lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC(C)(C)c1cc(NC(=O)Cc2ccc(-n3cnc4cc(-c5ccc(S(C)(=O)=O)cc5)ccc43)cc2)no1
InChIKey: LMFNJXLDISVWLF-UHFFFAOYSA-N
Target: Proto-oncogene tyrosine-protein kinase receptor Ret (SINGLE PROTEIN), Homo sapiens
UniProt: P07949
Assay: Inhibition of RET isoform 15 M918T mutant (unknown origin) expressed in mouse BAF3 cells assessed as reduction in cell proliferation supplemented with fresh medium containing compound for every 2 to 3 days and measured daily
Measurement: IC50 = 1.6 nM (pChEMBL 8.800000190734863)
Descriptors: MW 528.63, ALogP 5.56, HBA 7, HBD 1, PSA 107.09, QED 0.31
Compound (SMILES): C=CC(=O)Nc1cc(Nc2ncc(Cl)c(Nc3ccccc3S(=O)(=O)C(C)C)n2)c(OC)cc1N(C)CCN(C)C
InChIKey: GDRLJBDXWDATLA-UHFFFAOYSA-N
Target: EML4-ALK (CHIMERIC PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of EML4/ALK (unknown origin) transfected in mouse BAF3 cells assessed as reduction in cell viability after 72 hrs by MTS assay
Measurement: EC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 602.16, ALogP 4.93, HBA 10, HBD 3, PSA 128.79, QED 0.23
Compound (SMILES): NC(=O)c1ccn(-c2cccc(OC(=O)NCCN3CCN(c4ccccc4)CC3)c2)c1
InChIKey: WGOUWABLRGOCPZ-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG expressed in HEK293 cells incubated for 72 hrs by patch clamp assay
Measurement: IC50 = 5248.07 nM (pChEMBL 5.28000020980835)
Descriptors: MW 433.51, ALogP 2.49, HBA 6, HBD 2, PSA 92.83, QED 0.6
Compound (SMILES): COC(=O)C1CC(=O)N(c2cc(C)c(S(N)(=O)=O)c(C)c2Cl)C1
InChIKey: DNALKYILSFHWTG-UHFFFAOYSA-N
Target: Carbonic anhydrase 13 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8N1Q1
Assay: Binding affinity to recombinant human CA13 by DSF-based fluorescence thermal shift assay
Measurement: Kd = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 360.82, ALogP 1.13, HBA 5, HBD 1, PSA 106.77, QED 0.81
Compound (SMILES): NS(=O)(=O)c1ccc(CCNC(=O)CN2C(=O)NC3(CCCC3)C2=O)cc1
InChIKey: RFPXNPAWDLLRQG-UHFFFAOYSA-N
Target: Carbonic anhydrase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Inhibition of human carbonic anhydrase 7 incubated for 15 mins prior to testing by stopped-flow CO2 hydration assay
Measurement: Ki = 4.7 nM (pChEMBL 8.329999923706055)
Descriptors: MW 394.45, ALogP -0.14, HBA 5, HBD 3, PSA 138.67, QED 0.58
Compound (SMILES): CC1(C2CC2)NC(=O)N(CC(=O)Nc2ccc(Cl)c(S(=O)(=O)N3CCCCC3)c2)C1=O
InChIKey: UJFOHASZAXASED-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of Alexa Fluor 647 labelled ligand from His6-tagged BRD4 BD2 (1 to 477 residues)/BD1 Y97A mutant (unknown origin) after 30 mins by TR-FRET assay
Measurement: IC50 = 31622.78 nM (pChEMBL 4.5)
Descriptors: MW 468.96, ALogP 2.17, HBA 5, HBD 2, PSA 115.89, QED 0.62
Compound (SMILES): Cc1cccc(NC(=O)CN2CCN(c3cccc4ccccc34)CC2)c1
InChIKey: LEQVQRFGBPYNQZ-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Agonist activity at human D4 receptor expressed in CHOK1 cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 30 mins by Eu-cAMP tracer based TR-FRET assay
Measurement: EC50 = 108.5 nM (pChEMBL 6.960000038146973)
Descriptors: MW 359.47, ALogP 3.91, HBA 3, HBD 1, PSA 35.58, QED 0.77
Compound (SMILES): N=C(N)NC(=O)c1nc(-c2cc3ccccc3o2)c(N)nc1N
InChIKey: ZKLNPUKNSARQMG-UHFFFAOYSA-N
Target: Plasminogen (SINGLE PROTEIN), Homo sapiens
UniProt: P00747
Assay: Inhibition of plasmin (unknown origin) using chromogenic H-D-Ile-L-propyl-L-arginine-p-nitroaniline as substrate
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 311.31, ALogP 0.68, HBA 7, HBD 5, PSA 169.93, QED 0.34
Compound (SMILES): NC(=O)c1ncn([C@H]2[C@H](O)[C@H](O)[C@]3(CO)C[C@H]23)n1
InChIKey: NBDHEWVPZVSZLX-GEKCLDMMSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30542
Assay: Agonist activity at human A1A adenosine receptor expressed in HEK cell membranes incubated for 60 mins by [35S]GTPgammaS binding assay
Measurement: EC50 = 758 nM (pChEMBL 6.119999885559082)
Descriptors: MW 254.25, ALogP -2.35, HBA 7, HBD 4, PSA 134.49, QED 0.48
Compound (SMILES): COc1cc(N[C@@H](C)c2cc3cc(Cl)ccc3[nH]c2=O)ccc1C#N
InChIKey: POQQQCAOZAXQHW-NSHDSACASA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: IDH1-R132H and IDH1-R132C Enzymatic Assay: Assays were performed in a 384-well black plate. An aliquot of 250 nL of compound was incubated with 10 μL of 30 nM IDH1-R132H or 10 nM IDH1-R132C recombinant protein in assay buffer (50 mM Tris pH=7.5, 150 mM NaCl, 5 mM MgCl2, 0.1% (w/v) Bovine Serum Albumin, and 0.01% Triton X-100) in each well at 25° C. for 15 minutes. After the plate was centrifuged briefly, an aliquot of 10 μL of 2 mM α-ketoglutarate and 20 μM NADPH solution prepared in assay buffer was then added to each well and the reaction was maintained at 25° C. for 45 minutes. An aliquot of 10 μL of diaphorase solution (0.15 U/mL diaphorase and 30 μM Resazurin in assay buffer) was added to each well. The plate was maintained at 25° C. for 15 minutes and then read on a plate reader with excitation and emission wavelengths at 535 nm and 590 nm, respectively. The IC50 of a given compound was calculated by fitting the dose response curve of inhibition of NADPH consumption at a given concentration with the four parameter logistic equation.
