NPASS Compound

Natural Product: NPC599840

Natural Product ID	NPC599840
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	OBKXEAXTFZPCHS-UHFFFAOYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1469
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds]

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 24 24 0 0 0 0 0 0 0 0999 V2000 -3.7819 0.0783 -1.6568 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.3318 0.3050 -0.4957 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4956 1.6047 -0.0384 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6886 -0.7478 0.2767 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2108 -0.4859 0.5071 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4081 -0.3449 -0.7405 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0124 -0.0886 -0.3858 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4988 1.1754 -0.1565 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8147 1.4545 0.1721 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6925 0.3851 0.2736 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2307 -0.9051 0.0461 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9055 -1.1378 -0.2795 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3754 2.1389 -0.1617 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7706 -1.7069 -0.2838 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1311 -0.9346 1.2800 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0960 0.4152 1.1281 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8431 -1.4061 1.0471 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4410 -1.3112 -1.3231 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8020 0.4502 -1.3941 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8193 2.0110 -0.2290 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1947 2.4467 0.3536 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7517 0.5270 0.5270 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8922 -1.7642 0.1142 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5635 -2.1589 -0.4550 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 2 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 2 0 10 11 1 0 11 12 2 0 12 7 1 0 3 13 1 0 4 14 1 0 4 15 1 0 5 16 1 0 5 17 1 0 6 18 1 0 6 19 1 0 8 20 1 0 9 21 1 0 10 22 1 0 11 23 1 0 12 24 1 0 M END

Standard InCHIKey	OBKXEAXTFZPCHS-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C10H12O2/c11-10(12)8-4-7-9-5-2-1-3-6-9/h1-3,5-6H,4,7-8H2,(H,11,12)
SMILES	O=C(O)CCCc1ccccc1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	164.08	Volume:	179.994 ? Van der Waals volume.
Dense:	0.912	LogP:	2.293 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.894 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-1.911 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	7.0
TPSA:	37.3 ? Topological Polar Surface Area.	H-Bond Acceptor:	2.0
H-Bond Donor:	1.0	Rings:	1.0
Heavy Atoms:	2.0

MedChem Properties

QED Drug-Likeness Score:	0.739	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	1.293	Fsp³:	0.3
MCE-18:	5.0 ? 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:	Rejected
Golden Triangle Rule:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.002	Fluc inhibitor:	0.001 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.051 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.044 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.963	Promiscuous compounds:	0.432

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.67	MDCK Permeability:	-4.529
Pgp-inhibitor:	0.006	Pgp-substrate:	0.024
PAMPA:	0.978 ? 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):	0.069
20% Bioavailability (F20%):	0.007	30% Bioavailability (F30%):	0.033
50% Bioavailability (F50%):	0.011

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.244	MRP1:	0.713
Plasma Protein Binding (PPB):	96.718%	Volume Distribution (VD):	-0.754
Fu:	3.219% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.454
OATP1B3 inhibitor:	0.776	BCRP inhibitor:	0.011
BSEP inhibitor:	0.566

ADMET: Metabolism

CYP1A2-inhibitor:	0.101	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.012	CYP2C19-substrate:	0.003
CYP2C9-inhibitor:	0.998	CYP2C9-substrate:	0.001
CYP2D6-inhibitor:	0.01	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.017	CYP3A4-substrate:	0.005
CYP2B6-substrate:	0.943	CYP2C8-inhibitor:	0.104
HLM stability:	0.003 ? 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):

6.331

Half-life (T1/2):

