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Compound Filters for Drug Design

Aggregators filterDescription: Identifies propensity for aggregation by comparingtanimoto simmilarity coefficent and logP of chosen compounds toa database of known aggregators.Reference:Irwin et. al., 2015, J. Med. Chem REOS filter Description: Functional group filters for the removal of problematic structuresdubbed REOS (rapid elimination of swill; program developed atVertex). Reactive, toxic and other undesirable moieties such asnitro groups, preoxides, triflates, aldehydes, acetals, etc.functional group filter - MAINReference: based on Walters & Murcko, 2002, Adv. Drug Deliv. Rev. Read in desired SDF file Write filtered database PAINS filterDescription: Substructure Filter for Removal of Pan AssayInterference Compounds (PAINS) from Screening Libraries and forTheir Exclusion in Bioassays. Reference: Baell & Holloway, 2010, J. Med. Chem. Read in desired SDF file Write filtered database Write filtered database Read in desired SDF file Lipinski (Rule-of-5) filterDescription: A set of rules to identifiy drug-like compounds. Onerule break is allowd. Rules:-Molecular Weight ≤ 500 Da-logP ≤ 5-H-bond donor ≤ 5-H-bond acceptor ≤ 10Reference: Lipinski et. al., 2001, Adv. Drug Deliv. Rev. Read in desired SDF file Write filtered database Read in desired SDF file Rule-of-3 filterDescription: Rules designed to support “fragment-based” drugresearch. Hits obtained using this filter can be useful for fragmentlibraries used to generate potential leads. Rules:-Molecular Weight ≤ 300 Da-logP ≤ 3-H-bond donor ≤ 3-H-bond acceptor ≤ 3Reference:Congreve et. al.,2003, Drug Discov. Today Write filtered database Read in desired SDF file Rule-of-4 filterDescription: A set of rules for identifying protein-protein interactioninhibitors. With this filter molecules need to exceed the values.Rules:-Molecular Weight ≥ 400 Da-logP ≥ 4-Number of rings ≥ 4-H-bond acceptor ≥ 4Reference: Morelli et. al., 2011, Curr. Opin. Chem. Biol. Write filtered database Veber filterDescription: Two rules that compounds must adhere to foroptimized oral bioavailability.Rules:-Polar Surface Area ≤ 140 Å^2-Rotatable bonds ≤ 10Reference: Veber et. al., 2002, J. Med. Chem. Read in desired SDF file Write filtered database Mozziconacci filterDescription: Rule based filter for drug-like molecules.Rules:- Number of Halogen atoms ≤ 7- Number of Nitrogens ≥ 1- Number of oxygen ≥ 1- Number of rings ≤ 6- Rotatable bonds ≤15Reference: Mozziconacci et. al. Read in desired SDF file Write filtered database Read in desired SDF file Write filtered database Egan filterDescription: Rule based filter for Bioavailability Rules:- LogP ≤ 5.88- Total Polar Surface Ares ≤ 131.6 Å^2Reference: Egan et. al., 2000, J. Med. Chem. Read in desired SDF file Van de Waterbeemd filterDescription: Rule based filter for blood brain permeability andactivity within the central nervous system. Rules:- Molecular Weight ≤ 450- Total Polar Surface Ares ≤ 90 Å^2Reference: Van de Waterbeemd et. al., 1998, J. Drug Targ. Write filtered database Read in desired SDF file Murcko filter Description: Rule based filter for finding compounds with centralnervous system activity. Rules:- 200 ≤ Molecular weight ≤ 400- logP ≤ 5.2- H bond acceptor ≤ 4- H bond donor ≤ 3- Number of rotatable bonds ≤ 7Reference: Ajay et. al., 1999, J. Med. Chem Write filtered database Alternative filter configurations Tools REOS physiochemical propery filter Rules:- Hbond donor ≤ 5,- H-bond acceptors ≤ 10, - -2 ≤ formal charge ≤ +2,- Number of rotatable bonds ≤ 8,- 