lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1ccnc(CNC(=O)c2cn(Cc3ccc(Cn4ccccc4=O)cc3)nc2C(F)(F)F)c1F
InChIKey: NKTBXDIJVDKJRR-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 in human liver microsomes assessed as reduction in 4 hydroxy-diclofenac metabolite formation incubated for 30 mins in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 515.47, ALogP 3.63, HBA 7, HBD 1, PSA 91.04, QED 0.36
Compound (SMILES): Cc1cc(-c2n[nH]c(C)c2-c2ccc(-c3cccc(S(N)(=O)=O)c3)cc2)ccn1
InChIKey: PGECWGQWQVBMPM-UHFFFAOYSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Mus musculus
UniProt: Q5S006
Assay: Inhibition of mouse full-length LRRK2 G2019S mutant transfected in HEK293 cells using LRRKtide as substrate in presence of ATP by incubated for 1 hr TR-FRET based ADAPTA assay
Measurement: EC50 = 1080 nM (pChEMBL 5.96999979019165)
Descriptors: MW 404.5, ALogP 4.07, HBA 4, HBD 2, PSA 101.73, QED 0.54
Compound (SMILES): CNC(=O)[C@@]12C[C@@H]1[C@@H](n1cnc3c(NCCc4ccc(OC)c(O)c4)nc(OCC(C)C)nc31)[C@H](O)[C@@H]2O
InChIKey: WUWAIBYOOHQJEL-MRAWFPONSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Agonist activity at human adenosine A3A receptor stably expressed in HEK293 cells assessed as beta arrestin 2 recruitment potency by luciferase based NanoBiT assay
Measurement: EC50 = 51.5 nM (pChEMBL 7.289999961853027)
Descriptors: MW 526.59, ALogP 1.26, HBA 11, HBD 5, PSA 163.88, QED 0.26
Compound (SMILES): CC(C)C[C@H](N)c1cc(C#N)c2cc(-c3ccncc3)ccc2n1
InChIKey: FMNWOBLAZAYOSG-SFHVURJKSA-N
Target: Serine/threonine-protein kinase Chk1 (SINGLE PROTEIN), Homo sapiens
UniProt: O14757
Assay: Inhibition of CHK1 (unknown origin)
Measurement: IC50 = 998 nM (pChEMBL 6)
Descriptors: MW 316.41, ALogP 4.21, HBA 4, HBD 1, PSA 75.59, QED 0.78
Compound (SMILES): COC(=O)Nc1cc(-c2ccc(OC[C@@](C)(N)CC(C)C)c(C(F)F)c2)ccn1
InChIKey: FXQJMZONPDKEJC-NRFANRHFSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin) incubated for 10 mins in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 407.46, ALogP 5.01, HBA 5, HBD 2, PSA 86.47, QED 0.64
Compound (SMILES): CCNNC(=O)c1csc(-c2cccnc2)n1
InChIKey: RRMRRJHOOJCCFB-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of recombinant HDAC6 (unknown origin) using Boc-Lys(acetyl)-AMC as substrate preincubated for 1 hr followed by substrate addition and measured after 2 hrs by fluorescence based microplate reader analysis
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 248.31, ALogP 1.46, HBA 5, HBD 2, PSA 66.91, QED 0.8
Compound (SMILES): CNC(=O)c1ccc(F)c(-c2cnc3cc(-c4cnn(C)c4)c(OC)nn23)c1
InChIKey: MIWWARHIDNFXAZ-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of wild type partial length human FLT3 (V592 to Y969 residues) expressed in bacterial expression system using Ulight-p70S6K peptide substrate incubated for 90 mins in presence of ATP by HTRF assay
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 380.38, ALogP 2.3, HBA 7, HBD 1, PSA 86.34, QED 0.59
Compound (SMILES): Cc1ncsc1-c1ccc(CNC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)COCCOCCOCCOCC(F)(F)c2cnc(-c3ccc(C(C(=O)NO)c4ccccc4F)cc3)nc2)C(C)(C)C)cc1
InChIKey: JCIGJBGCHCAMMB-DGTRGAFGSA-N
Target: Histone deacetylase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UKV0
Assay: Inhibition of recombinant HDAC9 (unknown origin) using Boc-Lys(TFA)-AMC as substrate by fluorescence based plate reader assay
Measurement: IC50 = 340 nM (pChEMBL 6.46999979019165)
Descriptors: MW 1006.11
Compound (SMILES): CSCC[C@H](NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)CC[C@H](NS(=O)(=O)c1ccc(Cl)c(C(F)(F)F)c1)C(=O)O)C(N)=O
InChIKey: OMGNESNLXGMXAS-FHWLQOOXSA-N
Target: Neutrophil collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P22894
Assay: Inhibition of human recombinant MMP-8 (Phe21 to Gly467 residues) using MOCAc-Pro-Leu-Gly-Leu-A2pr(Dnp)-Ala-Arg-NH2 as fluorogenic substrate preincubated for 15 mins followed by substrate addition by fluorescence based analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 690.16, ALogP 1.24, HBA 8, HBD 6, PSA 213.86, QED 0.13
Compound (SMILES): O=C(O)CC1CCC2(CC1)CCC(c1ccc(NC(=O)c3nnc(Nc4ccc(F)c(F)c4)o3)cn1)CC2
InChIKey: QKTPNXWLDUSRAW-UHFFFAOYSA-N
Target: Diacylglycerol O-acyltransferase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75907
Assay: Inhibition of human DGAT1 in serum starved HEK293 cells assessed as inhibition of triglyceride synthesis incubated for 20 mins followed by 13C-addition of 13C-oleic acid pre-complexed with BSA for 120 mins by LC-MS-based mass spectrophotometric analysis
Measurement: IC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 525.56, ALogP 6.05, HBA 7, HBD 3, PSA 130.24, QED 0.34
Compound (SMILES): C[C@H]1CCCCN1c1nnc2ccc(O[C@@H]3CC[C@H](NC(=O)Nc4cc(C(C)(C)C)nn4-c4cnn(CCN(C)C)c4)c4ccccc43)cn12
InChIKey: PPZSTJQLZOPKBO-LGXAAPQCSA-N
Target: Mitogen-activated protein kinase 13 (SINGLE PROTEIN), Homo sapiens
UniProt: O15264
Assay: Inhibition of recombinant human full length His-tagged p38delta expressed in baculovirus expression system preincubated for 2 hrs followed by ATP addition and measured after 1 hr by Alpha screen assay
Measurement: IC50 = 4100 nM (pChEMBL 5.389999866485596)
Descriptors: MW 679.87, ALogP 6.13, HBA 11, HBD 2, PSA 122.67, QED 0.19
Compound (SMILES): COc1ccc(CNC(=O)c2cc(C(=O)Nc3ccccc3N)ccc2N2CCOCC2)cc1O
InChIKey: DASFUHPVLAUFCK-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 in human HeLa cells using BOC-K(Ac)-AMC as substrate measured after 30 mins by fluorescence based microtiter plate reader assay
Measurement: IC50 = 668 nM (pChEMBL 6.170000076293945)
Descriptors: MW 476.53, ALogP 3, HBA 7, HBD 4, PSA 126.15, QED 0.39
Compound (SMILES): O=c1[nH]c2ccccc2nc1/C=C/c1ccccc1Br
InChIKey: WRGLRCQOQDVMSQ-MDZDMXLPSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of FGFR3 (unknown origin)
Measurement: IC50 = 77680 nM (pChEMBL 4.110000133514404)
Descriptors: MW 327.18, ALogP 3.86, HBA 2, HBD 1, PSA 45.75, QED 0.78
Compound (SMILES): Nc1nc(N[C@H]2CC3CCC2C3)sc1C(=O)c1ccccc1[N+](=O)[O-]
InChIKey: JRNXAQINDCOHGS-CBINBANVSA-N
Target: Cyclin-dependent kinase 5/CDK5 activator 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q15078
Assay: Inhibition of CDK5/p35 (unknown origin)
Measurement: IC50 = 159 nM (pChEMBL 6.800000190734863)
Descriptors: MW 358.42, ALogP 3.47, HBA 7, HBD 2, PSA 111.15, QED 0.48
Compound (SMILES): COc1ccc(N(C)C(=O)[C@H](Cc2cc(F)cc(F)c2)NC(=O)CN2CCN(CC(=O)N[C@@H](Cc3cc(F)cc(F)c3)C(=O)N(C)c3ccc(OC)cc3)C(=O)C2)cc1
InChIKey: GGDYDLLLKOBJEX-BCRBLDSWSA-N
Target: Structural capsid protein (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q76129