1.011

ADMET: Toxicity

hERG Blockers:	0.106	hERG Blockers (10um):	0.261
Human Hepatotoxicity (H-HT):	0.483	Drug-induced Liver Injury (DILI):	0.228
AMES Toxicity:	0.236	Rat Oral Acute Toxicity:	0.14
Maximum Recommended Daily Dose:	0.254	Skin Sensitization:	0.593
Carcinogencity:	0.296	Eye Corrosion:	0.708
Eye Irritation:	0.99	Respiratory Toxicity:	0.428
Drug-induced Neurotoxicity:	0.308	Ototoxicity:	0.437
Hematotoxicity:	0.412	Drug-induced Nephrotoxicity:	0.608
Genotoxicity:	0.041	RPMI-8226 Immunitoxicity:	0.026
A549 Cytotoxicity:	0.016	Hek293 Cytotoxicity:	0.06
BCF:	0.201 ? 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:	2.852 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	3.803 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.179 ? 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
NPO49406	Streptomyces sp. Al-Dhabi-97	Genus	Streptomycetaceae	Bacteria	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
AC50	95
Potency	6
IC50	18
Inhibition	26
FC	1
Ki	5
Activity	18
GI50	60
EC50	1
DILI_Concern	1
HepSE_liver fatty	1
Hit score	1
log1/Ki	1
HepSE_hepatic failure	1
HepSE_cholecystitis	1
HepSE_cholelithiasis	1
HepSE_Combined Scores	1
HepSE_bilirubinemia	1
HepSE_cirrhosis	1
HepSE_liver function tests abnormal	1
HepSE_hepatic necrosis	1
HepSE_hepatomegaly	1
HepSE_jaundice	2
TGI	1
HepSE_liver disease	1
HepSE_elevated liver function tests	1
HepSE_hepatitis	1

Activity Type	# Activity
Individual protein	112
Cell line	81
Single protein	9
Unchecked	9
Organism	14
Protein family	8
No target	1
Phenotype	15

