Natural Product: NPC32189

Natural Product IDNPC32189
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Schisandrin C
IUPAC Name n.a.
Synonyms Schisandrin C; Wuweizisu C
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL437412
PubChem CID 443027
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000238] Tannins
        • [CHEMONTID:0001710] Hydrolyzable tannins

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

  Chemical Representations

Standard InCHIKey HTBWBWWADZJXID-TXEJJXNPSA-N
Standard InCHI InChI=1S/C22H24O6/c1-11-5-13-7-15-19(27-9-25-15)21(23-3)17(13)18-14(6-12(11)2)8-16-20(22(18)24-4)28-10-26-16/h7-8,11-12H,5-6,9-10H2,1-4H3/t11-,12+
SMILES C[C@H]1Cc2cc3c(c(c2-c2c(C[C@H]1C)cc1c(c2OC)OCO1)OC)OCO3

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   384.16 Volume:   383.208
?
Van der Waals volume.
Dense:   1.002 LogP:   3.5
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.263
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.882
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   26.0
TPSA:   55.38
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   0.0 Rings:   5.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.774 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.716 Fsp3:   0.455
MCE-18:   91.125
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.91 Fluc inhibitor:   0.342
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.56
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.098
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.308 Promiscuous compounds:   0.526

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.924 MDCK Permeability:   -4.702
Pgp-inhibitor:   0.686 Pgp-substrate:   0.009
PAMPA:   0.046
?
The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).
 Human Intestinal Absorption (HIA):   0.0
20% Bioavailability (F20%):   0.009 30% Bioavailability (F30%):   0.0
50% Bioavailability (F50%):   0.106

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.987 MRP1:   0.992
Plasma Protein Binding (PPB):   95.428% Volume Distribution (VD):   0.257
Fu: 4.834%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.861
OATP1B3 inhibitor:   0.803 BCRP inhibitor:   0.002
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.997
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.982
CYP2C9-inhibitor:   0.998 CYP2C9-substrate:   1.0
CYP2D6-inhibitor:   0.999 CYP2D6-substrate:   0.999
CYP3A4-inhibitor:   0.905 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.998 CYP2C8-inhibitor:   0.0
HLM stability:   0.619
?
Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):  3.742 Half-life (T1/2):  0.525

ADMET: Toxicity

hERG Blockers:  0.287 hERG Blockers (10um):  0.608
Human Hepatotoxicity (H-HT):  0.515 Drug-induced Liver Injury (DILI):  0.637
AMES Toxicity:  0.633 Rat Oral Acute Toxicity:  0.502
Maximum Recommended Daily Dose:  0.62 Skin Sensitization:  0.506
Carcinogencity:  0.945 Eye Corrosion:  0.004
Eye Irritation:  0.605 Respiratory Toxicity:  0.829
Drug-induced Neurotoxicity:  0.775 Ototoxicity:  0.423
Hematotoxicity:  0.695 Drug-induced Nephrotoxicity:  0.509
Genotoxicity:  0.693 RPMI-8226 Immunitoxicity:  0.197
A549 Cytotoxicity:  0.331 Hek293 Cytotoxicity:  0.663
BCF:   2.429
?
Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].
 IGC50:   4.352
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.831
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.184
?
96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

