lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC1(C)c2cc(OCCN3CCOCC3)ccc2C(=O)c2c1oc1cc(C#Cc3cc(C(=O)NC4CC4)ccn3)ccc21
InChIKey: ZJSYBNVFNSNIMP-UHFFFAOYSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: Inhibition of TRKA (unknown origin)
Measurement: IC50 = 1.3 nM (pChEMBL 8.890000343322754)
Descriptors: MW 575.67, ALogP 4.7, HBA 7, HBD 1, PSA 93.9, QED 0.33
Compound (SMILES): CO[C@@H]1c2c3c(cc(O)c2C(=O)O[C@@H]1C)O[C@@]1(C)[C@@H](O)C[C@H]2C(C)(C)C(=O)C=C[C@]2(C)[C@@H]1C3
InChIKey: NGKDELKJNZLSFY-WQVXKCIISA-N
Target: Tyrosine-protein phosphatase non-receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P18031
Assay: Inhibition of PTP1B (unknown origin) using pNPP as substrate by spectrophotometer analysis
Measurement: IC50 = 63100 nM (pChEMBL 4.199999809265137)
Descriptors: MW 456.54, ALogP 3.5, HBA 7, HBD 2, PSA 102.29, QED 0.62
Compound (SMILES): O=C(Nc1ccc2cn[nH]c2c1)N1CCN(c2ncccc2Cl)CC1
InChIKey: IKKAKSKUFKDOND-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily V member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NER1
Assay: Agonist activity at human TRPV1 expressed in HEK293 cells assessed as increase in intracellular calcium accumulation measured at 180 sec by fluorescence based microplate reader analysis
Measurement: EC50 = 89 nM (pChEMBL 7.050000190734863)
Descriptors: MW 356.82, ALogP 2.97, HBA 4, HBD 2, PSA 77.15, QED 0.74
Compound (SMILES): COCCn1c(=O)n(C)c2cnc3ccc(-c4ccc(NC(=O)NCCN(C)C)cc4F)cc3c21
InChIKey: XFJCLEGONBCXID-UHFFFAOYSA-N
Target: Serine-protein kinase ATM (SINGLE PROTEIN), Homo sapiens
UniProt: Q13315
Assay: Inhibition of ATM (unknown origin) by FRET assay
Measurement: IC50 < 1 nM (pChEMBL 9)
Descriptors: MW 480.54, ALogP 3.02, HBA 7, HBD 2, PSA 93.42, QED 0.4
Compound (SMILES): CC(C)(C)[C@H](NC(=O)C(F)(F)F)C(=O)N1C[C@H]2[C@@H]([C@H]1C(=O)N[C@@H](C[C@@H]1CCNC1=O)C(=O)C(=O)NC1CC1)C2(C)C
InChIKey: MPDPCSZJIQTMDD-IEOZYHAZSA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Inhibition of full length SARS-CoV-2 3CLpro expressed in Escherichia coli BL21 (DE3) cells using (DABCYL)KTSAVLQSGFRKM(Glu)(EDANS) peptide as substrate preincubated for 30 mins followed by substrate addition and measured after 1.5 hrs by FRET assay
Measurement: IC50 = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 585.62, ALogP 0.42, HBA 6, HBD 4, PSA 153.78, QED 0.29
Compound (SMILES): Fc1ccc(-c2nc3ccc(Br)cn3n2)cc1
InChIKey: MIBOVHXUHZRLSK-UHFFFAOYSA-N
Target: Aryl hydrocarbon receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35869
Assay: Agonist activity at AhR in human recombinant HepG2-Lucia AhR cell incubated for 24 hrs by luciferase reporter gene assay
Measurement: EC50 = 1185 nM (pChEMBL 5.929999828338623)
Descriptors: MW 292.11, ALogP 3.3, HBA 3, HBD 0, PSA 30.19, QED 0.69
Compound (SMILES): C[C@]12Cc3cnn(-c4ccc(F)cc4)c3C=C1CCC[C@@H]2[C@H](O)c1c(F)c(F)c(F)c(F)c1F
InChIKey: SSRKMRKOAIRANV-MNCIPDHPSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P06536
Assay: Agonist activity at glucocorticoid receptor in rat INS-1 832/13 cells transfected with CCL2-promoter luciferase plasmid construct assessed as reduction in IL-1 beta induced inflammation by luciferase reporter gene assay
Measurement: IC50 = 25.12 nM (pChEMBL 7.599999904632568)
Descriptors: MW 478.44, ALogP 6.19, HBA 3, HBD 1, PSA 38.05, QED 0.28
Compound (SMILES): Clc1ncc(Cl)c(-c2c[nH]c3ncncc23)n1
InChIKey: SNCPRBGMFLEHRJ-UHFFFAOYSA-N
Target: Ribosomal protein S6 kinase alpha-5 (SINGLE PROTEIN), Homo sapiens
UniProt: O75582
Assay: Inhibition of full-length N-terminal His-TEV-tagged inactive form of MSK1 (2 to 802 residues) (unknown origin) expressed in HEK293 cells using FAM-PSKPAATRKRRWSAPESR-NH2 as substrate preincubated for 1 hr followed by activation with ERK2 and substrate addition measured after 2 hrs by microfluidic chip based electrophoresis
Measurement: IC50 = 19.95 nM (pChEMBL 7.699999809265137)
Descriptors: MW 266.09, ALogP 2.72, HBA 4, HBD 1, PSA 67.35, QED 0.69
Compound (SMILES): Cc1nc(C)n(CC(=O)N2CCN(c3sc(C(F)(F)F)nc3-c3cnc(C(C)(C)C)nc3)C[C@H]2C)n1
InChIKey: JSLHIASGSJBGLL-CYBMUJFWSA-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 = 8.7 nM (pChEMBL 8.0600004196167)
Descriptors: MW 522.6, ALogP 3.86, HBA 9, HBD 0, PSA 92.93, QED 0.51
Compound (SMILES): O=C(CNc1ccccc1)NC1CCCN(c2ncnc3[nH]ccc23)C1
InChIKey: INJVALJRNIUGCB-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK (unknown origin) incubated 30 mins by FRET assay
Measurement: IC50 = 390 nM (pChEMBL 6.409999847412109)
Descriptors: MW 350.43, ALogP 2.15, HBA 5, HBD 3, PSA 85.94, QED 0.66
Compound (SMILES): Cc1c(CC#N)ccnc1-c1cccc(-c2cnc3c(c2Cl)C2(CC[C@@](C)(C(N)=O)C2)CN3)c1F
InChIKey: JCBRYERBCGOMNV-AVJYQCBHSA-N
Target: Mitogen-activated protein kinase kinase kinase kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92918
Assay: Inhibition of HPK1 (unknown origin) assessed as inhibition constant by Lanthascreen binding assay
Measurement: Ki = 0.39 nM (pChEMBL 9.40999984741211)
Descriptors: MW 489.98, ALogP 5.32, HBA 5, HBD 2, PSA 104.69, QED 0.52
Compound (SMILES): CCC(CN)=C1CN(c2nc(Oc3cnc(C(C)O)nc3)nc3[nH]c4c(NC)cc(F)cc4c23)C1
InChIKey: WYPNEVJSSFIDEP-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of hERG potassium channel assessed as maximum inhibition rate at -80 mV holding potential incubated for 120 seconds by whole cell-automated voltage clamp analysis assay
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 478.53, ALogP 3.41, HBA 9, HBD 4, PSA 138.1, QED 0.29
Compound (SMILES): CN1C(=O)C(F)=C[C@]2(C)[C@H]3CC[C@]4(C)[C@@H](O)/C(=C/c5cncnc5)C[C@H]4[C@@H]3CC[C@@H]12