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT224	Individual protein	Alpha-2c adrenergic receptor	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT145	Individual protein	Mu opioid receptor	Homo sapiens	AC50	>	10000.0	nM	PMID[37468498]
NPT291	Individual protein	Serotonin 2b (5-HT2b) receptor	Homo sapiens	AC50	>	10000.0	nM	PMID[37468498]
NPT1410	Individual protein	GABA receptor alpha-1 subunit	Rattus norvegicus	AC50	>	30000.0	nM	PMID[37468498]
NPT228	Individual protein	Norepinephrine transporter	Homo sapiens	AC50	>	10000.0	nM	PMID[37468498]
NPT1788	Individual protein	Alpha-1a adrenergic receptor	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT282	Individual protein	MAP kinase ERK2	Homo sapiens	Potency	=	39810.7	nM	PubChem BioAssay data set
NPT222	Individual protein	Alpha-2a adrenergic receptor	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT232	Individual protein	Cannabinoid CB1 receptor	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT263	Individual protein	Muscarinic acetylcholine receptor M2	Homo sapiens	AC50	>	10000.0	nM	PMID[37468498]
NPT230	Individual protein	Bradykinin B2 receptor	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT1464	Individual protein	Phosphodiesterase 4D	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT222	Individual protein	Alpha-2a adrenergic receptor	Homo sapiens	AC50	>	10000.0	nM	PMID[37468498]
NPT242	Individual protein	Dopamine D1 receptor	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT244	Individual protein	Dopamine D3 receptor	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT297	Individual protein	Neurokinin 1 receptor	Homo sapiens	AC50	>	10000.0	nM	PMID[37468498]
NPT290	Individual protein	Serotonin 2a (5-HT2a) receptor	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT252	Individual protein	Histamine H2 receptor	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT227	Individual protein	Beta-3 adrenergic receptor	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT218	Individual protein	Adenosine A3 receptor	Homo sapiens	AC50	>	10000.0	nM	PMID[37468498]
NPT239	Individual protein	Cholecystokinin A receptor	Homo sapiens	AC50	>	10000.0	nM	PMID[37468498]
NPT303	Individual protein	Vasopressin V1a receptor	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT259	Individual protein	Melanocortin receptor 4	Homo sapiens	AC50	>	10000.0	nM	PMID[37468498]
NPT225	Individual protein	Beta-1 adrenergic receptor	Homo sapiens	AC50	>	10000.0	nM	PMID[37468498]
NPT261	Individual protein	Monoamine oxidase A	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT252	Individual protein	Histamine H2 receptor	Homo sapiens	AC50	>	10000.0	nM	PMID[37468498]
NPT1858	Individual protein	Dopamine D2 receptor	Rattus norvegicus	Ki	n.a.	n.a.	n.a.	PMID[21055848]
NPT1163	Individual protein	Glutamate (NMDA) receptor subunit zeta 1	Rattus norvegicus	AC50	>	30000.0	nM	PMID[37468498]
NPT266	Individual protein	Muscarinic acetylcholine receptor M5	Homo sapiens	AC50	>	10000.0	nM	PMID[37468498]
NPT3056	Individual protein	Dopamine D3 receptor	Rattus norvegicus	Ki	n.a.	n.a.	n.a.	PMID[21055848]
NPT1070	Individual protein	Sigma-1 receptor	Cavia porcellus	Ki	>	10000.0	nM	PMID[21055848]
NPT248	Individual protein	Estrogen receptor beta	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT1788	Individual protein	Alpha-1a adrenergic receptor	Homo sapiens	AC50	>	10000.0	nM	PMID[37468498]
NPT1788	Individual protein	Alpha-1a adrenergic receptor	Homo sapiens	AC50	=	14041.7	nM	PMID[37468498]
NPT232	Individual protein	Cannabinoid CB1 receptor	Homo sapiens	AC50	>	10000.0	nM	PMID[37468498]
NPT1785	Individual protein	Serotonin 7 (5-HT7) receptor	Homo sapiens	AC50	>	10000.0	nM	PMID[37468498]
NPT243	Individual protein	Dopamine D2 receptor	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT2879	Individual protein	Equilibrative nucleoside transporter 1	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT2769	Individual protein	Thromboxane A2 receptor	Homo sapiens	AC50	>	10000.0	nM	PMID[37468498]
NPT216	Individual protein	Adenosine A1 receptor	Homo sapiens	AC50	>	10000.0	nM	PMID[37468498]
NPT223	Individual protein	Alpha-2b adrenergic receptor	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT242	Individual protein	Dopamine D1 receptor	Homo sapiens	AC50	>	10000.0	nM	PMID[37468498]
NPT1407	Individual protein	GABA-B receptor 1	Homo sapiens	AC50	>	10000.0	nM	PMID[37468498]
