NPASS Compound

Natural Product: NPC283230

Natural Product ID	NPC283230
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	AZMQTBXLMHEDNG-JCNFZPKBSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	5317802
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

RDKit 3D 69 73 0 0 0 0 0 0 0 0999 V2000 0.9743 -2.3758 0.6296 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0837 -2.2974 -0.8806 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.3119 -2.5169 -1.4609 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3235 -1.7687 -0.6913 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3295 -2.5859 -0.2683 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3623 -2.1088 0.5269 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3425 -0.7565 0.8893 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3549 0.1071 0.4938 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3596 -0.4112 -0.2983 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5312 0.7452 -0.6114 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8518 0.9642 -0.5726 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3122 2.2022 -0.8495 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4258 3.2116 -1.1621 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9597 2.9684 -1.2005 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4475 1.7147 -0.9243 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7722 1.3701 -0.9609 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4371 0.9210 -2.1293 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5510 4.1773 -1.5425 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.5770 5.1159 -1.9223 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6427 4.5382 -1.4748 O 0 0 0 0 0 0 0 0 0 0 0 0 1.9746 0.0183 -0.3314 C 0 0 1 0 0 0 0 0 0 0 0 0 1.8129 -1.1150 -1.3794 C 0 0 2 0 0 0 0 0 0 0 0 0 1.3005 -0.5549 -2.6860 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1579 -1.4822 -1.6491 O 0 0 0 0 0 0 0 0 0 0 0 0 3.1923 0.6430 -0.4327 O 0 0 0 0 0 0 0 0 0 0 0 0 4.1706 0.7746 0.5366 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3600 1.4467 0.2618 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3747 1.6174 1.1704 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2400 1.1106 2.4237 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0878 0.4406 2.7438 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0569 0.2696 1.8140 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2627 1.4322 0.8320 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.5795 1.8853 2.0059 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3609 -0.2615 1.6814 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.1923 -0.3074 3.0861 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3914 -2.9353 0.9582 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.3632 -4.2941 0.5633 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2760 -1.6580 1.0592 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9750 -2.3961 1.0970 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5360 -3.3962 0.8407 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6528 -3.2267 -1.1808 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5624 -3.6018 -1.3761 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2855 -2.2810 -2.5293 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2981 -3.6282 -0.5741 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3951 2.3545 -0.8129 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2645 1.6358 -2.3525 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8392 -0.0685 -1.9326 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6947 0.9008 -2.9433 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5390 5.1846 -3.0227 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7135 6.0872 -1.4172 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8390 -0.4044 0.6815 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2408 -0.3190 -2.7061 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6032 -1.2438 -3.4883 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8481 0.4186 -2.8362 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2965 -2.4329 -1.4321 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5024 1.8626 -0.7231 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2792 2.1553 0.8851 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0512 1.2535 3.1319 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9496 0.0272 3.7274 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1836 -0.2641 2.1300 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9964 1.0831 2.4541 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3220 2.3494 2.6972 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9269 2.7123 1.6887 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7586 0.5286 3.5663 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1225 -0.2008 3.3030 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5459 -1.2692 3.5099 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2360 -4.4107 -0.5400 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4690 -4.8169 1.0054 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2629 -4.8378 0.9014 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 4 5 2 0 5 6 1 0 6 7 2 0 7 8 1 0 8 9 2 0 9 10 1 0 10 11 2 0 11 12 1 0 12 13 2 0 13 14 1 0 14 15 2 0 15 16 1 0 16 17 1 0 14 18 1 0 18 19 1 0 19 20 1 0 11 21 1 0 21 22 1 0 22 23 1 0 22 24 1 6 21 25 1 0 25 26 1 0 26 27 2 0 27 28 1 0 28 29 2 0 29 30 1 0 30 31 2 0 8 32 1 0 32 33 1 0 7 34 1 0 34 35 1 0 6 36 1 0 36 37 1 0 22 2 1 0 31 26 1 0 9 4 1 0 15 10 1 0 20 13 1 0 1 38 1 0 1 39 1 0 1 40 1 0 2 41 1 6 3 42 1 0 3 43 1 0 5 44 1 0 12 45 1 0 17 46 1 0 17 47 1 0 17 48 1 0 19 49 1 0 19 50 1 0 21 51 1 1 23 52 1 0 23 53 1 0 23 54 1 0 24 55 1 0 27 56 1 0 28 57 1 0 29 58 1 0 30 59 1 0 31 60 1 0 33 61 1 0 33 62 1 0 33 63 1 0 35 64 1 0 35 65 1 0 35 66 1 0 37 67 1 0 37 68 1 0 37 69 1 0 M END

