NPASS Compound

Natural Product: NPC13985

Natural Product ID	NPC13985
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	[(5R,5Ar,8As,9R)-8-Oxo-9-(3,4,5-Trimethoxyphenyl)-5A,6,8A,9-Tetrahydro-5H-[2]Benzofuro[5,6-F][1,3]Benzodioxol-5-Yl] Acetate
IUPAC Name	[(5R,5aR,8aS,9R)-8-oxo-9-(3,4,5-trimethoxyphenyl)-5a,6,8a,9-tetrahydro-5H-[2]benzofuro[5,6-f][1,3]benzodioxol-5-yl] acetate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL454333
PubChem CID	233299
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0001392] Lignans, neolignans and related compounds [CHEMONTID:0001510] Lignan lactones [CHEMONTID:0000047] Podophyllotoxins

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 57 61 0 0 0 0 0 0 0 0999 V2000 6.2841 -0.3667 -0.1805 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4064 0.7546 -0.1795 O 0 0 0 0 0 0 0 0 0 0 0 0 4.0446 0.4644 -0.1586 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3516 0.3086 -1.3413 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0664 0.4532 -2.5134 O 0 0 0 0 0 0 0 0 0 0 0 0 3.4258 0.3080 -3.7724 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0039 0.0216 -1.2964 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3559 -0.1086 -0.0948 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0407 0.0455 1.0912 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3875 0.3324 1.0517 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0655 0.4850 2.2545 O 0 0 0 0 0 0 0 0 0 0 0 0 3.4102 0.3535 3.4759 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0692 -0.4116 -0.1026 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.5324 -1.3006 1.0364 C 0 0 2 0 0 0 0 0 0 0 0 0 0.2412 -2.5354 1.1556 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4889 -2.6740 1.1981 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.6523 -3.5889 1.2182 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.9342 -3.1727 0.7631 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9637 -1.6673 0.8882 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.6825 -1.0182 -0.2743 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.3083 0.4416 -0.2051 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9659 0.7492 -0.1182 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5311 2.0547 -0.0516 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4852 3.0519 -0.0746 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3680 4.4443 -0.0235 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6572 4.9796 0.2887 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5066 3.9345 -0.1625 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.8259 2.7392 -0.1616 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2658 1.4327 -0.2285 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0836 -1.1546 -0.0031 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.9107 -1.7830 -0.9102 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3966 -2.2251 -1.9684 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.3771 -1.9224 -0.6198 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6635 -0.5885 -1.2020 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1556 -0.2192 0.4842 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7775 -1.2921 0.1700 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1695 0.1270 -4.5846 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7555 -0.5903 -3.7779 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8304 1.1771 -4.0541 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4870 -0.0951 -2.2596 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5224 -0.0581 2.0408 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1240 0.5286 4.3036 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9424 -0.6529 3.5176 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6274 1.1319 3.5446 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2811 -1.0205 -1.0312 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4046 -0.6861 1.9754 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6874 -3.5846 1.4661 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1579 -3.5236 -0.2564 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5474 -1.3608 1.8061 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4058 -1.4609 -1.2429 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5444 2.2941 0.0178 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7681 5.1751 1.3646 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8390 5.9313 -0.2493 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3139 1.1682 -0.2971 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5990 -2.8844 -0.1409 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7285 -1.0614 -0.0008 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9236 -1.8804 -1.5746 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 1 0 4 7 1 0 7 8 2 0 8 9 1 0 9 10 2 0 10 11 1 0 11 12 1 0 8 13 1 0 13 14 1 0 14 15 1 0 15 16 2 0 15 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 2 0 22 23 1 0 23 24 2 0 24 25 1 0 25 26 1 0 26 27 1 0 27 28 1 0 28 29 2 0 20 30 1 0 30 31 1 0 31 32 2 0 31 33 1 0 10 3 1 0 22 13 1 0 28 24 1 0 19 14 1 0 29 21 1 0 1 34 1 0 1 35 1 0 1 36 1 0 6 37 1 0 6 38 1 0 6 39 1 0 7 40 1 0 9 41 1 0 12 42 1 0 12 43 1 0 12 44 1 0 13 45 1 6 14 46 1 1 18 47 1 0 18 48 1 0 19 49 1 1 20 50 1 6 23 51 1 0 26 52 1 0 26 53 1 0 29 54 1 0 33 55 1 0 33 56 1 0 33 57 1 0 M END

