methiothepin [Ligand Id: 89] activity data from GtoPdb and ChEMBL
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| ChEMBL ligand: CHEMBL93240 (Methiotepin, Methiothepin, Methiothepine, Metitepine, NSC-759875, RO 8-6837, RO-8-6837) |
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| DB | Assay description | Assay Type | Standard value | Standard parameter | Original value | Original units | Original parameter | Reference |
|---|---|---|---|---|---|---|---|---|
| D1 receptor/Dopamine D1 receptor in Rat (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL265] [GtoPdb: 214] [UniProtKB: P18901] | ||||||||
| ChEMBL | Half-maximal inhibition of [3H]-SCH- 23390 binding to Dopamine receptor D1 in rat striatal homogenate | B | 8.7 | pKi | 2 | nM | Ki | J Med Chem (2002) 45: 344-359 [PMID:11784139] |
| D2 receptor/Dopamine D2 receptor in Rat (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL339] [GtoPdb: 215] [UniProtKB: P61169] | ||||||||
| ChEMBL | Half-maximal inhibition of [3H]spiperone binding to Dopamine receptor D2 in rat striatal homogenate | B | 9.4 | pKi | 0.4 | nM | Ki | J Med Chem (2002) 45: 344-359 [PMID:11784139] |
| G protein-coupled receptor in Human cytomegalovirus (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL3559679] [UniProtKB: Q9IP65] | ||||||||
| ChEMBL | Allosteric modulatory activity at FLAG-tagged human cytomegalovirus US28 receptor delta300 mutant expressed in HEK293T cells by PathDetectElk1 assay | B | 6.48 | pEC50 | 331.13 | nM | EC50 | Bioorg Med Chem Lett (2014) 24: 3744-3747 [PMID:25052428] |
| ChEMBL | Allosteric modulatory activity at FLAG-tagged human cytomegalovirus US28 receptor delta300 mutant expressed in HEK293T cells by PathDetectElk1 assay | B | 6.48 | pEC50 | 330 | nM | EC50 | Bioorg Med Chem Lett (2014) 24: 3744-3747 [PMID:25052428] |
| Human herpesvirus 5 chemokine receptor in Human cytomegalovirus (strain AD169) (HHV-5) (Human herpesvirus 5) (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL4259] [UniProtKB: P69332] | ||||||||
| ChEMBL | Allosteric modulatory activity at FLAG-tagged wild type human cytomegalovirus US28 receptor expressed in HEK293T cells by PathDetectElk1 assay | B | 6.45 | pEC50 | 354.81 | nM | EC50 | Bioorg Med Chem Lett (2014) 24: 3744-3747 [PMID:25052428] |
| ChEMBL | Allosteric modulatory activity at FLAG-tagged wild type human cytomegalovirus US28 receptor expressed in HEK293T cells by PathDetectElk1 assay | B | 6.46 | pEC50 | 350 | nM | EC50 | Bioorg Med Chem Lett (2014) 24: 3744-3747 [PMID:25052428] |
| 5-HT1A receptor/Serotonin 1a (5-HT1a) receptor in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL214] [GtoPdb: 1] [UniProtKB: P08908] | ||||||||
| ChEMBL | Binding affinity to 5-HT1 (unknown origin) | B | 6.2 | pKi | 630.96 | nM | Ki | J Nat Prod (2021) 84: 713-723 [PMID:32870011] |
| GtoPdb | - | - | 8.1 | pKi | - | - | - |
Eur J Pharmacol (1998) 355: 245-56 [PMID:9760039]; Naunyn Schmiedebergs Arch Pharmacol (1998) 357: 205-17 [PMID:9550290] |
