: MW 384.36, ALogP 4.14, HBA 5, HBD 2, PSA 72.94, QED 0.67
Compound (SMILES): Cn1nc(C(F)(F)F)cc1-c1sc(C(=O)Nc2ccccc2Cl)cc1N
InChIKey: GZRDMKKYBOTFAJ-UHFFFAOYSA-N
Target: ORAI1/STIM1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96D31
Assay: Inhibition of recombinant human STIM1/Orai1 expressed in HEK293 cells assessed as inhibition of peak basal signal after 30 mins by fluo4-AM dye-based FLIPR assay
Measurement: IC50 > 1200 nM (pChEMBL 5.921000003814697)
Descriptors: MW 400.81, ALogP 4.66, HBA 5, HBD 2, PSA 72.94, QED 0.67
Compound (SMILES): Cn1nc(-c2ccccc2F)cc1-c1ccc(C(=O)Nc2c(F)cccc2F)s1
InChIKey: HHDZFQUYOHXTKF-UHFFFAOYSA-N
Target: ORAI1/STIM1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96D31
Assay: Inhibition of recombinant human STIM1/Orai1 expressed in HEK293 cells assessed as inhibition of peak basal signal after 30 mins by fluo4-AM dye-based FLIPR assay
Measurement: IC50 < 600 nM (pChEMBL 6.2220001220703125)
Descriptors: MW 413.42, ALogP 5.49, HBA 4, HBD 1, PSA 46.92, QED 0.48
Compound (SMILES): Cn1nc(-c2ccccc2F)cc1-c1ccc(C(=O)Nc2c(F)cncc2F)s1
InChIKey: OYSGHQLSJZFEDB-UHFFFAOYSA-N
Target: ORAI1/STIM1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96D31
Assay: Inhibition of recombinant human STIM1/Orai1 expressed in HEK293 cells assessed as inhibition of peak basal signal after 30 mins by fluo4-AM dye-based FLIPR assay
Measurement: IC50 < 600 nM (pChEMBL 6.2220001220703125)
Descriptors: MW 414.41, ALogP 4.88, HBA 5, HBD 1, PSA 59.81, QED 0.52
Compound (SMILES): Cn1nc(-c2ccccc2F)cc1-c1ccc(C(=O)Nc2ccncc2F)s1
InChIKey: GLJPZURHCFAEIO-UHFFFAOYSA-N
Target: ORAI1/STIM1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96D31
Assay: Inhibition of recombinant human STIM1/Orai1 expressed in HEK293 cells assessed as inhibition of peak basal signal after 30 mins by fluo4-AM dye-based FLIPR assay
Measurement: IC50 < 600 nM (pChEMBL 6.2220001220703125)
Descriptors: MW 396.42, ALogP 4.74, HBA 5, HBD 1, PSA 59.81, QED 0.54
Compound (SMILES): Cn1nc(-c2ccccc2F)cc1-c1ccc(C(=O)Nc2ncccc2F)s1
InChIKey: MDCRNIYVGXNRNA-UHFFFAOYSA-N
Target: ORAI1/STIM1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96D31
Assay: Inhibition of recombinant human STIM1/Orai1 expressed in HEK293 cells assessed as inhibition of peak basal signal after 30 mins by fluo4-AM dye-based FLIPR assay
Measurement: IC50 < 600 nM (pChEMBL 6.2220001220703125)
Descriptors: MW 396.42, ALogP 4.74, HBA 5, HBD 1, PSA 59.81, QED 0.54
Compound (SMILES): Cn1nc(-c2ccccc2F)cc1-c1ccc(C(=O)Nc2ncc(Cl)cc2F)s1
InChIKey: WYBQSBONLOWMSI-UHFFFAOYSA-N
Target: ORAI1/STIM1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96D31
Assay: Inhibition of recombinant human STIM1/Orai1 expressed in HEK293 cells assessed as inhibition of peak basal signal after 30 mins by fluo4-AM dye-based FLIPR assay
Measurement: IC50 < 600 nM (pChEMBL 6.2220001220703125)
Descriptors: MW 430.87, ALogP 5.39, HBA 5, HBD 1, PSA 59.81, QED 0.47
Compound (SMILES): Cn1nc(-c2ccccc2F)cc1-c1ccc(C(=O)Nc2ccccc2Cl)s1
InChIKey: GJOWYFYOGGCDOK-UHFFFAOYSA-N
Target: ORAI1/STIM1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96D31
Assay: Inhibition of recombinant human STIM1/Orai1 expressed in HEK293 cells assessed as inhibition of peak basal signal after 30 mins by fluo4-AM dye-based FLIPR assay
Measurement: IC50 < 600 nM (pChEMBL 6.2220001220703125)
Descriptors: MW 411.89, ALogP 5.86, HBA 4, HBD 1, PSA 46.92, QED 0.46
Compound (SMILES): Cn1nc(-c2ccccc2)cc1-c1ccc(C(=O)Nc2c(F)cccc2F)s1
