NPASS Compound

Natural Product: NPC469399

Natural Product ID	NPC469399
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Paeonivayin
IUPAC Name	n.a.
Synonyms	Paeonivayin
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1077667
PubChem CID	46882920
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0002049] Terpene glycosides

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 74 79 0 0 0 0 0 0 0 0999 V2000 0.4989 1.2649 -2.5016 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9523 0.9672 -2.2911 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6804 0.4951 -3.4970 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0570 0.0691 -3.1055 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9928 -0.6856 -1.7818 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5904 -1.3484 -1.6490 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1374 -0.0134 -1.1051 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5361 0.2541 -0.7124 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7537 1.7139 -1.1554 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7996 2.3615 -0.9640 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.5944 2.1123 -1.7742 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.0061 0.0866 0.6800 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3369 0.2346 0.9124 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.4940 -0.3598 0.6779 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5542 -1.4386 0.0566 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.7613 0.2497 1.1540 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.9606 -0.3643 0.9115 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.1496 0.2091 1.3592 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.1240 1.4102 2.0560 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.9235 2.0171 2.2943 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.7481 1.4327 1.8415 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0793 0.0421 -0.3175 O 0 0 0 0 0 0 0 0 0 0 0 0 0.2007 -0.6945 0.7473 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2851 0.1855 1.9993 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7094 0.3870 2.4635 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6590 0.4600 1.2852 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4835 -0.6976 0.3485 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3724 -1.4653 0.6361 O 0 0 0 0 0 0 0 0 0 0 0 0 3.6863 -1.6200 0.3490 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8755 -0.9047 0.0613 O 0 0 0 0 0 0 0 0 0 0 0 0 6.0570 -1.6166 0.0281 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0523 -2.8481 0.2475 O 0 0 0 0 0 0 0 0 0 0 0 0 7.3244 -0.9611 -0.2596 C 0 0 0 0 0 0 0 0 0 0 0 0 7.4116 0.3920 -0.5124 C 0 0 0 0 0 0 0 0 0 0 0 0 8.6398 0.9951 -0.7853 C 0 0 0 0 0 0 0 0 0 0 0 0 9.7947 0.2578 -0.8096 C 0 0 0 0 0 0 0 0 0 0 0 0 9.7210 -1.0959 -0.5586 C 0 0 0 0 0 0 0 0 0 0 0 0 8.4990 -1.6809 -0.2897 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9678 0.4409 1.7618 O 0 0 0 0 0 0 0 0 0 0 0 0 2.0560 -0.5836 3.3791 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.5083 -0.3340 3.0070 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.5614 -0.7723 -4.0835 O 0 0 0 0 0 0 0 0 0 0 0 0 1.0931 0.3301 -2.6082 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8736 1.7995 -1.6028 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6101 1.8788 -3.4163 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1346 -0.2643 -4.0919 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7700 1.3841 -4.1890 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6835 0.9801 -2.9702 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7857 -1.3912 -1.6292 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1775 -1.6594 -2.6073 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6646 -2.0882 -0.8482 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7698 -1.0115 0.9633 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4644 0.7433 1.4025 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.9670 -1.3093 0.3620 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.0905 -0.2891 1.1593 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.0869 1.8218 2.3879 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8931 2.9522 2.8359 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7904 1.9194 2.0331 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5811 -1.4467 0.9569 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1456 1.1719 1.7267 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7836 1.3737 2.9802 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4093 1.3930 0.7464 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3691 -0.3078 -0.6792 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7750 -2.1663 1.3215 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6031 -2.4042 -0.4290 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4852 0.9667 -0.4899 H 0 0 0 0 0 0 0 0 0 0 0 0 8.6893 2.0530 -0.9804 H 0 0 0 0 0 0 0 0 0 0 0 0 10.7248 0.7603 -1.0245 H 0 0 0 0 0 0 0 0 0 0 0 0 10.6478 -1.6719 -0.5809 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4618 -2.7479 -0.0946 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4253 1.2514 1.4206 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9509 -0.9776 3.2371 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0212 -0.3773 3.8857 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8689 -1.2203 -4.6195 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 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 2 0 9 11 1 0 8 12 1 0 12 13 1 0 13 14 1 0 14 15 2 0 14 16 1 0 16 17 2 0 17 18 1 0 18 19 2 0 19 20 1 0 20 21 2 0 7 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 26 27 1 0 27 28 1 0 27 29 1 0 29 30 1 0 30 31 1 0 31 32 2 0 31 33 1 0 33 34 2 0 34 35 1 0 35 36 2 0 36 37 1 0 37 38 2 0 26 39 1 0 25 40 1 0 24 41 1 0 4 42 1 0 7 2 1 0 11 2 1 0 8 5 1 0 21 16 1 0 28 23 1 0 38 33 1 0 1 43 1 0 1 44 1 0 1 45 1 0 3 46 1 0 3 47 1 0 4 48 1 0 5 49 1 0 6 50 1 0 6 51 1 0 12 52 1 0 12 53 1 0 17 54 1 0 18 55 1 0 19 56 1 0 20 57 1 0 21 58 1 0 23 59 1 0 24 60 1 0 25 61 1 0 26 62 1 0 27 63 1 0 29 64 1 0 29 65 1 0 34 66 1 0 35 67 1 0 36 68 1 0 37 69 1 0 38 70 1 0 39 71 1 0 40 72 1 0 41 73 1 0 42 74 1 0 M END