NPT251	Individual protein	Histamine H1 receptor	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT291	Individual protein	Serotonin 2b (5-HT2b) receptor	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT249	Individual protein	Glucocorticoid receptor	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT264	Individual protein	Muscarinic acetylcholine receptor M3	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT299	Individual protein	Androgen Receptor	Rattus norvegicus	AC50	>	30000.0	nM	PMID[37468498]
NPT295	Individual protein	Serotonin transporter	Homo sapiens	AC50	>	10000.0	nM	PMID[37468498]
NPT263	Individual protein	Muscarinic acetylcholine receptor M2	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT226	Individual protein	Beta-2 adrenergic receptor	Homo sapiens	AC50	>	10000.0	nM	PMID[37468498]
NPT294	Individual protein	Serotonin 6 (5-HT6) receptor	Homo sapiens	AC50	>	10000.0	nM	PMID[37468498]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT262	Individual protein	Muscarinic acetylcholine receptor M1	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT267	Individual protein	Neuropeptide Y receptor type 1	Homo sapiens	AC50	>	10000.0	nM	PMID[37468498]
NPT217	Individual protein	Adenosine A2a receptor	Homo sapiens	AC50	>	10000.0	nM	PMID[37468498]
NPT108	Individual protein	Estrogen receptor alpha	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT2719	Individual protein	Voltage-gated L-type calcium channel alpha-1C subunit	Rattus norvegicus	AC50	>	30000.0	nM	PMID[37468498]
NPT298	Individual protein	Neurokinin 2 receptor	Homo sapiens	AC50	>	10000.0	nM	PMID[37468498]
NPT246	Individual protein	Dopamine transporter	Homo sapiens	AC50	=	3200.0	nM	PMID[37468498]
NPT31	Individual protein	Cyclooxygenase-2	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT247	Individual protein	Endothelin receptor ET-A	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT271	Individual protein	Delta opioid receptor	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT1647	Individual protein	Vasopressin V2 receptor	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT145	Individual protein	Mu opioid receptor	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT1814	Individual protein	Glucagon receptor	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT265	Individual protein	Muscarinic acetylcholine receptor M4	Homo sapiens	AC50	>	10000.0	nM	PMID[37468498]
NPT290	Individual protein	Serotonin 2a (5-HT2a) receptor	Homo sapiens	AC50	>	10000.0	nM	PMID[37468498]
NPT292	Individual protein	Serotonin 2c (5-HT2c) receptor	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT245	Individual protein	Dopamine D4 receptor	Homo sapiens	AC50	>	10000.0	nM	PMID[37468498]
NPT686	Individual protein	Histone deacetylase 3	Homo sapiens	IC50	=	260000.0	nM	PMID[21874153]
NPT707	Individual protein	NAD-dependent protein deacylase sirtuin-5, mitochondrial	Homo sapiens	IC50	>	100000.0	nM	PMID[22583019]
NPT5318	Individual protein	Corticotropin releasing factor receptor 1	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT689	Individual protein	Histone deacetylase 5	Homo sapiens	IC50	>	2000000.0	nM	PMID[21874153]
NPT72	Individual protein	Solute carrier organic anion transporter family member 1B3	Homo sapiens	Inhibition	=	71.09	%	PMID[23571415]
NPT30134	Single protein	Gastric inhibitory polypeptide receptor	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT713	Individual protein	Bile salt export pump	Homo sapiens	FC	=	3.0	n.a.	PMID[22464344]
NPT5301	Individual protein	Motilin receptor	Homo sapiens	AC50	>	10000.0	nM	PMID[37468498]
NPT987	Individual protein	Histamine H3 receptor	Homo sapiens	AC50	>	10000.0	nM	PMID[37468498]
NPT684	Individual protein	Histone deacetylase 1	Homo sapiens	IC50	=	64000.0	nM	PMID[21874153]
NPT73	Individual protein	Solute carrier organic anion transporter family member 1B1	Homo sapiens	Inhibition	=	62.24	%	PMID[23571415]
NPT4358	Individual protein	Type-1 angiotensin II receptor	Homo sapiens	AC50	>	10000.0	nM	PMID[37468498]
NPT692	Individual protein	Histone deacetylase 6	Homo sapiens	Inhibition	n.a.	n.a.	%	PMID[21874153]
NPT542	Individual protein	Progesterone receptor	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT3735	Individual protein	Neurotensin receptor 1	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT692	Individual protein	Histone deacetylase 6	Homo sapiens	IC50	=	240000.0	nM	PMID[21874153]
