NPASS Compound

Natural Product: NPC488420

Natural Product ID	NPC488420
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	AHOONYRTRBKKRD-GTVAQFAZSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
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 81 84 0 0 0 0 0 0 0 0999 V2000 3.3963 -0.0390 1.6682 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1591 -0.6929 0.3361 C 0 0 2 0 0 0 0 0 0 0 0 0 4.3694 -0.3594 -0.5322 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6485 -0.8269 -0.0270 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0603 -1.9350 -0.3275 O 0 0 0 0 0 0 0 0 0 0 0 0 6.4791 0.0189 0.8527 C 0 0 0 0 0 0 0 0 0 0 0 0 7.9273 0.1051 0.3631 C 0 0 2 0 0 0 0 0 0 0 0 0 8.6245 1.0093 1.3932 C 0 0 0 0 0 0 0 0 0 0 0 0 7.9769 0.8582 -0.9064 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9258 1.2922 -1.4087 O 0 0 0 0 0 0 0 0 0 0 0 0 9.1851 1.0742 -1.5237 O 0 0 0 0 0 0 0 0 0 0 0 0 1.9959 -0.0801 -0.4109 C 0 0 1 0 0 0 0 0 0 0 0 0 1.8835 -0.8549 -1.7229 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4102 -1.2115 -1.8629 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.2331 -0.1590 -1.0438 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.0805 1.1432 -1.8160 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6286 -0.3398 -0.6664 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0525 0.0479 0.5323 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1493 0.6671 1.5192 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4877 0.8607 2.7012 O 0 0 0 0 0 0 0 0 0 0 0 0 0.2116 1.0470 0.9849 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6687 -0.1743 0.2015 C 0 0 2 0 0 0 0 0 0 0 0 0 0.3951 -1.3678 1.0448 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4774 -0.1793 0.8236 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.6986 -1.6788 0.7874 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9566 0.3103 2.1499 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4366 0.1858 2.3302 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2184 -0.1360 1.1075 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.6761 0.6544 -0.0551 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9761 2.1226 0.2687 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.5432 0.3240 -1.2584 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2355 0.4213 -0.3371 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.9969 -0.4232 -1.5956 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6102 -0.9427 -1.6004 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2821 -1.8533 -2.3639 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.5366 0.3370 1.3139 O 0 0 0 0 0 0 0 0 0 0 0 0 0.1257 -2.5100 -1.5579 O 0 0 0 0 0 0 0 0 0 0 0 0 4.2605 -0.5542 2.1324 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6680 1.0109 1.5176 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5635 -0.2057 2.3874 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1379 -1.7847 0.3993 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3215 0.7575 -0.6647 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1596 -0.7445 -1.5763 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1228 1.0590 0.9502 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5780 -0.4774 1.8651 H 0 0 0 0 0 0 0 0 0 0 0 0 8.3649 -0.8924 0.3182 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1322 2.0079 1.2836 H 0 0 0 0 0 0 0 0 0 0 0 0 9.7053 1.0867 1.1890 H 0 0 0 0 0 0 0 0 0 0 0 0 8.3741 0.5911 2.3699 H 0 0 0 0 0 0 0 0 0 0 0 0 9.3073 1.7224 -2.2639 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3027 0.9845 -0.5769 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2434 -0.2229 -2.5306 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4268 -1.8071 -1.6801 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1931 -1.0865 -2.9629 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4749 0.8815 -2.8481 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9515 1.4241 -1.9817 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7636 1.9375 -1.4698 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0843 1.9410 0.3746 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8181 1.2939 1.8474 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0039 -1.0883 2.0706 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3342 -2.0876 0.6656 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3191 -1.9743 1.2812 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3021 -2.0320 -0.0458 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2310 -2.0457 1.7181 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7142 -2.2386 0.8434 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4732 -0.2968 2.9410 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6995 1.3568 2.3742 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8756 1.1172 2.7995 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6905 -0.6132 3.0922 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3255 -1.2130 0.9196 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0098 2.7325 -0.6561 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0342 2.1072 0.6542 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2931 2.5270 1.0197 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7406 -0.7508 -1.3467 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1159 0.7641 -2.1961 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.5241 0.8368 -1.1279 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7607 1.4057 -0.5514 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0332 0.2816 -2.4840 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7772 -1.1499 -1.7939 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.9408 -0.1887 2.0454 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9082 -3.0882 -1.4196 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 4 6 1 0 6 7 1 0 7 8 1 0 7 9 1 0 9 10 2 0 9 11 1 0 2 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 6 15 17 1 0 17 18 2 0 18 19 1 0 19 20 2 0 19 21 1 0 21 22 1 0 22 23 1 1 18 24 1 0 24 25 1 1 24 26 1 0 26 27 1 0 27 28 1 0 28 29 1 0 29 30 1 0 29 31 1 0 29 32 1 0 32 33 1 0 33 34 1 0 34 35 2 0 28 36 1 0 14 37 1 0 22 12 1 0 32 24 1 0 22 15 1 0 34 17 1 0 1 38 1 0 1 39 1 0 1 40 1 0 2 41 1 1 3 42 1 0 3 43 1 0 6 44 1 0 6 45 1 0 7 46 1 6 8 47 1 0 8 48 1 0 8 49 1 0 11 50 1 0 12 51 1 6 13 52 1 0 13 53 1 0 14 54 1 6 16 55 1 0 16 56 1 0 16 57 1 0 21 58 1 0 21 59 1 0 23 60 1 0 23 61 1 0 23 62 1 0 25 63 1 0 25 64 1 0 25 65 1 0 26 66 1 0 26 67 1 0 27 68 1 0 27 69 1 0 28 70 1 6 30 71 1 0 30 72 1 0 30 73 1 0 31 74 1 0 31 75 1 0 31 76 1 0 32 77 1 6 33 78 1 0 33 79 1 0 36 80 1 0 37 81 1 0 M END