InChIKey: SBXZSRFONFSDQE-UHFFFAOYSA-N
Target: ORAI1/STIM1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96D31
Assay: Inhibition of recombinant human STIM1/Orai1 expressed in HEK293 cells assessed as inhibition of peak basal signal after 30 mins by fluo4-AM dye-based FLIPR assay
Measurement: IC50 < 600 nM (pChEMBL 6.2220001220703125)
Descriptors: MW 395.43, ALogP 5.35, HBA 4, HBD 1, PSA 46.92, QED 0.51
Compound (SMILES): Cn1nc(-c2ccccc2)cc1-c1ccc(C(=O)Nc2c(F)cncc2F)s1
InChIKey: CHDDORXKKCJWIV-UHFFFAOYSA-N
Target: ORAI1/STIM1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96D31
Assay: Inhibition of recombinant human STIM1/Orai1 expressed in HEK293 cells assessed as inhibition of peak basal signal after 30 mins by fluo4-AM dye-based FLIPR assay
Measurement: IC50 = 600 nM (pChEMBL 6.21999979019165)
Descriptors: MW 396.42, ALogP 4.74, HBA 5, HBD 1, PSA 59.81, QED 0.54
Compound (SMILES): Cn1nc(-c2ccccc2)cc1-c1ccc(C(=O)Nc2ccncc2F)s1
InChIKey: PVUOYXVOPFAWHK-UHFFFAOYSA-N
Target: ORAI1/STIM1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96D31
Assay: Inhibition of recombinant human STIM1/Orai1 expressed in HEK293 cells assessed as inhibition of peak basal signal after 30 mins by fluo4-AM dye-based FLIPR assay
Measurement: IC50 < 600 nM (pChEMBL 6.2220001220703125)
Descriptors: MW 378.43, ALogP 4.6, HBA 5, HBD 1, PSA 59.81, QED 0.56
Compound (SMILES): Cn1nc(-c2ccccc2)cc1-c1ccc(C(=O)Nc2ncccc2F)s1
InChIKey: LZILUFBFRZRISY-UHFFFAOYSA-N
Target: ORAI1/STIM1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96D31
Assay: Inhibition of recombinant human STIM1/Orai1 expressed in HEK293 cells assessed as inhibition of peak basal signal after 30 mins by fluo4-AM dye-based FLIPR assay
Measurement: IC50 = 600 nM (pChEMBL 6.21999979019165)
Descriptors: MW 378.43, ALogP 4.6, HBA 5, HBD 1, PSA 59.81, QED 0.56
Compound (SMILES): Cn1nc(-c2ccccc2)cc1-c1ccc(C(=O)Nc2ncc(Cl)cc2F)s1
InChIKey: GPWAAAYMQAUUQB-UHFFFAOYSA-N
Target: ORAI1/STIM1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96D31
Assay: Inhibition of recombinant human STIM1/Orai1 expressed in HEK293 cells assessed as inhibition of peak basal signal after 30 mins by fluo4-AM dye-based FLIPR assay
Measurement: IC50 < 600 nM (pChEMBL 6.2220001220703125)
Descriptors: MW 412.88, ALogP 5.26, HBA 5, HBD 1, PSA 59.81, QED 0.5
Compound (SMILES): Cn1nc(-c2ccccc2)cc1-c1ccc(C(=O)Nc2ccccc2F)s1
InChIKey: CSOKCGISQMQGLY-UHFFFAOYSA-N
Target: ORAI1/STIM1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96D31
Assay: Inhibition of recombinant human STIM1/Orai1 expressed in HEK293 cells assessed as inhibition of peak basal signal after 30 mins by fluo4-AM dye-based FLIPR assay
Measurement: IC50 < 600 nM (pChEMBL 6.2220001220703125)
Descriptors: MW 377.44, ALogP 5.21, HBA 4, HBD 1, PSA 46.92, QED 0.53
Compound (SMILES): Cn1nc(-c2ccccc2)cc1-c1ccc(C(=O)Nc2ccccc2Cl)s1
InChIKey: FAWRABBETVKTCP-UHFFFAOYSA-N
Target: ORAI1/STIM1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96D31
Assay: Inhibition of recombinant human STIM1/Orai1 expressed in HEK293 cells assessed as inhibition of peak basal signal after 30 mins by fluo4-AM dye-based FLIPR assay
Measurement: IC50 < 600 nM (pChEMBL 6.2220001220703125)
Descriptors: MW 393.9, ALogP 5.72, HBA 4, HBD 1, PSA 46.92, QED 0.48
Compound (SMILES): Cn1nc(-c2nccs2)cc1-c1ccc(C(=O)Nc2c(F)cccc2F)s1
InChIKey: KAUZLIOZBLLYFJ-UHFFFAOYSA-N
Target: ORAI1/STIM1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96D31
