NPASS Compound

Natural Product: NPC487661

Natural Product ID	NPC487661
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	VFAYVFXEKSOZAD-RQRAGIARSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	122180304
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0001819] Isoindoles and derivatives [CHEMONTID:0002496] Isoindolines [CHEMONTID:0001820] Isoindolones

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 76 80 0 0 0 0 0 0 0 0999 V2000 -5.1177 0.1567 -2.0591 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3939 -0.5546 -0.7461 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.5405 -1.7757 -0.7556 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0758 -1.4952 -0.7051 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3218 -1.9812 0.2641 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9173 -1.8810 0.5574 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.1463 -3.0993 0.0944 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1233 -3.1585 0.5628 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9408 -4.3277 0.1484 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0528 -3.8828 -0.5462 O 0 0 0 0 0 0 0 0 0 0 0 0 1.5442 -2.0690 1.4553 C 0 0 1 0 0 0 0 0 0 0 0 0 2.9926 -2.1469 1.8438 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1273 -0.6918 1.0284 C 0 0 1 0 0 0 0 0 0 0 0 0 2.1785 -0.1722 0.0774 C 0 0 2 0 0 0 0 0 0 0 0 0 2.5029 1.2433 0.4167 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5258 1.8121 -0.4935 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2670 2.6853 -1.5208 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4418 2.9815 -2.1333 N 0 0 0 0 0 0 0 0 0 0 0 0 5.4562 2.3217 -1.5280 C 0 0 0 0 0 0 0 0 0 0 0 0 6.8192 2.2527 -1.7269 C 0 0 0 0 0 0 0 0 0 0 0 0 7.6166 1.4621 -0.9135 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0175 0.7380 0.1087 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6617 0.7844 0.3342 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8820 1.5777 -0.4862 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6739 -0.4382 -1.2139 N 0 0 0 0 0 0 0 0 0 0 0 0 0.4374 -0.7354 -1.2181 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1151 -0.7115 0.1330 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.8707 0.5759 0.2894 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7708 1.4542 -0.5464 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7570 0.8227 1.4514 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3063 2.2330 1.3185 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3519 2.5266 2.2838 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1330 3.1546 3.2911 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.7349 2.0394 2.0361 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8922 1.5410 0.5962 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1799 0.2738 0.4539 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8073 2.5768 -0.4503 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1875 -1.0297 -2.4590 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.7763 0.9948 -2.2736 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0375 0.3290 -2.1827 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3480 -0.5785 -2.9154 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4560 -0.9164 -0.7140 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7070 -2.4172 -1.6506 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7953 -2.3528 0.1823 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6168 -0.8882 -1.4536 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9146 -2.5979 1.0020 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7642 -1.9339 1.6998 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5604 -3.8449 -0.5423 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3531 -5.0119 -0.4866 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2603 -4.9407 1.0425 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8867 -3.8391 -1.5416 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9775 -2.2564 2.4298 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6823 -2.4708 1.0580 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3188 -1.1754 2.2985 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1052 -2.9134 2.6646 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9402 -0.0161 1.8879 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1285 -0.7863 0.1705 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6161 1.8787 0.5364 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9404 1.2011 1.4702 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3262 3.1018 -1.8410 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5924 3.6169 -2.9528 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2946 2.8119 -2.5205 H 0 0 0 0 0 0 0 0 0 0 0 0 8.6931 1.3860 -1.0449 H 0 0 0 0 0 0 0 0 0 0 0 0 7.6499 0.1107 0.7552 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2265 0.1968 1.1540 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0626 0.8475 2.3460 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5304 0.0786 1.6232 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4127 2.8973 1.6052 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4853 2.5031 0.2819 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4978 2.8355 2.2168 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9691 1.2279 2.7499 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2920 -0.3319 1.4220 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8625 2.7810 -0.8538 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4996 3.5572 0.0110 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1639 2.4132 -1.2896 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1189 -0.5600 -3.3037 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 2 0 5 6 1 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 1 0 8 11 1 0 11 12 1 0 11 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 1 0 19 20 2 0 20 21 1 0 21 22 2 0 22 23 1 0 23 24 2 0 14 25 1 0 25 26 2 0 27 26 1 6 27 28 1 0 28 29 2 0 28 30 1 0 30 31 1 0 31 32 1 0 32 33 2 0 32 34 1 0 34 35 1 0 35 36 2 0 35 37 1 0 26 38 1 0 36 2 1 0 27 6 1 0 27 13 1 0 24 16 1 0 24 19 1 0 1 39 1 0 1 40 1 0 1 41 1 0 2 42 1 6 3 43 1 0 3 44 1 0 4 45 1 0 5 46 1 0 6 47 1 1 7 48 1 0 9 49 1 0 9 50 1 0 10 51 1 0 11 52 1 1 12 53 1 0 12 54 1 0 12 55 1 0 13 56 1 1 14 57 1 1 15 58 1 0 15 59 1 0 17 60 1 0 18 61 1 0 20 62 1 0 21 63 1 0 22 64 1 0 23 65 1 0 30 66 1 0 30 67 1 0 31 68 1 0 31 69 1 0 34 70 1 0 34 71 1 0 36 72 1 0 37 73 1 0 37 74 1 0 37 75 1 0 38 76 1 0 M END