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 353.81, ALogP 4.23, HBA 4, HBD 2, PSA 77.91, QED 0.74
Compound (SMILES): CN1CCC(Nc2ccc(C(=O)Nc3cc(-c4cc(C#N)cs4)n[nH]3)cc2)CC1
InChIKey: HGLWPJISHDLCTE-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: Binding affinity to human non-phosphorylated ABL1 F317L mutant (S229 to K512 residues) expressed in mammalian expression system after 60 mins by Kinomescan method
Measurement: Kd = 6900 nM (pChEMBL 5.159999847412109)
Descriptors: MW 406.52, ALogP 3.77, HBA 6, HBD 3, PSA 96.84, QED 0.6
Compound (SMILES): CC(C)C[C@H](NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)COCCOCCNC(=O)COCCOCCNC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCCCCCC(=O)O)C(=O)O)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@H](C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)C(C)C)[C@@H](C)O
InChIKey: FVISARNFWVOCKF-WYWYUZAJSA-N
Target: Calcitonin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30988
Assay: Displacement of [125I]-labeled rat calcitonin from human calcitonin receptor expressed in BHK tkts13 cell membranes incubated for 1 hr by scintillation proximity assay
Measurement: IC50 = 0.027 nM (pChEMBL 10.569999694824219)
Descriptors: MW 4166.7
Compound (SMILES): Fc1ccc2c(c1)CC(CCN1CCCN(c3ccccn3)CC1)C2
InChIKey: RVMUAKCKCUJBKV-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H]-N-methylspiperone from human dopamine D4 receptor by liquid scintillation counting
Measurement: Ki = 104.71 nM (pChEMBL 6.980000019073486)
Descriptors: MW 339.46, ALogP 3.54, HBA 3, HBD 0, PSA 19.37, QED 0.85
Compound (SMILES): Cc1cc(C(=O)NC2CCC(=Cc3cccc(Oc4ccc(C(F)(F)F)cn4)c3)CC2)cnc1N
InChIKey: HPWXZEVJFZKRBB-NYXAKURHSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using midazolam as substrate preincubated for 5 mins followed by NADPH cofactor addition and measured after 10 mins by LC-MS/MS analysis
Measurement: IC50 > 12.5 nM (pChEMBL 7.9029998779296875)
Descriptors: MW 482.51, ALogP 5.93, HBA 5, HBD 2, PSA 90.13, QED 0.47
Compound (SMILES): NS(=O)(=O)c1ccc(OP(=O)(O)c2ccccc2)cc1
InChIKey: HADGOFIYAKWMTA-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human recombinant carbonic anhydrase 12 preincubated with enzyme for 1 hr prior to testing by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 30.8 nM (pChEMBL 7.510000228881836)
Descriptors: MW 313.27, ALogP 1.22, HBA 4, HBD 2, PSA 106.69, QED 0.83
Compound (SMILES): CS(=O)(=O)Nc1cc(-c2ccncc2)cnc1Cl
InChIKey: KDSFLYIZGIJKAW-UHFFFAOYSA-N
Target: Inhibitor of nuclear factor kappa-B kinase subunit beta (SINGLE PROTEIN), Homo sapiens
UniProt: O14920
Assay: Inhibition of IKK2 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 283.74, ALogP 2.17, HBA 4, HBD 1, PSA 71.95, QED 0.88
Compound (SMILES): C[C@@H]1NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](CS)NC(=O)[C@@H]2CCCN2C(=O)[C@H]2CCCN2C(=O)[C@H](Cc2ccccc2)NC1=O
InChIKey: NKZFUEPYJJNRCM-PLUWKHBFSA-N
Target: Melanocortin receptor 3 (SINGLE PROTEIN), Mus musculus
UniProt: P33033
Assay: Displacement of [125I]-NDP-MSH from mouse melanocortin receptor 3 expressed in HEK293 cell mebranes incubated for 1 hr by automatic gamma counting method
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 924.09, ALogP -0.56, HBA 10, HBD 8, PSA 258.31, QED 0.13
Compound (SMILES): NS(=O)(=O)c1ccc(N2CC(C(=O)N/N=C/c3ccccc3)CC2=O)cc1
InChIKey: BNOSIOACPICPJD-RGVLZGJSSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Binding affinity to recombinant human CA9 by DSF-based fluorescence thermal shift assay
Measurement: Kd = 59 nM (pChEMBL 7.230000019073486)
Descriptors: MW 386.43, ALogP 0.84, HBA 5, HBD 2, PSA 121.93, QED 0.58
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCCCCCC(=O)O)C(=O)O)[C@@H](C)O)C(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O
InChIKey: SGIDMYDYTBFBSN-TYRZRTKUSA-N
Target: Calcitonin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30988
Assay: Displacement of [125I]-labeled rat calcitonin from human calcitonin receptor expressed in BHK tkts13 cell membranes incubated for 1 hr by scintillation proximity assay
Measurement: IC50 = 0.069 nM (pChEMBL 10.15999984741211)
Descriptors: MW 4071.7
Compound (SMILES): O=C(Nc1ccc(Cl)cc1)Nc1ccc(-c2cc(Cl)cc(Cl)c2)s1
InChIKey: XFOCMFZFOPJMOP-UHFFFAOYSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Mus musculus
UniProt: P47746
Assay: Allosteric modulator activity at CB1 receptor in mouse cerebellar membranes assessed as suppression of 100 nM CP55,940-induced [35S]GTPgammaS binding incubated for 60 mins by scintillation counting method
Measurement: IC50 = 3311.31 nM (pChEMBL 5.480000019073486)
Descriptors: MW 397.71, ALogP 7.02, HBA 2, HBD 2, PSA 41.13, QED 0.49
Compound (SMILES): Cc1cc(-c2ccc(C(=O)[C@@H]3CCCC[C@H]3C(=O)Nc3cnn(C)c3S(N)(=O)=O)cc2)n[nH]1
InChIKey: IVYACETTWFJKQK-IAGOWNOFSA-N
Target: Solute carrier organic anion transporter family member 1B1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y6L6
Assay: Substrate activity at recombinant human OATP1B1 expressed in HEK293 cells assessed as reduction in pivastatin uptake
Measurement: IC50 = 2500 nM (pChEMBL 5.599999904632568)
Descriptors: MW 470.56, ALogP 2.39, HBA 7, HBD 3, PSA 152.83, QED 0.47
Compound (SMILES): CN(C)c1ccc(C(=O)N(CC(=O)NCc2ccccc2)Cc2ccc(C(=O)Nc3ccccc3N)cc2)cc1
InChIKey: SIRNCVDOMIOFAK-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of human full length N-terminal GST-tagged HDAC6 expressed in baculovirus infected Sf9 insect cells ZMAL as substrate incubated for 90 mins by fluorescence assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 535.65, ALogP 4.55, HBA 5, HBD 3, PSA 107.77, QED 0.26
