NPASS Compound

Natural Product: NPC11453

Natural Product ID	NPC11453
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(2S,3S)-2,3-Bis(5-Methoxy-3,4-Methylenedioxybenzyl)Butane-1,4-Diol Diacetate
IUPAC Name	[(2S,3S)-3-(acetyloxymethyl)-4-(7-methoxy-1,3-benzodioxol-5-yl)-2-[(7-methoxy-1,3-benzodioxol-5-yl)methyl]butyl] acetate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL523996
PubChem CID	11720286
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0001392] Lignans, neolignans and related compounds [CHEMONTID:0001969] Dibenzylbutane lignans

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 66 69 0 0 0 0 0 0 0 0999 V2000 4.0231 -4.0349 2.0118 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7463 -3.5504 1.3565 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6499 -4.0258 1.7318 O 0 0 0 0 0 0 0 0 0 0 0 0 2.7384 -2.6192 0.3759 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7049 -2.0434 -0.3523 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7335 -1.3690 0.5794 C 0 0 1 0 0 0 0 0 0 0 0 0 1.5802 -0.3411 1.3278 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2217 0.6828 0.4921 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4747 0.5492 -0.0713 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0562 1.5267 -0.8378 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3855 2.7060 -1.0735 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1335 2.8889 -0.5332 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5718 1.8890 0.2342 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6863 4.1611 -0.9259 O 0 0 0 0 0 0 0 0 0 0 0 0 2.6972 4.8195 -1.6380 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7059 3.8495 -1.7898 O 0 0 0 0 0 0 0 0 0 0 0 0 5.3314 1.3744 -1.4040 O 0 0 0 0 0 0 0 0 0 0 0 0 6.0230 0.1412 -1.1526 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4172 -0.7356 -0.0528 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.3098 -0.1092 1.0362 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5188 0.5329 0.4776 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4850 1.7989 -0.0241 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6456 2.3878 -0.5193 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8628 1.7053 -0.5156 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8965 0.4266 -0.0083 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7161 -0.1370 0.4814 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2099 -0.0075 -0.1260 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.0609 1.0872 -0.4104 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1421 2.0320 -0.9320 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.6339 3.6670 -1.0313 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.4135 4.3796 -1.0464 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3243 -1.4156 -0.9728 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0839 -2.4880 -0.6130 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.8764 -3.7302 -0.1974 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7328 -4.1544 -0.0633 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.9924 -4.6710 0.1266 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7881 -4.0080 1.2090 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3504 -3.3251 2.7965 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8385 -5.0516 2.3669 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3034 -2.7854 -1.0306 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1393 -1.2421 -1.0023 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4294 -2.1078 1.3423 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0428 0.1381 2.1637 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4321 -0.8799 1.8481 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0684 -0.3577 0.0878 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5940 2.1084 0.6415 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3744 5.1222 -2.6611 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1287 5.6789 -1.0992 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4671 -0.7040 -1.6079 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0818 -0.0674 -0.0621 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0246 0.1589 -1.6282 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0228 0.2005 -0.5897 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7639 0.5483 1.7207 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6861 -0.9443 1.7103 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6082 2.4186 -0.0788 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8131 -1.1383 0.8816 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.5567 1.4776 0.5207 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8138 0.8448 -1.1880 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6741 3.7563 -1.6181 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0212 4.4990 0.0013 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5267 5.3773 -1.5272 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8634 -1.6286 -1.9894 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0934 -0.6235 -1.2981 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6661 -5.4521 0.8228 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7719 -4.0677 0.6191 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3226 -5.1188 -0.8225 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 2 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 2 0 9 10 1 0 10 11 2 0 11 12 1 0 12 13 2 0 12 14 1 0 14 15 1 0 15 16 1 0 10 17 1 0 17 18 1 0 6 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 2 0 25 27 1 0 27 28 1 0 28 29 1 0 23 30 1 0 30 31 1 0 19 32 1 0 32 33 1 0 33 34 1 0 34 35 2 0 34 36 1 0 13 8 1 0 26 21 1 0 16 11 1 0 29 24 1 0 1 37 1 0 1 38 1 0 1 39 1 0 5 40 1 0 5 41 1 0 6 42 1 1 7 43 1 0 7 44 1 0 9 45 1 0 13 46 1 0 15 47 1 0 15 48 1 0 18 49 1 0 18 50 1 0 18 51 1 0 19 52 1 6 20 53 1 0 20 54 1 0 22 55 1 0 26 56 1 0 28 57 1 0 28 58 1 0 31 59 1 0 31 60 1 0 31 61 1 0 32 62 1 0 32 63 1 0 36 64 1 0 36 65 1 0 36 66 1 0 M END

Standard InCHIKey	HIELASMWAXKZPF-WOJBJXKFSA-N
Standard InCHI	InChI=1S/C26H30O10/c1-15(27)31-11-19(5-17-7-21(29-3)25-23(9-17)33-13-35-25)20(12-32-16(2)28)6-18-8-22(30-4)26-24(10-18)34-14-36-26/h7-10,19-20H,5-6,11-14H2,1-4H3/t19-,20-/m1/s1
SMILES	CC(=O)OC[C@@H](Cc1cc(c2c(c1)OCO2)OC)[C@H](Cc1cc(c2c(c1)OCO2)OC)COC(=O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	502.18	Volume:	490.837 ? Van der Waals volume.
Dense:	1.023	LogP:	2.589 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.803 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.773 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	13.0	Rigid Bonds:	22.0
TPSA:	107.98 ? Topological Polar Surface Area.	H-Bond Acceptor:	10.0
H-Bond Donor:	0.0	Rings:	4.0
Heavy Atoms:	10.0