Standard InCHIKey	VFAYVFXEKSOZAD-RQRAGIARSA-N
Standard InCHI	InChI=1S/C32H38N2O4/c1-19-7-6-8-24-15-23(18-35)21(3)30-28(16-22-17-33-27-10-5-4-9-26(22)27)34-31(38)32(24,30)29(37)12-11-25(36)14-20(2)13-19/h4-6,8-10,13,15,17,19,21,24,28,30,33,35H,7,11-12,14,16,18H2,1-3H3,(H,34,38)/b8-6+,20-13+/t19-,21+,24-,28-,30-,32+/m0/s1
SMILES	C[C@H]1C/C=C/[C@H]2C=C(CO)[C@@H](C)[C@H]3[C@H](Cc4c[nH]c5ccccc45)N=C([C@@]23C(=O)CCC(=O)C/C(=C/1)/C)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	514.28	Volume:	550.036 ? Van der Waals volume.
Dense:	0.935	LogP:	3.358 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.915 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.634 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	34.0
TPSA:	102.75 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	3.0	Rings:	5.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.458	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.981	Fsp³:	0.469
MCE-18:	137.191 ? 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:	0.672	Fluc inhibitor:	0.061 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.288 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.334 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.005	Promiscuous compounds:	0.368

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.296	MDCK Permeability:	-4.764
Pgp-inhibitor:	0.944	Pgp-substrate:	0.086
PAMPA:	0.07 ? 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%):	0.019	30% Bioavailability (F30%):	0.564
50% Bioavailability (F50%):	0.88

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.899
Plasma Protein Binding (PPB):	90.663%	Volume Distribution (VD):	0.089
Fu:	9.548% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.998
OATP1B3 inhibitor:	0.989	BCRP inhibitor:	0.0
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.399
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.082
CYP2C9-inhibitor:	0.034	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.005	CYP2D6-substrate:	0.165
CYP3A4-inhibitor:	0.009	CYP3A4-substrate:	0.474
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.993
HLM stability:	0.975 ? 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):

5.916

Half-life (T1/2):

0.578

ADMET: Toxicity

hERG Blockers:	0.002	hERG Blockers (10um):	0.014
Human Hepatotoxicity (H-HT):	1.0	Drug-induced Liver Injury (DILI):	0.998
AMES Toxicity:	0.53	Rat Oral Acute Toxicity:	0.459
Maximum Recommended Daily Dose:	0.21	Skin Sensitization:	1.0
Carcinogencity:	0.837	Eye Corrosion:	0.0
Eye Irritation:	0.752	Respiratory Toxicity:	0.602
Drug-induced Neurotoxicity:	0.012	Ototoxicity:	0.937
Hematotoxicity:	0.639	Drug-induced Nephrotoxicity:	0.998
Genotoxicity:	1.0	RPMI-8226 Immunitoxicity:	0.032
A549 Cytotoxicity:	0.001	Hek293 Cytotoxicity:	0.076
BCF:	0.663 ? 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:	3.523 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.231 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.494 ? 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
NPO41095	Chaetomium globosum TW1-1	Strain	Chaetomiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[26068802]
NPO41095	Chaetomium globosum TW1-1	Strain	Chaetomiaceae	Eukaryota	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	6

Activity Type	# Activity
Cell line	5
Others	1

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
NPT659	Cell line	SMMC-7721	Homo sapiens	IC50	>	40000.0	nM	PMID[26068802]
NPT116	Cell line	HL-60	Homo sapiens	IC50	>	40000.0	nM	PMID[26068802]
NPT81	Cell line	A549	Homo sapiens	IC50	>	40000.0	nM	PMID[26068802]
NPT83	Cell line	MCF7	Homo sapiens	IC50	>	40000.0	nM	PMID[26068802]
NPT660	Cell line	SW480	Homo sapiens	IC50	>	40000.0	nM	PMID[26068802]
NPT27	Others	Unspecified	n.a.	IC50	>	40000.0	nM	PMID[26068802]

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 NPC487661 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	13537
0.1-0.2	34922
0.2-0.3	1170
0.3-0.4	184
0.4-0.5	17
0.5-0.6	14
0.6-0.7	10
0.7-0.8	0
0.8-0.85	0
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8636	High Similarity	NPC271862
0.732	Intermediate Similarity	NPC487663
0.7188	Intermediate Similarity	NPC487662
0.7041	Intermediate Similarity	NPC487664
0.6875	Remote Similarity	NPC195239
0.6842	Remote Similarity	NPC157828
0.65	Remote Similarity	NPC98715
0.6465	Remote Similarity	NPC267965
0.6436	Remote Similarity	NPC225821
0.6373	Remote Similarity	NPC46225
0.6311	Remote Similarity	NPC487657
0.6176	Remote Similarity	NPC266192
0.6117	Remote Similarity	NPC132211
0.6038	Remote Similarity	NPC487658
0.5943	Remote Similarity	NPC267926
0.5905	Remote Similarity	NPC203614
0.5888	Remote Similarity	NPC235885
0.5849	Remote Similarity	NPC204491
0.5741	Remote Similarity	NPC487660
0.5607	Remote Similarity	NPC141428
0.5607	Remote Similarity	NPC87856
0.5596	Remote Similarity	NPC2395
0.5556	Remote Similarity	NPC151976
0.5455	Remote Similarity	NPC57690
0.5413	Remote Similarity	NPC147446
0.5221	Remote Similarity	NPC487659
0.5185	Remote Similarity	NPC11445
0.5044	Remote Similarity	NPC290529

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC487661 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	5284
0.2-0.3	130
0.3-0.4	28
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