InChIKey: PDLKGOROWUPNJC-BTJCDENPSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Displacement of [3H]methyltrienolone from Androgen receptor expressed in human MDA-MB-453 cells
Measurement: IC50 = 59 nM (pChEMBL 7.230000019073486)
Descriptors: MW 411.52, ALogP 3.77, HBA 4, HBD 1, PSA 66.32, QED 0.76
Compound (SMILES): Cc1cc(Oc2ccc(Cn3nc4ccc(Cl)cc4c3C(=O)NS(=O)(=O)c3ccc(NCCc4ccncc4)c([N+](=O)[O-])c3)cc2)cc(C)c1Cl
InChIKey: RCFHHUFGFWHXSJ-UHFFFAOYSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Inhibition of MCL-1 (unknown origin) by fluorescence polarization competition assay
Measurement: Ki = 1770 nM (pChEMBL 5.75)
Descriptors: MW 745.64, ALogP 7.88, HBA 10, HBD 2, PSA 158.35, QED 0.09
Compound (SMILES): N.N.Nc1nc2c(ncn2[C@@H]2O[C@@H]3COP(=O)(O)O[C@H]4[C@@H](F)[C@H](n5cnc6c(N)ncnc65)O[C@@H]4COP(=O)(O)O[C@@H]2[C@@H]3F)c(=O)[nH]1
InChIKey: RCXGYDPPYKVDAP-BOGCYVOXSA-N
Target: Stimulator of interferon genes protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q86WV6
Assay: Displacement of radiolabeled [3H]-2',3'-cGAMP from human STING HAQ variant incubated for 2 hrs by scintillation counting method
Measurement: IC50 < 1 nM (pChEMBL 9)
Descriptors: MW 678.4, ALogP -0.39, HBA 18, HBD 5, PSA 289.19, QED 0.17
Compound (SMILES): Clc1ccc(Nc2nc3ccccc3c3[nH]c(C4CCCCCCCC4)nc23)cc1Cl
InChIKey: VLFOIGWFHOKUEU-UHFFFAOYSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99720
Assay: Displacement of [3H]-LSD from human sigma1 receptor expressed in human HEK293T cell membrane incubated for 90 mins by radioligand binding assay
Measurement: Ki = 5150 nM (pChEMBL 5.289999961853027)
Descriptors: MW 453.42, ALogP 8.38, HBA 3, HBD 2, PSA 53.6, QED 0.33
Compound (SMILES): N#CC1CCOCC1n1cc(C(N)=O)c(Nc2ccc3c(c2)C2CC2B(O)O3)n1
InChIKey: JNKIEYOXMKANPE-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of JAK1 (unknown origin) preincubated for 20 mins followed by 33P-ATP addition and measured after 2 hrs by filter binding assay
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 393.21
Compound (SMILES): COc1cc2nccc(Oc3ccc(Nc4nn(C)cc4C(=O)Nc4ccc(OC(F)F)cc4)cc3F)c2cc1OC
InChIKey: ICYUVEQFEPNPJV-UHFFFAOYSA-N
Target: Tyrosine-protein kinase receptor UFO (SINGLE PROTEIN), Homo sapiens
UniProt: P30530
Assay: Inhibition of recombinant AXL (unknown origin) using poly (Glu,Tyr) 4:1 as substrate incubated for 60 mins in presence of ATP by ELISA
Measurement: IC50 = 64.4 nM (pChEMBL 7.190000057220459)
Descriptors: MW 579.54, ALogP 6.51, HBA 9, HBD 2, PSA 108.76, QED 0.19
Compound (SMILES): Cc1cccc(C)c1-c1nc(N)nc2ccccc12
InChIKey: WDEKWTDKUSEYRW-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Displacement of [3H]ZM241385 from human adenosine A2A receptor expressed in HEK293 cell membrane incubated for 1 hr by microplate beta scintillation counting based radioligand inhibition assay
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 249.32, ALogP 3.5, HBA 3, HBD 1, PSA 51.8, QED 0.72
Compound (SMILES): COc1ccc(N2Cc3cnc(NCC4CC4)nc3C3(CCN(Cc4cnc(N)s4)C3)C2=O)cc1
InChIKey: ZLVDDYSMLCYSBC-UHFFFAOYSA-N
Target: S-adenosylmethionine synthase isoform type-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P31153
Assay: Inhibition of recombinant human MAT2A expressed in baculovirus infected Sf9 cells assessed as S-adenosyl methionine production using L-methionine as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins in presence of ATP
Measurement: IC50 = 410 nM (pChEMBL 6.389999866485596)
Descriptors: MW 491.62, ALogP 3.04, HBA 9, HBD 2, PSA 109.5, QED 0.52
Compound (SMILES): COc1cccc(NC(=S)NC(=O)C23CC4CC(CC(C4)C2)C3)c1
InChIKey: NADDXTNWNPDOCX-UHFFFAOYSA-N
Target: P2X purinoceptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBL9
Assay: Antagonist activity at human P2X2 receptor expressed in human 1321N1 cells assessed as reduction in intracellular Ca2+ influx incubated for 30 mins by Fura-2 AM based fluorescence assay
Measurement: IC50 = 2306 nM (pChEMBL 5.639999866485596)
Descriptors: MW 344.48, ALogP 3.72, HBA 3, HBD 2, PSA 50.36, QED 0.82
Compound (SMILES): CCCCCNC(=O)/N=C(\N)NCCCc1cnc(N)s1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: RZWKIWSVEPQMPP-UHFFFAOYSA-N
Target: Histamine H1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35367
Assay: Displacement of [3H] mepyramine from human histamine H1 receptor stably expressed in baculovirus infected Sf9 cell membrane co-expressing RGS4 incubated for 60 mins by scintillation counting analysis
Measurement: Ki = 9549.93 nM (pChEMBL 5.019999980926514)
Descriptors: MW 312.44, ALogP 1.46, HBA 4, HBD 4, PSA 118.42, QED 0.33
Compound (SMILES): CN1CCN(c2ccc(Nc3nc(Oc4cccc5c4C(=O)CC5)c4cc[nH]c4n3)cc2C#N)CC1
InChIKey: JZSCRIGOGNPMQG-UHFFFAOYSA-N
Target: Focal adhesion kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q05397
Assay: Inhibition of FAK (unknown origin) using Fluorescein-Poly GAT as substrate incubated for 30 mins and measured after 60 mins by Lanthascreen assay
Measurement: IC50 = 20.55 nM (pChEMBL 7.690000057220459)
Descriptors: MW 479.54, ALogP 4.25, HBA 8, HBD 2, PSA 110.17, QED 0.44
Compound (SMILES): Cc1c([C@@H](C)Nc2nnc(C(F)(F)F)c3ccc(N4CCNCC4)cc23)cccc1C(F)(F)F
InChIKey: AXWSVASPJVKAPC-CQSZACIVSA-N
Target: Son of sevenless homolog 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07889
Assay: Binding affinity to N-terminal his-TEV-Avi-tagged human recombinant SOS1 expressed in Escherichia coli assessed as inhibition constant incubated for 10 to 15 mins by HTRF displacement assay
Measurement: Ki = 59 nM (pChEMBL 7.230000019073486)
Descriptors: MW 483.46, ALogP 5.56, HBA 5, HBD 2, PSA 53.08, QED 0.48
Compound (SMILES): O=C1c2ccccc2C(=O)c2c1cc(S(=O)(=O)N[C@@H](CO)C(=O)O)c(O)c2O
InChIKey: ABRGLDHFMGSAGG-JTQLQIEISA-N