Assay: Inhibition of recombinant human STIM1/Orai1 expressed in HEK293 cells assessed as inhibition of peak basal signal after 30 mins by fluo4-AM dye-based FLIPR assay
Measurement: IC50 < 600 nM (pChEMBL 6.2220001220703125)
Descriptors: MW 402.45, ALogP 4.8, HBA 6, HBD 1, PSA 59.81, QED 0.53
Compound (SMILES): Cn1nc(-c2nccs2)cc1-c1ccc(C(=O)Nc2c(F)cncc2F)s1
InChIKey: ZAUMNKFDDVAMTI-UHFFFAOYSA-N
Target: ORAI1/STIM1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96D31
Assay: Inhibition of recombinant human STIM1/Orai1 expressed in HEK293 cells assessed as inhibition of peak basal signal after 30 mins by fluo4-AM dye-based FLIPR assay
Measurement: IC50 = 600 nM (pChEMBL 6.21999979019165)
Descriptors: MW 403.44, ALogP 4.2, HBA 7, HBD 1, PSA 72.7, QED 0.55
Compound (SMILES): Cn1nc(-c2nccs2)cc1-c1ccc(C(=O)Nc2ccncc2F)s1
InChIKey: IRLDBYVLSNVEPT-UHFFFAOYSA-N
Target: ORAI1/STIM1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96D31
Assay: Inhibition of recombinant human STIM1/Orai1 expressed in HEK293 cells assessed as inhibition of peak basal signal after 30 mins by fluo4-AM dye-based FLIPR assay
Measurement: IC50 < 600 nM (pChEMBL 6.2220001220703125)
Descriptors: MW 385.45, ALogP 4.06, HBA 7, HBD 1, PSA 72.7, QED 0.57
Compound (SMILES): Cn1nc(-c2nccs2)cc1-c1ccc(C(=O)Nc2ncccc2F)s1
InChIKey: TUMHROIRXUWFRA-UHFFFAOYSA-N
Target: ORAI1/STIM1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96D31
Assay: Inhibition of recombinant human STIM1/Orai1 expressed in HEK293 cells assessed as inhibition of peak basal signal after 30 mins by fluo4-AM dye-based FLIPR assay
Measurement: IC50 = 600 nM (pChEMBL 6.21999979019165)
Descriptors: MW 385.45, ALogP 4.06, HBA 7, HBD 1, PSA 72.7, QED 0.57
Compound (SMILES): Cn1nc(-c2nccs2)cc1-c1ccc(C(=O)Nc2ncc(Cl)cc2F)s1
InChIKey: HLCWYVVFTZGONF-UHFFFAOYSA-N
Target: ORAI1/STIM1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96D31
Assay: Inhibition of recombinant human STIM1/Orai1 expressed in HEK293 cells assessed as inhibition of peak basal signal after 30 mins by fluo4-AM dye-based FLIPR assay
Measurement: IC50 < 600 nM (pChEMBL 6.2220001220703125)
Descriptors: MW 419.89, ALogP 4.71, HBA 7, HBD 1, PSA 72.7, QED 0.52
Compound (SMILES): COc1ccccc1-c1ccc(S(=O)(=O)Nc2cccc(-c3nnn[nH]3)c2)s1
InChIKey: PXNKGZAABVGNTA-UHFFFAOYSA-N
Target: fructose-2,6-bisphosphatase 3/4 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q16875
Assay: Inhibition of PFKFB3/PFKFB4 in human Panc1 cells assessed as fructose -2,6-bisphosphate production preincubated for 1 hr followed by addition of D-glucose measured after 2 hrs by spectrophotometry
Measurement: IC50 = 11000 nM (pChEMBL 4.960000038146973)
Descriptors: MW 413.48, ALogP 3.4, HBA 7, HBD 2, PSA 109.86, QED 0.5
Compound (SMILES): Cc1ccc(-c2ccc(S(=O)(=O)Nc3cccc(-c4nnn[nH]4)c3)s2)cc1
InChIKey: LPPVVGXUJRZVRB-UHFFFAOYSA-N
Target: fructose-2,6-bisphosphatase 3/4 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q16875
Assay: Inhibition of PFKFB3/PFKFB4 in human Panc1 cells assessed as fructose -2,6-bisphosphate production preincubated for 1 hr followed by addition of D-glucose measured after 2 hrs by spectrophotometry
Measurement: IC50 = 13800 nM (pChEMBL 4.860000133514404)
Descriptors: MW 397.49, ALogP 3.7, HBA 6, HBD 2, PSA 100.63, QED 0.53
Compound (SMILES): COC(=O)c1cccc(NS(=O)(=O)c2sc3ccc(Cl)cc3c2C)c1
InChIKey: ZLBHXMKNUSHLCO-UHFFFAOYSA-N
Target: fructose-2,6-bisphosphatase 3/4 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q16875