  Species Source

Organism ID Organism Name Taxonomy Level Family SuperKingdom Isolation Part Collection Location Collection Time Reference
NPO14102 Kadsura interior Species Schisandraceae Eukaryota n.a. n.a. n.a. PMID[12350139]
NPO24804 Schisandra rubriflora Species Schisandraceae Eukaryota n.a. leaf n.a. PMID[16494492]
NPO24804 Schisandra rubriflora Species Schisandraceae Eukaryota n.a. stem n.a. PMID[16494492]
NPO8187 Schisandra chinensis Species Schisandraceae Eukaryota n.a. n.a. n.a. PMID[16562834]
NPO24804 Schisandra rubriflora Species Schisandraceae Eukaryota fruits n.a. n.a. PMID[17190445]
NPO24804 Schisandra rubriflora Species Schisandraceae Eukaryota n.a. fruit n.a. PMID[17190445]
NPO24804 Schisandra rubriflora Species Schisandraceae Eukaryota n.a. n.a. n.a. PMID[17489633]
NPO24804 Schisandra rubriflora Species Schisandraceae Eukaryota leaves and stems n.a. n.a. PMID[20146529]
NPO33401 schisandra sphenathera Species Schisandraceae Eukaryota stems n.a. n.a. PMID[23237974]
NPO7385 Schisandra sphenanthera Species Schisandraceae Eukaryota fruits n.a. n.a. PMID[23265871]
NPO8187 Schisandra chinensis Species Schisandraceae Eukaryota n.a. fruit n.a. PMID[24155209]
NPO8187 Schisandra chinensis Species Schisandraceae Eukaryota n.a. n.a. n.a. PMID[24959987]
NPO8187 Schisandra chinensis Species Schisandraceae Eukaryota n.a. n.a. n.a. PMID[25302569]
NPO14102 Kadsura interior Species Schisandraceae Eukaryota n.a. stem n.a. PMID[8946749]
NPO25239 Kadsura peltigera Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8187 Schisandra chinensis Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14102 Kadsura interior Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24804 Schisandra rubriflora Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7385 Schisandra sphenanthera Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25679 Aloe rubroviolacea Species Asphodelaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25539 Alternaria mali Species Pleosporaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO225 Eupatorium angustifolium Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25811 Euphorbia erythraea Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25648 Gnaphalium liebmannii Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26233 Helenium autumnale Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26046 Pseudogynoxys engleri Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25917 Sorghum sativum Species Poaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23979 Synadenium compactum n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO16407 Tinospora tuberculata Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25239 Kadsura peltigera Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO8187 Schisandra chinensis Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO14102 Kadsura interior Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO24804 Schisandra rubriflora Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO26233 Helenium autumnale Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO7385 Schisandra sphenanthera Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO7385 Schisandra sphenanthera Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO25239 Kadsura peltigera Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8187 Schisandra chinensis Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14102 Kadsura interior Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO26233 Helenium autumnale Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24804 Schisandra rubriflora Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7385 Schisandra sphenanthera Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO26233 Helenium autumnale Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO24804 Schisandra rubriflora Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO25239 Kadsura peltigera Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO8187 Schisandra chinensis Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO8187 Schisandra chinensis Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO7385 Schisandra sphenanthera Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO25648 Gnaphalium liebmannii Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25917 Sorghum sativum Species Poaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25239 Kadsura peltigera Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO225 Eupatorium angustifolium Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25811 Euphorbia erythraea Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14102 Kadsura interior Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16407 Tinospora tuberculata Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26233 Helenium autumnale Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24804 Schisandra rubriflora Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25679 Aloe rubroviolacea Species Asphodelaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25539 Alternaria mali Species Pleosporaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7385 Schisandra sphenanthera Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23979 Synadenium compactum n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO26046 Pseudogynoxys engleri Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8187 Schisandra chinensis Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[UNPD]

Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].



  NP Quantity Composition/Concentration

Organism ID Organism Name Organism Material Preparation Organism Part NP Quantity (Standard) NP Quantity (Minimum) NP Quantity (Maximum) Quantity Unit Reference

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].



 Biological Activity

Molecular-level activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT82 Cell line MDA-MB-231 Homo sapiens IC50 > 100000.0 nM PMID[18063366]
NPT1086 Cell line SK-HEP1 Homo sapiens IC50 > 100000.0 nM PMID[18063366]
NPT2548 Cell line SNU-638 Homo sapiens IC50 > 100000.0 nM PMID[18063366]
NPT396 Cell line T47D Homo sapiens IC50 > 100000.0 nM PMID[18063366]
NPT148 Cell line HCT-15 Homo sapiens IC50 > 100000.0 nM PMID[18063366]
NPT111 Cell line K562 Homo sapiens IC50 > 100000.0 nM PMID[18063366]
NPT81 Cell line A549 Homo sapiens IC50 > 100000.0 nM PMID[18063366]
NPT80 Cell line Raji Homo sapiens Activity = 70.0 % PMID[12350139]
NPT116 Cell line HL-60 Homo sapiens IC50 = 41200.0 nM PMID[16562834]
NPT165 Cell line HeLa Homo sapiens IC50 > 100000.0 nM PMID[23237974]
NPT659 Cell line SMMC-7721 Homo sapiens IC50 > 100000.0 nM PMID[23237974]
NPT65 Cell line HepG2 Homo sapiens IC50 = 3850.0 nM PMID[30448414]
NPT1114 Organism Human immunodeficiency virus Human immunodeficiency virus EC50 = 1.2 ug.mL-1 PMID[14987069]
NPT1114 Organism Human immunodeficiency virus Human immunodeficiency virus IC50 = 3100.0 nM PMID[9834179]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 > 100000.0 nM PMID[23237974]
NPT2 Others Unspecified n.a. Activity = 2.6 % PMID[12350139]
NPT2 Others Unspecified n.a. Activity = 50.7 % PMID[12350139]
NPT2 Others Unspecified n.a. Activity = 73.6 % PMID[12350139]
NPT2 Others Unspecified n.a. Activity = 92.1 % PMID[12350139]
NPT2 Others Unspecified n.a. Activity = 187.0 % PMID[25302569]