Standard InCHIKey	ZHQGREQIJCCKHT-AJJQULSGSA-N
Standard InCHI	InChI=1S/C30H32O12/c1-28-13-19(31)18-12-30(28,29(18,27(37)42-28)15-39-25(36)17-10-6-3-7-11-17)41-26-23(34)22(33)21(32)20(40-26)14-38-24(35)16-8-4-2-5-9-16/h2-11,18-23,26,31-34H,12-15H2,1H3/t18-,19-,20-,21-,22+,23-,26+,28+,29+,30-/m1/s1
SMILES	CC12CC(C3CC1(C3(C(=O)O2)COC(=O)C4=CC=CC=C4)OC5C(C(C(C(O5)COC(=O)C6=CC=CC=C6)O)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	584.19	Volume:	557.852 ? Van der Waals volume.
Dense:	1.047	LogP:	1.474 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.698 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.827 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	10.0	Rigid Bonds:	32.0
TPSA:	178.28 ? Topological Polar Surface Area.	H-Bond Acceptor:	12.0
H-Bond Donor:	4.0	Rings:	7.0
Heavy Atoms:	12.0

MedChem Properties

QED Drug-Likeness Score:	0.248	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.769	Fsp³:	0.5
MCE-18:	137.8 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.379	Fluc inhibitor:	0.001 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.031 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.528 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.051	Promiscuous compounds:	0.001

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.88	MDCK Permeability:	-5.074
Pgp-inhibitor:	0.047	Pgp-substrate:	0.166
PAMPA:	0.99 ? 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):	0.048
20% Bioavailability (F20%):	0.195	30% Bioavailability (F30%):	0.818
50% Bioavailability (F50%):	0.989

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.088	MRP1:	0.997
Plasma Protein Binding (PPB):	61.64%	Volume Distribution (VD):	-0.738
Fu:	52.205% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.136
OATP1B3 inhibitor:	0.994	BCRP inhibitor:	0.002
BSEP inhibitor:	0.805

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.025
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.028
CYP2C9-inhibitor:	0.003	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.007
CYP3A4-inhibitor:	0.043	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.993 ? 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):

1.798

Half-life (T1/2):

1.443

ADMET: Toxicity

hERG Blockers:	0.143	hERG Blockers (10um):	0.797
Human Hepatotoxicity (H-HT):	0.034	Drug-induced Liver Injury (DILI):	0.678
AMES Toxicity:	0.249	Rat Oral Acute Toxicity:	0.047
Maximum Recommended Daily Dose:	0.66	Skin Sensitization:	0.166
Carcinogencity:	0.669	Eye Corrosion:	0.0
Eye Irritation:	0.005	Respiratory Toxicity:	0.002
Drug-induced Neurotoxicity:	0.717	Ototoxicity:	0.799
Hematotoxicity:	0.002	Drug-induced Nephrotoxicity:	0.184
Genotoxicity:	0.081	RPMI-8226 Immunitoxicity:	0.091
A549 Cytotoxicity:	0.028	Hek293 Cytotoxicity:	0.71
BCF:	0.551 ? 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:	3.508 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.371 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.475 ? 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
NPO30226	Paeonia albiflora	Species	Paeoniaceae	Eukaryota	roots	n.a.	n.a.	PMID[19691309]
NPO30226	Paeonia albiflora	Species	Paeoniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO30226	Paeonia albiflora	Species	Paeoniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO30226	Paeonia albiflora	Species	Paeoniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]

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

Activity Type	# Activity
Inhibition	4
IC50	1

Activity Type	# Activity
Cell line	5

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
NPT848	Cell line	N9	Homo sapiens	Inhibition	=	86.7	%	PubChem BioAssay data set
NPT848	Cell line	N9	Homo sapiens	Inhibition	=	88.3	%	PMID[26100440]
NPT848	Cell line	N9	Homo sapiens	Inhibition	=	82.0	%	PubChem BioAssay data set
NPT848	Cell line	N9	Homo sapiens	Inhibition	=	82.6	%	PMID[18293903]
NPT848	Cell line	N9	Homo sapiens	IC50	>	100000.0	nM	PMID[23434131]

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 NPC469399 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	11851
0.1-0.2	33717
0.2-0.3	3991
0.3-0.4	240
0.4-0.5	26
0.5-0.6	20
0.6-0.7	7
0.7-0.8	0
0.8-0.85	2
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8333	Intermediate Similarity	NPC133430
0.8056	Intermediate Similarity	NPC478832
0.6463	Remote Similarity	NPC469417
0.6341	Remote Similarity	NPC469448
0.6265	Remote Similarity	NPC469477
0.619	Remote Similarity	NPC34066
0.619	Remote Similarity	NPC190862
0.6118	Remote Similarity	NPC469422
0.6023	Remote Similarity	NPC469419
0.5889	Remote Similarity	NPC469396
0.5889	Remote Similarity	NPC469458
0.5889	Remote Similarity	NPC149002
0.5824	Remote Similarity	NPC469418
0.5778	Remote Similarity	NPC469420
0.5732	Remote Similarity	NPC478831
0.5591	Remote Similarity	NPC80360
0.5543	Remote Similarity	NPC469398
0.5532	Remote Similarity	NPC260300
0.5444	Remote Similarity	NPC88176
0.5408	Remote Similarity	NPC188217
0.5342	Remote Similarity	NPC114096
0.5306	Remote Similarity	NPC478828
0.5149	Remote Similarity	NPC469421
0.5111	Remote Similarity	NPC222102
0.5098	Remote Similarity	NPC478826
0.5098	Remote Similarity	NPC478827
0.5056	Remote Similarity	NPC303429
0.5056	Remote Similarity	NPC56594
0.5052	Remote Similarity	NPC195114

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC469399 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3450
0.1-0.2	5542
0.2-0.3	157
0.3-0.4	1
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