NPT685	Individual protein	Histone deacetylase 2	Homo sapiens	IC50	=	65000.0	nM	PMID[21874153]
NPT688	Individual protein	Histone deacetylase 4	Homo sapiens	IC50	>	2000000.0	nM	PMID[21874153]
NPT20556	Single protein	Replicase polyprotein 1ab	Severe acute respiratory syndrome coronavirus 2	Inhibition	=	20.4	%	Identification of inhibitors of SARS-Cov2 M-Pro enzymatic activity using a small molecule repurposing screen
NPT692	Individual protein	Histone deacetylase 6	Homo sapiens	Inhibition	=	15.31	%	HDAC6 screening dataset using tau-based substrate in an enzymatic assay yields selective inhibitors and activators
NPT29430	Single protein	Neuronal acetylcholine receptor protein alpha-4 subunit	Homo sapiens	AC50	>	10000.0	nM	PMID[37468498]
NPT692	Individual protein	Histone deacetylase 6	Homo sapiens	Inhibition	=	-4.8	%	HDAC6 screening dataset using tau-based substrate in an enzymatic assay yields selective inhibitors and activators
NPT98	Individual protein	HERG	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT22587	Single protein	Taste receptor type 2 member 39	Homo sapiens	Inhibition	=	40.0	%	EP-2323502-B1
NPT4729	Individual protein	Cholecystokinin B receptor	Homo sapiens	AC50	>	10000.0	nM	PMID[37468498]
NPT691	Individual protein	Histone deacetylase 9	Homo sapiens	IC50	>	2000000.0	nM	PMID[21874153]
NPT690	Individual protein	Histone deacetylase 7	Homo sapiens	IC50	>	2000000.0	nM	PMID[21874153]
NPT3952	Individual protein	Endothelin receptor ET-B	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT93	Individual protein	Survival motor neuron protein	Homo sapiens	Potency	=	1122.0	nM	PubChem BioAssay data set
NPT5975	Individual protein	Cyclooxygenase-1	Rattus norvegicus	AC50	>	30000.0	nM	PMID[37468498]
NPT591	Individual protein	Glycogen synthase kinase-3 beta	Homo sapiens	Inhibition	=	125.6	%	PMID[17566732]
NPT92	Individual protein	Serotonin 1a (5-HT1a) receptor	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT28787	Single protein	Voltage-gated N-type calcium channel alpha-1B subunit	Rattus norvegicus	AC50	>	10000.0	nM	PMID[37468498]
NPT5104	Individual protein	Phosphodiesterase 3A	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT28814	Single protein	Ghrelin receptor	Homo sapiens	AC50	>	10000.0	nM	PMID[37468498]
NPT20859	Single protein	Neuropeptide Y receptor type 2	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT92	Individual protein	Serotonin 1a (5-HT1a) receptor	Homo sapiens	AC50	>	10000.0	nM	PMID[37468498]
NPT28448	Single protein	Corticotropin releasing factor receptor 2	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT6127	Individual protein	Bradykinin B1 receptor	Homo sapiens	AC50	>	10000.0	nM	PMID[37468498]
NPT30151	Single protein	Melanocortin receptor 3	Homo sapiens	AC50	>	10000.0	nM	PMID[37468498]
NPT687	Individual protein	Histone deacetylase 8	Homo sapiens	IC50	=	93000.0	nM	PMID[21874153]
NPT5666	Individual protein	Histone deacetylase 6	Mus musculus	Inhibition	n.a.	n.a.	%	PMID[21874153]
NPT49	Individual protein	DNA-(apurinic or apyrimidinic site) lyase	Homo sapiens	Potency	n.a.	1062.1	nM	PubChem BioAssay data set
NPT425	Individual protein	Serotonin 3a (5-HT3a) receptor	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT406	Cell line	RXF 393	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT1083	Cell line	A-375	Homo sapiens	Activity	=	87.33	%	PMID[35818137]
NPT1083	Cell line	A-375	Homo sapiens	Inhibition	n.a.	n.a.	%	PMID[35818137]
NPT367	Cell line	MDA-N	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT147	Cell line	SK-MEL-2	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT374	Cell line	SF-539	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT384	Cell line	TK-10	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT386	Cell line	KM12	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT372	Cell line	HOP-92	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT382	Cell line	OVCAR-5	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT398	Cell line	UACC-62	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT394	Cell line	EKVX	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT387	Cell line	M14	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT371	Cell line	UO-31	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT395	Cell line	SF-268	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT389	Cell line	RPMI-8226	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT76	Cell line	C6	Rattus norvegicus	Activity	n.a.	n.a.	n.a.	PMID[25461306]