Standard InCHIKey	AZMQTBXLMHEDNG-JCNFZPKBSA-N
Standard InCHI	InChI=1S/C29H32O8/c1-16-12-17-13-20(31-3)24(32-4)26(33-5)22(17)23-19(14-21-25(27(23)34-6)36-15-35-21)28(29(16,2)30)37-18-10-8-7-9-11-18/h7-11,13-14,16,28,30H,12,15H2,1-6H3/t16-,28-,29-/m0/s1
SMILES	C[C@H]1Cc2cc(c(c(c2-c2c(cc3c(c2OC)OCO3)[C@@H]([C@@]1(C)O)Oc1ccccc1)OC)OC)OC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	508.21	Volume:	513.951 ? Van der Waals volume.
Dense:	0.989	LogP:	4.036 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.812 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.311 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	28.0
TPSA:	84.84 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	1.0	Rings:	5.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.488	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.872	Fsp³:	0.379
MCE-18:	100.75 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.37	Fluc inhibitor:	0.299 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.477 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.577 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.038	Promiscuous compounds:	0.092

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.77	MDCK Permeability:	-4.743
Pgp-inhibitor:	0.613	Pgp-substrate:	0.018
PAMPA:	0.093 ? 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%):	0.005	30% Bioavailability (F30%):	0.0
50% Bioavailability (F50%):	0.3

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.586	MRP1:	0.986
Plasma Protein Binding (PPB):	96.917%	Volume Distribution (VD):	0.101
Fu:	2.777% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.986
OATP1B3 inhibitor:	0.985	BCRP inhibitor:	0.013
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.996	CYP1A2-substrate:	0.047
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.019
CYP2C9-inhibitor:	0.988	CYP2C9-substrate:	0.017
CYP2D6-inhibitor:	0.977	CYP2D6-substrate:	0.474
CYP3A4-inhibitor:	0.999	CYP3A4-substrate:	0.011
CYP2B6-substrate:	0.051	CYP2C8-inhibitor:	0.021
HLM stability:	0.031 ? 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):

4.885

Half-life (T1/2):

0.739

ADMET: Toxicity

hERG Blockers:	0.277	hERG Blockers (10um):	0.51
Human Hepatotoxicity (H-HT):	0.771	Drug-induced Liver Injury (DILI):	0.71
AMES Toxicity:	0.343	Rat Oral Acute Toxicity:	0.253
Maximum Recommended Daily Dose:	0.595	Skin Sensitization:	0.559
Carcinogencity:	0.812	Eye Corrosion:	0.0
Eye Irritation:	0.184	Respiratory Toxicity:	0.637
Drug-induced Neurotoxicity:	0.564	Ototoxicity:	0.731
Hematotoxicity:	0.619	Drug-induced Nephrotoxicity:	0.737
Genotoxicity:	0.097	RPMI-8226 Immunitoxicity:	0.148
A549 Cytotoxicity:	0.206	Hek293 Cytotoxicity:	0.596
BCF:	2.037 ? 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:	4.158 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.276 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.039 ? 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
NPO8187	Schisandra chinensis	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[16562834]
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]
NPO8187	Schisandra chinensis	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8187	Schisandra chinensis	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO8187	Schisandra chinensis	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
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]
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

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

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 NPC283230 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	16266
0.1-0.2	31338
0.2-0.3	2012
0.3-0.4	126
0.4-0.5	76
0.5-0.6	24
0.6-0.7	16
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.6761	Remote Similarity	NPC83049
0.6761	Remote Similarity	NPC320471
0.6761	Remote Similarity	NPC118162
0.6571	Remote Similarity	NPC126405
0.6571	Remote Similarity	NPC53669
0.6571	Remote Similarity	NPC77237
0.6571	Remote Similarity	NPC297271
0.6571	Remote Similarity	NPC224472
0.6571	Remote Similarity	NPC16791
0.6571	Remote Similarity	NPC217708
0.6479	Remote Similarity	NPC79322
0.6286	Remote Similarity	NPC198461
0.619	Remote Similarity	NPC53722
0.619	Remote Similarity	NPC201404
0.619	Remote Similarity	NPC290714
0.6133	Remote Similarity	NPC29727
0.5735	Remote Similarity	NPC76415
0.5735	Remote Similarity	NPC218510
0.5672	Remote Similarity	NPC304821
0.5667	Remote Similarity	NPC145722
0.5667	Remote Similarity	NPC256776
0.5667	Remote Similarity	NPC185680
0.5571	Remote Similarity	NPC295297
0.5333	Remote Similarity	NPC32189
0.5325	Remote Similarity	NPC280778
0.527	Remote Similarity	NPC191352
0.5217	Remote Similarity	NPC230538
0.5217	Remote Similarity	NPC229172
0.5217	Remote Similarity	NPC103637
0.5217	Remote Similarity	NPC36531
0.519	Remote Similarity	NPC63061
0.519	Remote Similarity	NPC475229
0.5181	Remote Similarity	NPC88557
0.5079	Remote Similarity	NPC216434
0.5079	Remote Similarity	NPC103448
0.5079	Remote Similarity	NPC606558
0.5077	Remote Similarity	NPC326144
0.5072	Remote Similarity	NPC220577
0.5068	Remote Similarity	NPC85141
0.5065	Remote Similarity	NPC258322

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC283230 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3609
0.1-0.2	5402
0.2-0.3	136
0.3-0.4	3
0.4-0.5	0
0.5-0.6	0
0.6-0.7	0
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
		NPD

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