Compound (SMILES): COc1cc(C2CN(C(=O)c3cc(COC[C@@H](O)CO)ccn3)C2)ccc1OCc1ccc(C2CC2)cc1
InChIKey: LTTJGQBDGMNWHJ-SANMLTNESA-N
Target: Serine/threonine-protein kinase Chk1 (SINGLE PROTEIN), Homo sapiens
UniProt: O14757
Assay: Inhibition of human full length N-terminal GST-tagged CHK1 expressed in baculovirus infected Sf21 insect cells using CHKtide as substrate
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 518.61, ALogP 3.66, HBA 7, HBD 2, PSA 101.35, QED 0.38
Compound (SMILES): CC(C)c1cc(C(=O)N2Cc3ccccc3C2)c(O)c2cnoc12
InChIKey: MFZKTINXWPQHBG-UHFFFAOYSA-N
Target: Heat shock protein HSP 90-beta (SINGLE PROTEIN), Homo sapiens
UniProt: P08238
Assay: Inhibition of HSP90beta (unknown origin) incubated for 24 hrs by fluorescence polarization assay
Measurement: IC50 = 180 nM (pChEMBL 6.75)
Descriptors: MW 322.36, ALogP 3.81, HBA 4, HBD 1, PSA 66.57, QED 0.78
Compound (SMILES): Cc1cc(N2CC(C(=O)N/N=C/c3ccccc3)CC2=O)cc(C)c1S(N)(=O)=O
InChIKey: NEEUKYCSJKNGPX-SSDVNMTOSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Binding affinity to recombinant human CA9 by DSF-based fluorescence thermal shift assay
Measurement: Kd = 2000 nM (pChEMBL 5.699999809265137)
Descriptors: MW 414.49, ALogP 1.45, HBA 5, HBD 2, PSA 121.93, QED 0.57
Compound (SMILES): NS(=O)(=O)c1ccc(NC(=O)CN2C(=O)NC3(CCCCCC3)C2=O)cc1
InChIKey: WALKBCDYHSEIBJ-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human carbonic anhydrase 9 incubated for 15 mins prior to testing by stopped-flow CO2 hydration assay
Measurement: Ki = 4.3 nM (pChEMBL 8.369999885559082)
Descriptors: MW 394.45, ALogP 0.92, HBA 5, HBD 3, PSA 138.67, QED 0.65
Compound (SMILES): Cl.N=C(N)c1ccc(CC2OB(O)c3cc(C(F)(F)F)ccc32)cc1OCc1cccnc1
InChIKey: SJWIYNDYLDXFMU-UHFFFAOYSA-N
Target: Neutrophil elastase (SINGLE PROTEIN), Homo sapiens
UniProt: P08246
Assay: Inhibition of human neutrophil elastase using MeOSuc-AAPV-AMC as substrate incubated for 40 mins by FLINT assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 441.22
Compound (SMILES): CSCC[C@@H]1NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](Cc2cnc[nH]2)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](CO)NC(C)=O)CSSC[C@@H](C(=O)N[C@H](C(=O)N[C@@H](Cc2c[nH]c3ccccc23)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](Cc2ccccc2)C(N)=O)C(C)C)C(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCSC)NC(=O)[C@H]([C@@H](C)O)NC(=O)CNC(=O)[C@@H](CCCCN)NC(=O)[C@H](CCSC)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC1=O
InChIKey: VDIQLFPDZSQICF-WCAMJISASA-N
Target: Tissue factor pathway inhibitor (SINGLE PROTEIN), Homo sapiens
UniProt: P10646
Assay: Inhibition of C-terminus 10x-His-taged human TFPI-1 (29 to 282 residues) assessed as inhibition of factor 10a using S-2222 substrate incubated for 115 mins by micro-plate reader based assay
Measurement: EC50 = 3.2 nM (pChEMBL 8.489999771118164)
Descriptors: MW 2911.53
Compound (SMILES): CC(C)(C)c1cc(NC(=O)Cc2ccc(-n3cnc4cc(-c5ccc(S(C)(=O)=O)cc5)ccc43)cc2)no1
InChIKey: LMFNJXLDISVWLF-UHFFFAOYSA-N
Target: Proto-oncogene tyrosine-protein kinase receptor Ret (SINGLE PROTEIN), Homo sapiens
UniProt: P07949
Assay: Inhibition of RET isoform 9 C634W mutant in human TT cells assessed as reduction in cell proliferation supplemented with fresh medium containing compound for every 2 to 3 days and measured during compound dosing
Measurement: IC50 = 0.67 nM (pChEMBL 9.170000076293945)
Descriptors: MW 528.63, ALogP 5.56, HBA 7, HBD 1, PSA 107.09, QED 0.31
Compound (SMILES): C=CC(=O)Nc1cc(Nc2ncc(Cl)c(Nc3ccccc3S(=O)(=O)C(C)C)n2)c(OC)cc1N(C)CCN(C)C
InChIKey: GDRLJBDXWDATLA-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of wild type EGFR (unknown origin) transfected in mouse BAF3 cells assessed as reduction in cell viability after 72 hrs by MTS assay
Measurement: EC50 = 32 nM (pChEMBL 7.5)
Descriptors: MW 602.16, ALogP 4.93, HBA 10, HBD 3, PSA 128.79, QED 0.23
Compound (SMILES): COC(=O)C1CC(=O)N(c2cc(C)c(S(N)(=O)=O)c(C)c2Cl)C1
InChIKey: DNALKYILSFHWTG-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Binding affinity to recombinant human CA1 assessed as intrinsic dissociation constant by DSF-based fluorescence thermal shift assay
Measurement: Kd = 0.77 nM (pChEMBL 9.109999656677246)
Descriptors: MW 360.82, ALogP 1.13, HBA 5, HBD 1, PSA 106.77, QED 0.81
Compound (SMILES): NS(=O)(=O)c1ccc(CCNC(=O)CN2C(=O)NC3(CCCC3)C2=O)cc1
InChIKey: RFPXNPAWDLLRQG-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human carbonic anhydrase 9 incubated for 15 mins prior to testing by stopped-flow CO2 hydration assay
Measurement: Ki = 122.2 nM (pChEMBL 6.909999847412109)
Descriptors: MW 394.45, ALogP -0.14, HBA 5, HBD 3, PSA 138.67, QED 0.58
Compound (SMILES): CC1(C2CC2)NC(=O)N(CC(=O)Nc2ccc(Cl)c(S(=O)(=O)N3CCCCC3)c2)C1=O
InChIKey: UJFOHASZAXASED-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of Alexa Fluor 647 labelled ligand from His6-tagged BRD4 BD2 (1 to 477 residues)/BD1 Y97A mutant (unknown origin) after 30 mins by TR-FRET assay
Measurement: IC50 > 50118.72 nM (pChEMBL 4.300000190734863)
Descriptors: MW 468.96, ALogP 2.17, HBA 5, HBD 2, PSA 115.89, QED 0.62
Compound (SMILES): Cc1cccc(NC(=O)CN2CCN(c3cccc4ccccc34)CC2)c1
InChIKey: LEQVQRFGBPYNQZ-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Antagonist activity at human D4 receptor expressed in CHOK1 cells assessed as suppression of dopamine-induced inhibition of forskolin-stimulated cAMP accumulation measured after 30 mins by Eu-cAMP tracer based TR-FRET assay