Target: Pyruvate kinase PKLR (SINGLE PROTEIN), Homo sapiens
UniProt: P30613
Assay: Inhibition of PKL (unknown origin) for 30 mins by Kinase-Glo Max reagent based luminescence assay
Measurement: IC50 = 900 nM (pChEMBL 6.050000190734863)
Descriptors: MW 407.36, ALogP -0.4, HBA 8, HBD 5, PSA 178.3, QED 0.35
Compound (SMILES): Cc1nc(-c2cnc(NC3CC3)n(C)c2=O)ccc1Oc1ccnc(-c2cnn(C)c2)c1
InChIKey: ZJIRIQBCHHNGDO-UHFFFAOYSA-N
Target: Macrophage colony-stimulating factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07333
Assay: Inhibition of N-terminal His6-tagged recombinant human CSF1R (542 to 919 residues) measured by spectrophotometric analysis
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 429.48, ALogP 3.31, HBA 9, HBD 1, PSA 99.75, QED 0.5
Compound (SMILES): CN1C(=S)[C@@H](NC(=O)c2nc(Cc3ccccc3)n(C3CCC3)n2)COc2ccccc21
InChIKey: KWULYOXEBVCWFW-SFHVURJKSA-N
Target: Receptor-interacting serine/threonine-protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13546
Assay: Binding affinity to wild-type human partial length RIPK1 (M1 to K305 residues) expressed in bacterial expression system incubated for 1 hr under shaking condition by Kinomescan method
Measurement: Kd = 301 nM (pChEMBL 6.519999980926514)
Descriptors: MW 447.56, ALogP 3.55, HBA 6, HBD 1, PSA 72.28, QED 0.6
Compound (SMILES): C[C@@H](C(=O)Nc1ccc(C#N)cc1)[C@H]1CC[C@@H](c2ccnc3ccc(F)cc32)CC1
InChIKey: OYXQJDKQBDHYAT-QRQLOZEOSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 in IFN-gamma stimulated human HeLa cells in presence of heme measured after 20 hrs by heme-competitive binding assay
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 401.49, ALogP 5.79, HBA 3, HBD 1, PSA 65.78, QED 0.6
Compound (SMILES): CCN(Cc1ccc(C(=O)NO)cc1)C(=O)c1cc(Cl)c(O)cc1O
InChIKey: AFGXIYGANOBZCW-UHFFFAOYSA-N
Target: Heat shock protein HSP 90-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P07900
Assay: Inhibition of His-tagged N-terminal recombinant HSP90alpha (unknown origin) expressed in Escherichia coli BL21 (DE3) incubated for 4 hrs by fluorescence polarization based microplate reader assay
Measurement: IC50 = 693 nM (pChEMBL 6.159999847412109)
Descriptors: MW 364.79, ALogP 2.53, HBA 5, HBD 4, PSA 110.1, QED 0.48
Compound (SMILES): CC[C@H](N1Cc2cc(-c3ccn4nc(N)c(C(=O)NC5CC5)c4n3)cc(NS(C)(=O)=O)c2C1=O)C(F)(F)F
InChIKey: PKKGUQHKALIMOX-INIZCTEOSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of PI3Kgamma (unknown origin) in rhMPC1 stimulated human THP-1 cells assessed as reduction in Akt phosphorylation level at Ser473 residue preincubated for 60 mins followed by rhMCP-1 stimulation and measured after 2 mins by AlphaLisa assay
Measurement: IC50 = 31 nM (pChEMBL 7.510000228881836)
Descriptors: MW 551.55, ALogP 2.54, HBA 8, HBD 3, PSA 151.79, QED 0.41
Compound (SMILES): CCNC(=O)[C@@H]1CN(C(=O)c2ccc(C(=O)N3C[C@@H](C(=O)N[C@H]4C[C@@H]4c4ccccc4)[C@H](C(=O)N[C@H]4C[C@@H]4c4ccccc4)C3)cc2)C[C@H]1C(=O)N[C@H]1C[C@@H]1c1ccccc1
InChIKey: HLWOSHGABMZUHP-CDIXZCHFSA-N
Target: Toll-like receptor 1/2 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q15399
Assay: Agonist activity at TLR1/TLR2 in human THP-1 derived macrophages assessed as stimulation of TNF alpha release measured for 4 hrs by ELISA based assay
Measurement: EC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 820.99, ALogP 4.22, HBA 6, HBD 4, PSA 157.02, QED 0.16
Compound (SMILES): CCCN(CCC)C(=O)Cn1c(=O)n2cc(-c3ccccc3)nc2c2ccccc21
InChIKey: INPAQILXZCAOTK-UHFFFAOYSA-N
Target: Translocator protein (SINGLE PROTEIN), Rattus norvegicus
UniProt: P16257
Assay: Displacement of [3H]-PK11195 from TSPO receptor in rat heart microsomes incubated for 15 mins by scintillation method
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 402.5, ALogP 3.96, HBA 5, HBD 0, PSA 59.61, QED 0.47
Compound (SMILES): Nc1ncnc2c1ncn2[C@@H]1O[C@H](COP(=O)(O)OP(=O)(O)OP(=O)(O)O)[C@@H](OC(=O)c2cccc3ccccc23)[C@H]1OC(=O)c1cccc2ccccc12
InChIKey: PSBROSWEMLTASJ-BQOYKFDPSA-N
Target: P2X purinoceptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P51575
Assay: Agonist activity at human P2X1R expressing CHO cells assessed as reduction in intracellular Ca2+ influx pretreated with Fluo-4 for 1 hr followed by compound addition and further incubated for 30 mins in presence of ATP by multimode plate reader analysis
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 815.52, ALogP 4.41, HBA 16, HBD 5, PSA 291.27, QED 0.08
Compound (SMILES): O=C(O)c1cc(Cl)cnc1O
InChIKey: XBHXNMLFJZTSAS-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Binding affinity to human DYRK1A (127 to 485 residues) expressed in Escherichia coli BL21 (DE3) cells assessed as dissociation constant by isothermal titration calorimetry assay
Measurement: Kd = 680000 nM (pChEMBL 3.1700000762939453)
Descriptors: MW 173.55, ALogP 1.14, HBA 3, HBD 2, PSA 70.42, QED 0.67
Compound (SMILES): S=c1[nH]cn[nH]1
InChIKey: AFBBKYQYNPNMAT-UHFFFAOYSA-N
Target: Glutaminyl-peptide cyclotransferase (SINGLE PROTEIN), Homo sapiens
UniProt: Q16769
Assay: Inhibition of recombinant human QC using H-Gln-AMC hydrobromide as fluorogenic substrate incubated for 6 hrs by fluorometric microplate reader analysis
Measurement: IC50 = 2090 nM (pChEMBL 5.679999828338623)
Descriptors: MW 101.13, ALogP 0.47, HBA 2, HBD 2, PSA 44.47, QED 0.47
Compound (SMILES): CCN1C(=O)N[C@@H](CCC(C)(F)F)CCOCCOc2nc(cc3ccnn23)-c2ccnc(c2)[C@H]1C
InChIKey: YUARDLVSUBRLFK-MJGOQNOKSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Agonist activity at human OX2R expressed in CHO cells incubated for 1 to 2 hrs by IP-one detection reagent based fluorescence assay
Measurement: EC50 = 0.2 nM (pChEMBL 9.699999809265137)