Assay: Inhibition of PFKFB3/PFKFB4 in human NUGC3 cells assessed as fructose -2,6-bisphosphate production preincubated for 1 hr followed by addition of D-glucose measured after 2 hrs by spectrophotometry
Measurement: IC50 = 4000 nM (pChEMBL 5.400000095367432)
Descriptors: MW 395.89, ALogP 4.45, HBA 5, HBD 1, PSA 72.47, QED 0.66
Compound (SMILES): CNc1nc(-c2nc3cnc(N4CCN(C)CC4)cc3n2Cc2ccncc2)cn2c(C)nnc12
InChIKey: LAXUANUISYQZNT-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: BRD4-H4 Tetraacetylated Peptide Inhibition AlphaScreen: This assay is used to determine whether the compounds inhibit the interaction between the first (BRD4-BD1) or the second (BRD4-BD2) bromodomain of BRD4 and the tetraacetylated histone H4 peptide.Compounds are diluted in serial dilution 1:5 in assay buffer from 10 mM stock in DMSO (100 μM start concentration) in white OptiPlate-384 (PerkinElmer). A mix consisting of 15 nM GST-BRD4-BD1 protein (aa 44-168) or 150 nM GST-BRD4-BD2 (aa 333-460) and 15 nM biotinylated Acetyl-Histone H4 (Lys5, 8, 12, 16) peptide is prepared in assay buffer (50 mM HEPES pH=7.4; 25 mM NaCl; 0.05% Tween 20; 0.1% bovine serum albumin (BSA); 10 mM dithiothreitol (DTT)). 6 μl of the mix is added to the compound dilutions. Subsequently, 6 μl of premixed AlphaLISA Glutathione Acceptor Beads and AlphaScreen Streptavidin Donor Beads from PerkinElmer (in assay buffer at a concentration of 10 μg/ml each) are added and the samples are incubated for 30 min at RT in the dark (shaking 300 rpm). Afterwards, the signal is measured in a PerkinElmer Envision HTS Multilabel Reader using the AlphaScreen protocol from PerkinElmer.Each plate contains negative controls where biotinylated Acetyl-Histone H4 peptide and GST-BRD4-BD1 or GST-BRD4-BD2 are left out and replaced by assay buffer. Negative control values are entered as low basis value when using the software GraphPad Prism for calculations. Furthermore, a positive control (probe molecule JQ1+ with protein/peptide mix) is pipetted. Determination of IC50 values are carried out using GraphPad Prism 3.03 software (or updates thereof).
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 469.56, ALogP 2.08, HBA 11, HBD 1, PSA 105.19, QED 0.41
Compound (SMILES): CN1CCC2(CC1)CN(C(=O)Cn1cc(NC(=O)c3cnn4cccnc34)c(-c3cc(Cl)ccc3OC(F)F)n1)CCO2
InChIKey: CKXMMAUXSSURLT-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: JAK Enzyme Assay: The activity of the isolated recombinant JAK1 and JAK2 kinase domain was measured by monitoring phosphorylation of a peptide derived from JAK3 (Val-Ala-Leu-Val-Asp-Gly-Tyr-Phe-Arg-Leu-Thr-Thr, fluorescently labeled on the N-terminus with 5-carboxyfluorescein) using the Caliper LabChip® technology (Caliper Life Sciences, Hopkinton, Mass.). To determine inhibition constants (Ki), compounds were diluted serially in DMSO and added to 50 μL kinase reactions containing purified enzyme (1.5 nM JAK1, or 0.2 nM JAK2), 100 mM HEPES buffer (pH 7.2), 0.015% Brij-35, 1.5 μM peptide substrate, ATP (25 μM), 10 mM MgCl2, 4 mM DTT at a final DMSO concentration of 2%. Reactions were incubated at 22° C. in 384-well polypropylene microtiter plates for 30 minutes and then stopped by addition of 25 μL of an EDTA containing solution (100 mM HEPES buffer (pH 7.2), 0.015% Brij-35, 150 mM EDTA), resulting in a final EDTA concentration of 50 mM. After termination of the kinase reaction, the proportion of phosphorylated product was determined as a fraction of total peptide substrate using the Caliper LabChip® 3000 according to the manufacturer's specifications.