Assay: Displacement of NUP153 peptide from HIV1 capsid protein by surface plasmon resonance-based competition assay
Measurement: IC50 = 3470 nM (pChEMBL 5.460000038146973)
Descriptors: MW 820.84, ALogP 3.49, HBA 8, HBD 2, PSA 140.83, QED 0.16
Compound (SMILES): COc1cc(/C=C/c2cc(=O)oc3c2ccc2oc(-c4cccc(F)c4)cc23)cc(OC)c1
InChIKey: SVFJYZVSHWUWHU-VOTSOKGWSA-N
Target: Polyunsaturated fatty acid 5-lipoxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P09917
Assay: Inhibition of human LOX-5 in presence of LOX substrate solution incubated for 10 mins by Varioskan-flash microplate spectrophotometer reader
Measurement: IC50 = 13900 nM (pChEMBL 4.860000133514404)
Descriptors: MW 442.44, ALogP 6.53, HBA 5, HBD 0, PSA 61.81, QED 0.29
Compound (SMILES): C[C@@H]1CN(c2ccc(-c3n[nH]c4cnc(N5[C@H](C)CN(C(=O)N(C)C)C[C@@H]5C)nc34)cn2)CCN1
InChIKey: RWYJMMHOMKOPEY-ZACQAIPSSA-N
Target: Activin receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q04771
Assay: HTRF Assay (100 uM ATP): ALK2 (aa 147-end) was obtained from BPS biosciences. The enzymatic assays were conducted in white 384-well polystyrene plates in a final volume of 8 μL. The inhibitors were serially diluted in DMSO and added to the plate wells prior to addition of the other reaction components. The assays were carried out at 25° C. in the assay buffer (50 mM HEPES, pH 7.1, 10% Glycerol, 0.01% Brij50, 10 mM MgCl2, 1 mM EGTA, 5 mM DTT, and 0.01% BSA), containing 50 nM LANCE Ultra ULight-DNA Topoisomerase 2-alpha peptide (Perkin Elmer TRF0130), and 100 uM ATP. The final concentration of DMSO in the assay was 1% and the enzyme concentration was 2.5 nM for ALK2. The reactions were allowed to proceed for 2-4 hr after which, the reaction was quenched by addition of EDTA at a final concentration of 20 mM along with 1.5 nM LANCE Ultra Europium-anti-phospho-DNA Topoisomerase 2-alpha (Thr1342) antibody (Perkin Elmer TRF0218). The reaction was read on a PHERAstar FS plate reader (BMG Labtech). IC50 determination was performed by fitting percent control activity versus the log of the inhibitor concentration using the IDBS XLFit and GraphPad Prism 5.0 software.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 478.61, ALogP 1.79, HBA 8, HBD 2, PSA 109.41, QED 0.59
Compound (SMILES): O=C1CCCc2[nH]c(-c3ccncc3)cc21
InChIKey: FQYKIBPUNQVZRF-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase N1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16512
Assay: Inhibition of PKN1 (unknown origin) by TR-FRET-based tracer displacement assay
Measurement: IC50 = 1300 nM (pChEMBL 5.889999866485596)
Descriptors: MW 212.25, ALogP 2.6, HBA 2, HBD 1, PSA 45.75, QED 0.79
Compound (SMILES): Cc1ccc(CC(C)CNC(=O)/N=C(\N)NCCCc2cnc(N)s2)cc1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: ZZDDLWVPLCUTER-UHFFFAOYSA-N
Target: Histamine H2 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P25021
Assay: Displacement of [3H]UR-DE257 from human histamine H2 receptor stably expressed in baculovirus infected Sf9 cell membrane co-expressing RG-Salpha S incubated for 60 mins by scintillation counting analysis
Measurement: Kd = 12.2 nM (pChEMBL 7.909999847412109)
Descriptors: MW 388.54, ALogP 2.46, HBA 4, HBD 4, PSA 118.42, QED 0.31
Compound (SMILES): CC(C)CN(Cc1ccc(C(=O)NO)cc1)S(=O)(=O)c1cc(F)c(F)c(F)c1F
InChIKey: ORRALXXDFMZZIR-UHFFFAOYSA-N
Target: Histone deacetylase 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96DB2
Assay: Inhibition of full length human recombinant HDAC11 expressed in Sf9 baculovirus system using FAM-labeled acetylated peptide as substrate by measuring fluorescence intensity by EMSA method
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 434.41, ALogP 3.21, HBA 4, HBD 2, PSA 86.71, QED 0.23
Compound (SMILES): C[C@@H](C1CC1)N1Cc2cc(-c3ccn4nc(N)c(C(=O)NC5CC5)c4n3)cc(S(C)(=O)=O)c2C1=O
InChIKey: NLRPOLHEDYFDBC-LBPRGKRZSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3Kdelta (unknown origin) using PIP2 as substrate preincubated for 1 hr followed by substrate addition and measured after 60 mins in presence of ATP by ADP-glo assay
Measurement: IC50 = 560 nM (pChEMBL 6.25)
Descriptors: MW 494.58, ALogP 2.03, HBA 8, HBD 2, PSA 139.76, QED 0.53
Compound (SMILES): COc1cc2c(NC3CCN(Cc4ccccc4)CC3)nc(NCCCN(C)C)nc2cc1OCc1ccccc1
InChIKey: CLMKFAVBRRFUGX-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase, H3 lysine-79 specific (SINGLE PROTEIN), Homo sapiens
UniProt: Q8TEK3
Assay: Inhibition of DOTL1 (unknown origin) using [3H]SAM and HeLa oligo nucleosomes as substrates incubated for 1 hr
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 554.74, ALogP 5.66, HBA 8, HBD 2, PSA 74.78, QED 0.21
Compound (SMILES): O=C(N[C@@H](Cc1coc2ccccc12)B(O)O)[C@H]1CCOC1
InChIKey: LPDJLONKZFUKOX-HZMBPMFUSA-N
Target: Proteasome subunit beta type-8 (SINGLE PROTEIN), Homo sapiens
UniProt: P28062
Assay: Inhibition of 20S immunoproteasome beta-5i subunit in human PBMC using Ac-ANW-luciferin substrate preincubated for 2 hrs followed by substrate addition and measured after 30 mins by luminometric analysis
Measurement: IC50 = 55 nM (pChEMBL 7.260000228881836)
Descriptors: MW 303.12
Compound (SMILES): Clc1cc(Cl)cc(Cc2nnc(CCc3c[nH]c4ccccc34)n2CCCc2c[nH]cn2)c1
InChIKey: DWNKUUCRZQVTHP-UHFFFAOYSA-N
Target: Somatostatin receptor type 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P32745
Assay: Activity Assays: Measurement of forskolin stimulated inhibition of cAMP was performed via time-resolved fluorescence resonance energy transfer (TR-FRET) LANCE assay (AD0262, PerkinElmer Life Science, Inc., Boston Mass.). Recombinant Chinese hamster ovary (CHO-K1) cells expressing human somatostatin SSTR4 cells (ES-524-CF, PerkinElmer Life Science, Inc., Boston Mass.) were thawed (37° C.), resuspended in 10 mL Hanks' balanced salt solution no phenol red (HBSS, Invitrogen, Carlsbad Calif.), and then centrifuged (150×g, 5 minutes). Cellular pellet resuspended in stimulation buffer containing HBSS 1×, HEPES 5 mM, Protease free BSA 0.1% (PerkinElmer), and 3-Isobutyl-1-methylxanthine 0.5 mM (pH 7.4) and seeded in 96-well plates at 4000 cells/well. LANCE cAMP assay was performed per manufacture instruction with assessment of respective compound, somatostatin-28 (Sigma-Aldrich Co., St. Louis, Mo.) as control agonist, against 5 μM forskolin, performed in triplicate across concentration curve. Fluorescence signal was measured at 20 hours (excitation 340 nm and emission 665 nm, 400-μs delay) via TR-FRET (FLUOSTAR Omega-F, BMG Labtech, Inc., Cary, N.C.). Data was calculated via GraphPad PRISM-5 software.