| ChEMBL | Displacement of [3H]8-OH-DPAT from human 5-HT1A receptor expressed in CHO-K1 cell membranes incubated for 60 mins by microbeta scintillation counting method | B | 8.32 | pKi | 4.8 | nM | Ki | Eur J Med Chem (2019) 180: 383-397 [PMID:31325785] |
| ChEMBL | Displacement of [3H]8-OH-DPAT from human recombinant 5-HT1A receptor expressed in membranes after 60 mins by microbeta scintillation counting method | B | 8.34 | pKi | 4.6 | nM | Ki | Bioorg Med Chem Lett (2016) 26: 5315-5321 [PMID:27692547] |
| ChEMBL | Displacement of [3H]8-OH-DPAT from recombinant human 5-HT1A receptor expressed in HEK293 cell membranes after 60 mins by liquid scintillation counting method | B | 8.4 | pKi | 4 | nM | Ki | Bioorg Med Chem Lett (2018) 28: 2039-2049 [PMID:29730027] |
| ChEMBL | Ability to displace [3H]5-CT (2.0 nM) from HeLa cells of human 5-hydroxytryptamine 1A receptor | B | 8.66 | pKi | 2.2 | nM | Ki | J Med Chem (2003) 46: 265-283 [PMID:12519065] |
| 5-HT2A receptor/Serotonin 2a (5-HT2a) receptor in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL224] [GtoPdb: 6] [UniProtKB: P28223] | ||||||||
| GtoPdb | - | - | 8.5 | pKi | - | - | - | Naunyn Schmiedebergs Arch Pharmacol (2004) 370: 114-23 [PMID:15322733] |
| ChEMBL | Displacement of [3H]-ketanserin from human human 5-HT2A receptor transfected in CHO-K1 cells measured after 60 mins by scintillation counting method | B | 8.7 | pKi | 2 | nM | Ki | J Med Chem (2021) 64: 12603-12629 [PMID:34436892] |
| 5-HT2A receptor/Serotonin 2a (5-HT2a) receptor in Rat (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL322] [GtoPdb: 6] [UniProtKB: P14842] | ||||||||
| ChEMBL | Half-maximal inhibition of [3H]- Ketanserin binding to 5-hydroxytryptamine 2A receptor in rat cerebral cortex homogenate | B | 9.4 | pKi | 0.4 | nM | Ki | J Med Chem (2002) 45: 344-359 [PMID:11784139] |
| 5-HT2C receptor/Serotonin 2c (5-HT2c) receptor in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL225] [GtoPdb: 8] [UniProtKB: P28335] | ||||||||
| GtoPdb | - | - | 8.4 | pKi | - | - | - | Naunyn Schmiedebergs Arch Pharmacol (2004) 370: 114-23 [PMID:15322733] |
| ChEMBL | Antagonist activity at serotonin-activated human recombinant 5HT-2C receptor expressed in HEK293 cells assessed as decrease in intracellular calcium level after 5 mins measured for 1 min by fluorescence assay | F | 9.42 | pEC50 | 0.38 | nM | EC50 | Eur J Med Chem (2013) 63: 558-569 [PMID:23537943] |
| 5-HT5A receptor/Serotonin 5a (5-HT5a) receptor in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL3426] [GtoPdb: 10] [UniProtKB: P47898] | ||||||||
| ChEMBL | Binding affinity for rodent 5-hydroxytryptamine 5A receptor | B | 7 | pKi | 100 | nM | Ki | J Med Chem (2003) 46: 2795-2812 [PMID:12825922] |
| ChEMBL | Binding affinity to 5-HT5A (unknown origin) | B | 7.5 | pKi | 31.62 | nM | Ki | J Nat Prod (2021) 84: 713-723 [PMID:32870011] |
| GtoPdb | - | - | 8.9 | pKi | - | - | - |
FEBS Lett (1994) 355: 242-6 [PMID:7988681]; Eur J Pharmacol (2001) 418: 157-67 [PMID:11343685] |
| ChEMBL | Binding affinity towards human 5-hydroxytryptamine 5A receptor | B | 9 | pKi | 1 | nM | Ki | J Med Chem (2003) 46: 2795-2812 [PMID:12825922] |