Measurement: Ki = 2.34 nM (pChEMBL 8.630000114440918)
Descriptors: MW 615.04, ALogP 3.42, HBA 10, HBD 1, PSA 119.12, QED 0.34
Compound (SMILES): CCCNC(=O)c1ccc(N2CCN(S(=O)(=O)c3ccc(OC(C)C)cc3)CC2)cc1OCC(=O)O
InChIKey: WWWWXIYDYUUKGQ-UHFFFAOYSA-N
Target: Prostaglandin D2 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q13258
Assay: Displacement of [3H]-PGD2 from PGD2 receptor in human platelet membranes after 2 hrs by micro beta scintillation counting analysis
Measurement: Ki = 20000 nM (pChEMBL 4.699999809265137)
Descriptors: MW 519.62, ALogP 2.59, HBA 7, HBD 2, PSA 125.48, QED 0.46
Compound (SMILES): O=C(N/N=C/c1cc(Cl)c2ncccc2c1)[C@@H]1C[C@H]1c1ccccc1
InChIKey: AEEZPLOFQLTNDU-CKGAZFRFSA-N
Target: Transient receptor potential cation channel subfamily M member 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NZQ8
Assay: Inhibition of human TRPM5 transfected in HEK293 cells assessed as inhibition of KCl-stimulated membrane potential by FLIPR assay
Measurement: IC50 = 340 nM (pChEMBL 6.46999979019165)
Descriptors: MW 349.82, ALogP 4.14, HBA 3, HBD 1, PSA 54.35, QED 0.57
Compound (SMILES): O=C(N[C@H]1CC[C@H](CCN2CCC(c3noc4cc(F)ccc34)CC2)CC1)c1ccnc(N2CCOCC2)c1
InChIKey: VWGPRFQVSJZKGC-OKDASEJXSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Radioligand Binding Assay: Aliquots of membrane preparations were thawed at RT, resuspended in assay buffer (D2, D3: 50 mM Tris-HCl, 120 mM NaCl, 5 mM MgCl2, 1 mM EDTA, 5 mM KCl, 1.5 mM CaCl2, pH=7.4; 5-HT2A: 50 mM Tris-HCl, 10 mM MgCl2, 1 mM EGTA, pH=7.4), homogenized with a Polytron for 20-30 sec at 12,000 rpm and adjusted to a final concentration of approximately 7.5 ug protein/well (D2, D3) and 15 ug protein/well (5-HT2A), respectively.The binding affinity (Ki) of the compounds was determined using radioligand binding. Membranes were incubated in a total volume of 200 ul with a fixed concentration of radioligand (final concentration approximately 0.7 nM [3H]-spiperone for D2, 0.5 nM [3H]-spiperone for D3, and 1.1 nM [3H]-ketanserin for 5-HT2A) and ten concentrations of test compound in ranging between 10 uM-0.1 nM for 1 h at RT. At the end of the incubation, the reaction mixtures were filtered on to unifilter 96-well white microplates with bonded GF/C filters.
Measurement: Ki = 5.747 nM (pChEMBL 8.239999771118164)
Descriptors: MW 535.66, ALogP 4.76, HBA 7, HBD 1, PSA 83.73, QED 0.47
Compound (SMILES): COc1cc(OC)cc(N(CC#Cc2cnn(C)c2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: GEYJBCMVIQPSQS-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of FGFR3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in presence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 479.54, ALogP 3.97, HBA 9, HBD 0, PSA 83.12, QED 0.34
Compound (SMILES): Nc1ccccc1NC(=O)CCCCCNC(=O)C1CCN(c2ccncc2)CC1
InChIKey: QXIVWXIJYGTSFF-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: HDAC enzyme inhibitionAssay: HDAC enzyme inhibition assays were performed using purified HDACs 1-10 essentially as described in Beckers et al., 2007, Int. J. Cancer., 121:1138-48 and Perez-Balado et al., 2007, J. Med. Chem., 50:2497-2505. Inhibition assays using nuclear extract were performed essentially as described in Herman et al., 2006, Nat. Chem. Biol., 2:551-558. Briefly, the purified HDACs or nuclear extract were incubated with an acetylated substrate in the absence of the compound to be assayed and with increasing concentrations of the compound. The rate of substrate deacetylation was measured under each condition, and half-maximal inhibitory concentration with regard to each HDAC was determined by standard means.
Measurement: IC50 = 955 nM (pChEMBL 6.019999980926514)
Descriptors: MW 409.53, ALogP 3.2, HBA 5, HBD 3, PSA 100.35, QED 0.44
Compound (SMILES): CCCN(Cc1ccc(CN)cc1)C(=O)C1=Cc2ccc(C(=O)Nc3cccc(C)c3)cc2N=C(N)C1
InChIKey: NXLIEOISWQPZLA-UHFFFAOYSA-N
Target: Toll-like receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYK1
Assay: Pharmacological Assay: For TLR8 and TLR7 activity testing, HEK-Blue human TLR8 or TLR7 cells (Invivogen, San Diego, Calif., USA) are used, respectively. These cells are designed for studying the stimulation of human TLR8 or TLR7 by monitoring the activation of NF-κB. A SEAP (secreted embryonic alkaline phosphatase) reporter gene is placed under the control of the IFN-b minimal promoter fused to five NF-κB and AP-1-binding sites. Therefore the reporter expression is regulated by the NF-κB promoter upon stimulation of human TLR8 or TLR7 for 20 hours. The cell culture supernatant SEAP reporter activity was determined using Quanti Blue kit (Invivogen, San Diego, Ca, USA) at a wavelength of 640 nm, a detection medium that turns purple/blue in the presence of alkaline phosphatase.