Standard InCHIKey	SASVNKPCTLROPQ-RGXPITOMSA-N
Standard InCHI	InChI=1S/C24H24O9/c1-11(25)33-22-14-8-17-16(31-10-32-17)7-13(14)20(21-15(22)9-30-24(21)26)12-5-18(27-2)23(29-4)19(6-12)28-3/h5-8,15,20-22H,9-10H2,1-4H3/t15-,20+,21+,22-/m0/s1
SMILES	COc1c(OC)cc(cc1OC)[C@H]1[C@@H]2C(=O)OC[C@@H]2[C@H](c2c1cc1OCOc1c2)OC(=O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	456.14	Volume:	438.898 ? Van der Waals volume.
Dense:	1.039	LogP:	2.053 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.293 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.106 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	27.0
TPSA:	98.75 ? Topological Polar Surface Area.	H-Bond Acceptor:	9.0
H-Bond Donor:	0.0	Rings:	5.0
Heavy Atoms:	9.0

MedChem Properties

QED Drug-Likeness Score:	0.629	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.815	Fsp³:	0.417
MCE-18:	97.235 ? 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:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.215	Fluc inhibitor:	0.327 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.202 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.291 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.223	Promiscuous compounds:	0.666

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.956	MDCK Permeability:	-4.855
Pgp-inhibitor:	0.243	Pgp-substrate:	0.001
PAMPA:	0.055 ? 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%):	0.002	30% Bioavailability (F30%):	0.0
50% Bioavailability (F50%):	0.019

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.98	MRP1:	0.999
Plasma Protein Binding (PPB):	96.773%	Volume Distribution (VD):	-0.328
Fu:	3.809% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.538
OATP1B3 inhibitor:	0.262	BCRP inhibitor:	0.0
BSEP inhibitor:	0.998

ADMET: Metabolism

CYP1A2-inhibitor:	0.011	CYP1A2-substrate:	0.247
CYP2C19-inhibitor:	0.992	CYP2C19-substrate:	0.074
CYP2C9-inhibitor:	0.044	CYP2C9-substrate:	0.006
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.999
CYP3A4-inhibitor:	0.996	CYP3A4-substrate:	0.986
CYP2B6-substrate:	0.001	CYP2C8-inhibitor:	0.484
HLM stability:	0.459 ? 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):

3.519

Half-life (T1/2):

2.0

ADMET: Toxicity

hERG Blockers:	0.174	hERG Blockers (10um):	0.563
Human Hepatotoxicity (H-HT):	0.869	Drug-induced Liver Injury (DILI):	0.987
AMES Toxicity:	0.744	Rat Oral Acute Toxicity:	0.577
Maximum Recommended Daily Dose:	0.916	Skin Sensitization:	0.966
Carcinogencity:	0.726	Eye Corrosion:	0.0
Eye Irritation:	0.111	Respiratory Toxicity:	0.461
Drug-induced Neurotoxicity:	0.856	Ototoxicity:	0.748
Hematotoxicity:	0.922	Drug-induced Nephrotoxicity:	0.989
Genotoxicity:	0.993	RPMI-8226 Immunitoxicity:	0.388
A549 Cytotoxicity:	0.445	Hek293 Cytotoxicity:	0.379
BCF:	0.929 ? 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:	3.486 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.514 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.509 ? 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
NPO29147	Hernandia ovigera	Species	Hernandiaceae	Eukaryota	n.a.	trunk bark	n.a.	DOI[10.1016/S0040-4039(01)98402-3]
NPO29147	Hernandia ovigera	Species	Hernandiaceae	Eukaryota	twigs	n.a.	n.a.	PMID[12141878]
NPO20275	Juniperus sabina	Species	Cupressaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[34203980]
NPO20275	Juniperus sabina	Species	Cupressaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[37894884]
NPO20275	Juniperus sabina	Species	Cupressaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO29147	Hernandia ovigera	Species	Hernandiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO20275	Juniperus sabina	Species	Cupressaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO20275	Juniperus sabina	Species	Cupressaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO20275	Juniperus sabina	Species	Cupressaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO29147	Hernandia ovigera	Species	Hernandiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO20275	Juniperus sabina	Species	Cupressaceae	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