Measurement: EC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 479.42, ALogP 5.8, HBA 4, HBD 2, PSA 75.18, QED 0.28
Compound (SMILES): Cc1[nH]c2cc(Nc3ncc(Cl)c(Nc4ccccc4NS(C)(=O)=O)n3)ccc2c1C(=O)N1CCC(C)CC1
InChIKey: IDOYZDKYHYCQEW-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of N-terminal GST-tagged human ceritinib-resistant ALK G1202R mutant (1058 to 1620 residues) cytoplasmic domain expressed in baculovirus infected Sf21 cells incubated for 1 hrs in the presence of ATP by mobility shift assay
Measurement: IC50 = 6.5 nM (pChEMBL 8.1899995803833)
Descriptors: MW 568.1, ALogP 5.65, HBA 7, HBD 4, PSA 132.11, QED 0.23
Compound (SMILES): O=C(c1cnc2c(cnn2CC2CC2)c1C(F)(F)F)N1CCN(c2ccc(F)cc2F)CC1
InChIKey: QZBSALDEUVKOGG-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13255
Assay: Agonist activity at mGlu1 receptor (unknown origin) expressed in human Flp-In-T-REx-293 cells by luciferase based GloSensor cAMP Assay
Measurement: EC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 465.43, ALogP 4.1, HBA 5, HBD 0, PSA 54.26, QED 0.54
Compound (SMILES): CCCCCCNNC(=O)c1cnc(NCCc2ccccc2)nc1
InChIKey: DDAMDJOJXKOHBK-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of recombinant human HDAC8 using (Abz-SRGK(thio-TFA)FFRR-NH2) as substrate preincubated for 5 mins followed by substrate addition by fluorescence based analysis
Measurement: IC50 = 28 nM (pChEMBL 7.550000190734863)
Descriptors: MW 341.46, ALogP 2.95, HBA 5, HBD 3, PSA 78.94, QED 0.43
Compound (SMILES): CCCCCCCCCCCOc1cccc(CCC(=O)NC[C@@H](O)COP(=O)(O)OC[C@H](NC(=O)CCCC)C(=O)O)c1
InChIKey: BMRCIIZGJWUFPB-IAPPQJPRSA-N
Target: Probable G-protein coupled receptor 174 (SINGLE PROTEIN), Mus musculus
UniProt: Q3U507
Assay: Antagonist activity at mouse GPR174 transfected in human HEK293FT cells co-transfected with AP-TGFalpha assessed as inhibition of LysoPalloT-NH-C3-ph-m-O-C11-induced AP-TGFalpha release incubated for 90 mins by TGFalpha shedding assay
Measurement: IC50 = 6.607 nM (pChEMBL 8.180000305175781)
Descriptors: MW 644.74, ALogP 4.9, HBA 8, HBD 5, PSA 180.72, QED 0.07
Compound (SMILES): O=C(Nc1nc2cccc([C@@H]3CCC4(C3)CN(C(=O)[C@@H]3CC3(F)F)C4)n2n1)C1CC1
InChIKey: SOKYMLHPKZYWKI-KGLIPLIRSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of recombinant human TYK2 using GGMEDIYFEFMGGKKK as substrate incubated for 40 mins in presence of Mg/ATP mixture by [gamma p33]-ATP based scintillation counting method
Measurement: IC50 = 404 nM (pChEMBL 6.389999866485596)
Descriptors: MW 415.44, ALogP 2.83, HBA 5, HBD 1, PSA 79.6, QED 0.83
Compound (SMILES): Cc1ccc(O)c(C)c1-n1c(N)c(C(N)=O)c2nc3ccccc3nc21
InChIKey: KBWZVVPCJMAFMN-UHFFFAOYSA-N
Target: Ephrin type-B receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P54753
Assay: Inhibition of full length Nano-luc fused EPHB3 in human HEK-293T cells incubated for 2 hrs by cell based NanoBRET target engagement assay
Measurement: IC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 347.38, ALogP 2.58, HBA 6, HBD 3, PSA 120.05, QED 0.51
Compound (SMILES): Cc1c(-c2ccc(-c3c[nH]nc3-c3ccnc(N4CCOCC4)c3)cc2)ccc(S(N)(=O)=O)c1C
InChIKey: OUWOAMPJEASGND-UHFFFAOYSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Mus musculus
UniProt: Q5S006
Assay: Inhibition of mouse full-length wild type LRRK2 transfected in HEK293 cells using LRRKtide as substrate incubated for 1 hr in presence of ATP by TR-FRET based ADAPTA assay
Measurement: EC50 = 76000 nM (pChEMBL 4.119999885559082)
Descriptors: MW 489.6, ALogP 3.91, HBA 6, HBD 2, PSA 114.2, QED 0.44
Compound (SMILES): CCCCn1cc(C(=O)N[C@H](C(N)=O)C(C)(C)C)c2ccccc21
InChIKey: JXGXKMDAAOWHLR-MRXNPFEDSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]-CP55940 from N-terminal 3HA-tagged human CB2 receptor expressed in human HEK293-EBNA cells incubated for 60 mins by radioligand competitive binding assay based liquid scintillation counter
Measurement: Ki = 1.32 nM (pChEMBL 8.880000114440918)
Descriptors: MW 329.44, ALogP 3.07, HBA 3, HBD 2, PSA 77.12, QED 0.85
Compound (SMILES): COC(C)(C)C(=O)NC(=O)Nc1ccc(Oc2ccnc(-c3ccc(C)nc3)c2)c(C)n1
InChIKey: PCXFPRAKEYSDMS-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of VEGFR2 (unknown origin) measured by spectrophotometric analysis
Measurement: IC50 > 3300 nM (pChEMBL 5.480999946594238)
Descriptors: MW 435.48, ALogP 4.02, HBA 7, HBD 2, PSA 115.33, QED 0.6
Compound (SMILES): CN1C(=O)[C@@H](N2CCc3c(nn(Cc4ccccc4)c3C(N)=O)C2=O)COc2cc(Cl)ccc21
InChIKey: KIBQDIDFPAQGOU-SFHVURJKSA-N
Target: LIM domain kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P53671
Assay: Inhibition of PAK mediated recombinant LIMK2 phosphorylation (347 to 659 residues) (unknown origin) incubated for 45 mins followed by ATP addition measured after 180 mins by RapidFire Mass Spectrometry kinase assay
Measurement: IC50 = 7.943 nM (pChEMBL 8.100000381469727)
Descriptors: MW 479.92, ALogP 2.11, HBA 6, HBD 1, PSA 110.76, QED 0.62
Compound (SMILES): COc1cc2cnnc(N[C@H](C)c3cccc(C(F)(F)F)c3C)c2cc1OC
InChIKey: FZGCUSRTDSOYLS-GFCCVEGCSA-N
Target: Son of sevenless homolog 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07889