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 495.63, ALogP 4.92, HBA 5, HBD 3, PSA 113.81, QED 0.41
Compound (SMILES): Cc1cnc(Nc2ccc(N(C)C)cc2)nc1Nc1cc(C2CC2)n[nH]1
InChIKey: KZZMCJYADBLOBD-UHFFFAOYSA-N
Target: Insulin-like growth factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08069
Assay: Inhibition of human IGF1R kinase domain (M954 to C1367 residues) tri-phosphorylated enzyme form expressed in baculovirus based expression system using poly-EY peptide incubated for 2 hrs by luciferase-luciferin coupled chemiluminescent assay
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 349.44, ALogP 3.94, HBA 6, HBD 3, PSA 81.76, QED 0.63
Compound (SMILES): CC1(C)OC2=C(C(=O)C(=O)c3ccccc32)C1n1cc(C[Se]c2ccccc2)nn1
InChIKey: DRDCWILTIUDZCE-UHFFFAOYSA-N
Target: NAD(P)H dehydrogenase [quinone] 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P15559
Assay: Activation of NQO1 in human A549 cells assessed as decrease in cell survival incubated for 2 hrs measured after 7 days in presence of NQO1 inhibitor dicoumarol by Hoechst 33258 staining based assay
Measurement: IC50 > 3200 nM (pChEMBL 5.494999885559082)
Descriptors: MW 464.38
Compound (SMILES): CC(C)(C)c1cc(NC(=O)Nc2ccc(Oc3ccnc(Nc4ccc5[nH]ncc5c4)n3)c3ccccc23)n(-c2cccc(CN3CCCC3=O)c2)n1
InChIKey: XAJQBNVFUKELGZ-UHFFFAOYSA-N
Target: Proto-oncogene tyrosine-protein kinase Src (SINGLE PROTEIN), Homo sapiens
UniProt: P12931
Assay: c-Src and Syk Enzyme Inhibition Assay: The inhibitory activities of compounds of the invention against c-Src and Syk enzymes (Invitrogen), are evaluated in a similar fashion to that described hereinabove. The relevant enzyme (3000 ng/mL or 2000 ng/mL respectively, 2.5 uL) is incubated with the test compound (either 4 ug/mL, 0.4 ug/mL, 0.04 ug/mL, or 0.004 ug/mL, 2.5 uL each) for 2 hr at RT. The FRET peptides (8 uM, 2.5 uL), and appropriate ATP solutions (2.5 uL, 800 uM for c-Src, and 60 uM ATP for Syk) are then added to the enzymes/compound mixtures and incubated for 1 hr. Development reagent (protease, 5 uL) is added for 1 hr prior to detection in a fluorescence microplate reader (Varioskan Flash, ThermoFisher Scientific).
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 706.81, ALogP 8.29, HBA 9, HBD 4, PSA 154.98, QED 0.12
Compound (SMILES): Cn1nc2c(c1-c1ccccc1)CCN(C(=O)c1cccc(Cl)c1Cl)C2
InChIKey: HSFGLIHNCQMIRG-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: Radioligand Binding: Human or rat P2X7-1321 N1 cells were collected and frozen @−80° C. On the day of the experiment, cell membrane preparations were made according to standard published methods. The total assay volume was 100 μl:10 μl compound (10×)+(b) 40 μl tracer (2.5×)+50 μl membrane (2×). The tracer used for the assay was tritiated A-804598. The compound can be prepared as described in the literature. (Donnelly-Roberts, D. Neuropharmacology 2008, 56 (1), 223-229.) Compounds, tracer and membranes were incubated for 1 hour @ 4° C. The assay was terminated by filtration (GF/B filters pre-soaked with 0.3% PEI) and washed with washing buffer (Tris-HCl 50 mM). The IC50 generated in the binding assay was corrected for tracer concentration and affinity of the tracer to derive at the affinity (Ki) of the test compounds.
Measurement: Ki = 178 nM (pChEMBL 6.75)
Descriptors: MW 386.28, ALogP 4.59, HBA 3, HBD 0, PSA 38.13, QED 0.65
Compound (SMILES): Cc1cncc(-c2cc3c(cn2)cnn3-c2cccc(N3CCC(N)CC3)n2)n1
InChIKey: COOCHYZLHYBZPZ-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: Kinase Binding Assay: PIM-1, -2, and -3 enzymes were generated as fusion proteins expressed in bacteria and purified by IMAC column chromatography (Sun, X., Chiu, J. F., and He, Q. Y. (2005) Expert Rev. Proteomics, 2:649-657). A fluorescent-labeled Pim-specific peptide substrate, was custom synthesized by American Peptide Company (Sunnyvale, Calif.). Reaction Buffer contained 10 mM HEPES, pH 7.2, 10 mM MgCl2, 0.01% Tween 20, 2 mM DTT. Termination Buffer contained 190 mM HEPES, pH 7.2, 0.015% Brij-35, 0.2% Coating Reagent 3 (Caliper Life Sciences, Hopkinton, Mass.), 20 mM EDTA. Separation Buffer contained 100 mM HEPES, pH 7.2, 0.015% Brij-35, 0.1% Coating Reagent 3, 1:200 Coating Reagent 8 (Caliper Life Sciences, Hopkinton, Mass.), 10 mM EDTA and 5% DMSO.PIM reactions were carried out in a final volume of 10 uL per well in a 384-well plate. A standard enzymatic reaction, initiated by the addition of 5 uL 2Ã¿Â¿ATP and test compound to 5 uL of 2x enzyme and FAM-peptide, contained 20 uM PIM1, 50 uM PIM2, or 55 uM PIM3, 1 uM FAM-peptide, and 10 uM ATP, in Reaction Buffer. After 90 minutes of incubation at room temperature, the phosphorylation reaction was stopped by the addition of 10 uL Termination Buffer. The product and substrate in each independent reaction were separated on a 12-sipper microfluidic chip (Caliper Life Sciences, Hopkinton, Mass.) run on a Caliper LC3000 (Caliper Life Sciences, Hopkinton, Mass.). The separation of product and substrate was optimized by choosing voltages and pressure using Caliper's Optimizer software (Hopkinton, Mass.). The separation conditions used a downstream voltage of -500V, an upstream voltage of -2150V, and a screening pressure of -1.2 psi. The product and substrate fluorophore were excited at 488 nm and detected at 530 nm. Substrate conversion was calculated from the electropherogram using HTS Well Analyzer software (Caliper Life Sciences, Hopkinton, Mass.). Ki values for the test compound were calculated.
