NPASS Compound

Natural Product: NPC158188

Natural Product ID	NPC158188
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Quiquelignan A
IUPAC Name	(2S)-2-[4-[(1S,2S)-1-ethoxy-3-hydroxy-1-(4-hydroxy-3-methoxyphenyl)propan-2-yl]oxy-3,5-dimethoxyphenyl]-5,7-dihydroxy-2,3-dihydrochromen-4-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL598315
PubChem CID	46232229
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0002585] O-methylated flavonoids [CHEMONTID:0002595] 3'-O-methylated flavonoids

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 72 75 0 0 0 0 0 0 0 0999 V2000 -3.6461 -0.5760 3.8432 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8821 -1.0595 2.4336 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3630 -0.0843 1.5735 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.5735 -0.4389 0.2403 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.4296 0.6737 -0.3095 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0900 1.9979 -0.2189 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9389 2.9571 -0.7209 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1480 2.6246 -1.3261 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.5028 1.3044 -1.4253 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6417 0.3625 -0.9185 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.7169 0.9293 -2.0286 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.1524 -0.3932 -2.1631 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.0117 3.5755 -1.8366 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.2657 -0.4444 -0.5039 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.3474 -1.3550 0.0381 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0206 -1.1434 0.2390 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8403 -1.5944 -0.7698 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3570 -2.2242 -1.9064 O 0 0 0 0 0 0 0 0 0 0 0 0 1.2600 -2.6666 -2.8988 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1918 -1.4004 -0.6089 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7043 -0.7759 0.5202 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8264 -0.3494 1.4847 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4638 -0.5220 1.3647 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3849 -0.0588 2.3909 O 0 0 0 0 0 0 0 0 0 0 0 0 0.1824 0.5838 3.5293 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1626 -0.6046 0.6039 C 0 0 2 0 0 0 0 0 0 0 0 0 4.5804 0.0818 1.8811 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0751 -0.0213 1.9352 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6112 -0.4022 2.9792 O 0 0 0 0 0 0 0 0 0 0 0 0 6.7896 0.3443 0.7223 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0779 0.3616 -0.4685 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7266 0.0410 -0.5098 O 0 0 0 0 0 0 0 0 0 0 0 0 6.7968 0.7139 -1.5902 C 0 0 0 0 0 0 0 0 0 0 0 0 8.1481 1.0340 -1.5551 C 0 0 0 0 0 0 0 0 0 0 0 0 8.8237 1.0033 -0.3404 C 0 0 0 0 0 0 0 0 0 0 0 0 8.1256 0.6549 0.7915 C 0 0 0 0 0 0 0 0 0 0 0 0 8.7501 0.6088 2.0249 O 0 0 0 0 0 0 0 0 0 0 0 0 8.8350 1.3810 -2.6900 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.4959 -0.7173 -1.9916 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4379 0.2083 -2.4976 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.7214 0.0281 3.8295 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4735 0.1611 4.0529 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6288 -1.3780 4.5955 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9694 -1.2171 2.2983 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3090 -2.0017 2.3119 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0774 -1.4014 0.1350 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1494 2.2516 0.2515 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6970 4.0033 -0.6643 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8981 -0.6790 -0.9851 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.2723 -0.3650 -2.2308 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8809 -1.0079 -1.2560 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.7609 -0.9271 -3.0472 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0758 4.4623 -1.3529 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7431 0.5516 -0.4967 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9171 -3.4578 -2.4555 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7308 -3.0229 -3.7975 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8617 -1.7799 -3.2088 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8668 -1.7406 -1.3755 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2239 0.1372 2.3675 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6283 1.0442 4.1234 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8644 1.4025 3.1432 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8029 -0.1075 4.1156 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6298 -1.6443 0.5888 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1374 -0.4290 2.7618 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3227 1.1434 1.8134 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2948 0.7440 -2.5228 H 0 0 0 0 0 0 0 0 0 0 0 0 9.8708 1.2496 -0.3012 H 0 0 0 0 0 0 0 0 0 0 0 0 9.2292 -0.2327 2.3442 H 0 0 0 0 0 0 0 0 0 0 0 0 9.5977 0.8329 -3.0817 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5688 -0.5062 -2.5592 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7944 -1.7535 -2.1965 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9815 1.0301 -2.7413 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 2 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 2 0 9 11 1 0 11 12 1 0 8 13 1 0 4 14 1 0 14 15 1 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 1 0 17 20 1 0 20 21 2 0 21 22 1 0 22 23 2 0 23 24 1 0 24 25 1 0 21 26 1 0 26 27 1 0 27 28 1 0 28 29 2 0 28 30 1 0 30 31 2 0 31 32 1 0 31 33 1 0 33 34 2 0 34 35 1 0 35 36 2 0 36 37 1 0 34 38 1 0 14 39 1 0 39 40 1 0 10 5 1 0 23 16 1 0 32 26 1 0 36 30 1 0 1 41 1 0 1 42 1 0 1 43 1 0 2 44 1 0 2 45 1 0 4 46 1 1 6 47 1 0 7 48 1 0 10 49 1 0 12 50 1 0 12 51 1 0 12 52 1 0 13 53 1 0 14 54 1 6 19 55 1 0 19 56 1 0 19 57 1 0 20 58 1 0 22 59 1 0 25 60 1 0 25 61 1 0 25 62 1 0 26 63 1 1 27 64 1 0 27 65 1 0 33 66 1 0 35 67 1 0 37 68 1 0 38 69 1 0 39 70 1 0 39 71 1 0 40 72 1 0 M END