200 ≤ Molecular weight ≤ 500- 20 ≤ number of heavy atoms ≤ 50, - -2 ≤ logP ≤ 5Reference: based on Walters & Murcko, 2002, Adv. Drug Deliv. Rev. ,Huggins et. al , 2011, ACS Chem. Biol. Read in desired SDF fileIDEALLY for REOS property filter - Yourmolecules should be ionised beforehand Write filtered database Write compounds failing Write compounds failing Write compounds failing Write compounds failing Write compounds failing Write compounds failing Write compounds failing Write compounds failing Write compounds failing Write compounds failing Write compounds failing Write compounds failing Additional filters, they need proprietary knime nodes, in implementation Write filtered database Write compounds failing Read in desired SDF file Oprea filter (not finished)Description: Rule A set of rules based on the lead-like vs drug-likecom-parison.Rules: Molecular Weight < 450 -3.5 ≤ logP < 4.5 -4 ≤ logD ≤ 4 number of rings ≤ 4 non-terminal single bonds ≤ 10, H-bond donor ≤ 5, H-bond acceptor ≤ 8Reference: Oprea et. al., 1999, J. Che. Inf. Comput. Sci. Fichert filter Description: Rules for structure-permeability based on a set of 41small drug-like molecules. LogD is the main property thatdetermines permeability, with structures passing this filter beinghighly permeable in the Cacao-2 model.Rules: Molecular weight ≤ 5000 ≤ logD ≤ 3Reference: Fichert et. al., 2003, Med. Chem. Lett. Write compounds failing Read in desired SDF file Write filtered database Write compounds failing Read in desired SDF file Write filtered database Ghose filter A set of rules for drug-likeness derived from characterizing 6304compounds taken from the Comprehensive Medicinal ChemistryDatabase.Rules: 180 ≤ Molecular Weight ≤ 480 , 40 ≤ Molecular refrac-tivity ≤ 130, -0.4 ≤ logP ≤ 5.6 , 20 ≤ number of atoms ≤70Reference: Ghose et. al., 1999, J. Comb. Chem. COMPOUND FILTERS FORDRUG DESIGN Authors: Sebastjan Kralj &Marko JukičPlease cite: https://www.mdpi.com/1422-0067/23/10/5727 The filters can be started and tested usingthis ZINC test sample set Node 946Node 951Node 953Node 975Node 977Node 978Node 981Node 983Node 985Node 988Node 991Node 995Node 999Node 1096Node 1100Node 1105Node 1116Node 1117Node 1125Node 1126Node 1127Node 1131Node 1134Node 1140Node 1146Node 1148Node 1155Node 1159Node 1162Node 1164Node 1165Node 1169Node 1170Node 1172Node 1175Node 1176Node 1178Node 1180Node 1181Node 1186Node 1187Node 1189Node 1190Node 1197Node 1199Node 1201Node 1204Node 1207Node 1213ZINC databse testsetNode 1215Node 1216Node 1217Node 1218Node 1219Node 1220Node 1221Node 1222Node 1223Node 1224Node 1225Node 1226Node 1227Node 1228Node 1230Node 1231 Aggregators_sorter REOS filter (based on theSchrödinger REOS node) SDF Writer SDF Writer SDF Writer SDF Writer SDF Writer SDF Writer SDF Writer SDF Writer SDF Writer SDF Writer SDF Writer Remove rows withmissing SMILES SDF Writer SDF Writer SDF Writer SDF Writer REOS physiochemicalproperty filter REOS functionalgroup filter PAINS filter SDF Writer Low simmilarity Medium simmilarity High simmilarity SDF Writer Lipinski filter SDF Writer Rule-of-3 SDF Writer Rule-of-4 SDF Writer Veber filter SDF Writer Mozziconacci SDF Writer Egan SDF Writer Van deWaterbeemd filer SDF Writer Murcko filter SDF Writer SDF Writer Oprea filter SDF Writer SDF Writer Fichert filter SDF Writer Ghose filter SDF Reader SDF Reader SDF Reader SDF Reader SDF Reader SDF Reader SDF Reader SDF Reader SDF Reader SDF Reader SDF Reader SDF Reader SDF Reader SDF Reader SDF Reader SDF Writer SDF Reader Aggregators filterDescription: Identifies propensity for aggregation by