| ChEMBL | Binding affinity towards human 5-hydroxytryptamine 5A receptor was evaluated using [3H]-5-CT as radioligand | B | 9 | pKi | 1 | nM | Ki | J Med Chem (2003) 46: 2795-2812 [PMID:12825922] |
| 5-HT5A receptor in Mouse [GtoPdb: 10] [UniProtKB: P30966] | ||||||||
| GtoPdb | - | - | 7 | pKi | - | - | - |
Mol Pharmacol (1993) 43: 313-9 [PMID:8450829]; Eur J Pharmacol (2001) 418: 157-67 [PMID:11343685] |
| 5-HT5A receptor in Rat [GtoPdb: 10] [UniProtKB: P35364] | ||||||||
| GtoPdb | - | - | 7.5 | pKi | - | - | - | Proc Natl Acad Sci USA (1993) 90: 3452-6 [PMID:7682702] |
| 5-HT6 receptor/Serotonin 6 (5-HT6) receptor in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL3371] [GtoPdb: 11] [UniProtKB: P50406] | ||||||||
| ChEMBL | Displacement of [3H]LSDm from human recombinant 5-HT6 receptor expressed in HEK293 cell membrane after 60 mins by liquid scintillation counting analysis | B | 8.39 | pKi | 4.1 | nM | Ki | J Med Chem (2014) 57: 4543-4557 [PMID:24805037] |
| ChEMBL | Displacement of [3H]LSD from human recombinant 5-HT6 receptor expressed in HEK-293 cells incubated for 60 mins by scintillation counting method | B | 8.39 | pKi | 4.1 | nM | Ki | Eur J Med Chem (2015) 92: 221-235 [PMID:25557493] |
| ChEMBL | Displacement of [3H]-LSD from human 5-HT6 receptor expressed in HEK cell membrane incubated for 60 mins by microplate beta scintillation counting analysis | B | 8.89 | pKi | 1.3 | nM | Ki | Bioorg Med Chem (2023) 84: 117256-117256 [PMID:37003157] |
| ChEMBL | Displacement of [3H]-LSD from human 5-HT6 receptor expressed in CHO-K1 cell membranes after 60 mins by scintillation counting | B | 9 | pKi | 1 | nM | Ki | J Med Chem (2017) 60: 7483-7501 [PMID:28763213] |
| ChEMBL | Displacement of [3H]-LSD from recombinant human 5HT6 receptor expressed in CHOK1 cell membranes measured after 1 hr by microbeta counting method | B | 9.01 | pKi | 0.98 | nM | Ki | Eur J Med Chem (2020) 191: 112149-112149 [PMID:32105980] |
| ChEMBL | Displacement of [3H]-LSD from human 5-HT6 receptor transfected in CHO-K1 cells measured after 60 mins by scintillation counting method | B | 9.03 | pKi | 0.93 | nM | Ki | J Med Chem (2021) 64: 12603-12629 [PMID:34436892] |
| ChEMBL | Displacement of [3H]LSD from recombinant human 5-HT6 receptor expressed in CHO cells cell membranes after 60 mins by liquid scintillation counting method | B | 9.05 | pKi | 0.9 | nM | Ki | Bioorg Med Chem Lett (2018) 28: 2039-2049 [PMID:29730027] |
| ChEMBL | Binding affinity towards human 5-hydroxytryptamine 6 receptor was evaluated using [3H]-LSD as radioligand | B | 9.4 | pKi | 0.4 | nM | Ki | J Med Chem (2003) 46: 2795-2812 [PMID:12825922] |
| GtoPdb | - | - | 9.4 | pKi | - | - | - |
J Neurochem (1996) 66: 47-56 [PMID:8522988]; Mol Pharmacol (1998) 54: 577-583 [PMID:9730917]; Mol Pharmacol (1997) 52: 515-523 [PMID:9284367] |
| ChEMBL | Displacement of [3H]LSD from human 5HT6 receptor expressed in CHO-K1 membrane incubated for 60 mins by solid scintillation counting analysis | B | 9.52 | pKi | 0.3 | nM | Ki | Eur J Med Chem (2021) 225: 113792-113792 [PMID:34530376] |
