NPASS Compound

Natural Product: NPC477716

Natural Product ID	NPC477716
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Petrosaspongiolide m
IUPAC Name	[(1S,3R,4aR,4bS,6aS,10aS,10bS,12aS)-3-(2-hydroxy-5-oxo-2H-furan-3-yl)-4b,7,7,10a-tetramethyl-1,3,4,4a,5,6,6a,8,9,10,10b,11,12,12a-tetradecahydronaphtho[2,1-f]isochromen-1-yl] acetate
Synonyms	Petrosaspongiolide M
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	17748437
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001283] Terpene lactones [CHEMONTID:0001538] Diterpene lactones

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 73 77 0 0 0 0 0 0 0 0999 V2000 -3.3046 -4.2402 -1.0751 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3851 -3.3037 0.0854 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8066 -3.7688 1.1690 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.0124 -1.9735 -0.0181 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.1221 -1.1458 1.1463 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.7879 -0.4898 1.4475 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.8449 -1.3816 2.1611 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4937 -0.6572 2.2657 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9764 -0.4671 0.8505 C 0 0 2 0 0 0 0 0 0 0 0 0 2.4460 -0.2732 0.7272 C 0 0 1 0 0 0 0 0 0 0 0 0 3.1081 -1.6391 0.9811 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5927 -1.5492 0.8895 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1226 -0.4870 0.0014 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2041 -0.0117 -1.0630 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7661 0.0245 -0.7152 C 0 0 2 0 0 0 0 0 0 0 0 0 2.0437 1.2716 -1.2131 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5554 0.8923 -1.2211 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1235 0.5788 0.2087 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.2818 0.0558 0.1419 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.2729 1.1713 -0.2225 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6659 0.5907 -0.2893 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.0071 -0.1335 0.8315 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.6251 1.7327 -0.3840 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3529 3.0230 -0.4083 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5830 3.7925 -0.5077 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7323 5.0414 -0.5563 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.6190 2.8936 -0.5425 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.0927 1.6025 -0.4694 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.4844 0.9550 -1.6498 O 0 0 0 0 0 0 0 0 0 0 0 0 0.1004 1.8928 0.9313 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4500 -0.8780 -2.3094 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6738 1.3906 -1.4787 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0197 0.6755 1.7129 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4445 -3.9680 -1.7430 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2731 -4.2077 -1.6280 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1948 -5.2841 -0.7097 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5043 -1.7115 1.9943 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0106 0.3814 2.1028 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6434 -2.3381 1.6588 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2107 -1.5589 3.1781 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2957 0.2803 2.8010 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1985 -1.2403 2.8940 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7325 -1.4359 0.3186 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7603 -2.2784 0.1173 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7634 -2.0979 1.9082 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0354 -1.4060 1.9189 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9746 -2.5673 0.5827 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5284 0.4090 0.5586 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0474 -0.9056 -0.4988 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2639 -0.8158 -1.2882 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2427 2.1547 -0.6140 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3261 1.3863 -2.2754 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3989 0.0617 -1.9049 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0383 1.7657 -1.5621 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3393 -0.7242 -0.6406 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2782 1.8691 0.6531 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0356 1.6482 -1.1706 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7319 0.0083 -1.2361 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3389 3.4233 -0.3590 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5031 1.0762 0.4244 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3309 1.6175 -2.3766 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5113 1.8924 1.8503 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1057 2.3464 1.0681 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4278 2.6150 0.2372 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8523 -0.5206 -3.1651 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5135 -0.9534 -2.5319 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0642 -1.8993 -2.0446 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4570 1.5393 -2.5629 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2692 2.1740 -0.8416 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7819 1.3969 -1.3802 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2424 0.8204 2.5233 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8865 0.2370 2.2939 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3801 1.6246 1.3172 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 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 1 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 21 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 18 30 1 1 14 31 1 0 14 32 1 0 10 33 1 1 22 5 1 0 19 6 1 0 18 9 1 0 15 10 1 0 28 23 1 0 1 34 1 0 1 35 1 0 1 36 1 0 5 37 1 1 6 38 1 1 7 39 1 0 7 40 1 0 8 41 1 0 8 42 1 0 9 43 1 6 11 44 1 0 11 45 1 0 12 46 1 0 12 47 1 0 13 48 1 0 13 49 1 0 15 50 1 6 16 51 1 0 16 52 1 0 17 53 1 0 17 54 1 0 19 55 1 6 20 56 1 0 20 57 1 0 21 58 1 6 24 59 1 0 28 60 1 0 29 61 1 0 30 62 1 0 30 63 1 0 30 64 1 0 31 65 1 0 31 66 1 0 31 67 1 0 32 68 1 0 32 69 1 0 32 70 1 0 33 71 1 0 33 72 1 0 33 73 1 0 M END