NPT393	Cell line	HCT-116	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT380	Cell line	U-251	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT457	Cell line	BT-549	Homo sapiens	GI50	n.a.	1000000.0	nM	PubChem BioAssay data set
NPT392	Cell line	SNB-75	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT306	Cell line	PC-3	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT81	Cell line	A549	Homo sapiens	IC50	=	9750000.0	nM	PMID[35818137]
NPT458	Cell line	IGROV-1	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT90	Cell line	DU-145	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT378	Cell line	NCI/ADR-RES	Homo sapiens	GI50	n.a.	21183.61	nM	PubChem BioAssay data set
NPT76	Cell line	C6	Rattus norvegicus	Activity	=	20.0	%	PMID[25461306]
NPT519	Cell line	SH-SY5Y	Homo sapiens	Activity	n.a.	n.a.	n.a.	PMID[24044874]
NPT388	Cell line	NCI-H322M	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT519	Cell line	SH-SY5Y	Homo sapiens	Activity	n.a.	n.a.	n.a.	PMID[25595686]
NPT373	Cell line	SK-MEL-5	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT370	Cell line	NCI-H23	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT858	Cell line	LNCaP	Homo sapiens	IC50	=	2324000.0	nM	PMID[21055848]
NPT400	Cell line	MDA-MB-435	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT402	Cell line	Hs-578T	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT385	Cell line	SR	Homo sapiens	GI50	n.a.	28510.18	nM	PubChem BioAssay data set
NPT377	Cell line	OVCAR-3	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT397	Cell line	NCI-H460	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT399	Cell line	SF-295	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT308	Cell line	CAKI-1	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT405	Cell line	NCI-H226	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT306	Cell line	PC-3	Homo sapiens	IC50	=	2273000.0	nM	PMID[21055848]
NPT148	Cell line	HCT-15	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT396	Cell line	T47D	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT1083	Cell line	A-375	Homo sapiens	Activity	=	7.4	%	PMID[35818137]
NPT391	Cell line	HCC 2998	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT379	Cell line	HOP-62	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT323	Cell line	SW-620	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT82	Cell line	MDA-MB-231	Homo sapiens	IC50	=	11660000.0	nM	PMID[35818137]
NPT403	Cell line	UACC-257	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT1083	Cell line	A-375	Homo sapiens	Activity	=	5.38	%	PMID[35818137]
NPT1083	Cell line	A-375	Homo sapiens	IC50	=	8940000.0	nM	PMID[35818137]
NPT83	Cell line	MCF7	Homo sapiens	IC50	=	10680000.0	nM	PMID[35818137]
NPT1083	Cell line	A-375	Homo sapiens	TGI	=	10.0	%	PMID[35818137]
NPT112	Cell line	MOLT-4	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT146	Cell line	SK-OV-3	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT401	Cell line	786-0	Homo sapiens	GI50	n.a.	3388.44	nM	PubChem BioAssay data set
NPT455	Cell line	NCI-H522	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT111	Cell line	K562	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT369	Cell line	ACHN	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT116	Cell line	HL-60	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT368	Cell line	SN12C	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT376	Cell line	A498	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT81	Cell line	A549	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT82	Cell line	MDA-MB-231	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT390	Cell line	LOX IMVI	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT83	Cell line	MCF7	Homo sapiens	GI50	n.a.	1000000.0	nM	PubChem BioAssay data set
NPT404	Cell line	CCRF-CEM	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT381	Cell line	OVCAR-8	Homo sapiens	GI50	n.a.	17338.04	nM	PubChem BioAssay data set
NPT456	Cell line	OVCAR-4	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT383	Cell line	SNB-19	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT375	Cell line	Malme-3M	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT139	Cell line	HT-29	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT170	Cell line	SK-MEL-28	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT407	Cell line	COLO 205	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT28438	Unchecked	Unchecked	n.a.	EC50	n.a.	n.a.	n.a.	PMID[33848153]
