NPASS Compound

Natural Product: NPC475789

Natural Product ID	NPC475789
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	24,28-Epoxyergost-5-Ene-3Beta,7Alpha-Diol
IUPAC Name	(3S,7S,8S,9S,10R,13R,14S,17R)-10,13-dimethyl-17-[(2R)-4-(2-propan-2-yloxiran-2-yl)butan-2-yl]-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthrene-3,7-diol
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL515957
PubChem CID	10048354
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0003567] Ergostane steroids [CHEMONTID:0001403] Ergosterols 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 77 81 0 0 0 0 0 0 0 0999 V2000 -4.0286 -1.7208 1.9323 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9408 -1.9469 0.7595 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1167 -2.8327 1.1275 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4201 -0.6715 0.1117 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1667 0.2543 0.9201 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.8929 -0.6307 0.0480 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.7995 -0.2893 -1.2404 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3269 -0.0874 -1.1733 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9195 1.0406 -0.2315 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5165 2.3573 -0.6663 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5648 1.0151 0.2407 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3508 2.2290 1.1723 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1654 2.3210 1.3608 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6358 1.0896 0.6661 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3301 1.0569 -0.5361 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0513 -0.0575 -1.4079 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2452 -0.8929 -0.9107 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3893 0.0859 -0.7965 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0499 0.9298 0.4218 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9294 2.1643 0.4741 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3191 1.6336 0.4478 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6640 0.4575 -0.0520 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7311 -0.5213 -0.6663 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7805 -1.8139 0.1126 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1896 -2.3535 -0.0749 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2594 -1.4222 0.3862 C 0 0 0 0 0 0 0 0 0 0 0 0 6.1035 0.0033 -0.0127 C 0 0 0 0 0 0 0 0 0 0 0 0 7.4703 -1.8788 -0.1530 O 0 0 0 0 0 0 0 0 0 0 0 0 4.1896 -0.9026 -2.0878 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7721 2.7671 1.7408 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.1853 2.3629 -1.3298 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3935 -0.8096 2.4614 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9959 -1.5962 1.5480 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0281 -2.6091 2.5861 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3488 -2.5231 0.0076 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4406 -2.4815 2.1508 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9797 -2.6800 0.4515 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8307 -3.9013 1.1751 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2512 0.0853 1.9919 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3426 1.3116 0.6107 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9938 -1.2047 -1.8792 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3684 0.5098 -1.7260 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9101 -1.0691 -0.7900 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9362 0.0233 -2.1775 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5736 0.8047 0.6766 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7557 3.0023 0.2350 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4607 2.2522 -1.2023 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7426 2.9261 -1.1868 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4525 0.1457 0.9659 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7912 2.0298 2.1600 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7821 3.1383 0.7580 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5858 3.2601 1.0131 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4363 2.2227 2.4394 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2664 0.2254 1.3048 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7154 -0.8005 -1.6617 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4135 0.3073 -2.4189 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9883 -1.2950 0.0774 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4165 -1.6533 -1.6869 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3954 0.6792 -1.7317 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4870 0.3091 1.2750 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7312 2.9233 -0.2627 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1521 2.2288 0.8634 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6225 -1.6948 1.1827 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0981 -2.5342 -0.3759 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3247 -3.3064 0.5059 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3713 -2.5909 -1.1554 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3012 -1.5085 1.5055 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6815 0.6257 0.7116 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5380 0.2193 -1.0039 H 0 0 0 0 0 0 0 0 0 0 0 0 8.0991 -1.1356 -0.3277 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6647 -0.2376 -2.8295 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2792 -0.8340 -2.1737 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8336 -1.9272 -2.3192 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3257 2.2641 2.3930 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8679 2.5062 -1.6891 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7505 2.2242 -2.2799 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4224 3.2507 -0.7558 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 2 4 1 0 4 5 1 0 5 6 1 0 4 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 9 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 2 0 22 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 26 27 1 0 26 28 1 0 23 29 1 0 20 30 1 0 15 31 1 0 6 4 1 0 15 11 1 0 19 14 1 0 23 18 1 0 27 22 1 0 1 32 1 0 1 33 1 0 1 34 1 0 2 35 1 0 3 36 1 0 3 37 1 0 3 38 1 0 5 39 1 0 5 40 1 0 7 41 1 0 7 42 1 0 8 43 1 0 8 44 1 0 9 45 1 0 10 46 1 0 10 47 1 0 10 48 1 0 11 49 1 0 12 50 1 0 12 51 1 0 13 52 1 0 13 53 1 0 14 54 1 0 16 55 1 0 16 56 1 0 17 57 1 0 17 58 1 0 18 59 1 0 19 60 1 0 20 61 1 0 21 62 1 0 24 63 1 0 24 64 1 0 25 65 1 0 25 66 1 0 26 67 1 0 27 68 1 0 27 69 1 0 28 70 1 0 29 71 1 0 29 72 1 0 29 73 1 0 30 74 1 0 31 75 1 0 31 76 1 0 31 77 1 0 M END