Standard InCHIKey	RVWQZLJUVIFAOY-GQLPRRODSA-N
Standard InCHI	InChI=1S/C27H40O6/c1-15(28)31-24-16-7-8-21-26(4,12-9-20-25(2,3)10-6-11-27(20,21)5)18(16)14-19(32-24)17-13-22(29)33-23(17)30/h13,16,18-21,23-24,30H,6-12,14H2,1-5H3/t16-,18+,19+,20-,21-,23?,24+,26-,27-/m0/s1
SMILES	CC(=O)O[C@H]1[C@H]2CC[C@@H]3[C@]4(CCCC([C@@H]4CC[C@]3([C@@H]2C[C@@H](O1)C5=CC(=O)OC5O)C)(C)C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	460.28	Volume:	477.598 ? Van der Waals volume.
Dense:	0.964	LogP:	3.769 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.704 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.943 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	28.0
TPSA:	82.06 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	1.0	Rings:	5.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.6	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.9	Fsp³:	0.852
MCE-18:	92.48 ? 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:	0.672	Fluc inhibitor:	0.002 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.017 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.0 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.122	Promiscuous compounds:	0.43

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.726	MDCK Permeability:	-4.844
Pgp-inhibitor:	0.095	Pgp-substrate:	0.009
PAMPA:	0.263 ? 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):	0.001
20% Bioavailability (F20%):	0.084	30% Bioavailability (F30%):	0.235
50% Bioavailability (F50%):	0.924

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.068	MRP1:	0.509
Plasma Protein Binding (PPB):	97.003%	Volume Distribution (VD):	0.094
Fu:	3.784% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	0.998	BCRP inhibitor:	0.085
BSEP inhibitor:	0.934

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.955	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.098	CYP2C9-substrate:	0.235
CYP2D6-inhibitor:	0.047	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.365	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.19
HLM stability:	0.553 ? 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):

6.169

Half-life (T1/2):

0.961

ADMET: Toxicity

hERG Blockers:	0.047	hERG Blockers (10um):	0.381
Human Hepatotoxicity (H-HT):	0.658	Drug-induced Liver Injury (DILI):	0.912
AMES Toxicity:	0.86	Rat Oral Acute Toxicity:	0.803
Maximum Recommended Daily Dose:	0.944	Skin Sensitization:	0.996
Carcinogencity:	0.975	Eye Corrosion:	0.004
Eye Irritation:	0.432	Respiratory Toxicity:	0.923
Drug-induced Neurotoxicity:	0.261	Ototoxicity:	0.423
Hematotoxicity:	0.813	Drug-induced Nephrotoxicity:	0.965
Genotoxicity:	0.944	RPMI-8226 Immunitoxicity:	0.123
A549 Cytotoxicity:	0.416	Hek293 Cytotoxicity:	0.639
BCF:	2.007 ? 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:	4.837 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.592 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	6.089 ? 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
NPO3351	Petrosaspongia nigra	Species	Thorectidae	Eukaryota	n.a.	the southern coast of New Caledonia	1987-NOV; 1988-DEC	PMID[9599251]
NPO3351	Petrosaspongia nigra	Species	Thorectidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO3351	Petrosaspongia nigra	Species	Thorectidae	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	4
Activity	6
IC50	2

Activity Type	# Activity
Individual protein	9
Cell line	2
Others	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT2586	Individual protein	Phospholipase A2, acidic	Naja naja	Inhibition	=	5.4	%	PMID[17407277]
NPT2945	Individual protein	Phospholipase A2 group 1B	Sus scrofa	Inhibition	=	11.4	%	PMID[17407277]
NPT2586	Individual protein	Phospholipase A2, acidic	Naja naja	Activity	=	11.5	%	PMID[9599251]
NPT545	Individual protein	Phospholipase A2 group 1B	Homo sapiens	Inhibition	=	79.4	%	PMID[17407277]
NPT545	Individual protein	Phospholipase A2 group 1B	Homo sapiens	Activity	=	68.6	%	PMID[9599251]
NPT545	Individual protein	Phospholipase A2 group 1B	Homo sapiens	IC50	=	1600	nM	PMID[9599251]
NPT4422	Individual protein	Phospholipase A2 (Bee)	Apis mellifera	Inhibition	=	60.8	%	PMID[17407277]
NPT4422	Individual protein	Phospholipase A2 (Bee)	Apis mellifera	Activity	=	71	%	PMID[9599251]
NPT4422	Individual protein	Phospholipase A2 (Bee)	Apis mellifera	IC50	=	600	nM	PMID[9599251]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT113	Cell line	RAW264.7	Mus musculus	Activity	=	7.3	ug/ml	PMID[17407277]
NPT113	Cell line	RAW264.7	Mus musculus	Activity	=	0.22	ug/ml	PMID[17407277]
NPT2	Others	Unspecified	n.a.	Activity	=	12.3	%	PMID[9599251]

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 NPC477716 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	18506
0.1-0.2	26650
0.2-0.3	4388
0.3-0.4	273
0.4-0.5	33
0.5-0.6	5
0.6-0.7	0
0.7-0.8	0
0.8-0.85	1
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	NPC477721
0.8254	Intermediate Similarity	NPC477717
0.7419	Intermediate Similarity	NPC477722
0.5821	Remote Similarity	NPC489286
0.5652	Remote Similarity	NPC477718
0.5556	Remote Similarity	NPC477719
0.5217	Remote Similarity	NPC472815
0.5211	Remote Similarity	NPC606820

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC477716 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6763
0.1-0.2	2299
0.2-0.3	87
0.3-0.4	1
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