NPT20555	Organism	SARS-CoV-2	Severe acute respiratory syndrome coronavirus 2	Inhibition	=	-0.11	%	Cytopathic SARS-Cov2 screening on VERO-E6 cells in a large repurposing effort
NPT20555	Organism	SARS-CoV-2	Severe acute respiratory syndrome coronavirus 2	IC50	>	20000.0	nM	Screening of ~5500 FDA-approved drugs and clinical candidates for anti-SARS-CoV-2 activity
NPT28658	Protein family	Histone deacetylase	Rattus norvegicus	Activity	=	14.0	%	PMID[25461306]
NPT28438	Unchecked	Unchecked	n.a.	Inhibition	n.a.	n.a.	%	PMID[21874153]
NPT28438	Unchecked	Unchecked	n.a.	Potency	=	819.9	nM	PubChem BioAssay data set
NPT28438	Unchecked	Unchecked	n.a.	Activity	n.a.	n.a.	n.a.	PMID[33848153]
NPT20555	Organism	SARS-CoV-2	Severe acute respiratory syndrome coronavirus 2	Hit score	=	0.1706	n.a.	Identification of potential treatments for COVID-19 through artificial intelligence-enabled phenomic analysis of human cells infected with SARS-CoV-2
NPT28438	Unchecked	Unchecked	n.a.	log1/Ki	=	3.22	n.a.	PMID[915902]
NPT20555	Organism	SARS-CoV-2	Severe acute respiratory syndrome coronavirus 2	IC50	>	19952.62	nM	Screening of ~5500 FDA-approved drugs and clinical candidates for anti-SARS-CoV-2 activity
NPT28438	Unchecked	Unchecked	n.a.	Potency	n.a.	16360.1	nM	PubChem BioAssay data set
NPT28833	No target	No relevant target	n.a.	Activity	n.a.	n.a.	n.a.	PMID[25595686]
NPT28438	Unchecked	Unchecked	n.a.	Activity	n.a.	n.a.	n.a.	PMID[24044874]
NPT28438	Unchecked	Unchecked	n.a.	Ki	>	10000.0	nM	PMID[21055848]
NPT28658	Protein family	Histone deacetylase	Rattus norvegicus	Activity	n.a.	n.a.	n.a.	PMID[25461306]
NPT28438	Unchecked	Unchecked	n.a.	Activity	n.a.	n.a.	n.a.	PMID[35818137]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	Potency	n.a.	6.6	nM	PubChem BioAssay data set
NPT30138	Protein family	Histone deacetylase	Homo sapiens	Activity	n.a.	n.a.	n.a.	PMID[17566732]
NPT173	Organism	Klebsiella pneumoniae	Klebsiella pneumoniae	Inhibition	=	14.97	%	CO-ADD screening of NIH (USA) - Clinical Collection
NPT30138	Protein family	Histone deacetylase	Homo sapiens	Inhibition	n.a.	n.a.	%	PMID[21055848]
NPT30138	Protein family	Histone deacetylase	Homo sapiens	Inhibition	=	40.0	%	PMID[21055848]
NPT30138	Protein family	Histone deacetylase	Homo sapiens	Inhibition	n.a.	n.a.	%	PMID[24044874]
NPT20	Organism	Candida albicans	Candida albicans	Inhibition	=	6.54	%	CO-ADD screening of NIH (USA) - Clinical Collection
NPT28797	Organism	Cryptococcus neoformans	Cryptococcus neoformans	Inhibition	=	-6.41	%	CO-ADD screening of NIH (USA) - Clinical Collection
NPT30138	Protein family	Histone deacetylase	Homo sapiens	Ki	=	2800.0	nM	PMID[19520580]
NPT605	Organism	Homo sapiens	Homo sapiens	DILI_Concern	n.a.	n.a.	n.a.	PMID[26948801]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	Inhibition	=	7.47	%	CO-ADD screening of NIH (USA) - Clinical Collection
NPT19	Organism	Escherichia coli	Escherichia coli	Inhibition	=	8.43	%	CO-ADD screening of NIH (USA) - Clinical Collection
NPT18	Organism	Pseudomonas aeruginosa	Pseudomonas aeruginosa	Inhibition	=	13.63	%	CO-ADD screening of NIH (USA) - Clinical Collection
NPT20596	Phenotype	Hepatotoxicity	n.a.	HepSE_liver fatty	=	0.0	n.a.	PMID[22194678]
NPT20596	Phenotype	Hepatotoxicity	n.a.	HepSE_hepatic failure	=	0.0	n.a.	PMID[22194678]
NPT20596	Phenotype	Hepatotoxicity	n.a.	HepSE_cholecystitis	=	0.0	n.a.	PMID[22194678]
NPT20596	Phenotype	Hepatotoxicity	n.a.	HepSE_cholelithiasis	=	0.0	n.a.	PMID[22194678]
NPT20596	Phenotype	Hepatotoxicity	n.a.	HepSE_Combined Scores	=	1.0	n.a.	PMID[22194678]
NPT20596	Phenotype	Hepatotoxicity	n.a.	HepSE_bilirubinemia	=	1.0	n.a.	PMID[22194678]
NPT20596	Phenotype	Hepatotoxicity	n.a.	HepSE_cirrhosis	=	0.0	n.a.	PMID[22194678]
NPT20596	Phenotype	Hepatotoxicity	n.a.	HepSE_liver function tests abnormal	=	0.0	n.a.	PMID[22194678]
NPT20596	Phenotype	Hepatotoxicity	n.a.	HepSE_hepatic necrosis	=	0.0	n.a.	PMID[22194678]
NPT20596	Phenotype	Hepatotoxicity	n.a.	HepSE_hepatomegaly	=	0.0	n.a.	PMID[22194678]
NPT20596	Phenotype	Hepatotoxicity	n.a.	HepSE_jaundice	=	0.0	n.a.	PMID[22194678]
NPT747	Organism	Acinetobacter baumannii	Acinetobacter baumannii	Inhibition	=	2.48	%	CO-ADD screening of NIH (USA) - Clinical Collection
NPT20596	Phenotype	Hepatotoxicity	n.a.	HepSE_liver disease	=	0.0	n.a.	PMID[22194678]