Descriptors: MW 502.57, ALogP 4.49, HBA 7, HBD 1, PSA 93.88, QED 0.57
Compound (SMILES): O=C(Cc1ccccc1)Nc1nnc(N[C@H]2CCN(c3nnc(NC(=O)CCc4cn(Cc5ccc(OC(F)(F)F)cc5)nn4)s3)C2)s1
InChIKey: GMUSGZURQRIDBC-FQEVSTJZSA-N
Target: Glutaminase kidney isoform, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: O94925
Assay: Allosteric inhibition of human GLS1 using glutamine as substrate incubated for 60 mins by NADH/NADPH-based absorbance analysis
Measurement: IC50 = 381.48 nM (pChEMBL 6.420000076293945)
Descriptors: MW 699.75, ALogP 4.37, HBA 14, HBD 3, PSA 164.97, QED 0.16
Compound (SMILES): Cc1ccccc1-c1ccc2c(ccn2Cc2coc(/C=C/c3ccc(C(F)(F)F)cc3)n2)c1
InChIKey: KARCTBDGAQJPSD-MDWZMJQESA-N
Target: Receptor tyrosine-protein kinase erbB-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P04626
Assay: Inhibition of human HER2 incubated for 25 mins by ADP-Glo reagent based microplate reader analysis
Measurement: IC50 = 13340 nM (pChEMBL 4.880000114440918)
Descriptors: MW 458.48, ALogP 7.84, HBA 3, HBD 0, PSA 30.96, QED 0.27
Compound (SMILES): O=C1N(CCN2C(=O)C(O)(c3c[nH]c4ccccc34)c3ccccc32)c2ccccc2C1(O)c1c[nH]c2ccccc12
InChIKey: SHOSTGAKQJDIJR-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of electric eel AChE by Ellman's method
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 554.61, ALogP 4.51, HBA 4, HBD 4, PSA 112.66, QED 0.25
Compound (SMILES): Cn1cnc2c(NCc3ccccc3)nc(Nc3cccc(S(N)(=O)=O)c3)nc21
InChIKey: PHRMLZQDPCVBGF-UHFFFAOYSA-N
Target: cGMP-specific 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O76074
Assay: Inhibition of human PDE5 using [3H]cGMP as substrate incubated for 10 mins by liquid scintillation counter analysis
Measurement: IC50 = 4460 nM (pChEMBL 5.349999904632568)
Descriptors: MW 409.48, ALogP 2.37, HBA 8, HBD 3, PSA 127.82, QED 0.45
Compound (SMILES): Nc1nccc(-c2sc(C3CCN(C4CC4)CC3)nc2-c2cccc(NS(=O)(=O)c3cc(F)ccc3F)c2F)n1
InChIKey: GQNWRWISEOKRCC-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Inhibition of N-terminal His-tagged human recombinant B-Raf V600E mutant (448 to 723 residues) expressed in Escherichia coli BL21 (DE3) by Lanthascreen assay
Measurement: IC50 = 4.4 nM (pChEMBL 8.359999656677246)
Descriptors: MW 586.66, ALogP 5.41, HBA 8, HBD 2, PSA 114.1, QED 0.3
Compound (SMILES): CCn1cc(Nc2ncc3c(C)nn(-c4ccc(C#N)cc4)c3n2)cn1
InChIKey: ZKHWUKCTVZPIOU-UHFFFAOYSA-N
Target: eIF-2-alpha kinase GCN2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P2K8
Assay: Inhibition of GCN2 (unknown origin)
Measurement: IC50 = 56 nM (pChEMBL 7.25)
Descriptors: MW 344.38, ALogP 2.96, HBA 8, HBD 1, PSA 97.24, QED 0.61
Compound (SMILES): COc1cc(/C=C/c2cc(/C=C/c3ccc(O)c(OC)c3)n(-c3cc(Cl)cc(Cl)c3)n2)ccc1O
InChIKey: RPVPSYKTHKIHEW-FCXRPNKRSA-N
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Homo sapiens
UniProt: P05067
Assay: Inhibition of amyloid beta 40 secretion transfected in human H4 cells incubated for 20 to 24 hrs by LPECL assay
Measurement: IC50 = 6300 nM (pChEMBL 5.199999809265137)
Descriptors: MW 509.39, ALogP 6.95, HBA 6, HBD 2, PSA 76.74, QED 0.28
Compound (SMILES): Nc1nnc2c([nH]c3ccccc32)c1-c1ccccc1
InChIKey: DHDZFJQQXROKLC-UHFFFAOYSA-N
Target: SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P51532
Assay: Inhibition of His-tagged SMARCA4 (unknown origin) (1448 to 1575 residues) using biotinylated ARTKQTARKSTGG-K(Ac)-APR-K(Ac)-QLAT-K(Ac)-AAR-K(Ac)-SAPGG-K as substrate incubated for 10 mins by TR-FRET assay
Measurement: IC50 = 5300 nM (pChEMBL 5.28000020980835)
Descriptors: MW 260.3, ALogP 3.36, HBA 3, HBD 2, PSA 67.59, QED 0.55
Compound (SMILES): COc1cc2cc(C(=O)CCC(=O)ONCc3ccccc3)sc2cc1OC
InChIKey: DXVFESMCXICVBV-UHFFFAOYSA-N
Target: Stimulator of interferon genes protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q86WV6
Assay: Agonist activity at STING in human THP1-Dual cells assessed as ISG pathway activation incubated for 24 hrs by Quanti-Luc or Quanti-blue reagent based luminescence assay
Measurement: EC50 = 6140 nM (pChEMBL 5.210000038146973)
Descriptors: MW 399.47, ALogP 4.13, HBA 7, HBD 1, PSA 73.86, QED 0.43
Compound (SMILES): O=C(O)/C=C/C(=O)NNC(=O)c1cnccc1Nc1cc(Cl)c(Nc2ccccc2[N+](=O)[O-])c(Cl)c1
InChIKey: KNGWJZXEDNHKQS-AATRIKPKSA-N
Target: Alpha-ketoglutarate-dependent dioxygenase FTO (SINGLE PROTEIN), Homo sapiens
UniProt: Q9C0B1
Assay: Inhibition of FTO (unknown origin) demethylation activity by HPLC assay
Measurement: IC50 = 570 nM (pChEMBL 6.239999771118164)
Descriptors: MW 531.31, ALogP 4.19, HBA 8, HBD 5, PSA 175.59, QED 0.16
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(N)=O)NC(=O)CCCNS(=O)(=O)c1ccc(Oc2ccccc2)cc1)C(=O)N(C)[C@@H](CC(C)C)C(=O)N1CCC[C@H]1CC(N)=O
InChIKey: FPHZWTIGUNTHAS-RWCCSHLZSA-N
Target: 72 kDa type IV collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P08253
Assay: Inhibition of recombinant human MMP2 using MOCAc-Lys-Pro-Leu-Gly-Leu-A2pr(Dnp)-Ala-Arg-NH2 as a substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by fluroscence based assay
Measurement: IC50 = 0.055 nM (pChEMBL 10.260000228881836)
Descriptors: MW 986.16, ALogP 0.63, HBA 12, HBD 8, PSA 335.9, QED 0.05
Compound (SMILES): Cc1nc2cc(NC(=O)CCOCCOCCOCCOCCNC(=O)COc3cccc4c3C(=O)N(C3CCC(=O)NC3=O)C4=O)ccc2n1Cc1ccc(C(=O)NO)cc1F
InChIKey: MATDHSREQSFFRV-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of recombinant full length C-terminal His/Flag-tagged human HDAC1 (1 to 482 residues) using Z-Lys(Ac)-AMC as substrate preincubated for 90 mins followed by trypsin addition and measured after 30 mins by fluorescence based microplate reader analysis
Measurement: IC50 = 1494 nM (pChEMBL 5.829999923706055)
Descriptors: MW 875.86, ALogP 1.64, HBA 15, HBD 5, PSA 255.05, QED 0.03