Measurement: IC50 = 2521 nM (pChEMBL 5.599999904632568)
Descriptors: MW 359.47, ALogP 3.91, HBA 3, HBD 1, PSA 35.58, QED 0.77
Compound (SMILES): N=C(N)NC(=O)c1nc(-c2cc3ccccc3o2)c(N)nc1N
InChIKey: ZKLNPUKNSARQMG-UHFFFAOYSA-N
Target: Tissue-type plasminogen activator (SINGLE PROTEIN), Homo sapiens
UniProt: P00750
Assay: Inhibition of tissue-type plasminogen activator (unknown origin) using chromogenic H-D-Ile-L-propyl-L-arginine-p-nitroaniline as substrate
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 311.31, ALogP 0.68, HBA 7, HBD 5, PSA 169.93, QED 0.34
Compound (SMILES): NC(=O)c1ncn([C@H]2[C@H](O)[C@H](O)[C@]3(CO)C[C@H]23)n1
InChIKey: NBDHEWVPZVSZLX-GEKCLDMMSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30542
Assay: Agonist activity at human A1A adenosine receptor expressed in HEK cells assessed as inhibition of forskolin-stimulated cAMP production after 60 mins
Measurement: IC50 = 87 nM (pChEMBL 7.059999942779541)
Descriptors: MW 254.25, ALogP -2.35, HBA 7, HBD 4, PSA 134.49, QED 0.48
Compound (SMILES): CN1CCC(Nc2ccc(C(=O)Nc3cc(-c4cc(C#N)cs4)n[nH]3)cc2)CC1
InChIKey: HGLWPJISHDLCTE-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: Binding affinity to human phosphorylated ABL1 F317L mutant (S229 to K512 residues) expressed in mammalian expression system after 60 mins by Kinomescan method
Measurement: Kd = 460 nM (pChEMBL 6.340000152587891)
Descriptors: MW 406.52, ALogP 3.77, HBA 6, HBD 3, PSA 96.84, QED 0.6
Compound (SMILES): Fc1ccc2c(c1)CC(CCN1CCCN(c3ccccn3)CC1)C2
InChIKey: RVMUAKCKCUJBKV-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Displacement of [3H]-8-OH-DPAT from human 5HT1A receptor by liquid scintillation counting
Measurement: Ki = 614.5 nM (pChEMBL 6.210000038146973)
Descriptors: MW 339.46, ALogP 3.54, HBA 3, HBD 0, PSA 19.37, QED 0.85
Compound (SMILES): CS(=O)(=O)Nc1cc(-c2ccncc2)cnc1Cl
InChIKey: KDSFLYIZGIJKAW-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of JAK2 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 283.74, ALogP 2.17, HBA 4, HBD 1, PSA 71.95, QED 0.88
Compound (SMILES): C[C@@H]1NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](CS)NC(=O)[C@@H]2CCCN2C(=O)[C@H]2CCCN2C(=O)[C@H](Cc2ccccc2)NC1=O
InChIKey: NKZFUEPYJJNRCM-PLUWKHBFSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Mus musculus
UniProt: P56450
Assay: Displacement of [125I]-NDP-MSH from mouse melanocortin receptor 4 expressed in HEK293 cell mebranes incubated for 1 hr by automatic gamma counting method
Measurement: IC50 = 1900 nM (pChEMBL 5.71999979019165)
Descriptors: MW 924.09, ALogP -0.56, HBA 10, HBD 8, PSA 258.31, QED 0.13
Compound (SMILES): NS(=O)(=O)c1ccc(N2CC(C(=O)N/N=C/c3ccccc3)CC2=O)cc1
InChIKey: BNOSIOACPICPJD-RGVLZGJSSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Binding affinity to recombinant human CA12 by DSF-based fluorescence thermal shift assay
Measurement: Kd = 2500 nM (pChEMBL 5.599999904632568)
Descriptors: MW 386.43, ALogP 0.84, HBA 5, HBD 2, PSA 121.93, QED 0.58
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCCCCCC(=O)O)C(=O)O)[C@@H](C)O)C(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O
InChIKey: SGIDMYDYTBFBSN-TYRZRTKUSA-N
Target: Amylin receptor AMY3; CALCR/RAMP3 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60896
Assay: Displacement of [125I]-labeled rat amylin from human amylin receptor expressed in BHK tkts13 whole cells co-expressing RAMP3 incubated for 60 mins by scintillation proximity assay
Measurement: IC50 = 3.701 nM (pChEMBL 8.430000305175781)
Descriptors: MW 4071.7
Compound (SMILES): Cc1cc(-c2ccc(C(=O)[C@@H]3CCCC[C@H]3C(=O)Nc3cnn(C)c3S(N)(=O)=O)cc2)n[nH]1
InChIKey: IVYACETTWFJKQK-IAGOWNOFSA-N
Target: ATP-binding cassette sub-family C member 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q63120
Assay: Inhibition of Sprague-Dawley rat Mrp2 expressed in baculovirus infected Sf21 insect cell vesicles assessed as reduction in CDF uptake by fluorescence assay
Measurement: IC50 = 74000 nM (pChEMBL 4.130000114440918)
Descriptors: MW 470.56, ALogP 2.39, HBA 7, HBD 3, PSA 152.83, QED 0.47
Compound (SMILES): CN(C)c1ccc(C(=O)N(CC(=O)NCc2ccccc2)Cc2ccc(C(=O)Nc3ccccc3N)cc2)cc1
InChIKey: SIRNCVDOMIOFAK-UHFFFAOYSA-N
Target: Histone deacetylase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P56524
Assay: Inhibition of recombinant human N-terminal GST-fused and C-terminal His-tagged HDAC4 (627 to 1084 residues) expressed in baculovirus infected insect cells using Boc-Lys(TFa)-AMC as substrate preincubated for 5 mins followed by substrate addition and measured after 90 mins by fluorescence assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 535.65, ALogP 4.55, HBA 5, HBD 3, PSA 107.77, QED 0.26
Compound (SMILES): COc1cc(C2CN(C(=O)c3cc(COC[C@@H](O)CO)ccn3)C2)ccc1OCc1ccc(C2CC2)cc1
InChIKey: LTTJGQBDGMNWHJ-SANMLTNESA-N
Target: Casein kinase II subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P68400
Assay: Inhibition of human full length His6-tagged CK2alpha expressed in baculovirus infected Sf21 insect cells using Casein Kinase 2 substrate peptide
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 518.61, ALogP 3.66, HBA 7, HBD 2, PSA 101.35, QED 0.38
Compound (SMILES): CC(C)c1cc(C(=O)N2Cc3ccccc3C2)c(O)c2cnoc12
InChIKey: MFZKTINXWPQHBG-UHFFFAOYSA-N
Target: Heat shock protein HSP 90-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P07900