Assay: Inhibiting SOS1-Mediated GTP Nucleotide Exchange by Blocking Mant-GDP Exchange: Table 24: This Example illustrates that exemplary compounds of the present invention prevent KRas-mediated GTP nucleotide exchange mediated by SOS1 to inhibit KRas activity thereby inhibiting the generation of the downstream effector pERK. MKN1 cells (15,000/w) or H358 (30,000/w) were seeded in a black clear flat bottom 96-well cell culture plate (Corning, #3904) and incubated at 37° C. overnight. Assay day 1, cells were dosed with compounds of Formula (I) with a 10 μm starting concentration and serially diluted 3× for a total of 9 concentrations. The cells were incubated for approximately 0.5-1 hour with the compounds solubilized in DMSO at 37° C. Cells were immediately fixed by adding 50 μL of 4% formaldehyde to all wells in a fume hood and the plates were incubated for 20 minutes at room temperature. The formaldehyde was discarded from the plates and 150 μL of ice-cold methanol was added to permeabilize the cells for 10 minutes at −20° C. The methanol was discarded from each of the plates and any liquid remaining in the plate by tapping the plate against paper towels. Cells were then blocked with 150 μL of Odyssey blocking buffer (LI-COR Biosciences #927-50010) using 0.05% Tween for 1 hour at room temperature on a shaker. The blocking buffer was discarded and 50 μL of primary antibodies pERK (cell signaling Technology #9101L; Rabbit, 1:500) and GapDH (Millipore #MAB34; Mouse, 1:5000) diluted in Odyssey blocking buffer was added. The plates were incubated overnight at 4° C. on a shaker. On Assay Day 2, the primary antibody solution was removed. Each plate was washed 3× times with 150 μL of 1×PBST (PBS+0.1% Tween 20) and incubated with 50 μL of secondary antibodies: Anti-Rabbit (LI-COR Biosciences #926-32211) and Anti-Mouse (LI-COR Biosciences #68070) at 1:800 dilution in Odyssey blocking buffer with Tween at room temperature on a shaker for 2 hours (protected from light). The secondary antibody solution as removed and each plate was washed with PBST 3× times. Any liquid remaining was discarded and the plate was imaged using the Licor Odyssey machine according to the manufacturer's instruction, using a set focus length at 3 mm and both 800 nm and 700 nm filters. The GAPDH normalized scan values for each well were divided by the average of vehicle wells to get the % of pERK inhibition. The IC50 values were then calculated with the Graph pad Prism software.
Measurement: IC50 = 378 nM (pChEMBL 6.420000076293945)
Descriptors: MW 391.39, ALogP 5.15, HBA 5, HBD 1, PSA 56.27, QED 0.65
Compound (SMILES): CC(C)[C@H](NC(=O)OCc1ccccc1)C(=O)N[C@@H](CC(C)(C)C)C(=O)N[C@H](C=O)C[C@@H]1CCNC1=O
InChIKey: KAQZTNGABLBVAD-CMOCDZPBSA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Inhibition of His/SUMO tagged SARS-CoV2 main protease expressed in Escherichia coli BL21 (DE3) cells using Dabcyl-KTSAVLQSGFRKME-Edans as substrate preincubated for 60 mins followed by substrate addition and measured after 30 mins by fluorescence plate reader analysis
Measurement: IC50 = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 516.64, ALogP 2.07, HBA 6, HBD 4, PSA 142.7, QED 0.31
Compound (SMILES): NS(=O)(=O)c1cccc(NC(=O)c2cc(-c3cccc(Cl)c3)nc3ccc(Cl)cc23)c1
InChIKey: WULCZDMQCWOIQB-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human recombinant carbonic anhydrase 12 assessed as inhibition constant incubated for 10 mins by phenol red dye based stopped-flow CO2 hydration assay
Measurement: Ki = 527 nM (pChEMBL 6.28000020980835)
Descriptors: MW 472.35, ALogP 5.11, HBA 4, HBD 2, PSA 102.15, QED 0.43
Compound (SMILES): COC(=O)Nc1cc(-c2ccc(OC[C@@](C)(N)CC(C)C)c(OC(F)(F)F)c2)ccn1
InChIKey: HAPXQAGUUXSYBV-FQEVSTJZSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin) incubated for 10 mins in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 = 7800 nM (pChEMBL 5.110000133514404)
Descriptors: MW 441.45, ALogP 4.97, HBA 6, HBD 2, PSA 95.7, QED 0.6
Compound (SMILES): CC/C(=C(/c1ccc(/C=C/C(=O)O)cc1)c1[nH]c2ccccc2c1Cl)c1ccc(F)cc1Cl
InChIKey: HUQVRIJCSRWPQV-CCDJVQBGSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin)
Measurement: IC50 = 14300 nM (pChEMBL 4.840000152587891)
Descriptors: MW 480.37, ALogP 8.08, HBA 1, HBD 2, PSA 53.09, QED 0.22
Compound (SMILES): COc1cc(OCC(=O)Nc2cc(OC(F)(F)F)ccc2-n2cncn2)ccc1OC1COC1
InChIKey: KGZJVSVIUHWKQW-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14831
Assay: Negative allosteric modulation of mGlu7 (unknown origin) in cells expressing G protein-regulated inwardly rectifying potassium channels (GIRKs) assessed as inhibition of L-AP4-induced response measured by thallium flux assay
Measurement: IC50 = 812.83 nM (pChEMBL 6.090000152587891)
Descriptors: MW 480.4, ALogP 2.97, HBA 9, HBD 1, PSA 105.96, QED 0.5
Compound (SMILES): Fc1ccc2c(c1CNc1ncc(-c3cccnc3)c3nncn13)CCO2
InChIKey: GNJGTNXXYAEHGW-UHFFFAOYSA-N
Target: Polycomb protein EED (SINGLE PROTEIN), Homo sapiens
UniProt: O75530