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT20596	Phenotype	Hepatotoxicity	n.a.	HepSE_elevated liver function tests	=	0.0	n.a.	PMID[22194678]
NPT20596	Phenotype	Hepatotoxicity	n.a.	HepSE_hepatitis	=	0.0	n.a.	PMID[22194678]

Experimental ADME

Experiment Model	Experiment Tissue	ADME Type	ADME Relation	ADME Value	ADME Unit	Reference
n.a.	n.a.	LogP	=	2.42	n.a.	PMID[17300161]
Homo sapiens	n.a.	Papp	=	0.74	10^-6 cm/s	PMID[35818137]
Homo sapiens	n.a.	Papp	<	0.48	10^-6 cm/s	PMID[35818137]
n.a.	n.a.	log Pe	=	3.87	n.a.	PMID[17300161]

Experimental Toxicity

Quantitative toxicity

Experiment Model	Experiment Organism	Toxicity Type	Toxicity Relation	Toxicity Value	Toxicity Unit	Reference
-	Homo sapiens	DILI_severity_class	=	4.0	n.a.	PMID[26948801]

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 NPC599840 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	27920
0.1-0.2	19667
0.2-0.3	2019
0.3-0.4	213
0.4-0.5	31
0.5-0.6	5
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	Natural Product ID
0.6216	Remote Similarity	NPC44830
0.5938	Remote Similarity	NPC127343
0.5676	Remote Similarity	NPC607585
0.5556	Remote Similarity	NPC324569
0.5294	Remote Similarity	NPC95965
0.5152	Remote Similarity	NPC610108

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC599840 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	2978
0.1-0.2	5165
0.2-0.3	885
0.3-0.4	102
0.4-0.5	14
0.5-0.6	3
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	1

Similarity Score	Similarity Level	Drug ID	Developmental Stage
1.0	High Similarity	NPD226	Phase 4
0.6061	Remote Similarity	NPD225	Approved
0.6061	Remote Similarity	NPD227	Approved
0.5526	Remote Similarity	NPD9589	Approved
0.5526	Remote Similarity	NPD9590	Approved
0.5349	Remote Similarity	NPD1360	Phase 4

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