| ChEMBL | Displacement of [3H]-LSD from human 5HT6R expressed in CHO-K1 cell membranes incubated for 1 hr by scintillation counter method | B | 9.52 | pKi | 0.3 | nM | Ki | Eur J Med Chem (2021) 225: 113783-113783 [PMID:34461507] |
| ChEMBL | Antagonist activity at human cloned 5HT6 receptor expressed in HeLa cells assessed as inhibition of 5-HT-stimulated cAMP accumulation after 20 mins by enzyme-immunoassay | F | 6.9 | pIC50 | 127 | nM | IC50 | Bioorg Med Chem Lett (2008) 18: 738-743 [PMID:18053713] |
| ChEMBL | Antagonist activity at human recombinant 5-HT6 receptor assessed as inhibition of serotonin-induced cAMP accumulation | F | 7.96 | pIC50 | 11 | nM | IC50 | J Med Chem (2014) 57: 4543-4557 [PMID:24805037] |
| ChEMBL | Antagonist activity against human recombinant 5-HT6 receptor expressed in CHOK1 cells assessed as reduction in serotonin-induced increase in intracellular Ca2+ levels by aequorin based radiometric and luminescence plate counting method | F | 8.33 | pIC50 | 4.7 | nM | IC50 | Eur J Med Chem (2015) 92: 221-235 [PMID:25557493] |
| ChEMBL | Agonist activity at human 5-HT6 receptor expressed in CHOK1 cells assessed as calcium mobilization by radiometric and luminescence plate counting method | F | 8.33 | pIC50 | 4.7 | nM | IC50 | Eur J Med Chem (2015) 92: 221-235 [PMID:25557493] |
| ChEMBL | Displacement of [3H]LSD from human 5HT6 receptor by scintillation counting | B | 8.62 | pIC50 | 2.4 | nM | IC50 | J Med Chem (2010) 53: 2521-2527 [PMID:20170099] |
| 5-HT6 receptor/Serotonin 6 (5-HT6) receptor in Rat (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL3372] [GtoPdb: 11] [UniProtKB: P31388] | ||||||||
| ChEMBL | Displacement of [3H]-LSD from recombinant rat 5-Ht6 receptor expressed in HEK293 cells after 120 mins by liquid scintillation counting | B | 7 | pKi | 100 | nM | Ki | Bioorg Med Chem Lett (2016) 26: 2333-2338 [PMID:26996373] |
| ChEMBL | Displacement of [3H]-5HT from recombinant rat 5-Ht6 receptor expressed in HEK293 cells after 120 mins by liquid scintillation counting | B | 7 | pKi | 100 | nM | Ki | Bioorg Med Chem Lett (2016) 26: 2333-2338 [PMID:26996373] |
| ChEMBL | Displacement of [3H]-LSD from rat 5-Ht6 receptor expressed in HEK cells after 60 mins by liquid scintillation counting | B | 8.42 | pKi | 3.8 | nM | Ki | Bioorg Med Chem Lett (2016) 26: 2333-2338 [PMID:26996373] |
| GtoPdb | - | - | 9.4 | pKi | - | - | - |
Mol Pharmacol (1993) 43: 320-7 [PMID:7680751]; Neuropharmacology (1997) 36: 713-20 [PMID:9225298]; J Neurochem (1998) 71: 2169-77 [PMID:9798944]; Mol Pharmacol (1998) 54: 577-583 [PMID:9730917] |
| 5-HT7 receptor/Serotonin 7 (5-HT7) receptor in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL3155] [GtoPdb: 12] [UniProtKB: P34969] | ||||||||
| ChEMBL | Displacement of [3H]5-HT from recombinant human 5-HT7 receptor expressed in African green monkey COS7 cells | B | 8.4 | pKi | 3.98 | nM | Ki | Eur J Med Chem (2019) 183: 111705-111705 [PMID:31581003] |
| ChEMBL | Displacement of [3H]5-HT from human 5-hydroxytryptamine 7 receptor | B | 8.43 | pKi | 3.7 | nM | Ki | J Med Chem (2003) 46: 2795-2812 [PMID:12825922] |