Compound (SMILES): Cc1cccc2sc(NC(=O)CCN3CCN(C(C)C)CC3)nc12
InChIKey: VBLIZEIXBKDACF-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human recombinant AChe using acetylthiocholine iodide as substrate incubated for 10 mins by DTNB reagent based Ellman's method
Measurement: IC50 = 2750 nM (pChEMBL 5.559999942779541)
Descriptors: MW 346.5, ALogP 2.96, HBA 5, HBD 1, PSA 48.47, QED 0.9
Compound (SMILES): CCCCN(CCC1CCCCCC1)Cc1cc2ccccc2cc1O
InChIKey: WJILKOOXLPILKO-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of recombinant human BChE using butyrylthiocholine iodide as substrate preincubated for 1 to 30 mins followed by substrate addition by Ellman's method
Measurement: IC50 = 33.7 nM (pChEMBL 7.46999979019165)
Descriptors: MW 353.55, ALogP 6.51, HBA 2, HBD 1, PSA 23.47, QED 0.55
Compound (SMILES): CN1CCN(CCC2CCCCCC2)C[C@@H]1Cc1c[nH]c2ccccc12
InChIKey: XSBOVJKKJVDOBL-NRFANRHFSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of recombinant human BChE using butyrylthiocholine iodide as substrate preincubated for 1 to 30 mins followed by substrate addition by Ellman's method
Measurement: IC50 = 10.5 nM (pChEMBL 7.980000019073486)
Descriptors: MW 353.55, ALogP 4.69, HBA 2, HBD 1, PSA 22.27, QED 0.79
Compound (SMILES): Nc1nc(Nc2ccc(S(N)(=O)=O)cc2)nn1C(=O)Nc1ccc(-c2cccc(C(=O)O)c2)cc1
InChIKey: NUTNJONNFDPYEW-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Binding affinity to JAK2 JH2 (unknown origin) expressed in baculovirus infected Sf9 cells assessed as dissociation constant measured upto 30 mins in presence of tracer by competitive fluorescence polarization assay
Measurement: Kd = 129 nM (pChEMBL 6.889999866485596)
Descriptors: MW 493.51, ALogP 2.7, HBA 9, HBD 5, PSA 195.32, QED 0.27
Compound (SMILES): O=C(Cn1cnc2cccnc21)N1CCN(c2ccccc2-c2nc3ccccc3[nH]2)CC1
InChIKey: VMGIBKXRQBDEKY-UHFFFAOYSA-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 = 4.3 nM (pChEMBL 8.369999885559082)
Descriptors: MW 437.51, ALogP 3.32, HBA 6, HBD 1, PSA 82.94, QED 0.47
Compound (SMILES): C#CCn1cc(C#N)c2cc(NC(=O)c3cc(=O)[nH]cn3)ccc21
InChIKey: YBJMFEIOLJPAEW-UHFFFAOYSA-N
Target: Xanthine dehydrogenase/oxidase (SINGLE PROTEIN), Homo sapiens
UniProt: P47989
Assay: Inhibition of xanthine oxidase (unknown origin) using xanthine as substrate incubated for 15 mins followed by substrate addition by spectrophotometric analysis
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 317.31, ALogP 1.48, HBA 5, HBD 2, PSA 103.57, QED 0.71
Compound (SMILES): CC(C)(C)c1cc(NC(=O)N[C@H]2CC[C@@H](Oc3ccc4nnc(N5CCCCC5)n4c3)c3ccccc32)n(-c2cccc(CO)c2)n1
InChIKey: CYWAUYOYRABYEA-XZWHSSHBSA-N
Target: Mitogen-activated protein kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16539
Assay: Inhibition of human recombinant full length GST-tagged p38alpha expressed in Escherichia coli preincubated for 2 hrs followed by ATP addition and measured after 1 hr by Alpha screen assay
Measurement: IC50 = 0.6 nM (pChEMBL 9.220000267028809)
Descriptors: MW 634.78, ALogP 6.47, HBA 9, HBD 3, PSA 121.84, QED 0.19
Compound (SMILES): O=C(c1ccc(-c2nc(-c3ccc(C(F)(F)F)cc3)co2)nc1)N1CCN(Cc2ccc(OCC(F)(F)F)cc2)CC1
InChIKey: QQXNJEANVPWFMW-UHFFFAOYSA-N
Target: Signal transducer and activator of transcription 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P40763
Assay: Inhibition of human recombinant STAT3 (127 to 722 residues) transcriptional activity expressed in HEK293T cells in presence of IL-6 by Dual-luciferase reporter gene assay
Measurement: IC50 = 94.1 nM (pChEMBL 7.03000020980835)
Descriptors: MW 590.52, ALogP 6.32, HBA 6, HBD 0, PSA 71.7, QED 0.23
Compound (SMILES): Cc1cc(-c2cc3c(=O)n(C)cc(-c4cc(CS(=O)(=O)C(C)(C)C)ccc4Oc4ccc(F)cc4F)c3o2)cc(C)c1OCCO
InChIKey: WQZOSYSGHHHNNV-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of C-terminal His6-tagged BRD4 BD1 (unknown origin) using H-YSGRGK(Ac)GGK(Ac)GLGK(Ac)-GGAK(Ac)RHRK-Biotin-OH as substrate incubated for 1 hrs by HTRF assay
Measurement: IC50 = 3.3 nM (pChEMBL 8.479999542236328)
Descriptors: MW 651.73, ALogP 7.24, HBA 8, HBD 1, PSA 107.97, QED 0.18
Compound (SMILES): O=C(/C=C/c1ccco1)c1ccc(N2C(=O)[C@@H]3[C@H](C2=O)[C@@H]2C=C[C@H]3C2)cc1
InChIKey: CDKJSYMMXXELTE-XMLDZNDQSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Binding affinity to human CA1 assessed as inhibition constant using 4-nitrophenylacetate as substrate by spectrophotometrical analysis
Measurement: Ki = 0.4053 nM (pChEMBL 9.390000343322754)
Descriptors: MW 359.38, ALogP 3.49, HBA 4, HBD 0, PSA 67.59, QED 0.36
Compound (SMILES): CCC[C@@H]1NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O
InChIKey: SBBKYPXXEMUEFI-AXESKPDYSA-N
Target: Peptidyl-prolyl cis-trans isomerase A (SINGLE PROTEIN), Homo sapiens
UniProt: P62937
Assay: Binding affinity to CypA (unknown origin) assessed as inhibition constant by isomer specific proteolysis assay
Measurement: Ki > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 1231.68
Compound (SMILES): Cc1ccccc1-c1nc(N)nc2ccccc12
InChIKey: WNELVCPSUUYWIF-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Displacement of [3H]ZM241385 from human adenosine A2A receptor expressed in HEK293 cell membrane incubated for 1 hr by microplate beta scintillation counting based radioligand inhibition assay
Measurement: Ki = 3300 nM (pChEMBL 5.480000019073486)
Descriptors: MW 235.29, ALogP 3.19, HBA 3, HBD 1, PSA 51.8, QED 0.7
Compound (SMILES): Cc1cc(C)c(CNC(=O)c2cc(-c3ccc(N4CCN(C(=O)OC(C)(C)C)CC4)nc3)cc(NCCCCCCC(=O)NO)c2C)c(=O)[nH]1
InChIKey: RXBYSRVZIARRRO-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 (unknown origin) preincubated for 5 mins followed by substrate addition and measured after 30 mins by multimode microplate reader analysis
