NPASS Compound

Natural Product: NPC473285

Natural Product ID	NPC473285
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Cistanoside F
IUPAC Name	[(2R,3R,4R,5R,6R)-5,6-dihydroxy-2-(hydroxymethyl)-4-[(2R,3S,4S,5S,6R)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxyoxan-3-yl] (E)-3-(3,4-dihydroxyphenyl)prop-2-enoate
Synonyms	Cistanoside F
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL393549
PubChem CID	44429870
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000476] Cinnamic acids and derivatives [CHEMONTID:0001391] Hydroxycinnamic acids and derivatives [CHEMONTID:0000059] Coumaric acids and derivatives

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 62 64 0 0 0 0 0 0 0 0999 V2000 -4.5029 2.2182 -2.0478 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2866 1.6095 -0.6910 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9907 2.3961 0.3627 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6826 1.9574 1.7486 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3887 1.2603 1.9441 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8386 0.6333 0.7070 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9199 1.5856 -0.3376 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.5089 0.2985 0.8069 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.3555 -1.0213 0.4511 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7109 -1.8751 1.5029 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4503 -3.2321 0.8817 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1974 -3.4088 -0.2930 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.7176 -2.5747 -1.3077 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4721 -1.1689 -0.7978 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8492 -1.0910 -0.3622 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7793 -0.1792 -0.7904 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4483 0.6643 -1.6396 O 0 0 0 0 0 0 0 0 0 0 0 0 3.1388 -0.2431 -0.2183 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0490 0.6202 -0.6122 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3901 0.5950 -0.0803 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3273 1.5444 -0.5383 C 0 0 0 0 0 0 0 0 0 0 0 0 7.6078 1.5458 -0.0518 C 0 0 0 0 0 0 0 0 0 0 0 0 8.0490 0.6448 0.8894 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1469 -0.2800 1.3396 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8423 -0.2967 0.8572 C 0 0 0 0 0 0 0 0 0 0 0 0 9.3336 0.6670 1.3596 O 0 0 0 0 0 0 0 0 0 0 0 0 8.4616 2.5190 -0.5619 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7007 -2.5617 -2.4498 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1647 -1.7094 -3.4347 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8982 -4.1841 1.8033 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.4259 -1.9603 2.6790 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.6114 0.2239 2.8807 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.7831 1.2151 2.2350 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.6939 3.7529 0.1460 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.8212 1.7290 -2.7821 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5328 1.9554 -2.3642 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2981 3.2951 -2.0846 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6190 0.5671 -0.7040 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0966 2.3046 0.1569 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6668 2.8839 2.3947 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6244 1.9220 2.4291 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4822 -0.2039 0.3745 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3288 -1.4834 0.1777 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3065 -1.4459 1.7412 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6276 -3.4227 0.7067 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2101 -3.0518 -1.6873 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7462 -0.4093 -1.5534 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3985 -0.9823 0.5145 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7912 1.3829 -1.3643 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9831 2.2657 -1.2884 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4215 -1.0168 2.0765 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1704 -1.0449 1.2434 H 0 0 0 0 0 0 0 0 0 0 0 0 9.8799 -0.1357 1.6348 H 0 0 0 0 0 0 0 0 0 0 0 0 8.9418 3.1792 0.0368 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6794 -2.1320 -2.1727 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7857 -3.5478 -2.9083 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1835 -1.9434 -3.4802 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8972 -4.1415 1.7587 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3439 -2.2603 2.4419 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4916 -0.1927 2.6527 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5113 1.8855 2.4116 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7444 3.8792 -0.0870 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 6 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 2 0 16 18 1 0 18 19 2 3 19 20 1 0 20 21 2 0 21 22 1 0 22 23 2 0 23 24 1 0 24 25 2 0 23 26 1 0 22 27 1 0 13 28 1 0 28 29 1 0 11 30 1 0 10 31 1 0 5 32 1 0 4 33 1 0 3 34 1 0 7 2 1 0 14 9 1 0 25 20 1 0 1 35 1 0 1 36 1 0 1 37 1 0 2 38 1 0 3 39 1 0 4 40 1 0 5 41 1 0 6 42 1 0 9 43 1 0 10 44 1 0 11 45 1 0 13 46 1 0 14 47 1 0 18 48 1 0 19 49 1 0 21 50 1 0 24 51 1 0 25 52 1 0 26 53 1 0 27 54 1 0 28 55 1 0 28 56 1 0 29 57 1 0 30 58 1 0 31 59 1 0 32 60 1 0 33 61 1 0 34 62 1 0 M END

Standard InCHIKey	IDVRYIVYDAOHSS-CRADLMAESA-N
Standard InCHI	InChI=1S/C21H28O13/c1-8-14(26)15(27)16(28)21(31-8)34-19-17(29)20(30)32-12(7-22)18(19)33-13(25)5-3-9-2-4-10(23)11(24)6-9/h2-6,8,12,14-24,26-30H,7H2,1H3/b5-3+/t8-,12-,14-,15+,16+,17-,18-,19-,20-,21-/m1/s1
SMILES	CC1C(C(C(C(O1)OC2C(C(OC(C2OC(=O)C=CC3=CC(=C(C=C3)O)O)CO)O)O)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	488.15	Volume:	447.193 ? Van der Waals volume.
Dense:	1.092	LogP:	-1.151 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	-0.067 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-1.564 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	7.0	Rigid Bonds:	20.0
TPSA:	215.83 ? Topological Polar Surface Area.	H-Bond Acceptor:	13.0
H-Bond Donor:	8.0	Rings:	3.0
Heavy Atoms:	13.0