Assay: Binding affinity to N-terminal His6-tagged human HSP90alpha (1 to 241 residues) expressed in Escherichia coli BL21(DE3) cells by fluorescence thermal shift assay
Measurement: Kd = 610 nM (pChEMBL 6.210000038146973)
Descriptors: MW 322.36, ALogP 3.81, HBA 4, HBD 1, PSA 66.57, QED 0.78
Compound (SMILES): Cc1cc(N2CC(C(=O)N/N=C/c3ccccc3)CC2=O)cc(C)c1S(N)(=O)=O
InChIKey: NEEUKYCSJKNGPX-SSDVNMTOSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Binding affinity to recombinant human CA12 by DSF-based fluorescence thermal shift assay
Measurement: Kd = 29000 nM (pChEMBL 4.539999961853027)
Descriptors: MW 414.49, ALogP 1.45, HBA 5, HBD 2, PSA 121.93, QED 0.57
Compound (SMILES): NS(=O)(=O)c1ccc(NC(=O)CN2C(=O)NC3(CCCCCC3)C2=O)cc1
InChIKey: WALKBCDYHSEIBJ-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human carbonic anhydrase 12 incubated for 15 mins prior to testing by stopped-flow CO2 hydration assay
Measurement: Ki = 42.8 nM (pChEMBL 7.369999885559082)
Descriptors: MW 394.45, ALogP 0.92, HBA 5, HBD 3, PSA 138.67, QED 0.65
Compound (SMILES): Cl.N=C(N)c1ccc(CC2OB(O)c3cc(C(F)(F)F)ccc32)cc1OCc1cccnc1
InChIKey: SJWIYNDYLDXFMU-UHFFFAOYSA-N
Target: Urokinase-type plasminogen activator (SINGLE PROTEIN), Homo sapiens
UniProt: P00749
Assay: Inhibition of recombinant human C-terminal 10-His-tagged urokinase (M1 to L431 residues) expressed in mouse NS0 cells using Z-GGR-AMC as substrate incubated for 40 mins by FLINT assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 441.22
Compound (SMILES): CSCC[C@@H]1NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](Cc2cnc[nH]2)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](CO)NC(C)=O)CSSC[C@@H](C(=O)N[C@H](C(=O)N[C@@H](Cc2c[nH]c3ccccc23)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](Cc2ccccc2)C(N)=O)C(C)C)C(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCSC)NC(=O)[C@H]([C@@H](C)O)NC(=O)CNC(=O)[C@@H](CCCCN)NC(=O)[C@H](CCSC)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC1=O
InChIKey: VDIQLFPDZSQICF-WCAMJISASA-N
Target: Tissue factor pathway inhibitor (SINGLE PROTEIN), Homo sapiens
UniProt: P10646
Assay: Binding affinity to C-terminus 10x-His-taged human TFPI-1 (29 to 282 residues) incubated for 480 secs by SPR assay
Measurement: Kd < 1 nM (pChEMBL 9)
Descriptors: MW 2911.53
Compound (SMILES): CC(C)(C)c1cc(NC(=O)Cc2ccc(-n3cnc4cc(-c5ccc(S(C)(=O)=O)cc5)ccc43)cc2)no1
InChIKey: LMFNJXLDISVWLF-UHFFFAOYSA-N
Target: Proto-oncogene tyrosine-protein kinase receptor Ret (SINGLE PROTEIN), Homo sapiens
UniProt: P07949
Assay: Inhibition of RET isoform 9 M918T mutant in human MZ-CRC-1 cells assessed as reduction in cell proliferation supplemented with fresh medium containing compound for every 2 to 3 days and measured during compound dosing
Measurement: IC50 = 0.67 nM (pChEMBL 9.170000076293945)
Descriptors: MW 528.63, ALogP 5.56, HBA 7, HBD 1, PSA 107.09, QED 0.31
Compound (SMILES): C=CC(=O)Nc1cc(Nc2ncc(Cl)c(Nc3ccccc3S(=O)(=O)C(C)C)n2)c(OC)cc1N(C)CCN(C)C
InChIKey: GDRLJBDXWDATLA-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR T790M/L858R double mutant (unknown origin) transfected in mouse BAF3 cells assessed as reduction in cell viability after 72 hrs by MTS assay
Measurement: EC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 602.16, ALogP 4.93, HBA 10, HBD 3, PSA 128.79, QED 0.23
Compound (SMILES): CC(C)(O)CNC(=O)Cc1nc2cnc3[nH]ccc3c2n1[C@H]1CC[C@H](CC#N)CC1
InChIKey: NJKMSBSVJSQUBU-SHTZXODSSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Enzymatic Inhibition Assay: 11-point dosing series were made for each compound by serially diluting 1:3 or 1:4 in DMSO, with point 12 being a DMSO control. From the serial dilution plates, sample was transferred to a 384 wells assay plate (#781280, Greiner, Monroe, N.C.) using Labcyte Echo (Sunnyvale, Calif.), or Biosero ATS (San Diego, Calif.). The compounds were tested in duplicate. Column 12 was used for positive controls, and column 24 contained negative controls with no enzyme added. A compound from our internal collection, with inhibitory activity for JAK isoforms, was used as a reference compound. The final concentration of DMSO was <0.25% in a 20 μL reaction. Assay conditions for each of the proteins are summarized in Table 3. The enzyme reaction was initiated by the addition of 10 μL of enzyme and ATP mixture to 10 μL of substrate solution prepared in reaction buffer (50 mM MOPS pH 7.5, 10 mM MgCl2, 1 mM EDTA, 2 mM DTT, 0.002% Tween-20). The Tyk2 enzyme was pre-incubated with 2 mM ATP for 30 min prior to the reaction initiation. Immediately after the addition of the enzyme to the reaction mixture, the plate was centrifuged at 1000 rpm for 1 minute and incubated at 25° C. for 45 minutes for JAK3 and 90 minutes for JAK1, JAK2 and Tyk2. The reaction was quenched by the addition of 20 μL of 0.5% TFA containing 0.15 μM of internal standard peptide using Multidrop Combi reagent dispenser (Thermo Scientific, Waltham, Mass.). Several wells in column 24 were typically used for the product standard curve. After the quench, the assay plate was centrifuged at 3000 rpm for 3 minutes and sealed with pierceable aluminum foil (Cat#06644-001, Agilent) using a PlateLoc (Agilent Technologies, Santa Clara, Calif.). The plates then were transferred on to the RapidFire for the MS analysis. Compound inhibition was assessed by a decrease of the phosphorylated product levels in sample wells compared to the non-inhibited enzyme reaction.