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference





 Experimental ADME

Experiment Model Experiment Tissue ADME Type ADME Relation ADME Value ADME Unit Reference





 Experimental Toxicity

Quantitative toxicity

Experiment Model Experiment Organism Toxicity Type Toxicity Relation Toxicity Value Toxicity Unit Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity Carcinogenicity Mutagenicity Cardiotoxicity Respiratory Toxicity Eye Irritation Endocrine Disruption
Hepatotoxicity Carcinogenicity Mutagenicity Cardiotoxicity Respiratory Toxicity Eye Irritation Endocrine Disruption

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]


  Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

●  The left chart: Distribution of similarity level between NPC32189 and all remaining natural products in the NPASS database.
●  The right table: Most similar natural products (Tc>=0.5 or Top200).

Similarity Score Similarity Level Natural Product ID
0.9459 High Similarity NPC145722
0.9459 High Similarity NPC256776
0.9459 High Similarity NPC185680
0.7297 Intermediate Similarity NPC283114
0.7297 Intermediate Similarity NPC207702
0.7297 Intermediate Similarity NPC149008
0.7234 Intermediate Similarity NPC172171
0.7234 Intermediate Similarity NPC239254
0.7234 Intermediate Similarity NPC133934
0.7083 Intermediate Similarity NPC220577
0.7073 Intermediate Similarity NPC87295
0.6939 Remote Similarity NPC230538
0.6939 Remote Similarity NPC229172
0.6939 Remote Similarity NPC103637
0.6939 Remote Similarity NPC36531
0.6667 Remote Similarity NPC53722
0.6667 Remote Similarity NPC201404
0.6667 Remote Similarity NPC76415
0.6667 Remote Similarity NPC290714
0.6667 Remote Similarity NPC218510
0.6296 Remote Similarity NPC166506
0.6296 Remote Similarity NPC110763
0.6296 Remote Similarity NPC85141
0.6275 Remote Similarity NPC304821
0.62 Remote Similarity NPC184684
0.62 Remote Similarity NPC184641
0.5965 Remote Similarity NPC191352
0.5789 Remote Similarity NPC154971
0.5778 Remote Similarity NPC474295
0.5763 Remote Similarity NPC473323
0.5714 Remote Similarity NPC73467
0.5667 Remote Similarity NPC473425
0.5652 Remote Similarity NPC475868
0.5614 Remote Similarity NPC189239
0.5614 Remote Similarity NPC252286
0.5532 Remote Similarity NPC216434
0.5532 Remote Similarity NPC103448
0.5532 Remote Similarity NPC606558
0.5424 Remote Similarity NPC471154
0.5417 Remote Similarity NPC324962
0.54 Remote Similarity NPC141493
0.5333 Remote Similarity NPC198461
0.5312 Remote Similarity NPC63061
0.5312 Remote Similarity NPC475229
0.5306 Remote Similarity NPC206737
0.5306 Remote Similarity NPC289258
0.5306 Remote Similarity NPC611061
0.5294 Remote Similarity NPC865
0.5254 Remote Similarity NPC121661
0.52 Remote Similarity NPC326144
0.5192 Remote Similarity NPC184928
0.5161 Remote Similarity NPC126405
0.5161 Remote Similarity NPC53669
0.5161 Remote Similarity NPC77237
0.5161 Remote Similarity NPC297271
0.5161 Remote Similarity NPC258322
0.5161 Remote Similarity NPC224472
0.5161 Remote Similarity NPC16791
0.5161 Remote Similarity NPC217708
0.5079 Remote Similarity NPC79322

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

●  The left chart: Distribution of similarity level between NPC32189 and all drugs/candidates.
●  The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

Similarity Score Similarity Level Drug ID Developmental Stage
NPD

Bioactivity similarity

  Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.
Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity
B: biological targets similarity
C: networks similarity
D: cell-based bioactivity similarity
E: similarity based on clinical data