MedChem Properties

QED Drug-Likeness Score:	0.116	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.535	Fsp³:	0.571
MCE-18:	82.939 ? 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:	Rejected	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	1
Colloidal aggregators:	0.338	Fluc inhibitor:	0.552 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.404 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.721 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.617	Promiscuous compounds:	0.476

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.499	MDCK Permeability:	-5.106
Pgp-inhibitor:	0.0	Pgp-substrate:	0.951
PAMPA:	1.0 ? 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):	0.991
20% Bioavailability (F20%):	0.993	30% Bioavailability (F30%):	0.999
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.003	MRP1:	0.878
Plasma Protein Binding (PPB):	47.81%	Volume Distribution (VD):	-0.508
Fu:	49.56% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.003
OATP1B3 inhibitor:	0.866	BCRP inhibitor:	0.063
BSEP inhibitor:	0.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.001	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.081	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.001
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.797
HLM stability:	0.002 ? 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):

1.844

Half-life (T1/2):

2.965

ADMET: Toxicity

hERG Blockers:	0.033	hERG Blockers (10um):	0.525
Human Hepatotoxicity (H-HT):	0.412	Drug-induced Liver Injury (DILI):	0.514
AMES Toxicity:	0.818	Rat Oral Acute Toxicity:	0.397
Maximum Recommended Daily Dose:	0.241	Skin Sensitization:	0.976
Carcinogencity:	0.052	Eye Corrosion:	0.0
Eye Irritation:	0.061	Respiratory Toxicity:	0.03
Drug-induced Neurotoxicity:	0.236	Ototoxicity:	0.984
Hematotoxicity:	0.02	Drug-induced Nephrotoxicity:	0.06
Genotoxicity:	0.299	RPMI-8226 Immunitoxicity:	0.052
A549 Cytotoxicity:	0.274	Hek293 Cytotoxicity:	0.526
BCF:	0.41 ? 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:	2.881 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.884 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.825 ? 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
NPO6536	Marrubium velutinum	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17287127]
NPO6964	Cistanche tubulosa	Species	Orobanchaceae	Eukaryota	fresh stems	n.a.	n.a.	PMID[20159656]
NPO6964	Cistanche tubulosa	Species	Orobanchaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO6536	Marrubium velutinum	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO6964	Cistanche tubulosa	Species	Orobanchaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO6964	Cistanche tubulosa	Species	Orobanchaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO6536	Marrubium velutinum	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO6964	Cistanche tubulosa	Species	Orobanchaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO6536	Marrubium velutinum	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO6964	Cistanche tubulosa	Species	Orobanchaceae	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
Inhibition	5

Activity Type	# Activity
Individual protein	1
Cell line	4

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT43	Individual protein	Tyrosinase	Agaricus bisporus	Inhibition	=	10.92	%	PMID[24387703]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT993	Cell line	Hepatocyte	Mus musculus	Inhibition	=	2.0	%	PMID[18494522]
NPT993	Cell line	Hepatocyte	Mus musculus	Inhibition	=	4.0	%	PMID[20932762]
NPT993	Cell line	Hepatocyte	Mus musculus	Inhibition	=	7.7	%	PMID[25115700]
NPT993	Cell line	Hepatocyte	Mus musculus	Inhibition	=	21.2	%	PMID[22617493]

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 NPC473285 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	13173
0.1-0.2	31676
0.2-0.3	4318
0.3-0.4	528
0.4-0.5	116
0.5-0.6	31
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	0

Similarity Score	Similarity Level	Natural Product ID
0.6835	Remote Similarity	NPC472350
0.6835	Remote Similarity	NPC197316
0.6835	Remote Similarity	NPC89105
0.675	Remote Similarity	NPC134405
0.6548	Remote Similarity	NPC269141
0.6395	Remote Similarity	NPC112
0.631	Remote Similarity	NPC476376
0.6279	Remote Similarity	NPC252292
0.6145	Remote Similarity	NPC222433
0.5976	Remote Similarity	NPC46137
0.5952	Remote Similarity	NPC68092
0.5909	Remote Similarity	NPC298257
0.5909	Remote Similarity	NPC175214
0.5882	Remote Similarity	NPC232880
0.5882	Remote Similarity	NPC76406
0.5814	Remote Similarity	NPC611289
0.5778	Remote Similarity	NPC100998
0.5747	Remote Similarity	NPC263829
0.5663	Remote Similarity	NPC81515
0.5647	Remote Similarity	NPC483705
0.5568	Remote Similarity	NPC106677
0.5556	Remote Similarity	NPC205864
0.5556	Remote Similarity	NPC247032
0.5543	Remote Similarity	NPC610636
0.5484	Remote Similarity	NPC300894
0.5484	Remote Similarity	NPC23845
0.5444	Remote Similarity	NPC34587
0.5435	Remote Similarity	NPC34927
0.5385	Remote Similarity	NPC477294
0.5368	Remote Similarity	NPC106818
0.5349	Remote Similarity	NPC483706
0.5316	Remote Similarity	NPC886
0.5213	Remote Similarity	NPC96795
0.5213	Remote Similarity	NPC264632
0.5213	Remote Similarity	NPC232992
0.5169	Remote Similarity	NPC265648
0.5165	Remote Similarity	NPC476385
0.5161	Remote Similarity	NPC296954
0.5161	Remote Similarity	NPC119537
0.5152	Remote Similarity	NPC87403

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC473285 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5261
0.1-0.2	3770
0.2-0.3	110
0.3-0.4	8
0.4-0.5	0
0.5-0.6	0
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
0.6835	Remote Similarity	NPD7266	Phase 2

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