Standard InCHIKey	AHOONYRTRBKKRD-GTVAQFAZSA-N
Standard InCHI	InChI=1S/C30H44O7/c1-15(10-17(31)11-16(2)26(36)37)18-12-23(35)30(7)25-19(32)13-21-27(3,4)22(34)8-9-28(21,5)24(25)20(33)14-29(18,30)6/h15-16,18,21-23,34-35H,8-14H2,1-7H3,(H,36,37)/t15-,16+,18-,21+,22-,23-,28+,29-,30+/m1/s1
SMILES	C[C@H](CC(=O)C[C@H](C)C(=O)O)[C@H]1C[C@H]([C@@]2(C)C3=C(C(=O)C[C@]12C)[C@@]1(C)CC[C@H](C(C)(C)[C@@H]1CC3=O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	516.31	Volume:	541.559 ? Van der Waals volume.
Dense:	0.953	LogP:	2.167 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.167 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.712 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	24.0
TPSA:	128.97 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	3.0	Rings:	4.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.484	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.081	Fsp³:	0.8
MCE-18:	89.333 ? 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:	0.824	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.142 ? 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:	0.323	Promiscuous compounds:	0.333

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.335	MDCK Permeability:	-4.569
Pgp-inhibitor:	0.001	Pgp-substrate:	0.027
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):	0.0
20% Bioavailability (F20%):	0.001	30% Bioavailability (F30%):	0.0
50% Bioavailability (F50%):	0.098

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.996
Plasma Protein Binding (PPB):	85.321%	Volume Distribution (VD):	-0.289
Fu:	16.041% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.998	BCRP inhibitor:	0.0
BSEP inhibitor:	0.997

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.004
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.001	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.01
HLM stability:	0.025 ? 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):

3.553

Half-life (T1/2):

2.07

ADMET: Toxicity

hERG Blockers:	0.002	hERG Blockers (10um):	0.009
Human Hepatotoxicity (H-HT):	0.542	Drug-induced Liver Injury (DILI):	0.225
AMES Toxicity:	0.342	Rat Oral Acute Toxicity:	0.443
Maximum Recommended Daily Dose:	0.699	Skin Sensitization:	0.995
Carcinogencity:	0.743	Eye Corrosion:	0.001
Eye Irritation:	0.418	Respiratory Toxicity:	0.526
Drug-induced Neurotoxicity:	0.028	Ototoxicity:	0.786
Hematotoxicity:	0.656	Drug-induced Nephrotoxicity:	0.993
Genotoxicity:	0.917	RPMI-8226 Immunitoxicity:	0.108
A549 Cytotoxicity:	0.015	Hek293 Cytotoxicity:	0.081
BCF:	0.362 ? 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:	3.066 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.589 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.686 ? 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
NPO40142	Ganoderma weberianum	Species	Polyporaceae	Eukaryota	Fruiting Bodies	n.a.	n.a.	PMID[33107297]
NPO40142	Ganoderma weberianum	Species	Polyporaceae	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	2

Activity Type	# Activity
Cell line	1
Organism	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
NPT189	Cell line	Vero	Chlorocebus aethiops	IC50	>=	87000.0	nM	PMID[33107297]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	>=	17000.0	nM	PMID[33107297]

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 NPC488420 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	19126
0.1-0.2	27380
0.2-0.3	3051
0.3-0.4	218
0.4-0.5	55
0.5-0.6	14
0.6-0.7	5
0.7-0.8	0
0.8-0.85	3
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	NPC600686
0.8125	Intermediate Similarity	NPC55872
0.8	Intermediate Similarity	NPC95565
0.8	Intermediate Similarity	NPC609201
0.7969	Intermediate Similarity	NPC488423
0.7812	Intermediate Similarity	NPC241156
0.7812	Intermediate Similarity	NPC488419
0.7812	Intermediate Similarity	NPC600288
0.7778	Intermediate Similarity	NPC255809
0.6714	Remote Similarity	NPC16021
0.6479	Remote Similarity	NPC606047
0.6389	Remote Similarity	NPC25750
0.6389	Remote Similarity	NPC610087
0.6377	Remote Similarity	NPC157787
0.5946	Remote Similarity	NPC2436
0.5789	Remote Similarity	NPC488422
0.5753	Remote Similarity	NPC488421
0.5676	Remote Similarity	NPC51452
0.5616	Remote Similarity	NPC28656
0.5479	Remote Similarity	NPC125622
0.5429	Remote Similarity	NPC209882
0.5429	Remote Similarity	NPC607131
0.5385	Remote Similarity	NPC115303
0.5263	Remote Similarity	NPC243525
0.5263	Remote Similarity	NPC40765
0.5132	Remote Similarity	NPC10364
0.5063	Remote Similarity	NPC21358
0.5063	Remote Similarity	NPC234892

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC488420 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5892
0.1-0.2	3186
0.2-0.3	71
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