| ChEMBL | Displacement of [3H]-LSD from human recombinant 5-HT7 receptor expressed in CHO cells incubated for 60 mins by microbeta2 scintillation counter | B | 8.66 | pKi | 2.2 | nM | Ki | Bioorg Med Chem (2019) 27: 4163-4173 [PMID:31383628] |
| ChEMBL | Displacement of [3H]LSD from recombinant human 5-HT7 receptor expressed in CHO cells cell membranes after 60 mins by liquid scintillation counting method | B | 8.77 | pKi | 1.7 | nM | Ki | Bioorg Med Chem Lett (2018) 28: 2039-2049 [PMID:29730027] |
| ChEMBL | Displacement of [3H]SB269970 from human 5-HT7 receptor expressed in HEK cell membrane incubated for 60 mins by microplate beta scintillation counting analysis | B | 8.77 | pKi | 1.7 | nM | Ki | Bioorg Med Chem (2023) 84: 117256-117256 [PMID:37003157] |
| ChEMBL | Displacement of [3H]-LSD from human 5-HT7 receptor expressed in CHO-K1 cell membranes after 120 mins by scintillation counting | B | 9 | pKi | 1 | nM | Ki | J Med Chem (2017) 60: 7483-7501 [PMID:28763213] |
| ChEMBL | Displacement of [3H]LSD from human recombinant 5-HT7 receptor expressed in CHO-K1 cell membrane after 120 mins by liquid scintillation counting analysis | B | 9.05 | pKi | 0.9 | nM | Ki | J Med Chem (2014) 57: 4543-4557 [PMID:24805037] |
| ChEMBL | Displacement of [3H]-LSD from human 5-HT7 receptor transfected in CHO-K1 cells measured after 120 mins by scintillation counting method | B | 9.25 | pKi | 0.56 | nM | Ki | J Med Chem (2021) 64: 12603-12629 [PMID:34436892] |
| ChEMBL | Displacement of [3H]-LSD from recombinant human 5HT7 receptor expressed in CHOK1 cell membranes measured after 120 mins by microbeta counting method | B | 9.26 | pKi | 0.55 | nM | Ki | Eur J Med Chem (2020) 191: 112149-112149 [PMID:32105980] |
| GtoPdb | - | - | 9.4 | pKi | - | - | - |
Naunyn Schmiedebergs Arch Pharmacol (2001) 363: 620-32 [PMID:11414657]; Br J Pharmacol (1997) 122: 126-32 [PMID:9298538]; J Biol Chem (1993) 268: 23422-6 [PMID:8226867]; Br J Pharmacol (1998) 124: 1300-6 [PMID:9720804] |
| ChEMBL | Antagonist activity at human 5-HT7 receptor expressed in HEK293 cells assessed as inhibition of 5-CT-induced cAMP production preincubated for 15 mins followed by 5-CT addition measured after 15 mins by HTRF assay | F | 7.68 | pIC50 | 21 | nM | IC50 | Eur J Med Chem (2016) 112: 258-269 [PMID:26900658] |
| ChEMBL | Antagonist activity at human 5HT7 receptor expressed in CHO-K1 cells assessed as inhibition of 5CT-induced calcium flux incubated for 60 mins at 37 degC followed by 15 mins incubation at room temperature and subsequent 5CT addition by calcium 4 dye based FLIPR assay | F | 7.95 | pIC50 | 11.3 | nM | IC50 | Eur J Med Chem (2020) 207: 112709-112709 [PMID:32877805] |
| ChEMBL | Displacement of [3H]LSD from human recombinant 5HT7 receptor | B | 8.51 | pIC50 | 3.1 | nM | IC50 | Bioorg Med Chem (2008) 16: 2570-2578 [PMID:18083580] |
| ChEMBL | Antagonist activity at human recombinant 5-HT7 receptor assessed as inhibition of serotonin-induced cAMP accumulation | F | 8.82 | pIC50 | 1.5 | nM | IC50 | J Med Chem (2014) 57: 4543-4557 [PMID:24805037] |