Assay: ELISA (H3K27 Methylation) Assay: Representative compounds of the present disclosure were serially and separately diluted 3-fold in DMSO to obtain a total of eight or twelve concentrations. Then the compounds were added to G401 cell cultured in 384-well plate at 1:500 dilution to obtain the highest concentration of 20 μM. The cells were further cultured for 48 h before ELISA procedure.Histone extraction: Cells, in 384-well plate, were washed with PBS (10×PBS buffer (80 g NaCl (Sigma, S3014), 2 g KCl (Sigma, 60128), 14.4 g Na2HPO4 (Sigma, S5136), 2.4 g KH2PO4 (Sigma, P9791) to 1 L water, pH to 7.4) and lysed with the addition of lysis buffer (0.4N HCl; 45 μL per well). The plate was gently agitated at 4° C. for 30 min. The cell lysate was neutralized with neutralization buffer (0.5 M sodium phosphate dibasic, pH 12.5, 1 mM DTT; 36 μL per well). The plate was agitated to ensure the lysates were well mixed prior to the ELISA protocol.ELISA protocol: Cell lysates were transferred to the wells of a 384-well plate and the final volume was adjusted to 50 μL per well with PBS. The plate was sealed, centrifuged at 2,000 rpm for 2 min and incubated at 4′C for about 16 h. The plate was washed with TBST buffer (1×TBS (10×TBS: 24.2 g Tris (Sigma, T6066), 80 g NaCl (Sigma, S3014) to 1 L of water and adjust pH to 7.6 with HCl) with 0.1% Tween-20). Blocking buffer (TBST, 5% BSA; 50 μL per well) was added and the plate was incubated for 1 h at rt. The blocking buffer was removed and primary antibody was added (30 μL per well). The following dilutions were performed with blocking buffer: for anti-H3K27me3 antibody (Cell Signaling Technology, #9733), dilution was 1:1000; for anti-H3K27me2 antibody (Cell Signaling Technology, #9288), dilution was 1:100; for anti-H3 antibody (Abcam, Cat #24834), dilution was 1:1000. The primary antibody was incubated in the plate at rt for 1 h. The wells were washed with TBST and incubated with secondary antibody for 1 h at rt. For secondary antibodies, the following dilutions were carried out with blocking buffer: anti-rabbit antibody (Jackson ImmunoResearch, #111-035-003), dilution was 1:2000; and anti-mouse antibody (Cell signaling technology, #7076), dilution was 1:1000. After 1 h of incubation at rt, the wells were washed with TBST. ECL substrate (Pierce, #34080) was added at 30 μL per well and the plates were centrifuged at 2,000 rpm for 2 min. The signal was read using a PerkinElmer Envision Reader. The H3K27 methylation readouts were normalized using H3 signal and then percentage inhibition was calculated against the samples treated with DMSO. The data were then fit to a dose response curve using the program Helios to get the IC50 values of the test compound.
Measurement: IC50 = 9.7 nM (pChEMBL 8.010000228881836)
Descriptors: MW 362.37, ALogP 2.87, HBA 7, HBD 1, PSA 77.23, QED 0.6
Compound (SMILES): N#Cc1ccc(Nc2cnccc2SCc2ccccc2C(=O)[O-])c2ccccc12.[Na+]
InChIKey: VFQCYGPPRZHSKX-UHFFFAOYSA-M
Target: Solute carrier family 2, facilitated glucose transporter member 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NRM0
Assay: Inhibition of GLUT9 (unknown origin) expressed in HEK293T cells assessed as inhibition of uric acid-induced current by whole cell patch clamp technique
Measurement: IC50 = 9370 nM (pChEMBL 5.03000020980835)
Descriptors: MW 411.49, ALogP 5.84, HBA 5, HBD 2, PSA 86.01, QED 0.39
Compound (SMILES): O=C(NO)c1ccc2c(c1)CCN(S(=O)(=O)c1cc(F)c(F)c(F)c1F)C2
InChIKey: YGSMPRINJCSYQS-UHFFFAOYSA-N
Target: Histone deacetylase 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96DB2
Assay: Inhibition of full length human recombinant HDAC11 expressed in Sf9 baculovirus system using FAM-labeled acetylated peptide as substrate by measuring fluorescence intensity by EMSA method
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 404.34, ALogP 2.11, HBA 4, HBD 2, PSA 86.71, QED 0.27
Compound (SMILES): O=P(O)(O)OP(=O)(O)OP(=O)(O)OC[C@H]1O[C@@H](n2cnc3c(Nc4ccccc4)ncnc32)[C@H](O)[C@@H]1O
InChIKey: MXSCITZYHDRLLP-XNIJJKJLSA-N
Target: P2X2/P2X3 heterotrimeric receptor (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9UBL9
Assay: Agonist activity at human P2X2R/P2X3R 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: IC50 = 158.49 nM (pChEMBL 6.800000190734863)
Descriptors: MW 583.28, ALogP 0.53, HBA 14, HBD 7, PSA 265.14, QED 0.16
Compound (SMILES): CN[C@@H](C)C(=O)N[C@@H](CNC(=O)c1cc(S(=O)(=O)F)ccc1OC)C(=O)N1CCCC[C@H]1C(=O)N[C@@H]1CCc2ccccc21
InChIKey: UUJKVNYGEWQGHG-PVUOONDNSA-N
Target: Baculoviral IAP repeat-containing protein 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13489
Assay: Antagonist activity at N-terminal His-tagged cIAP2-BIR3 domain (unknown origin) expressed in Escherichia coli BL21 using AVPIAQKSEK-biotinylated peptide as substrate incubated for 2 hrs by DELFIA assay
Measurement: IC50 = 519 nM (pChEMBL 6.289999961853027)
Descriptors: MW 631.73, ALogP 1.36, HBA 8, HBD 4, PSA 163.01, QED 0.27
Compound (SMILES): CNC(=O)c1cncc(-c2cnn3cc(-c4cnn(C(C)C)c4)c(O[C@H]4CCOC4)nc23)c1
InChIKey: XKKGIGFZDVPVNO-SFHVURJKSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of recombinant human FGFR1 using biotin-EQEDEPEGDYFEWLE-amide as substrate preincubated for 5 to 10 mins followed by substrate addition and measured after 1 hr by HTRF assay
Measurement: IC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 447.5, ALogP 2.76, HBA 9, HBD 1, PSA 108.46, QED 0.48
Compound (SMILES): NS(=O)(=O)c1ccc(Nc2nc(N/N=C/c3ccccn3)nc(Nc3ccccc3)n2)cc1
InChIKey: YARRJWUINHALEQ-ZVHZXABRSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human CA 12 preincubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 70.5 nM (pChEMBL 7.150000095367432)