Standard InCHIKey	NEKARFIZRJHOEJ-ZNCVFNLDSA-N
Standard InCHI	InChI=1S/C28H46O3/c1-17(2)28(16-31-28)13-8-18(3)21-6-7-22-25-23(10-12-27(21,22)5)26(4)11-9-20(29)14-19(26)15-24(25)30/h15,17-18,20-25,29-30H,6-14,16H2,1-5H3/t18-,20+,21-,22+,23+,24-,25+,26+,27-,28?/m1/s1
SMILES	CC(C)C1(CO1)CCC(C)C2CCC3C2(CCC4C3C(C=C5C4(CCC(C5)O)C)O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	430.34	Volume:	473.796 ? Van der Waals volume.
Dense:	0.908	LogP:	4.918 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.57 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.555 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	23.0
TPSA:	52.99 ? Topological Polar Surface Area.	H-Bond Acceptor:	3.0
H-Bond Donor:	2.0	Rings:	5.0
Heavy Atoms:	3.0

MedChem Properties

QED Drug-Likeness Score:	0.432	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.88	Fsp³:	0.929
MCE-18:	86.778 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted	GSK Rule:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.632	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.008 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.018 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.122	Promiscuous compounds:	0.011

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.019	MDCK Permeability:	-4.919
Pgp-inhibitor:	0.124	Pgp-substrate:	0.073
PAMPA:	0.065 ? 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%):	0.012	30% Bioavailability (F30%):	0.097
50% Bioavailability (F50%):	0.992

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.851	MRP1:	1.0
Plasma Protein Binding (PPB):	82.316%	Volume Distribution (VD):	0.071
Fu:	18.99% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.049
OATP1B3 inhibitor:	0.63	BCRP inhibitor:	0.009
BSEP inhibitor:	0.978

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.812	CYP2C19-substrate:	0.002
CYP2C9-inhibitor:	0.217	CYP2C9-substrate:	0.001
CYP2D6-inhibitor:	0.042	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.826	CYP3A4-substrate:	0.872
CYP2B6-substrate:	0.998	CYP2C8-inhibitor:	0.191
HLM stability:	0.567 ? 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):

17.208

Half-life (T1/2):

1.387

ADMET: Toxicity

hERG Blockers:	0.56	hERG Blockers (10um):	0.814
Human Hepatotoxicity (H-HT):	0.746	Drug-induced Liver Injury (DILI):	0.137
AMES Toxicity:	0.412	Rat Oral Acute Toxicity:	0.216
Maximum Recommended Daily Dose:	0.894	Skin Sensitization:	0.256
Carcinogencity:	0.409	Eye Corrosion:	0.0
Eye Irritation:	0.018	Respiratory Toxicity:	0.728
Drug-induced Neurotoxicity:	0.398	Ototoxicity:	0.935
Hematotoxicity:	0.112	Drug-induced Nephrotoxicity:	0.112
Genotoxicity:	0.01	RPMI-8226 Immunitoxicity:	0.069
A549 Cytotoxicity:	0.238	Hek293 Cytotoxicity:	0.625
BCF:	2.387 ? 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:	5.04 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.138 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.725 ? 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
NPO11093	Pseudobersama mossambicensis	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[1479381]
NPO11093	Pseudobersama mossambicensis	Species	Meliaceae	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
IC12	3

Activity Type	# Activity
Organism	3

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
NPT312	Organism	Saccharomyces cerevisiae	Saccharomyces cerevisiae	IC12	=	0.4	ug ml-1	PMID[25747495]
NPT312	Organism	Saccharomyces cerevisiae	Saccharomyces cerevisiae	IC12	=	6.0	ug ml-1	PMID[17958396]
NPT312	Organism	Saccharomyces cerevisiae	Saccharomyces cerevisiae	IC12	>	50.0	ug ml-1	PMID[21401023]

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 NPC475789 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	19553
0.1-0.2	26921
0.2-0.3	3148
0.3-0.4	153
0.4-0.5	54
0.5-0.6	13
0.6-0.7	4
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
0.7407	Intermediate Similarity	NPC81306
0.7143	Intermediate Similarity	NPC109546
0.7143	Intermediate Similarity	NPC189972
0.7143	Intermediate Similarity	NPC47982
0.7119	Intermediate Similarity	NPC603646
0.7018	Intermediate Similarity	NPC84694
0.7018	Intermediate Similarity	NPC28862
0.7018	Intermediate Similarity	NPC143182
0.6897	Remote Similarity	NPC317927
0.6667	Remote Similarity	NPC474634
0.661	Remote Similarity	NPC234193
0.6441	Remote Similarity	NPC609126
0.5735	Remote Similarity	NPC218186
0.5606	Remote Similarity	NPC488870
0.5556	Remote Similarity	NPC23852
0.5469	Remote Similarity	NPC209620
0.5303	Remote Similarity	NPC152808
0.5161	Remote Similarity	NPC162742
0.5161	Remote Similarity	NPC304309
0.5161	Remote Similarity	NPC470228
0.5079	Remote Similarity	NPC22105
0.5079	Remote Similarity	NPC34019
0.5079	Remote Similarity	NPC107059
0.5075	Remote Similarity	NPC474752
0.5075	Remote Similarity	NPC474683

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC475789 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6779
0.1-0.2	2198
0.2-0.3	154
0.3-0.4	15
0.4-0.5	2
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