Measurement: IC50 = 7.4 nM (pChEMBL 8.130000114440918)
Descriptors: MW 408.51, ALogP 2.99, HBA 6, HBD 3, PSA 119.62, QED 0.58
Compound (SMILES): COC(=O)C1CC(=O)N(c2cc(C)c(S(N)(=O)=O)c(C)c2Cl)C1
InChIKey: DNALKYILSFHWTG-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Binding affinity to recombinant human CA2 assessed as intrinsic dissociation constant by DSF-based fluorescence thermal shift assay
Measurement: Kd = 0.016 nM (pChEMBL 10.800000190734863)
Descriptors: MW 360.82, ALogP 1.13, HBA 5, HBD 1, PSA 106.77, QED 0.81
Compound (SMILES): NS(=O)(=O)c1ccc(CCNC(=O)CN2C(=O)NC3(CCCC3)C2=O)cc1
InChIKey: RFPXNPAWDLLRQG-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human carbonic anhydrase 12 incubated for 15 mins prior to testing by stopped-flow CO2 hydration assay
Measurement: Ki = 6.2 nM (pChEMBL 8.210000038146973)
Descriptors: MW 394.45, ALogP -0.14, HBA 5, HBD 3, PSA 138.67, QED 0.58
Compound (SMILES): CC1(C2CC2)NC(=O)N(CC(=O)Nc2ccc(Cl)c(S(=O)(=O)N3CCCCC3)c2)C1=O
InChIKey: UJFOHASZAXASED-UHFFFAOYSA-N
Target: ATPase family AAA domain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6PL18
Assay: Binding affinity to His6/FLAG-tagged TEV fused ATAD2 bromodomain (950 to 1148 residues) (unknown origin) expressed in Escherichia coli BL21(DE3) cells by surface plasmon resonance
Measurement: Kd = 1995.26 nM (pChEMBL 5.699999809265137)
Descriptors: MW 468.96, ALogP 2.17, HBA 5, HBD 2, PSA 115.89, QED 0.62
Compound (SMILES): Cc1cccc(NC(=O)CN2CCN(c3cccc4ccccc34)CC2)c1
InChIKey: LEQVQRFGBPYNQZ-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Antagonist activity at human D2L receptor expressed in CHOK1 cells assessed as inhibition of dopamine-induced beta-arrestin recruitment measured after 90 mins by luminescence assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 359.47, ALogP 3.91, HBA 3, HBD 1, PSA 35.58, QED 0.77
Compound (SMILES): N=C(N)NC(=O)c1nc(-c2cc3ccccc3o2)c(N)nc1N
InChIKey: ZKLNPUKNSARQMG-UHFFFAOYSA-N
Target: Urokinase-type plasminogen activator (SINGLE PROTEIN), Homo sapiens
UniProt: P00749
Assay: Inhibition of human kidney uPA using chromogenic H-D-Ile-L-propyl-L-arginine-p-nitroaniline as substrate
Measurement: IC50 = 430 nM (pChEMBL 6.369999885559082)
Descriptors: MW 311.31, ALogP 0.68, HBA 7, HBD 5, PSA 169.93, QED 0.34
Compound (SMILES): CN1CCC(Nc2ccc(C(=O)Nc3cc(-c4cc(C#N)cs4)n[nH]3)cc2)CC1
InChIKey: HGLWPJISHDLCTE-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: Binding affinity to human non-phosphorylated ABL1 H396P mutant (S229 to K512 residues) expressed in mammalian expression system after 60 mins by Kinomescan method
Measurement: Kd = 280 nM (pChEMBL 6.550000190734863)
Descriptors: MW 406.52, ALogP 3.77, HBA 6, HBD 3, PSA 96.84, QED 0.6
Compound (SMILES): Fc1ccc2c(c1)CC(CCN1CCCN(c3ccccn3)CC1)C2
InChIKey: RVMUAKCKCUJBKV-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Displacement of [3H]-8-OH-DPAT from human 5HT1A receptor by liquid scintillation counting
Measurement: Ki = 588.84 nM (pChEMBL 6.230000019073486)
Descriptors: MW 339.46, ALogP 3.54, HBA 3, HBD 0, PSA 19.37, QED 0.85
Compound (SMILES): CS(=O)(=O)Nc1cc(-c2ccncc2)cnc1Cl
InChIKey: KDSFLYIZGIJKAW-UHFFFAOYSA-N
Target: Tyrosine-protein kinase SYK (SINGLE PROTEIN), Homo sapiens
UniProt: P43405
Assay: Inhibition of SYK (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 283.74, ALogP 2.17, HBA 4, HBD 1, PSA 71.95, QED 0.88
Compound (SMILES): C[C@@H]1NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](CS)NC(=O)[C@@H]2CCCN2C(=O)[C@H]2CCCN2C(=O)[C@H](Cc2ccccc2)NC1=O
InChIKey: NKZFUEPYJJNRCM-PLUWKHBFSA-N
Target: Melanocortin receptor 5 (SINGLE PROTEIN), Mus musculus
UniProt: P41149
Assay: Displacement of [125I]-NDP-MSH from mouse melanocortin receptor 5 expressed in HEK293 cell mebranes incubated for 1 hr by automatic gamma counting method
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 924.09, ALogP -0.56, HBA 10, HBD 8, PSA 258.31, QED 0.13
Compound (SMILES): NS(=O)(=O)c1ccc(N2CC(C(=O)N/N=C/c3ccccc3)CC2=O)cc1
InChIKey: BNOSIOACPICPJD-RGVLZGJSSA-N
Target: Carbonic anhydrase 13 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8N1Q1
Assay: Binding affinity to recombinant human CA13 by DSF-based fluorescence thermal shift assay
Measurement: Kd = 830 nM (pChEMBL 6.079999923706055)
Descriptors: MW 386.43, ALogP 0.84, HBA 5, HBD 2, PSA 121.93, QED 0.58
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCCCCCC(=O)O)C(=O)O)[C@@H](C)O)C(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O
InChIKey: SGIDMYDYTBFBSN-TYRZRTKUSA-N
Target: Calcitonin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30988
Assay: Displacement of [125I]-labeled human calcitonin from human calcitonin receptor expressed in BHK tkts13 whole cells incubated for 60 mins by scintillation proximity assay
Measurement: IC50 = 1.549 nM (pChEMBL 8.8100004196167)
Descriptors: MW 4071.7
Compound (SMILES): Cc1cc(-c2ccc(C(=O)[C@@H]3CCCC[C@H]3C(=O)Nc3cnn(C)c3S(N)(=O)=O)cc2)n[nH]1
InChIKey: IVYACETTWFJKQK-IAGOWNOFSA-N
Target: Bile salt export pump (SINGLE PROTEIN), Homo sapiens
UniProt: O95342
Assay: Inhibition of recombinant human BSEP expressed in baculovirus infected Sf21 insect cell vesicles assessed as reduction in NBD-taurocholate uptake by fluorescence assay
Measurement: IC50 = 74000 nM (pChEMBL 4.130000114440918)
Descriptors: MW 470.56, ALogP 2.39, HBA 7, HBD 3, PSA 152.83, QED 0.47
Compound (SMILES): CN(C)c1ccc(C(=O)N(CC(=O)NCc2ccccc2)Cc2ccc(C(=O)Nc3ccccc3N)cc2)cc1
InChIKey: SIRNCVDOMIOFAK-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of recombinant human C-terminal His-fusion tagged/N-terminal Strep-2 tagged HDAC8 (1 to 377 residues) expressed in insect cells using Boc-Lys(TFa)-AMC as substrate preincubated for 5 mins followed by substrate addition measured after 90 mins by fluorescence assay
Measurement: IC50 = 9210 nM (pChEMBL 5.039999961853027)
Descriptors: MW 535.65, ALogP 4.55, HBA 5, HBD 3, PSA 107.77, QED 0.26
Compound (SMILES): COc1cc(C2CN(C(=O)c3cc(COC[C@@H](O)CO)ccn3)C2)ccc1OCc1ccc(C2CC2)cc1
InChIKey: LTTJGQBDGMNWHJ-SANMLTNESA-N
Target: Mast/stem cell growth factor receptor Kit (SINGLE PROTEIN), Homo sapiens
UniProt: P10721
Assay: Inhibition of human N-terminal GST-tagged c-kit (544 to end residues) expressed in baculovirus infected Sf21 insect cells using Poly (Glu4-Tyr) (4:1) as substrate
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 518.61, ALogP 3.66, HBA 7, HBD 2, PSA 101.35, QED 0.38