Measurement: Ki = 3.12 nM (pChEMBL 8.510000228881836)
Descriptors: MW 386.46, ALogP 2.51, HBA 8, HBD 1, PSA 98.64, QED 0.58
Compound (SMILES): CN(C)Cc1ccc(-c2c(-c3cccc(OC(F)(F)F)c3)cc3n2C(CCOC(=O)C(F)(F)F)CNC3=O)cc1
InChIKey: PZOMINBBFNQNAN-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: Trans-Phosphorylation Assay: The inhibitory activity of putative kinase inhibitors and the potency of selected compounds were determined using a trans-phosphorylation assay.Specific peptide or protein substrates were trans-phosphorylated by their specific ser-thr or tyr kinase in the presence of ATP traced with 33P-gamma-ATP, and in the presence of their own optimal buffer and cofactors. At the end of the phosphorylation reaction, more than 98% unlabeled ATP and radioactive ATP were captured by an excess of the ion exchange dowex resin; the resin then settled down to the bottom of the reaction plate by gravity. Supernatant was subsequently withdrawn and transferred into a counting plate, then evaluated by beta-counting. Kinase Buffer (KB):The buffer for PIM2 assay was composed of HEPES 50 mM, at pH 7.5, with 1 mM MgCl2, 1 mM DTT, 3 uM Na3VO4, and 0.2 mg/mL BSA.Â  Full-length human PIM2 was expressed and purified as described in Fedorov O, et al., PNAS 2007 104, 51, 20523-28.
Measurement: IC50 = 38 nM (pChEMBL 7.420000076293945)
Descriptors: MW 569.5, ALogP 5.56, HBA 6, HBD 1, PSA 72.8, QED 0.28
Compound (SMILES): Cc1nc(-c2nc3ccccc3[nH]2)c(N2CCN(C(=O)Cn3cnc4cccnc43)[C@H](C)C2)s1
InChIKey: CTUWPSNEZJLVDO-OAHLLOKOSA-N
Target: C-X-C chemokine receptor type 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49682
Assay: Antagonist activity at recombinant human CXCR3 expressed in human CHO-K1 cells co-expressing Galpha15 incubated for 10 mins by Fluo-4AM dye based FLIPR assay
Measurement: IC50 = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 472.58, ALogP 3.48, HBA 8, HBD 1, PSA 95.83, QED 0.43
Compound (SMILES): CC(Oc1ccccc1S(N)(=O)=O)C(=O)NCC(O)CN1CCc2ccccc2C1
InChIKey: WPYXWTNKENKRIP-UHFFFAOYSA-N
Target: Protein arginine N-methyltransferase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: O14744
Assay: Biochemical Assay: Molecular Biology: Full-length human PRMT5 (NM_006109.3) transcript variant 1 clone was amplified from a fetal brain cDNA library, incorporating flanking 5′ sequence encoding a FLAG tag (MDYKDDDDK) (SEQ ID NO.:4) fused directly to Ala 2 of PRMT5. Full-length human MEP50 (NM_024102) clone was amplified from a human testis cDNA library incorporating a 5′ sequence encoding a 6-histidine tag (MHHHHHH) (SEQ ID NO.:5) fused directly to Arg 2 of MEP50. The amplified genes were sublconed into pENTR/D/TEV (Life Technologies) and subsequently transferred by Gateway attL×attR recombination to pDEST8 baculvirus expression vector (Life Technologies).Protein Expression. Recombinant baculovirus and Baculovirus-Infected Insect Cells (BIIC) were generated according to Bac-to-Bac kit instructions (Life Technologies) and Wasilko, 2006, respectively. Protein over-expression was accomplished by infecting exponentially growing Spodoptera frugiperda (SF9) cell culture at 1.2×106 cell/ml with a 5000 fold dilution of BIIC stock. Infections were carried out at 27° C. for 72 hours, harvested by centrifugation, and stored at −80° C. for purification.