Activity Type	# Activity
Potency	4
IC50	1
Ratio IC50	1

Activity Type	# Activity
Individual protein	3
Others	3

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT152	Individual protein	Nuclear factor erythroid 2-related factor 2	Homo sapiens	Potency	n.a.	16360.1	nM	PubChem BioAssay data set
NPT154	Individual protein	Mothers against decapentaplegic homolog 3	Homo sapiens	Potency	n.a.	3548.1	nM	PubChem BioAssay data set
NPT477	Individual protein	DNA dC->dU-editing enzyme APOBEC-3G	Homo sapiens	Potency	n.a.	1122.0	nM	PubChem BioAssay data set

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT2	Others	Unspecified	n.a.	IC50	=	0.15	ug.mL-1	PMID[12141878]
NPT2	Others	Unspecified	n.a.	Ratio IC50	=	10.0	n.a.	PMID[12141878]
NPT2	Others	Unspecified	n.a.	Potency	n.a.	2818.4	nM	PubChem BioAssay data set

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 NPC13985 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	24723
0.1-0.2	23734
0.2-0.3	1112
0.3-0.4	197
0.4-0.5	63
0.5-0.6	18
0.6-0.7	9
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC210642
0.7742	Intermediate Similarity	NPC273578
0.6711	Remote Similarity	NPC100465
0.6533	Remote Similarity	NPC152424
0.6094	Remote Similarity	NPC239890
0.6094	Remote Similarity	NPC209411
0.6	Remote Similarity	NPC80230
0.6	Remote Similarity	NPC104024
0.6	Remote Similarity	NPC101755
0.6	Remote Similarity	NPC304687
0.6	Remote Similarity	NPC65574
0.5976	Remote Similarity	NPC306475
0.5821	Remote Similarity	NPC237946
0.5821	Remote Similarity	NPC149505
0.5821	Remote Similarity	NPC32373
0.5672	Remote Similarity	NPC262455
0.5672	Remote Similarity	NPC177476
0.5588	Remote Similarity	NPC480477
0.5493	Remote Similarity	NPC119910
0.5488	Remote Similarity	NPC116759
0.5488	Remote Similarity	NPC14294
0.5429	Remote Similarity	NPC207584
0.5429	Remote Similarity	NPC19947
0.5412	Remote Similarity	NPC603930
0.5349	Remote Similarity	NPC185498
0.5323	Remote Similarity	NPC151423
0.5205	Remote Similarity	NPC115281
0.5161	Remote Similarity	NPC218841
0.5056	Remote Similarity	NPC179240

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC13985 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5385
0.1-0.2	3682
0.2-0.3	71
0.3-0.4	0
0.4-0.5	5
0.5-0.6	6
0.6-0.7	1
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
0.6957	Remote Similarity	NPD6234	Discontinued
0.5821	Remote Similarity	NPD4965	Approved
0.5821	Remote Similarity	NPD4966	Phase 4
0.5821	Remote Similarity	NPD4967	Phase 2
0.5765	Remote Similarity	NPD7240	Phase 4
0.5349	Remote Similarity	NPD7228	Phase 4
0.5227	Remote Similarity	NPD7237	Clinical (unspecified phase)

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