Standard InCHIKey	FEQZBFHFXKCFBZ-PTJQVGQKSA-N
Standard InCHI	InChI=1S/C29H32O11/c1-5-38-28(15-6-7-18(32)22(8-15)35-2)26(14-30)40-29-24(36-3)9-16(10-25(29)37-4)21-13-20(34)27-19(33)11-17(31)12-23(27)39-21/h6-12,21,26,28,30-33H,5,13-14H2,1-4H3/t21-,26-,28-/m0/s1
SMILES	CCO[C@@H](c1ccc(c(c1)OC)O)[C@@H](Oc1c(OC)cc(cc1OC)[C@@H]1CC(=O)c2c(O1)cc(cc2O)O)CO

Calculated Properties

Physi-Chem Properties

Molecular Weight:	556.19	Volume:	546.242 ? Van der Waals volume.
Dense:	1.018	LogP:	2.288 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.511 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.506 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	11.0	Rigid Bonds:	24.0
TPSA:	153.37 ? Topological Polar Surface Area.	H-Bond Acceptor:	11.0
H-Bond Donor:	4.0	Rings:	4.0
Heavy Atoms:	11.0

MedChem Properties

QED Drug-Likeness Score:	0.27	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.987	Fsp³:	0.345
MCE-18:	83.769 ? 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:	1
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.464	Fluc inhibitor:	0.3 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.046 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.729 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.095	Promiscuous compounds:	0.2

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.205	MDCK Permeability:	-4.844
Pgp-inhibitor:	0.58	Pgp-substrate:	0.006
PAMPA:	0.042 ? 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%):	0.003	30% Bioavailability (F30%):	0.525
50% Bioavailability (F50%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.916
Plasma Protein Binding (PPB):	95.273%	Volume Distribution (VD):	0.062
Fu:	3.894% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.992
BSEP inhibitor:	0.956

ADMET: Metabolism

CYP1A2-inhibitor:	0.993	CYP1A2-substrate:	0.02
CYP2C19-inhibitor:	0.391	CYP2C19-substrate:	0.628
CYP2C9-inhibitor:	0.014	CYP2C9-substrate:	0.001
CYP2D6-inhibitor:	0.179	CYP2D6-substrate:	0.967
CYP3A4-inhibitor:	0.632	CYP3A4-substrate:	0.731
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.999
HLM stability:	0.755 ? 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):

5.786

Half-life (T1/2):

1.815

ADMET: Toxicity

hERG Blockers:	0.176	hERG Blockers (10um):	0.377
Human Hepatotoxicity (H-HT):	0.919	Drug-induced Liver Injury (DILI):	0.97
AMES Toxicity:	0.91	Rat Oral Acute Toxicity:	0.389
Maximum Recommended Daily Dose:	0.812	Skin Sensitization:	0.967
Carcinogencity:	0.694	Eye Corrosion:	0.0
Eye Irritation:	0.156	Respiratory Toxicity:	0.275
Drug-induced Neurotoxicity:	0.782	Ototoxicity:	0.835
Hematotoxicity:	0.323	Drug-induced Nephrotoxicity:	0.915
Genotoxicity:	0.997	RPMI-8226 Immunitoxicity:	0.379
A549 Cytotoxicity:	0.979	Hek293 Cytotoxicity:	0.954
BCF:	1.265 ? 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:	3.812 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.431 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.443 ? 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
NPO32697	calamus quiquesetinervius	Species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[20056545]
NPO32697	calamus quiquesetinervius	Species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[20825224]
NPO32697	calamus quiquesetinervius	Species	n.a.	n.a.	n.a.	n.a.	n.a.	Database[COCONUT]

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
IC50	3

Activity Type	# Activity
Non-molecular	3

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
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	27400.0	nM	PMID[20056545]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	>	100000.0	nM	PMID[20056545]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	>	200000.0	nM	PMID[20056545]

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 NPC158188 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	16426
0.1-0.2	28478
0.2-0.3	4139
0.3-0.4	694
0.4-0.5	92
0.5-0.6	26
0.6-0.7	2
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
0.7349	Intermediate Similarity	NPC476365
0.6812	Remote Similarity	NPC236637
0.6087	Remote Similarity	NPC338131
0.5765	Remote Similarity	NPC602605
0.5647	Remote Similarity	NPC138688
0.5647	Remote Similarity	NPC72787
0.5647	Remote Similarity	NPC217795
0.5647	Remote Similarity	NPC58223
0.5616	Remote Similarity	NPC302950
0.5529	Remote Similarity	NPC36916
0.5529	Remote Similarity	NPC36
0.5529	Remote Similarity	NPC7154
0.5529	Remote Similarity	NPC125039
0.5529	Remote Similarity	NPC7688
0.5352	Remote Similarity	NPC32441
0.5352	Remote Similarity	NPC79943
0.5342	Remote Similarity	NPC321011
0.5342	Remote Similarity	NPC294852
0.5342	Remote Similarity	NPC188679
0.5256	Remote Similarity	NPC477841
0.525	Remote Similarity	NPC108456
0.5205	Remote Similarity	NPC274784
0.5205	Remote Similarity	NPC20709
0.5195	Remote Similarity	NPC326037
0.5195	Remote Similarity	NPC13858
0.5132	Remote Similarity	NPC474836
0.5116	Remote Similarity	NPC475784
0.506	Remote Similarity	NPC473990
0.5056	Remote Similarity	NPC236934

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC158188 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3708
0.1-0.2	5328
0.2-0.3	102
0.3-0.4	6
0.4-0.5	1
0.5-0.6	5
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
0.5616	Remote Similarity	NPD1934	Phase 0
0.5529	Remote Similarity	NPD6166	Phase 2
0.5529	Remote Similarity	NPD6167	Clinical (unspecified phase)
0.5529	Remote Similarity	NPD6168	Clinical (unspecified phase)
0.5352	Remote Similarity	NPD1552	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