| ChEMBL | Antagonist activity at 5HT7R receptor (unknown origin) assessed as forskolin-mediated cAMP accumulation preincubated for 30 mins followed by forskolin addition and measured after 30 mins by TR-FRET analysis | F | 9.09 | pIC50 | 0.82 | nM | IC50 | Bioorg Med Chem Lett (2019) 29: 126703-126703 [PMID:31627993] |
| ChEMBL | Displacement of [3H]lysergic acid from human recombinant 5HT7 receptor expressed in CHO cells | B | 9.22 | pEC50 | 0.6 | nM | EC50 | J Nat Prod (2006) 69: 432-435 [PMID:16562853] |
| 5-HT7 receptor in Mouse [GtoPdb: 12] [UniProtKB: P32304] | ||||||||
| GtoPdb | - | - | 8.2 | pKi | - | - | - | Mol Pharmacol (1993) 44: 229-36 [PMID:8394987] |
| 5-HT7 receptor/Serotonin 7 (5-HT7) receptor in Rat (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL3223] [GtoPdb: 12] [UniProtKB: P32305] | ||||||||
| ChEMBL | Binding affinity towards rat 5-hydroxytryptamine 7 receptor | B | 8.4 | pKi | 4 | nM | Ki | J Med Chem (2003) 46: 2795-2812 [PMID:12825922] |
| GtoPdb | - | - | 9.4 | pKi | - | - | - | J Biol Chem (1993) 268: 18200-4 [PMID:8394362] |
| 5-HT1B receptor in Human [GtoPdb: 2] [UniProtKB: P28222] | ||||||||
| GtoPdb | - | - | 8.5 | pKi | - | - | - |
J Neurochem (1996) 67: 2096-103 [PMID:8863519]; Eur J Pharmacol (1999) 380: 171-81 [PMID:10513577]; Mol Pharmacol (2000) 58: 1042-9 [PMID:11040052]; Eur J Pharmacol (1996) 314: 365-72 [PMID:8957260] |
| 5-HT1D receptor in Human [GtoPdb: 3] [UniProtKB: P28221] | ||||||||
| GtoPdb | - | - | 8.2 | pKi | - | - | - |
Eur J Pharmacol (1996) 314: 365-72 [PMID:8957260]; Naunyn Schmiedebergs Arch Pharmacol (1997) 356: 328-34 [PMID:9303569]; Mol Pharmacol (1996) 50: 1567-80 [PMID:8967979]; Mol Pharmacol (1991) 40: 143-8 [PMID:1652050] |
| 5-ht1e receptor in Human [GtoPdb: 4] [UniProtKB: P28566] | ||||||||
| GtoPdb | - | - | 7 | pKi | - | - | - |
J Neurochem (1996) 67: 2096-103 [PMID:8863519]; Proc Natl Acad Sci USA (1992) 89: 5517-21 [PMID:1608964]; Proc Natl Acad Sci USA (1993) 90: 408-12 [PMID:8380639]; Eur J Pharmacol (2004) 484: 127-39 [PMID:14744596] |
| 5-HT1F receptor in Human [GtoPdb: 5] [UniProtKB: P30939] | ||||||||
| GtoPdb | - | - | 6.2 | pKi | - | - | - |
Proc Natl Acad Sci USA (1993) 90: 408-12 [PMID:8380639]; Neuropharmacology (1997) 36: 569-76 [PMID:9225282] |
| 5-HT2B receptor in Human [GtoPdb: 7] [UniProtKB: P41595] | ||||||||
| GtoPdb | - | - | 9.2 | pKi | - | - | - |
Naunyn Schmiedebergs Arch Pharmacol (2004) 370: 114-23 [PMID:15322733]; Naunyn Schmiedebergs Arch Pharmacol (1998) 357: 17-24 [PMID:9459568] |
ChEMBL data shown on this page come from version 34:
Zdrazil B, Felix E, Hunter F, Manners EJ, Blackshaw J, Corbett S, de Veij M, Ioannidis H, Lopez DM, Mosquera JF, Magarinos MP, Bosc N, Arcila R, Kizilören T, Gaulton A, Bento AP, Adasme MF, Monecke P, Landrum GA, Leach AR. (2024). The ChEMBL Database in 2023: a drug discovery platform spanning multiple bioactivity data types and time periods. Nucleic Acids Res., 52(D1). DOI: 10.1093/nar/gkad1004. [EPMCID:10767899] [PMID:37933841]
Davies M, Nowotka M, Papadatos G, Dedman N, Gaulton A, Atkinson F, Bellis L, Overington JP. (2015) 'ChEMBL web services: streamlining access to drug discovery data and utilities.' Nucleic Acids Res., 43(W1). DOI: 10.1093/nar/gkv352. [EPMCID:25883136]