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 433.53, ALogP 0.64, HBA 6, HBD 3, PSA 121.96, QED 0.56
Compound (SMILES): C[C@@]1(c2cc(NC(=O)c3ccc(F)cn3)ccc2F)CS(=O)(=O)[C@@]2(CCOC2)C(=N)N1
InChIKey: VBGOWSNHHLRKMG-VQTJNVASSA-N
Target: Beta-secretase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Z0
Assay: HTRF FRET Assay: Inhibitor IC50s at purified human autoBACE-2 are determined in a time-resolved endpoint proteolysis assay that measures hydrolysis of the QSY7-EISEVNLDAEFC-Eu-amide FRET peptide substrate (BACE-HTRF assay). BACE-mediated hydrolysis of this peptide results in an increase in relative fluorescence (RFU) at 620 nm after excitation with 320 nm light Inhibitor compounds, prepared at 3x the desired final concentration in 1x BACE assay buffer (20 mM sodium acetate pH 5.0, 10% glycerol, 0.1% Brij-35) supplemented with 7.5% DMSO are pre-incubated with an equal volume of autoBACE-2 enzyme diluted in 1x BACE assay buffer (final enzyme concentration 1 nM) in black 384-well NUNC plates for 30 minutes at 30° C. The assay is initiated by addition of an equal volume of the QSY7-EISEVNLDAEFC-Eu-amide substrate (200 nM final concentration, Km=8 uM for 4 uM for autoBACE-2) prepared in 1x BACE assay buffer supplemented with 7.5% DMSO and incubated for 90 minutes at 30° C.
Measurement: Ki = 2.7 nM (pChEMBL 8.569999694824219)
Descriptors: MW 450.47, ALogP 1.98, HBA 6, HBD 3, PSA 121.24, QED 0.66
Compound (SMILES): Cc1cc(COc2cccc(-c3cc(NC4CC4)n4ncc(/C=C5\NC(=O)NC5=O)c4n3)c2)no1
InChIKey: UXWXYJUNIQAEIC-UKWGHVSLSA-N
Target: Casein kinase II subunit beta (SINGLE PROTEIN), Homo sapiens
UniProt: P67870
Assay: Inhibition Assay: 5 uM ATP: Test compounds dissolved and diluted in DMSO (2 μl) were added to a reaction mixture comprising 10 μl of 5× Reaction Buffer (40 mM MOPS pH 7.0, 5 mM EDTA), 10 μl of recombinant human PIM2 solution (4 ng PIM-2 dissolved in dilution buffer (20 mM MOPS pH 7.0; EDTA 1 mM; 5% Glycerol; 0.01% Brij 35; 0.1%; 0.1% 2-mercaptoethanol; 1 mg/ml BSA)) and 8 ul of water. Reactions were initiated by the addition of 10 ul of ATP Solution (49% (15 mM MgCl2; 5 uM ATP) 1% ([γ-33P]ATP: Stock 1 mCi/100 μl; 3000 Ci/mmol (Perkin Elmer)) and 10 ul of substrate peptide solution (RSRSSYPAGT (SEQ ID NO.: 6), dissolved in water at a concentration of 1 mM), Reactions were maintained for 10 min at 30° C. The reactions were quenched with 100 ul of 0.75% Phosphoric acid, then transferred to and filtered through a Phosphocellulose filter plate (Millipore, MSPH-N6B-50). After washing each well 4 times with 0.75% Phosphoric acid, scintillation fluid (20 uL) was added to each well and
Measurement: IC50 > 2500 nM (pChEMBL 5.6020002365112305)
Descriptors: MW 471.48, ALogP 3.03, HBA 9, HBD 3, PSA 135.68, QED 0.28
Compound (SMILES): CC(Nc1ncnc2[nH]cnc12)c1cc2ccccc2c(=O)n1-c1ccccc1
InChIKey: YJNXUORNGCBKSX-UHFFFAOYSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: O00329
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human p110delta/untagged recombinant full length p85alpha expressed in baculovirus infected Sf21 cells using phosphatidylinositol as substrate in presence of gamma-32P-ATP after 5 mins by thin layer chromatographic method
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 382.43, ALogP 3.83, HBA 6, HBD 2, PSA 88.49, QED 0.49
Compound (SMILES): CCCCCCOc1c(O)ccc2c1CN1CCc3cc(OC)c(O)cc3[C@@H]1C2
InChIKey: UENAJMHEKJGFHA-FQEVSTJZSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]N-methylspiperone from human D3 receptor expressed in HEKT cell membranes after 90 mins by microbeta scintillation counting method
Measurement: Ki = 195 nM (pChEMBL 6.710000038146973)
Descriptors: MW 397.52, ALogP 4.72, HBA 5, HBD 2, PSA 62.16, QED 0.66
Compound (SMILES): COCCOc1cc(NC(=O)N2CCCc3cc(C(F)(F)F)c(C=O)nc32)ncc1C#N
InChIKey: XNYAZIURZHFKEG-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Mus musculus
UniProt: Q03142
Assay: Inhibition of FGFR4 in mouse BAF3 cells assessed as reduction in cell viability incubated for 2 days by cell proliferation assay
Measurement: IC50 = 72 nM (pChEMBL 7.139999866485596)
Descriptors: MW 449.39, ALogP 3.19, HBA 7, HBD 1, PSA 117.44, QED 0.53