Compound (SMILES): CC(C)c1cc(C(=O)N2Cc3ccccc3C2)c(O)c2cnoc12
InChIKey: MFZKTINXWPQHBG-UHFFFAOYSA-N
Target: Heat shock protein HSP 90-beta (SINGLE PROTEIN), Homo sapiens
UniProt: P08238
Assay: Binding affinity to N-terminal His6-tagged human HSP90beta (1 to 239 residues) expressed in Escherichia coli BL21(DE3) cells by fluorescence thermal shift assay
Measurement: Kd = 26 nM (pChEMBL 7.579999923706055)
Descriptors: MW 322.36, ALogP 3.81, HBA 4, HBD 1, PSA 66.57, QED 0.78
Compound (SMILES): Cc1cc(N2CC(C(=O)N/N=C/c3ccccc3)CC2=O)cc(C)c1S(N)(=O)=O
InChIKey: NEEUKYCSJKNGPX-SSDVNMTOSA-N
Target: Carbonic anhydrase 13 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8N1Q1
Assay: Binding affinity to recombinant human CA13 by DSF-based fluorescence thermal shift assay
Measurement: Kd = 22000 nM (pChEMBL 4.659999847412109)
Descriptors: MW 414.49, ALogP 1.45, HBA 5, HBD 2, PSA 121.93, QED 0.57
Compound (SMILES): NS(=O)(=O)c1ccc(NC(=O)CN2C(=O)NC3(CCCCCC3)C2=O)cc1
InChIKey: WALKBCDYHSEIBJ-UHFFFAOYSA-N
Target: Carbonic anhydrase 13 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8N1Q1
Assay: Inhibition of human carbonic anhydrase 13 incubated for 15 mins prior to testing by stopped-flow CO2 hydration assay
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 394.45, ALogP 0.92, HBA 5, HBD 3, PSA 138.67, QED 0.65
Compound (SMILES): Cl.N=C(N)c1ccc(CC2OB(O)c3cc(C(F)(F)F)ccc32)cc1OCc1cccnc1
InChIKey: SJWIYNDYLDXFMU-UHFFFAOYSA-N
Target: Coagulation factor X (SINGLE PROTEIN), Homo sapiens
UniProt: P00742
Assay: Inhibition of recombinant human C-terminal 10-His-tagged factor Xa (L24 to K488 residues) expressed in baculovirus infected Sf21 insect cells using Mca-RPKPVE-Nval-WRK(Dnp)-NH2 as substrate incubated for 40 mins by FLINT assay
Measurement: IC50 = 31622.78 nM (pChEMBL 4.5)
Descriptors: MW 441.22
Compound (SMILES): CSCC[C@@H]1NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](Cc2cnc[nH]2)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](CO)NC(C)=O)CSSC[C@@H](C(=O)N[C@H](C(=O)N[C@@H](Cc2c[nH]c3ccccc23)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](Cc2ccccc2)C(N)=O)C(C)C)C(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCSC)NC(=O)[C@H]([C@@H](C)O)NC(=O)CNC(=O)[C@@H](CCCCN)NC(=O)[C@H](CCSC)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC1=O
InChIKey: VDIQLFPDZSQICF-WCAMJISASA-N
Target: Tissue factor pathway inhibitor (SINGLE PROTEIN), Homo sapiens
UniProt: P10646
Assay: Binding affinity to TFPI (unknown origin) incubated for 1.5 hrs using 0.5 nM tracer peptide JBT0131 by screening ELISA
Measurement: IC50 = 0.52 nM (pChEMBL 9.279999732971191)
Descriptors: MW 2911.53
Compound (SMILES): CC(C)(C)c1cc(NC(=O)Cc2ccc(-n3cnc4cc(-c5ccc(S(C)(=O)=O)cc5)ccc43)cc2)no1
InChIKey: LMFNJXLDISVWLF-UHFFFAOYSA-N
Target: Coiled-coil domain-containing protein 6/Tyrosine-protein kinase receptor RET (CHIMERIC PROTEIN), Homo sapiens
UniProt: P07949
Assay: Inhibition of CCDC6/RET in human TPC1 cells assessed as reduction in cell proliferation supplemented with fresh medium containing compound for every 2 to 3 days and measured during compound dosing
Measurement: IC50 = 0.67 nM (pChEMBL 9.170000076293945)
Descriptors: MW 528.63, ALogP 5.56, HBA 7, HBD 1, PSA 107.09, QED 0.31
Compound (SMILES): C=CC(=O)Nc1cc(Nc2ncc(Cl)c(Nc3ccccc3S(=O)(=O)C(C)C)n2)c(OC)cc1N(C)CCN(C)C
InChIKey: GDRLJBDXWDATLA-UHFFFAOYSA-N
Target: Receptor tyrosine-protein kinase erbB-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P04626
Assay: Inhibition of recombinant His-tagged human ErbB2 cytoplasmic domain expressed in baculovirus expression system by Z-LYTE assay
Measurement: IC50 = 37 nM (pChEMBL 7.429999828338623)
Descriptors: MW 602.16, ALogP 4.93, HBA 10, HBD 3, PSA 128.79, QED 0.23
Compound (SMILES): CC(C)(O)CNC(=O)Cc1nc2cnc3[nH]ccc3c2n1[C@H]1CC[C@H](CC#N)CC1
InChIKey: NJKMSBSVJSQUBU-SHTZXODSSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Enzymatic Inhibition Assay: 11-point dosing series were made for each compound by serially diluting 1:3 or 1:4 in DMSO, with point 12 being a DMSO control. From the serial dilution plates, sample was transferred to a 384 wells assay plate (#781280, Greiner, Monroe, N.C.) using Labcyte Echo (Sunnyvale, Calif.), or Biosero ATS (San Diego, Calif.). The compounds were tested in duplicate. Column 12 was used for positive controls, and column 24 contained negative controls with no enzyme added. A compound from our internal collection, with inhibitory activity for JAK isoforms, was used as a reference compound. The final concentration of DMSO was ≤0.25% in a 20 μL reaction. Assay conditions for each of the proteins are summarized in Table 3. The enzyme reaction was initiated by the addition of 10 μL of 2× enzyme and ATP mixture to 10 μL of 2× substrate solution prepared in reaction buffer (50 mM MOPS pH 7.5, 10 mM MgCl2, 1 mM EDTA, 2 mM DTT, 0.002% Tween-20). The Tyk2 enzyme was pre-incubated with 2 mM ATP for 30 min prior to the reaction initiation. Immediately after the addition of the enzyme to the reaction mixture, the plate was centrifuged at 1000 rpm for 1 minute and incubated at 25° C. for 45 minutes for JAK 3 and 90 minutes for JAK1, JAK2 and Tyk2. The reaction was quenched by the addition of 20 μL of 0.5% TFA containing 0.15 μM of internal standard peptide using Multidrop Combi reagent dispenser (Thermo Scientific, Waltham, Mass.). Several wells in column 24 were typically used for the product standard curve. After the quench, the assay plate was centrifuged at 3000 rpm for 3 minutes and sealed with pierceable aluminum foil (Cat #06644-001, Agilent) using a PlateLoc (Agilent Technologies, Santa Clara, Calif.). The plates then were transferred on to the RapidFire for the MS analysis. Compound inhibition was assessed by a decrease of the phosphorylated product levels in sample wells compared to the non-inhibited enzyme reaction. The assay conditions for the above assays are shown in Table 3 and the results of Ex. 1-209 as tested in these assays are shown in Table 4.TABLE 3Assay conditions for JAK family enzyme assays* [p], [ATP], [Substrate], [IS],Enzyme nM μM μM nMJAK1-JH1JH2 8.0 12.5 200 100JAK2-JH1JH2 7.0 or 3.6 30 40 100JAK3-JH1JH2 2.0 150 40 100Tyk2-JH1JH2   25 or 14.7 50 200 100*Reaction buffer: 50 mM MOPS, pH 7.5 10 mM MgCl2, 1 mM EDTA, 2 mM DTT, 0.002% Tween-20; IS stands for internal standard peptide; p stands for phospho-peptide (product); Substrate stands for peptide.