Measurement: IC50 = 2010 nM (pChEMBL 5.699999809265137)
Descriptors: MW 689.86, ALogP 5.22, HBA 9, HBD 5, PSA 168.99, QED 0.09
Compound (SMILES): C[C@@H](COCCC(=O)N1CCN2c3ncc(C(F)(F)F)cc3OC[C@@H]2C1)Oc1cn[nH]c(=O)c1C(F)(F)F
InChIKey: XIRFUJAKIMLEFY-JSGCOSHPSA-N
Target: Protein mono-ADP-ribosyltransferase TIPARP (SINGLE PROTEIN), Homo sapiens
UniProt: Q7Z3E1
Assay: Inhibition of PARP7 (unknown origin) using histone as substrate incubated for 1 hr by chemiluminescence assay
Measurement: IC50 = 1.75 nM (pChEMBL 8.760000228881836)
Descriptors: MW 551.44, ALogP 2.49, HBA 8, HBD 1, PSA 109.88, QED 0.41
Compound (SMILES): C=Cc1ncc2n1CCN(c1nc(OCC3CCCN3C)nc3c(F)c(-c4c(O)cccc4F)c(Cl)cc13)C2
InChIKey: QIWYHOUATIAHQN-UHFFFAOYSA-N
Target: GTPase KRas (SINGLE PROTEIN), Homo sapiens
UniProt: P01116
Assay: Inhibition of BODIPY loaded KRAS G12C mutant (unknown origin) assessed as inhibition of GDP-GTP exchange rate in presence of SOS1/GppNHp incubated for 2 hr by BODIPY fluorescence assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 553.01, ALogP 5.27, HBA 8, HBD 1, PSA 79.54, QED 0.35
Compound (SMILES): CC1(C)c2ccc3c(c2CC[C@@H]1O)C(=O)C(=O)c1c(CO)coc1-3
InChIKey: JACUFUQZLAOSFL-ZDUSSCGKSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of recombinant human IDO1 assessed as reduction in N-formylkynurenine formation using L-tryptophan as substrate and measured after 15 mins
Measurement: IC50 = 590 nM (pChEMBL 6.230000019073486)
Descriptors: MW 326.35, ALogP 2.4, HBA 5, HBD 2, PSA 87.74, QED 0.79
Compound (SMILES): O=c1[nH]c(=O)n(C2CC2)c2nc(Cc3nc4ccc(F)cc4[nH]3)n(Cc3ccccc3)c12
InChIKey: HLFAVWDNJHBPGF-UHFFFAOYSA-N
Target: Tryptophan 5-hydroxylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P17752
Assay: In Vitro Enzyme Activity Assay: These compounds according to the afore-mentioned examples were tested for tryptophan hydroxylase (TPH) inhibitory activity in a fluorescence-based in vitro assay, using recombinant human TPH1 (Swiss-Prot: P17752) and TPH2 (Swiss-Prot: Q8IWU9).The full-length coding sequences of human TPH1 and TPH2 were PCR amplified, ligated into a MBP fusion vector (pMalc2x, New England Biolabs, MA, USA) and transformed into SCS1 (Stratagene, CA, USA) to amplify plasmid DNA. For the overexpression of TPH proteins, the constructs were transformed into Rosetta (DE3) (Novagen®/EMD Millipore, MA, USA) and cultivated in terrific broth (TB) medium (AppliChem, Darmstadt, Germany) at 37° C. When the bacterial cultures reached an ≈2, expression was induced with 0.5 mM IPTG (AppliChem, Darmstadt, Germany) over night at 17° C. The purification of soluble proteins started with sonication-mediated cell disruption in lysis buffer (1×PBS pH 7.4, 0.5 M NaCl, 5% Glycerol+CHAPS, DTT, PMSF, benzonase), followed by affinity purification (MBPTrap, GE Healthcare, UK) and gel filtration (26/60 Superdex 200 prep grade, GE Healthcare, UK), according to the manufacturer's protocol. The quality of protein expression and solubility was controlled by SDS-PAGE and Coomassie blue staining.The enzymatic reaction was carried out in black 96-well flat bottom plates (Corning GmbH, Wiesbaden). TPH1 and TPH2 activities were measured in a reaction mixture containing 50 mM 4-Morpholineethanesulfonic acid (MES), pH 7.0, 40 μM tryptophan, 200 mM ammonium sulfate, 25 μM ferrous ammonium sulfate, 50 μM tetrahydrobiopterin, 25 μg/ml catalase, and 7 mM DTT. The reactions were initiated by adding TPH1 or TPH2 to a final concentration of 5 μg/ml. Initial velocity of the reactions was determined by following the change of fluorescence at 330 nm (excitation wavelength=300 nm) (Infinite M200, Tecan, Crailsheim).TPH1 and TPH2 inhibition was determined by measuring a compound dose response, using a serial dilution of a 5 mM DMSO stock solution. The potency of a given compound was calculated in GraphPad PRISM 6 software (San Diego, USA) with a Nonlinear Regression fit (log(inhibitor) vs. response-variable slope) using the relative fluorescence units (RFU) of the sample triplicates.
Measurement: IC50 = 1800 nM (pChEMBL 5.75)
Descriptors: MW 430.44, ALogP 2.88, HBA 6, HBD 2, PSA 101.36, QED 0.45
Compound (SMILES): CC(C1CCC1)N1C[C@H](O)C[C@]12CCN(C1CCCCC1)C2=O
InChIKey: ZADRWDRZZMSJGR-VNTLTUIWSA-N
Target: 11-beta-hydroxysteroid dehydrogenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28845
Assay: Inhibition of 11beta-HSD1 (unknown origin) using 3H-cortisone as substrate by scintillation proximity assay
Measurement: IC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 320.48, ALogP 2.55, HBA 3, HBD 1, PSA 43.78, QED 0.87
Compound (SMILES): COc1ccccc1C(=O)N(CC(=O)NC1CCCCC1)Cc1ccc(C(=O)NO)cc1F
InChIKey: RDKOJWPLMOJKIU-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of recombinant human C-terminal FLAG/His-tagged HDAC1 (1 to 482 residues) expressed in Sf9 insect cells using Z-Lys(Ac)-AMC as fluorogenic substrate incubated for 90 mins by microplate reader analysis
Measurement: IC50 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 457.5, ALogP 3.04, HBA 5, HBD 3, PSA 107.97, QED 0.42
Compound (SMILES): CSc1nc(-c2cccc(NC(=O)c3c(F)ccc(O)c3CN3C(=O)c4ccccc4C3=O)c2)c(-c2ccnc(NC(C)=O)c2)[nH]1
InChIKey: HPMLKUVOVSVMID-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of human EGFR L858R mutant expressed in Sf9 insect cells in presence of ATP measured by HTRF assay
Measurement: IC50 = 1.2 nM (pChEMBL 8.920000076293945)
Descriptors: MW 636.67, ALogP 5.71, HBA 8, HBD 4, PSA 157.38, QED 0.12
Compound (SMILES): Nc1ncnc2c1ncn2[C@@H]1O[C@H](CN(C/C=C/c2ccc(F)cc2)CC[C@H](N)C(=O)O)[C@@H](O)[C@H]1O