comparingtanimoto simmilarity coefficent and logP of chosen compounds toa database of known aggregators.Reference:Irwin et. al., 2015, J. Med. Chem REOS filter Description: Functional group filters for the removal of problematic structuresdubbed REOS (rapid elimination of swill; program developed atVertex). Reactive, toxic and other undesirable moieties such asnitro groups, preoxides, triflates, aldehydes, acetals, etc.functional group filter - MAINReference: based on Walters & Murcko, 2002, Adv. Drug Deliv. Rev. Read in desired SDF file Write filtered database PAINS filterDescription: Substructure Filter for Removal of Pan AssayInterference Compounds (PAINS) from Screening Libraries and forTheir Exclusion in Bioassays. Reference: Baell & Holloway, 2010, J. Med. Chem. Read in desired SDF file Write filtered database Write filtered database Read in desired SDF file Lipinski (Rule-of-5) filterDescription: A set of rules to identifiy drug-like compounds. Onerule break is allowd. Rules:-Molecular Weight ≤ 500 Da-logP ≤ 5-H-bond donor ≤ 5-H-bond acceptor ≤ 10Reference: Lipinski et. al., 2001, Adv. Drug Deliv. Rev. Read in desired SDF file Write filtered database Read in desired SDF file Rule-of-3 filterDescription: Rules designed to support “fragment-based” drugresearch. Hits obtained using this filter can be useful for fragmentlibraries used to generate potential leads. Rules:-Molecular Weight ≤ 300 Da-logP ≤ 3-H-bond donor ≤ 3-H-bond acceptor ≤ 3Reference:Congreve et. al.,2003, Drug Discov. Today Write filtered database Read in desired SDF file Rule-of-4 filterDescription: A set of rules for identifying protein-protein interactioninhibitors. With this filter molecules need to exceed the values.Rules:-Molecular Weight ≥ 400 Da-logP ≥ 4-Number of rings ≥ 4-H-bond acceptor ≥ 4Reference: Morelli et. al., 2011, Curr. Opin. Chem. Biol. Write filtered database Veber filterDescription: Two rules that compounds must adhere to foroptimized oral bioavailability.Rules:-Polar Surface Area ≤ 140 Å^2-Rotatable bonds ≤ 10Reference: Veber et. al., 2002, J. Med. Chem. Read in desired SDF file Write filtered database Mozziconacci filterDescription: Rule based filter for drug-like molecules.Rules:- Number of Halogen atoms ≤ 7- Number of Nitrogens ≥ 1- Number of oxygen ≥ 1- Number of rings ≤ 6- Rotatable bonds ≤15Reference: Mozziconacci et. al. Read in desired SDF file Write filtered database Read in desired SDF file Write filtered database Egan filterDescription: Rule based filter for Bioavailability Rules:- LogP ≤ 5.88- Total Polar Surface Ares ≤ 131.6 Å^2Reference: Egan et. al., 2000, J. Med. Chem. Read in desired SDF file Van de Waterbeemd filterDescription: Rule based filter for blood brain permeability andactivity within the central nervous system. Rules:- Molecular Weight ≤ 450- Total Polar Surface Ares ≤ 90 Å^2Reference: Van de Waterbeemd et. al., 1998, J. Drug Targ. Write filtered database Read in desired SDF file Murcko filter Description: Rule based filter for finding compounds with centralnervous system activity. Rules:- 200 ≤ Molecular weight ≤ 400- logP ≤ 5.2- H bond acceptor ≤ 4- H bond donor ≤ 3- Number of rotatable bonds ≤ 7Reference: Ajay et. al., 1999, J. Med. Chem Write filtered database Alternative filter configurations Tools REOS physiochemical propery filter Rules:- Hbond donor ≤ 5,- H-bond acceptors ≤ 10, - -2 ≤ formal charge ≤ +2,- Number of rotatable bonds ≤ 8,- 200 ≤ Molecular weight ≤ 500- 20 ≤ number of heavy atoms ≤ 50, - -2 ≤ logP ≤ 5Reference: based on Walters & Murcko, 2002, Adv. Drug Deliv. Rev. ,Huggins et. al , 