Measurement: IC50 = 0.3 nM (pChEMBL 9.520000457763672)
Descriptors: MW 408.51, ALogP 2.99, HBA 6, HBD 3, PSA 119.62, QED 0.58
Compound (SMILES): COC(=O)C1CC(=O)N(c2cc(C)c(S(N)(=O)=O)c(C)c2Cl)C1
InChIKey: DNALKYILSFHWTG-UHFFFAOYSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Binding affinity to recombinant human CA4 assessed as intrinsic dissociation constant by DSF-based fluorescence thermal shift assay
Measurement: Kd = 0.36 nM (pChEMBL 9.4399995803833)
Descriptors: MW 360.82, ALogP 1.13, HBA 5, HBD 1, PSA 106.77, QED 0.81
Compound (SMILES): NS(=O)(=O)c1ccc(CCNC(=O)CN2C(=O)NC3(CCCC3)C2=O)cc1
InChIKey: RFPXNPAWDLLRQG-UHFFFAOYSA-N
Target: Carbonic anhydrase 13 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8N1Q1
Assay: Inhibition of human carbonic anhydrase 13 incubated for 15 mins prior to testing by stopped-flow CO2 hydration assay
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 394.45, ALogP -0.14, HBA 5, HBD 3, PSA 138.67, QED 0.58
Compound (SMILES): CC1(C2CC2)NC(=O)N(CC(=O)Nc2ccc(Cl)c(S(=O)(=O)N3CCCCC3)c2)C1=O
InChIKey: UJFOHASZAXASED-UHFFFAOYSA-N
Target: ATPase family AAA domain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6PL18
Assay: Inhibition of ATAD2 bromodomain in human HUT78 chromatin lysate after 2 hrs by bromosphere competition binding assay
Measurement: IC50 = 15848.93 nM (pChEMBL 4.800000190734863)
Descriptors: MW 468.96, ALogP 2.17, HBA 5, HBD 2, PSA 115.89, QED 0.62
Compound (SMILES): Cc1cccc(NC(=O)CN2CCN(c3cccc4ccccc34)CC2)c1
InChIKey: LEQVQRFGBPYNQZ-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Agonist activity at human D4 receptor expressed in CHOK1 cells assessed as induction of beta-arrestin recruitment measured after 90 mins by luminescence assay
Measurement: EC50 = 9212 nM (pChEMBL 5.039999961853027)
Descriptors: MW 359.47, ALogP 3.91, HBA 3, HBD 1, PSA 35.58, QED 0.77
Compound (SMILES): N=C(N)NC(=O)c1nc(-c2cc3ccccc3o2)c(N)nc1N
InChIKey: ZKLNPUKNSARQMG-UHFFFAOYSA-N
Target: Urokinase-type plasminogen activator (SINGLE PROTEIN), Homo sapiens
UniProt: P00749
Assay: Inhibition of human kidney uPA using fluorogenic Z-Pyr-Gly-Arg-MCA as substrate measured after 15 mins by fluorometric analysis
Measurement: Ki = 302 nM (pChEMBL 6.519999980926514)
Descriptors: MW 311.31, ALogP 0.68, HBA 7, HBD 5, PSA 169.93, QED 0.34
Compound (SMILES): CN1CCC(Nc2ccc(C(=O)Nc3cc(-c4cc(C#N)cs4)n[nH]3)cc2)CC1
InChIKey: HGLWPJISHDLCTE-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: Binding affinity to human phosphorylated ABL1 H396P mutant (S229 to K512 residues) expressed in mammalian expression system after 60 mins by Kinomescan method
Measurement: Kd = 390 nM (pChEMBL 6.409999847412109)
Descriptors: MW 406.52, ALogP 3.77, HBA 6, HBD 3, PSA 96.84, QED 0.6
Compound (SMILES): Fc1ccc2c(c1)CC(CCN1CCCN(c3ccccn3)CC1)C2
InChIKey: RVMUAKCKCUJBKV-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Displacement of [3H]-ketanserin from human 5HT2A receptor by liquid scintillation counting
Measurement: Ki = 43 nM (pChEMBL 7.369999885559082)
Descriptors: MW 339.46, ALogP 3.54, HBA 3, HBD 0, PSA 19.37, QED 0.85
Compound (SMILES): CS(=O)(=O)Nc1cc(-c2ccncc2)cnc1Cl
InChIKey: KDSFLYIZGIJKAW-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of JAK3 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 283.74, ALogP 2.17, HBA 4, HBD 1, PSA 71.95, QED 0.88
Compound (SMILES): C[C@@H]1NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](CS)NC(=O)[C@@H]2CCCN2C(=O)[C@H]2CCCN2C(=O)[C@H](Cc2ccccc2)NC1=O
InChIKey: NKZFUEPYJJNRCM-PLUWKHBFSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P32245
Assay: Displacement of [125I]-NDP-MSH from human melanocortin receptor 4 expressed in HEK293 cell mebranes incubated for 1 hr by automatic gamma counting method
Measurement: IC50 = 19300 nM (pChEMBL 4.710000038146973)
Descriptors: MW 924.09, ALogP -0.56, HBA 10, HBD 8, PSA 258.31, QED 0.13
Compound (SMILES): NS(=O)(=O)c1ccc(N2CC(C(=O)N/N=C/c3ccccc3)CC2=O)cc1
InChIKey: BNOSIOACPICPJD-RGVLZGJSSA-N
Target: Carbonic anhydrase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9ULX7
Assay: Binding affinity to recombinant N-terminal His6x-tagged human CA14 (20 to 280 residues) catalytic domain expressed in Escherichia coli Rosetta 2 (DE3) by DSF-based fluorescence thermal shift assay
Measurement: Kd = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 386.43, ALogP 0.84, HBA 5, HBD 2, PSA 121.93, QED 0.58
Compound (SMILES): Cc1cc(-c2ccc(C(=O)[C@@H]3CCCC[C@H]3C(=O)Nc3cnn(C)c3S(N)(=O)=O)cc2)n[nH]1
InChIKey: IVYACETTWFJKQK-IAGOWNOFSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG by Ion-work assay
Measurement: IC50 > 33000 nM (pChEMBL 4.480999946594238)
Descriptors: MW 470.56, ALogP 2.39, HBA 7, HBD 3, PSA 152.83, QED 0.47