InChIKey: PPFBYDOMKLGSPH-SUIOFXLQSA-N
Target: Nicotinamide N-methyltransferase (SINGLE PROTEIN), Homo sapiens
UniProt: P40261
Assay: Inhibition of recombinant NNMT (unknown origin) assessed as reduction in MNA concentration incubated for 10 mins measured after 30 mins by LC-MS/MS-MRM analysis
Measurement: IC50 = 190 nM (pChEMBL 6.71999979019165)
Descriptors: MW 501.52, ALogP -0.02, HBA 11, HBD 5, PSA 185.87, QED 0.25
Compound (SMILES): CCS(=O)(=O)N1CCc2cc(C3CC3NCC3CCNCC3)ccc21
InChIKey: XXJFPDYHNSBYGX-UHFFFAOYSA-N
Target: Lysine-specific histone demethylase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: O60341
Assay: Inhibition of N-terminal His/GST-tagged human LSD1 (172 to 852 residues) expressed in expressed in baculovirus infected insect cells using biotinylated H3K4Me2 peptide as substrate by TR-FRET assay
Measurement: IC50 = 33630 nM (pChEMBL 4.46999979019165)
Descriptors: MW 363.53, ALogP 1.84, HBA 4, HBD 2, PSA 61.44, QED 0.81
Compound (SMILES): Cc1ccccc1C(C#N)c1nc(SC(C)C)[nH]c(=O)c1C
InChIKey: GILVFWCVCLOGND-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of recombinant wild-type p66/p51 HIV-1 reverse transcriptase incubated for 40 mins by picogreen dye-based spectrofluorometric analysis
Measurement: IC50 = 680 nM (pChEMBL 6.170000076293945)
Descriptors: MW 313.43, ALogP 3.54, HBA 4, HBD 1, PSA 69.54, QED 0.69
Compound (SMILES): CC(=O)Nc1ccc(S[C@H]2O[C@H](CO)[C@H](O)[C@H](n3cc(-c4cc(F)c(F)c(F)c4)nn3)[C@H]2O)cc1
InChIKey: IOAIBUSJDFUFDE-WHCFWRGISA-N
Target: Galectin-3 (SINGLE PROTEIN), Homo sapiens
UniProt: P17931
Assay: Binding affinity to human galectin-3 assessed as dissociation constant by competitive fluorescence polarization assay
Measurement: Kd = 37 nM (pChEMBL 7.429999828338623)
Descriptors: MW 510.49, ALogP 2.09, HBA 9, HBD 4, PSA 129.73, QED 0.37
Compound (SMILES): CCCCC1OC(=O)c2cc(OCc3ccc(CN4CCN(C)CC4)c(O)c3)ccc21
InChIKey: OAPLCUCLMSBGCV-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of Electric eel AChE by Ellman's method
Measurement: IC50 = 13620 nM (pChEMBL 4.869999885559082)
Descriptors: MW 424.54, ALogP 4.12, HBA 6, HBD 1, PSA 62.24, QED 0.64
Compound (SMILES): COc1ccc(CNCCc2ccc(S(N)(=O)=O)cc2)cc1OC
InChIKey: TZCPALNCOZRZIG-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of recombinant human CA1 pre-incubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 82.3 nM (pChEMBL 7.079999923706055)
Descriptors: MW 350.44, ALogP 1.68, HBA 5, HBD 2, PSA 90.65, QED 0.71
Compound (SMILES): CC(=O)Nc1nc2ccc(-c3cn([C@@H]4CN[C@H](C(=O)Nc5ccc(Br)cc5)C4)nn3)nc2s1
InChIKey: JJFYUQKAJYRNHL-YOEHRIQHSA-N
Target: Bcr/Abl fusion protein (CHIMERIC PROTEIN), Homo sapiens
UniProt: P11274
Assay: Inhibition of wild type Bcr-Abl (unknown origin) incubated for 1 hr in presence of ATP by ADP-Glo kinase assay
Measurement: IC50 = 6.99 nM (pChEMBL 8.15999984741211)
Descriptors: MW 527.41, ALogP 3.21, HBA 9, HBD 3, PSA 126.72, QED 0.36
Compound (SMILES): CCOc1cccnc1Oc1cncc(-c2ncc(C(=O)NC3CCS(=O)(=O)C3)cn2)c1
InChIKey: YCVMSJOECUPLAC-UHFFFAOYSA-N
Target: Diacylglycerol O-acyltransferase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96PD7
Assay: In Vitro DGAT2 Assay: For determination of IC50 values, the reactions were carried out in 384-well white Polyplates (Perkin Elmer) in a total volume of 20 μL. To 1 μL of compounds dissolved in 100% DMSO and spotted at the bottom of each well, 5 μL of 0.04% bovine serum albumin (BSA) (fatty acid free, Sigma Aldrich) was added and the mixture was incubated at room temperature for 15 minutes. hDGAT2 membrane fractions were diluted in 100 mM Hepes-NaOH, pH 7.4, 20 mM MgCl2 containing 200 nM methyl arachidonyl fluorophosphonate (Cayman Chemical; dried from ethyl acetate stock solution under argon gas and dissolved in DMSO as 5 mM stock). 10 μL of this enzyme working solution was added to the plates and incubation continued for 2 hours at room temperature. DGAT2 reactions were initiated by the addition of 4 μL of substrates containing 30 μM [1-14C]decanoyl-CoA (custom-synthesized by Perkin Elmer, 50 mCi/mmol) and 125 μM 1,2-didecanoyl-sn-glycerol (Avanti Polar Lipids) dissolved in 12.5% acetone. The reaction mixtures were incubated at room temperature for 40 min and the reactions were stopped by addition of 5 μL of 1% H3PO4. After the addition of 45 μL MicroScint-E (Perkin-Elmer), plates were sealed with Top Seal-A covers (Perkin-Elmer) and phase partitioning of substrates and products was achieved using a HT-91100 microplate orbital shaker (Big Bear Automation, Santa Clara, Calif.). Plates were centrifuged at 2,000×g for 1 minute in an Allegra 6R Centrifuge (Beckman Coulter) and then were sealed again with fresh covers before reading in a 1450 Microbeta Wallac Trilux Scintillation Counter (Perkin Elmer). DGAT2 activity was measured by quantifying the generated product [14C]tridecanoylglycerol in the upper organic phase.Background activity obtained using 50 μM of (R)-1-(2-((S)-1-(4-Chloro-1H-pyrazol-1-yl)ethyl)-3H-imidazo[4,5-b]pyridin-5-yl)piperidin-3-yl)(pyrrolidin-1-yl)methanone (WO 2013150416, Example 196-A) for complete inhibition of DGAT2 was subtracted from all reactions. Inhibitors were tested at eleven different concentrations to generate IC50 values for each compound. The eleven inhibitor concentrations employed typically included 50, 15.8, 5, 1.58, 0.50, 0.16, 0.05, 0.016, 0.005, 0.0016, and 0.0005 μM. The data were plotted as percentage of inhibition versus inhibitor concentration and fit to the equation, y=100/[1+(x/IC50)z], where IC50 is the inhibitor concentration at 50% inhibition and z is the Hill slope (the slope of the curve at its inflection point).