MedChem Properties

QED Drug-Likeness Score:	0.425	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.647	Fsp³:	0.462
MCE-18:	74.526 ? 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:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.106	Fluc inhibitor:	0.019 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.056 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.197 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.316	Promiscuous compounds:	0.208

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.856	MDCK Permeability:	-4.727
Pgp-inhibitor:	0.977	Pgp-substrate:	0.011
PAMPA:	0.018 ? 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%):	0.013	30% Bioavailability (F30%):	0.002
50% Bioavailability (F50%):	0.288

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.067	MRP1:	0.821
Plasma Protein Binding (PPB):	89.774%	Volume Distribution (VD):	-0.172
Fu:	11.996% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	0.982	BCRP inhibitor:	0.2
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.059	CYP1A2-substrate:	0.821
CYP2C19-inhibitor:	0.991	CYP2C19-substrate:	0.818
CYP2C9-inhibitor:	0.021	CYP2C9-substrate:	1.0
CYP2D6-inhibitor:	0.01	CYP2D6-substrate:	0.998
CYP3A4-inhibitor:	0.648	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.126	CYP2C8-inhibitor:	0.379
HLM stability:	0.762 ? 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):

2.454

Half-life (T1/2):

0.94

ADMET: Toxicity

hERG Blockers:	0.195	hERG Blockers (10um):	0.333
Human Hepatotoxicity (H-HT):	0.786	Drug-induced Liver Injury (DILI):	0.843
AMES Toxicity:	0.873	Rat Oral Acute Toxicity:	0.13
Maximum Recommended Daily Dose:	0.234	Skin Sensitization:	0.9
Carcinogencity:	0.778	Eye Corrosion:	0.0
Eye Irritation:	0.291	Respiratory Toxicity:	0.028
Drug-induced Neurotoxicity:	0.592	Ototoxicity:	0.707
Hematotoxicity:	0.564	Drug-induced Nephrotoxicity:	0.804
Genotoxicity:	0.948	RPMI-8226 Immunitoxicity:	0.106
A549 Cytotoxicity:	0.056	Hek293 Cytotoxicity:	0.191
BCF:	1.122 ? 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:	4.024 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.585 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.019 ? 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
NPO17040	Peperomia duclouxii	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[16499322]
NPO17040	Peperomia duclouxii	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17358082]
NPO17040	Peperomia duclouxii	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17547458]
NPO17040	Peperomia duclouxii	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO17040	Peperomia duclouxii	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO17040	Peperomia duclouxii	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO17040	Peperomia duclouxii	Species	Piperaceae	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
IC50	2

Activity Type	# Activity
Cell line	2

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
NPT1475	Cell line	WI-38 VA13	Homo sapiens	IC50	>	199000.0	nM	PMID[25419616]
NPT65	Cell line	HepG2	Homo sapiens	IC50	>	199000.0	nM	PMID[25419616]

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 NPC11453 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	18056
0.1-0.2	28623
0.2-0.3	2571
0.3-0.4	432
0.4-0.5	118
0.5-0.6	36
0.6-0.7	8
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8222	Intermediate Similarity	NPC143895
0.7609	Intermediate Similarity	NPC92693
0.7447	Intermediate Similarity	NPC40237
0.7273	Intermediate Similarity	NPC476748
0.7059	Intermediate Similarity	NPC191158
0.7059	Intermediate Similarity	NPC177644
0.6667	Remote Similarity	NPC192255
0.6538	Remote Similarity	NPC176586
0.6538	Remote Similarity	NPC210354
0.6481	Remote Similarity	NPC293757
0.6481	Remote Similarity	NPC668
0.614	Remote Similarity	NPC76687
0.6078	Remote Similarity	NPC283949
0.6	Remote Similarity	NPC474288
0.5957	Remote Similarity	NPC72796
0.5932	Remote Similarity	NPC136757
0.5932	Remote Similarity	NPC174512
0.5932	Remote Similarity	NPC216223
0.5926	Remote Similarity	NPC46591
0.5926	Remote Similarity	NPC226547
0.587	Remote Similarity	NPC150534
0.5849	Remote Similarity	NPC205915
0.5745	Remote Similarity	NPC600801
0.5686	Remote Similarity	NPC110958
0.5686	Remote Similarity	NPC19890
0.5593	Remote Similarity	NPC487679
0.5593	Remote Similarity	NPC56184
0.5593	Remote Similarity	NPC487678
0.5536	Remote Similarity	NPC166884
0.5536	Remote Similarity	NPC141569
0.5536	Remote Similarity	NPC185908
0.5536	Remote Similarity	NPC482891
0.5536	Remote Similarity	NPC477701
0.549	Remote Similarity	NPC218841
0.5439	Remote Similarity	NPC287124
0.5439	Remote Similarity	NPC477702
0.5424	Remote Similarity	NPC145569
0.5385	Remote Similarity	NPC151423
0.5333	Remote Similarity	NPC119949
0.5283	Remote Similarity	NPC211386
0.5254	Remote Similarity	NPC262455
0.5254	Remote Similarity	NPC177476
0.5254	Remote Similarity	NPC474158
0.5217	Remote Similarity	NPC81067
0.5217	Remote Similarity	NPC602945
0.5185	Remote Similarity	NPC158737
0.5167	Remote Similarity	NPC480477
0.5161	Remote Similarity	NPC32079
0.5094	Remote Similarity	NPC193779
0.5088	Remote Similarity	NPC485477

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC11453 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3945
0.1-0.2	4927
0.2-0.3	266
0.3-0.4	12
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