Descriptors: MW 461.51, ALogP 2.85, HBA 10, HBD 4, PSA 160.17, QED 0.23
Compound (SMILES): NS(=O)(=O)c1ccc(NCC/C(=N/CCO)c2ccccc2)cc1
InChIKey: SRRMPHRICLNCLF-JZJYNLBNSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human carbonic anhydrase 12 assessed as inhibition constant incubated for 15 mins prior to testing by phenol red based stopped-flow CO2 hydration assay
Measurement: Ki = 5.2 nM (pChEMBL 8.279999732971191)
Descriptors: MW 347.44, ALogP 1.62, HBA 5, HBD 3, PSA 104.78, QED 0.63
Compound (SMILES): Cl.Cl.Nc1nc(C(=O)NCc2ccccn2)cn2c1nc1ccccc12
InChIKey: WRWJZCORCAMKGM-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Displacement of [3H]HEMADO from human A3AR expressed in CHO-K1 cells membrane assessed as inhibition constant preincubated for 5 mins followed by [3H]HEMADO addition and measured after 1.5 hrs by TopCount scintillation counting method
Measurement: Ki = 1261.2 nM (pChEMBL 5.900000095367432)
Descriptors: MW 318.34, ALogP 1.79, HBA 6, HBD 2, PSA 98.2, QED 0.6
Compound (SMILES): C[C@H]1OC(=O)N(c2nc(-c3cnc(N)nc3C(F)(F)F)cc(N3CCOCC3)n2)[C@H]1CO
InChIKey: GFZKPRZGOZINHQ-SKDRFNHKSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition of PI3Kalpha (unknown origin) using L-alpha-phosphatidylinositol as substrate in presence of ATP by Kinase Glo luminescence assay
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 455.4, ALogP 1.08, HBA 10, HBD 2, PSA 139.82, QED 0.69
Compound (SMILES): CCC(=O)Nc1ccccc1Nc1n[nH]c2ccc(O[C@H](C)c3c(Cl)cncc3Cl)cc12
InChIKey: VISCPFTZJFACFT-CYBMUJFWSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of FGFR3 (unknown orgin) using Tyr 04 peptide as substrate incubated for 1 hr in presence of 75 uM ATP by FRET based Z'-LYTE assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 470.36, ALogP 6.5, HBA 5, HBD 3, PSA 91.93, QED 0.29
Compound (SMILES): Cc1cccc(C2NCCc3c2[nH]c2ccc(F)cc32)c1.Cl
InChIKey: NGNCWOWDNFZUSI-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Agonist activity at human 5HT2C receptor stably expressed in Flp-In-T-REx-293 cells assessed as increase in Gq-mediated calcium flux by Fluo-4 direct dye based FLIPR Tetra assay
Measurement: EC50 = 309.03 nM (pChEMBL 6.510000228881836)
Descriptors: MW 280.35, ALogP 3.85, HBA 1, HBD 2, PSA 27.82, QED 0.7
Compound (SMILES): Cc1nc(N[C@H](C)c2cc(N)cc(C(F)(F)F)c2)c2cc(O[C@H]3CCOC3)c(O)cc2n1
InChIKey: GLEBCUSYSCBWKF-BZNIZROVSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 in human liver microsomes at 10 uM using phenacetin as substrate preincubated for 10 mins followed by NADPH addition by LC/MS analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 448.45, ALogP 4.59, HBA 7, HBD 3, PSA 102.52, QED 0.49
Compound (SMILES): O[C@H](c1cc(Cl)cc2cncn12)C1CCCCC1
InChIKey: AVJCRIIDMDBAQC-AWEZNQCLSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 in human HeLa cells assessed as inhibition of kynurenine production incubated for 30 mins by microplate reader based analysis
Measurement: IC50 = 9.6 nM (pChEMBL 8.020000457763672)
Descriptors: MW 264.76, ALogP 3.6, HBA 3, HBD 1, PSA 37.53, QED 0.9
Compound (SMILES): NS(=O)(=O)c1ccc(NNCCC(=O)c2ccc3ccccc3c2)cc1
InChIKey: PUKIVUCMTLVWPO-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human carbonic anhydrase 12 assessed as inhibition constant incubated for 15 mins prior to testing by phenol red based stopped-flow CO2 hydration assay
Measurement: Ki = 7.5 nM (pChEMBL 8.119999885559082)
Descriptors: MW 369.45, ALogP 2.68, HBA 5, HBD 3, PSA 101.29, QED 0.34
Compound (SMILES): N#Cc1ccccc1CC(=O)N[C@@H](C[C@@H]1COc2c(Cl)cccc21)B(O)O
InChIKey: ANAHQGZCJNNCQJ-PBHICJAKSA-N
Target: Proteasome subunit beta type-8 (SINGLE PROTEIN), Homo sapiens
UniProt: P28062
Assay: Inhibition of 20S immunoproteasome beta-5i subunit in human PBMC using Ac-ANW-luciferin substrate preincubated for 2 hrs followed by substrate addition and measured after 30 mins by luminometric analysis
Measurement: IC50 = 51 nM (pChEMBL 7.289999961853027)
Descriptors: MW 384.63
Compound (SMILES): O=c1[nH]c2ccccc2nc1N/N=C/c1cccs1
InChIKey: GAXLWQSFFHWRJR-RIYZIHGNSA-N
Target: Phospholipase A2 group V (SINGLE PROTEIN), Homo sapiens
UniProt: P39877
Assay: Inhibition of human PLA2G5
Measurement: IC50 = 6280 nM (pChEMBL 5.199999809265137)
Descriptors: MW 270.32, ALogP 2.43, HBA 5, HBD 2, PSA 70.14, QED 0.57
Compound (SMILES): NC(=S)c1ccc(C(=O)N2CCN(Cc3ccccc3)CC2)cc1
InChIKey: LRWUYNOAVKINCT-UHFFFAOYSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P33533
Assay: Displacement of [3H]-(2-D-Ala)[Tyrosy1-3,5-]-DELTORPHIN II from Sprague-Dawley rat brain membrane delta opioid receptor incubated for 45 mins by liquid scintillation counting analysis
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 339.46, ALogP 2.28, HBA 3, HBD 1, PSA 49.57, QED 0.87
Compound (SMILES): CNC(=O)[C@@]12C[C@@H]1[C@@H](n1cnc3c(NCCc4ccccc4)nc(C#Cc4ccc(Cl)s4)nc31)[C@H](O)[C@@H]2O
InChIKey: KXUMVOXGLOSYAM-SASJIJFGSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Mus musculus
UniProt: Q61618
Assay: Displacement of [125I] N6-4-amino-3-iodobenzyl adenosine 5-N-methyluronamide from mouse A3A receptor stably expressed in HEK293 cell membrane by radioligand inhibition assay
Measurement: Ki = 1.91 nM (pChEMBL 8.720000267028809)
Descriptors: MW 549.06, ALogP 2.62, HBA 9, HBD 4, PSA 125.19, QED 0.27