Measurement: IC50 = 196 nM (pChEMBL 6.710000038146973)
Descriptors: MW 455.5, ALogP 2.04, HBA 9, HBD 1, PSA 133.26, QED 0.57
Compound (SMILES): O=C(CSc1c(-c2ccccc2)c2cc(Cl)ccc2[nH]c1=O)NC1CCCC1
InChIKey: VRXUFERDKQBCLY-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 10 (SINGLE PROTEIN), Homo sapiens
UniProt: P53779
Assay: Inhibition of JNK3 (unknown origin)
Measurement: IC50 = 58.17 nM (pChEMBL 7.239999771118164)
Descriptors: MW 412.94, ALogP 5, HBA 3, HBD 2, PSA 61.96, QED 0.58
Compound (SMILES): Cc1cccc(Cn2c(=O)oc3cc(-c4cnc5[nH]ccc5c4)ccc32)c1
InChIKey: DUBCJSFILAJRPH-UHFFFAOYSA-N
Target: TRAF2 and NCK-interacting protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UKE5
Assay: Inhibition of human recombinant TNIK (1 to 367 residues) using RLGRDKYKTLRQIRQ as substrate incubated for 40 mins in presence of Mg/ATP mix by [gamma p33]-ATP based radiometric scintillation counting method
Measurement: IC50 = 356 nM (pChEMBL 6.449999809265137)
Descriptors: MW 355.4, ALogP 4.49, HBA 4, HBD 1, PSA 63.82, QED 0.52
Compound (SMILES): CCN(CC)c1ccc(/C=C/C2=CC(/C=C/c3ccc(N(C)C)cc3)=[O+][B-](F)(F)O2)cn1
InChIKey: GPWDRYDBOAMQSO-AOEKMSOUSA-N
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Homo sapiens
UniProt: P05067
Assay: Binding affinity to amyloid beta (1 to 40) (unknown origin) monomer
Measurement: Kd = 105.8 nM (pChEMBL 6.980000019073486)
Descriptors: MW 439.32
Compound (SMILES): COCCCn1ccc2ccc(CN(C(=O)[C@H]3CNCCO3)C3CC3)cc21
InChIKey: OTFAWOGDENVOCF-HXUWFJFHSA-N
Target: Renin (SINGLE PROTEIN), Homo sapiens
UniProt: P00797
Assay: Inhibition of human recombinant renin using Nma-Lys-His-Pro-Phe-His-Leu-Val-Ile-His-Lys-Dnp substrate incubated for 1 hr by FRET
Measurement: IC50 = 118 nM (pChEMBL 6.929999828338623)
Descriptors: MW 371.48, ALogP 2.16, HBA 5, HBD 1, PSA 55.73, QED 0.72
Compound (SMILES): O=C(O)c1ccc(-c2nnc(Cc3c[nH]c4ccccc34)nc2-c2ccccc2)cc1
InChIKey: ZXARYBHJGXWEGB-UHFFFAOYSA-N
Target: G-protein coupled receptor 84 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NQS5
Assay: Antagonist activity at human Galphai2-fused GPR84 stably expressed in Flp-In-T-REx-293 cell membranes assessed as inhibition of PSB-16671-induced [35S]GTPgammaS binding preincubated for 15 mins followed by PSB-16671 addition and measured after 45 mins by liquid scintillation counting analysis
Measurement: IC50 = 87.1 nM (pChEMBL 7.059999942779541)
Descriptors: MW 406.45, ALogP 4.98, HBA 4, HBD 2, PSA 91.76, QED 0.43
Compound (SMILES): CC1(C)[C@H](C(=O)OCc2ccccc2)N2C(=O)[C@@H](NC(=O)Cc3ccccc3)[C@H]2S1(=O)=O
InChIKey: UZYSXBPXAKPXOD-SVFBPWRDSA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Inhibition of recombinant SARS-CoV-2 Main protease using ALNDFSNSGSDVLYQPPQTSITSAVLQ/SGFRKMAFPS-NH2 as substrate preincubated for 45 to 75 mins followed by substrate addition measured after 6 mins by SPE-MS inhibition assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 456.52, ALogP 1.2, HBA 6, HBD 1, PSA 109.85, QED 0.52
Compound (SMILES): O=C(Nc1cnn(Cc2cnc(N3CCC[C@H]3CN3CC[C@@H](O)C3)nc2)c1)c1cncc(-c2c(C(F)F)ccc(Cl)c2F)n1
InChIKey: KZXKBBPFAOQBPA-VQTJNVASSA-N
Target: Plasma kallikrein (SINGLE PROTEIN), Homo sapiens
UniProt: P03952
Assay: Inhibition of human plasma kallikrein assessed as substrate hydrolysis using acetyl-K-P-R-AFC as substrate by spectrofluorometric analysis
Measurement: IC50 = 0.4 nM (pChEMBL 9.399999618530273)
Descriptors: MW 628.06, ALogP 4.2, HBA 10, HBD 2, PSA 125.19, QED 0.28
Compound (SMILES): CC(C)OC(=O)Nc1ccc(C2=NN(C(=O)c3ccc(Br)cc3)C(c3ccccc3)C2C)cn1
InChIKey: MAXZDUQMLSMNEE-UHFFFAOYSA-N
Target: Apoptosis regulator Bcl-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P10415
Assay: Inhibition of biotin-linker-Beclin 1 BH3 peptide binding to human C-terminal 6His-tagged Bcl-2 (1 to 218 residues) expressed in Escherichia coli BL21 Star (DE3) pLysS measured after 3 hrs by AlphaLISA assay
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 521.42, ALogP 6.04, HBA 5, HBD 1, PSA 83.89, QED 0.44
Compound (SMILES): CCCCCCCCCCCCCCCC(=O)N[C@@H](CCC(=O)N[C@@H](CCC(=O)NCCCC[C@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](CO)NC(=O)[C@@H](N)Cc1cnc[nH]1)[C@@H](C)O)[C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@H](C(N)=O)[C@@H](C)O)C(C)C)C(=O)O)C(=O)O
InChIKey: PLOZQTWKPBKWFP-DAHHNKMNSA-N
Target: Glucagon receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P47871
Assay: Agonist activity at human GCGR expressed in frozen cells assessed as increase in cAMP production measured after 1 hr by HitHunter luminescence assay
Measurement: EC50 = 0.03 nM (pChEMBL 10.520000457763672)
Descriptors: MW 3825.3
Compound (SMILES): CCn1cc(-c2cc(Cn3ccnc3C)cc3c2CCN(Cc2cc(OC)ccn2)C3=O)c(C(F)(F)F)n1
InChIKey: GLOSEPKLMDGBBB-UHFFFAOYSA-N
Target: WD repeat-containing protein 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P61964
Assay: Competitive binding affinity to N-terminal 6xHis-SUMO-tagged human WDR5 (22 to 334 residues) expressed in Escherichia coli BL21-Gold (DE3) cells assessed as inhibition constant using 10-mer-Thr-FAM peptide as substrate incubated for 1 hr by Lantha Screen based TR-FRET assay
Measurement: Ki < 0.02 nM (pChEMBL 10.699000358581543)
Descriptors: MW 524.55, ALogP 4.74, HBA 7, HBD 0, PSA 78.07, QED 0.35
Compound (SMILES): Oc1cccc(Nc2ncnc3[nH]ncc23)c1
InChIKey: UPQLLPZRSBLUDF-UHFFFAOYSA-N
Target: Tau-tubulin kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5TCY1
Assay: Inhibition of recombinant human TTBK1 using RICDLHDDEEDEAMSITA as substrate incubated for 30 mins in presence of 33P-gamma-ATP
Measurement: IC50 = 9150 nM (pChEMBL 5.039999961853027)
Descriptors: MW 227.23, ALogP 1.8, HBA 5, HBD 3, PSA 86.72, QED 0.62
Compound (SMILES): CC1(C)CCc2c(C(C(=O)Nc3nccs3)N3Cc4c(cc(C#Cc5ccc(CN6CCC(CO)CC6)cc5)cc4C(F)F)C3=O)ncn21
InChIKey: XAARYUGOCWIQON-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR L858R/T790M/C797S mutant (unknown origin) phosphorylation expressed in mouse BaF3 cells measured after 4 hrs by HTRF assay
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 684.81, ALogP 5.9, HBA 8, HBD 2, PSA 103.59, QED 0.22
Compound (SMILES): Nc1ccc2ncnc(Nc3cccc4c3CCCC4)c2c1
InChIKey: DWGLCDYKSOYPSK-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of wild-type EGFR (14 to 721 residues) (unknown origin) by western blot analysis
Measurement: IC50 = 164.8 nM (pChEMBL 6.78000020980835)
Descriptors: MW 290.37, ALogP 3.83, HBA 4, HBD 2, PSA 63.83, QED 0.7