2011, ACS Chem. Biol. Read in desired SDF fileIDEALLY for REOS property filter - Yourmolecules should be ionised beforehand Write filtered database Write compounds failing Write compounds failing Write compounds failing Write compounds failing Write compounds failing Write compounds failing Write compounds failing Write compounds failing Write compounds failing Write compounds failing Write compounds failing Write compounds failing Additional filters, they need proprietary knime nodes, in implementation Write filtered database Write compounds failing Read in desired SDF file Oprea filter (not finished)Description: Rule A set of rules based on the lead-like vs drug-likecom-parison.Rules: Molecular Weight < 450 -3.5 ≤ logP < 4.5 -4 ≤ logD ≤ 4 number of rings ≤ 4 non-terminal single bonds ≤ 10, H-bond donor ≤ 5, H-bond acceptor ≤ 8Reference: Oprea et. al., 1999, J. Che. Inf. Comput. Sci. Fichert filter Description: Rules for structure-permeability based on a set of 41small drug-like molecules. LogD is the main property thatdetermines permeability, with structures passing this filter beinghighly permeable in the Cacao-2 model.Rules: Molecular weight ≤ 5000 ≤ logD ≤ 3Reference: Fichert et. al., 2003, Med. Chem. Lett. Write compounds failing Read in desired SDF file Write filtered database Write compounds failing Read in desired SDF file Write filtered database Ghose filter A set of rules for drug-likeness derived from characterizing 6304compounds taken from the Comprehensive Medicinal ChemistryDatabase.Rules: 180 ≤ Molecular Weight ≤ 480 , 40 ≤ Molecular refrac-tivity ≤ 130, -0.4 ≤ logP ≤ 5.6 , 20 ≤ number of atoms ≤70Reference: Ghose et. al., 1999, J. Comb. Chem. COMPOUND FILTERS FORDRUG DESIGN Authors: Sebastjan Kralj &Marko JukičPlease cite: https://www.mdpi.com/1422-0067/23/10/5727 The filters can be started and tested usingthis ZINC test sample set Node 946Node 951Node 953Node 975Node 977Node 978Node 981Node 983Node 985Node 988Node 991Node 995Node 999Node 1096Node 1100Node 1105Node 1116Node 1117Node 1125Node 1126Node 1127Node 1131Node 1134Node 1140Node 1146Node 1148Node 1155Node 1159Node 1162Node 1164Node 1165Node 1169Node 1170Node 1172Node 1175Node 1176Node 1178Node 1180Node 1181Node 1186Node 1187Node 1189Node 1190Node 1197Node 1199Node 1201Node 1204Node 1207Node 1213ZINC databse testsetNode 1215Node 1216Node 1217Node 1218Node 1219Node 1220Node 1221Node 1222Node 1223Node 1224Node 1225Node 1226Node 1227Node 1228Node 1230Node 1231 Aggregators_sorter REOS filter (based on theSchrödinger REOS node) SDF Writer SDF Writer SDF Writer SDF Writer SDF Writer SDF Writer SDF Writer SDF Writer SDF Writer SDF Writer SDF Writer Remove rows withmissing SMILES SDF Writer SDF Writer SDF Writer SDF Writer REOS physiochemicalproperty filter REOS functionalgroup filter PAINS filter SDF Writer Low simmilarity Medium simmilarity High simmilarity SDF Writer Lipinski filter SDF Writer Rule-of-3 SDF Writer Rule-of-4 SDF Writer Veber filter SDF Writer Mozziconacci SDF Writer Egan SDF Writer Van deWaterbeemd filer SDF Writer Murcko filter SDF Writer SDF Writer Oprea filter SDF Writer SDF Writer Fichert filter SDF Writer Ghose filter SDF Reader SDF Reader SDF Reader SDF Reader SDF Reader SDF Reader SDF Reader SDF Reader SDF Reader SDF Reader SDF Reader SDF Reader SDF Reader SDF Reader SDF Reader SDF Writer SDF Reader

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Created by: kralj
Created at: 2021-06-23
On NodePit since: 2022-05-25
Last update: 2024-04-18
Created with KNIME version: v4.7.0

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