Compound (SMILES): COc1cc([SeH])cc(OC)c1OC
InChIKey: AMSHOIFJKIQSFU-UHFFFAOYSA-N
Target: Carbonic anhydrase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Binding affinity to human CA7 assessed as inhibition constant by stopped-flow CO2 hydration assay
Measurement: Ki > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 247.15
Compound (SMILES): CC(C)c1cnc(N2CC(O)C2)c2cnc(Nc3ccnc(N4CC[C@@H](O)[C@@](C)(F)C4)n3)cc12
InChIKey: JREDDTPLOBGIFI-DVECYGJZSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of wild type EGFR in human A-431 cells preincubated for 4 to 5 hrs followed by EGF stimulation for 10 mins by AlphaLISA method
Measurement: IC50 = 25000 nM (pChEMBL 4.599999904632568)
Descriptors: MW 467.55, ALogP 2.77, HBA 9, HBD 3, PSA 110.53, QED 0.52
Compound (SMILES): CCNNC(=O)c1ccc(CN2c3ccccc3C=Cc3nc(C)nc(C)c32)cc1
InChIKey: ADHUUJWLMKPLLG-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of recombinant HDAC6 (unknown origin) using Boc-Lys(acetyl)-AMC as substrate preincubated for 1 hr followed by substrate addition and measured after 2 hrs by fluorescence based microplate reader analysis
Measurement: IC50 = 47 nM (pChEMBL 7.329999923706055)
Descriptors: MW 399.5, ALogP 4.17, HBA 5, HBD 2, PSA 70.15, QED 0.63
Compound (SMILES): Cc1cc(C(=O)C2=C(c3ccc(O)cc3)COc3cc(O)ccc32)ccc1OCCN1C=Cc2cccnc2C1
InChIKey: IWMRBSFBFQITCE-UHFFFAOYSA-N
Target: Progesterone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06401
Assay: Antagonist activity at progesterone receptor in human MCF7 cells
Measurement: IC50 > 100 nM (pChEMBL 7)
Descriptors: MW 532.6, ALogP 5.85, HBA 7, HBD 2, PSA 92.12, QED 0.29
Compound (SMILES): C[C@@H](C1CC1)N1Cc2cc(-c3ccn4nc(N)c(C(=O)N[C@@H](CO)C5CC5)c4n3)cc(OC(F)F)c2C1=O
InChIKey: SHTQVEFWTQUXFU-SGTLLEGYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition of PI3Kalpha (unknown origin) using PIP2 as substrate preincubated for 1 hr followed by substrate addition and measured after 60 mins in presence of ATP by ADP-glo assay
Measurement: IC50 = 1910 nM (pChEMBL 5.71999979019165)
Descriptors: MW 526.54, ALogP 2.83, HBA 8, HBD 3, PSA 135.08, QED 0.39
Compound (SMILES): NC1=N/C(=C\c2ccc3c(c2)OCO3)C(=O)N1
InChIKey: WKYMGORXOQPTTO-CLTKARDFSA-N
Target: Dual specificity protein kinase CLK2 (SINGLE PROTEIN), Mus musculus
UniProt: O35491
Assay: Inhibition of mouse recombinant GST-fused CLK2 expressed in Escherichia coli using GRSRSRSRSRSR peptide as substrate incubated for 30 mins in presence of ATP by scintillation counting method
Measurement: IC50 = 180 nM (pChEMBL 6.75)
Descriptors: MW 231.21, ALogP 0.2, HBA 5, HBD 2, PSA 85.94, QED 0.68
Compound (SMILES): N#Cc1ccc(-n2ccc(CC(=O)Nc3ccc(F)nc3)n2)cc1C(F)(F)F
InChIKey: TUMXUWXQSGSEJW-UHFFFAOYSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Antagonist activity at androgen receptor F877L/T877A dual mutant (unknown origin) expressed in PC-3 cells assessed as inhibition of transcriptional activity measured after 24 hrs by dual luciferase assay
Measurement: IC50 = 1120 nM (pChEMBL 5.949999809265137)
Descriptors: MW 389.31, ALogP 3.48, HBA 5, HBD 1, PSA 83.6, QED 0.55
Compound (SMILES): CCOCCN1CCN(CCC(=O)Nc2nc3c(C)cccc3s2)CC1
InChIKey: VJFHGIXPLWBJRF-UHFFFAOYSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q5U3Y7
Assay: Displacement of [3H]DTG from sigma 2 receptor in rat liver membranes measured after 120 mins by scintillation counting method
Measurement: Ki = 1600 nM (pChEMBL 5.800000190734863)
Descriptors: MW 376.53, ALogP 2.59, HBA 6, HBD 1, PSA 57.7, QED 0.72
Compound (SMILES): COc1cc(C(=O)c2csc(-c3ccc(OCc4ccc(C(=O)NO)cc4)cc3)n2)cc(OC)c1OC
InChIKey: UEAGAORBIBVWFW-UHFFFAOYSA-N
Target: Histone deacetylase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8WUI4
Assay: Inhibition of full length N-terminal GST-tagged human recombinant HDAC7 (501 to 952 residues) expressed in Baculovirus system using Ac-Leu-Gly-Lys (Ac)-AMC as substrate pretreated for 5 mins followed by substrate addition and measured after 30 mins
Measurement: IC50 = 40050 nM (pChEMBL 4.400000095367432)
Descriptors: MW 520.56, ALogP 4.76, HBA 9, HBD 2, PSA 116.21, QED 0.17
Compound (SMILES): NC(=O)c1cc2c(-c3ccc(C(=O)NCc4ccccc4O)s3)cccc2s1
InChIKey: BUMZHZANOYKXNE-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y463
Assay: Inhibition of NanoLuc-fused human DYRK1B expressed in HEK293T cells using Nano-Glo as substrate incubated for 2 hrs by NanoBRET assay
Measurement: IC50 = 3400 nM (pChEMBL 5.46999979019165)
Descriptors: MW 408.5, ALogP 4.36, HBA 5, HBD 3, PSA 92.42, QED 0.46
Compound (SMILES): CCS(=O)(=O)Nc1ccc(OCCNCC2COc3ccccc3O2)cc1.Cl
InChIKey: QYMWDYNNAYSCKX-UHFFFAOYSA-N
Target: Carbonic anhydrase 5A, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P35218
Assay: Inhibition of human recombinant CA5A assessed as inhibition constant pre-incubated for 15 mins measured by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 392.48, ALogP 2.26, HBA 6, HBD 2, PSA 85.89, QED 0.64
Compound (SMILES): CN1CCN(Cc2ccc(NC(=O)Nc3ccc(Oc4ccc5cccnc5c4)cc3)cc2C(F)(F)F)CC1
InChIKey: RVQLPYKLAJLXMV-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: In Vitro Biochemical Assay: The biochemical assays were carried out using the non-phosphorylated kinase domain of c-Abl, Bcr-Abl in Ba/F3 cells is in the phosphorylated state.
Measurement: Ki = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 535.57, ALogP 6.44, HBA 5, HBD 2, PSA 69.73, QED 0.3
Compound (SMILES): CC#CCOc1ccc2cc(C(c3ccc(C#N)cc3)n3cncn3)oc2c1
InChIKey: VCZRCOBTYSEEQW-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 in human liver microsomes using S-mephenytoin as substrate and measured by LC-MS/MS analysis
Measurement: IC50 = 2170 nM (pChEMBL 5.659999847412109)
Descriptors: MW 368.4, ALogP 3.94, HBA 6, HBD 0, PSA 76.87, QED 0.5
Compound (SMILES): Cc1nc(C)n(CC(=O)N2CCN(c3sc(C(F)(F)F)nc3-c3cnc(OC4CCC4)nc3)C[C@H]2C)n1
InChIKey: UYHRPCZNDBJPKM-CYBMUJFWSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of hERG expressed in CHO cells by Q patch-clamp method
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 536.58, ALogP 3.5, HBA 10, HBD 0, PSA 102.16, QED 0.47
Compound (SMILES): CCCCC#Cc1nc(N)c2nc(-c3cccs3)n([C@@H]3OC[C@@H](O)[C@H]3O)c2n1
InChIKey: MUHXGASCCALSAJ-PRIMNGNOSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Displacement of [3H] ZM241385 from wild type human A2AAR expressed in CHO cells assessed as dissociation constant incubated for 60 mins by radioligand binding assay
Measurement: Kd = 1.95 nM (pChEMBL 8.710000038146973)
Descriptors: MW 399.48, ALogP 1.93, HBA 9, HBD 3, PSA 119.31, QED 0.45
Compound (SMILES): Fc1ccc(OCC(F)F)c([C@H]2CCCN2c2ccn3ncc(-c4cn[nH]c4)c3n2)c1
InChIKey: BUDXUDKFJOVZTH-QGZVFWFLSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: Inhibition of TRKA G623R mutant (unknown origin) using TK-sub biotin peptide substrate preincubated for 30 mins followed by substrate addition and measured after 40 mins by FRET assay
Measurement: IC50 = 0.8 nM (pChEMBL 9.100000381469727)
Descriptors: MW 428.42, ALogP 4.24, HBA 6, HBD 1, PSA 71.34, QED 0.5
Compound (SMILES): Nc1sc(CCC(=O)NCCCCCCNc2ncnc3c2ncn3[C@@H]2O[C@H](CO)[C@@H](O)[C@H]2O)c(-c2cccc(C(F)(F)F)c2)c1C(=O)c1ccccc1
InChIKey: BDGRIBXDXGNZNA-OKEKRWOHSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Agonist activity at human A3 receptor expressed in Flp-In-CHO cells assessed as cAMP accumulation incubated for 30 mins in presence of forskolin by LANCE cAMP assay
Measurement: EC50 = 870.96 nM (pChEMBL 6.059999942779541)
Descriptors: MW 767.83, ALogP 4.72, HBA 13, HBD 6, PSA 197.74, QED 0.06
Compound (SMILES): Cc1cc(-c2ccn3nc(N)c(C(=O)N[C@H]4CCOC4)c3n2)cc2c1C(=O)N([C@@H](C)C1CC1)C2
InChIKey: RIBLFBUFUDRICQ-KSSFIOAISA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3Kdelta (unknown origin) using PIP2 as substrate preincubated for 1 hr followed by substrate addition and measured after 60 mins in presence of ATP by ADP-glo assay
Measurement: IC50 = 598 nM (pChEMBL 6.21999979019165)
Descriptors: MW 460.54, ALogP 2.56, HBA 7, HBD 2, PSA 114.85, QED 0.6
Compound (SMILES): CCCC[C@H](NC(C)=O)C(=O)N[C@H]1CSCc2cccc(c2)CSC[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccccc2)NC(=O)[C@H](Cc2c[nH]cn2)NC1=O
InChIKey: YBWGYSWBATYFBD-RQTVHLMQSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P32245
Assay: Displacement of [125I]NDP-alpha-MSH from human MC4R expressed in HEK293 cells by competitive binding assay
Measurement: IC50 = 9.1 nM (pChEMBL 8.039999961853027)
Descriptors: MW 1107.38
Compound (SMILES): O=C(Nc1nc2cccc(C3CCC4(CC3)CN(C(=O)C3(F)CC3)C4)n2n1)C1CC1
InChIKey: SQYLALYCIXZGJX-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of recombinant human TYK2 using GGMEDIYFEFMGGKKK as substrate incubated for 40 mins in presence of Mg/ATP mixture by [gamma p33]-ATP based scintillation counting method
Measurement: IC50 = 366 nM (pChEMBL 6.440000057220459)
Descriptors: MW 411.48, ALogP 3.07, HBA 5, HBD 1, PSA 79.6, QED 0.84
Compound (SMILES): CCNC(=O)[C@H]1O[C@@H](n2cnc3c(N[C@@H]4CCC[C@H]4Oc4cccc(Br)c4)ncnc32)[C@H](O)[C@@H]1O
InChIKey: LVIKZWXKFIGZQJ-SLHDEKGNSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Agonist activity at human adenosine A2B receptor expressed in CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation incubated for 30 mins by LANCE ultra assay
Measurement: EC50 = 4265.8 nM (pChEMBL 5.369999885559082)
Descriptors: MW 547.41, ALogP 1.76, HBA 10, HBD 4, PSA 143.65, QED 0.35
Compound (SMILES): Cc1cnc(Nc2ccc(F)c(C(F)(F)F)c2)nc1Nc1ccc2oc(=O)[nH]c2c1
InChIKey: HOEWEBRVZCXJLP-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin) in presence of NADPH
Measurement: IC50 = 700 nM (pChEMBL 6.159999847412109)
Descriptors: MW 419.34, ALogP 4.86, HBA 6, HBD 3, PSA 95.84, QED 0.41
Compound (SMILES): CCCCCCCCCCCCCCCC(=O)NCCCC[C@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCC(=O)O)NC(=O)COCCOCCNC(=O)c1ccc(-c2c3ccc(=O)cc-3oc3cc(O)ccc23)c(C(=O)O)c1)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CCC(=O)O)C(=O)NCCOCCOCC(=O)NCCCC[C@H](NC(=O)CNC(=O)[C@@H]1CSCC(=O)CSC[C@H](NC(=O)CN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](Cc2ccc(O)cc2)C(=O)N2CCC[C@H]2C(=O)N1)C(=O)NCC(N)=O
InChIKey: FYWPIBWNEIANCT-BZHUYTBPSA-N
Target: Kallikrein 1-related peptidase b5 (SINGLE PROTEIN), Mus musculus
UniProt: P15945
Assay: Inhibition of mouse KLK5 assessed as inhibition constant using Boc-VPR-AMC as fluorogenic substrate incubated for 30 mins by fluorescence plate reader assay
Measurement: Ki = 1.4 nM (pChEMBL 8.850000381469727)
Descriptors: MW 3080.44
Compound (SMILES): CCCc1cc(=O)[nH]c(SCC(=O)c2ccc3c(c2)CCCC(=O)N3)n1
InChIKey: WVRKQDZPZOUPNW-UHFFFAOYSA-N
Target: Aldo-keto reductase family 1 member C4 (SINGLE PROTEIN), Homo sapiens
UniProt: P17516
Assay: Inhibition of human recombinant AKR1C4 transfected in Escherichia coli BL21 (DE3) pLysS competent cells assessed as inhibition of NADP+ dependent oxidation of S-tetralol using S-tetralol as substrate incubated for 10 mins by fluorescence microplate reader assay
Measurement: IC50 = 360 nM (pChEMBL 6.440000057220459)
Descriptors: MW 371.46, ALogP 2.97, HBA 5, HBD 2, PSA 91.92, QED 0.46
Compound (SMILES): CC1(C)Oc2cc(C3(CCCCCC#N)CCC3)cc(O)c2[C@@H]2CC(=O)CC[C@H]21
InChIKey: VKMKNDIXGCZXCH-WOJBJXKFSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Agonist activity at human CB1 receptor expressed in CHO-K1 cells assessed as assessed as induction of beta-arrestin 2 recruitment measured for 90 mins by PathHunter assay
Measurement: EC50 = 7.5 nM (pChEMBL 8.119999885559082)
Descriptors: MW 395.54, ALogP 5.91, HBA 4, HBD 1, PSA 70.32, QED 0.61