NPASS Compound

Natural Product: NPC580203

Natural Product ID	NPC580203
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	23-acetoxy-24,25-epoxycholest-4-en-3-one
IUPAC Name	[(3~{R})-1-(3,3-dimethyloxiran-2-yl)-3-[(8~{S},9~{S},10~{R},13~{R},14~{S},17~{R})-10,13-dimethyl-3-oxo-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl]butyl] acetate
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 77 81 0 0 0 0 0 0 0 0999 V2000 4.9025 -2.5397 2.2986 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9289 -1.5041 1.8830 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8358 -1.3498 2.4760 O 0 0 0 0 0 0 0 0 0 0 0 0 4.2087 -0.6892 0.8334 O 0 0 0 0 0 0 0 0 0 0 0 0 3.3886 0.3388 0.3174 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0550 0.2089 -1.1028 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3178 -0.9895 -1.5719 C 0 0 1 0 0 0 0 0 0 0 0 0 3.0103 -2.2973 -1.2868 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8690 -0.9748 -1.6559 C 0 0 1 0 0 0 0 0 0 0 0 0 0.3865 -2.3423 -2.1752 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0078 -2.5344 -1.6245 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3602 -1.1548 -1.2187 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.5834 -0.9661 -0.4508 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.7510 -1.3491 -1.3946 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9741 -1.3867 -0.5292 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0867 -0.2108 0.3693 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2721 0.0581 0.8845 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.4035 1.2078 1.7683 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.1746 1.1637 2.7668 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.6039 2.4124 1.4469 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3529 2.1357 0.6796 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9555 0.6668 0.7172 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.5530 0.3522 2.1512 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7786 0.4830 -0.1685 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.5525 1.1780 0.3547 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3223 0.8686 -0.4580 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0622 -0.6269 -0.5762 C 0 0 2 0 0 0 0 0 0 0 0 0 0.0714 -1.1973 0.7616 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0818 1.6303 0.6804 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5073 2.8544 0.3103 O 0 0 0 0 0 0 0 0 0 0 0 0 4.9110 2.4603 -0.0765 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9480 3.3174 0.6858 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0413 2.6487 -1.5426 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4306 -3.5467 2.3911 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6991 -2.6402 1.5398 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3533 -2.3310 3.2928 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4775 0.3266 0.9368 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0391 0.3491 -1.6540 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4306 1.1008 -1.3902 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5934 -0.9353 -2.7225 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0460 -2.9814 -2.1545 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0498 -2.1858 -0.9506 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4777 -2.8128 -0.4867 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5751 -0.2758 -2.5204 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0624 -3.1623 -1.8945 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3193 -2.3667 -3.2797 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0314 -3.2711 -0.7969 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7085 -2.8530 -2.4442 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4476 -0.5482 -2.1616 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7672 -1.6263 0.4172 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8390 -0.6500 -2.2234 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5409 -2.3987 -1.6941 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9403 -2.3017 0.1252 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8606 -1.5153 -1.1817 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1418 -0.5720 0.6551 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2993 3.0793 0.8578 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3793 2.9828 2.3728 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5303 2.4586 -0.3851 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5319 2.7419 1.1098 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8828 -0.5153 2.1457 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1078 1.2412 2.6496 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4485 0.0647 2.7586 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0205 0.9794 -1.1542 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3929 1.0145 1.4438 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7330 2.2696 0.2435 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4378 1.3321 -1.4587 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5353 1.3272 0.0618 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9287 -1.5489 1.1201 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7215 -2.0733 0.8962 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2965 -0.3941 1.5309 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2450 1.6228 1.8062 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8772 2.7129 0.6723 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6541 3.4454 1.7265 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0691 4.2984 0.1868 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7784 1.9412 -2.0280 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0759 2.6865 -2.1120 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4938 3.6587 -1.8000 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 7 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 2 0 17 18 1 0 18 19 2 0 18 20 1 0 20 21 1 0 21 22 1 0 22 23 1 1 22 24 1 0 24 25 1 0 25 26 1 0 26 27 1 0 27 28 1 1 5 29 1 0 29 30 1 0 30 31 1 0 31 32 1 0 31 33 1 0 27 9 1 0 31 29 1 0 27 12 1 0 24 13 1 0 22 16 1 0 1 34 1 0 1 35 1 0 1 36 1 0 5 37 1 0 6 38 1 0 6 39 1 0 7 40 1 6 8 41 1 0 8 42 1 0 8 43 1 0 9 44 1 6 10 45 1 0 10 46 1 0 11 47 1 0 11 48 1 0 12 49 1 6 13 50 1 1 14 51 1 0 14 52 1 0 15 53 1 0 15 54 1 0 17 55 1 0 20 56 1 0 20 57 1 0 21 58 1 0 21 59 1 0 23 60 1 0 23 61 1 0 23 62 1 0 24 63 1 6 25 64 1 0 25 65 1 0 26 66 1 0 26 67 1 0 28 68 1 0 28 69 1 0 28 70 1 0 29 71 1 0 32 72 1 0 32 73 1 0 32 74 1 0 33 75 1 0 33 76 1 0 33 77 1 0 M END

Standard InCHIKey	GQKGDFOPNMTQJF-HYPMIEHGSA-N
Standard InCHI	InChI=1S/C29H44O4/c1-17(15-25(32-18(2)30)26-27(3,4)33-26)22-9-10-23-21-8-7-19-16-20(31)11-13-28(19,5)24(21)12-14-29(22,23)6/h16-17,21-26H,7-15H2,1-6H3/t17-,21+,22-,23+,24+,25?,26?,28+,29-/m1/s1
SMILES	CC(=O)OC(C[C@@H](C)[C@H]1CC[C@H]2[C@@H]3CCC4=CC(=O)CC[C@]4(C)[C@H]3CC[C@]12C)C1OC1(C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	456.32	Volume:	494.609 ? Van der Waals volume.
Dense:	0.923	LogP:	5.345 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.14 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.523 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	25.0
TPSA:	55.9 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	0.0	Rings:	5.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.361	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.711	Fsp³:	0.862
MCE-18:	88.148 ? 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:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.715	Fluc inhibitor:	0.001 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.006 ? 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:	0.296	Promiscuous compounds:	0.75

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.917	MDCK Permeability:	-4.852
Pgp-inhibitor:	0.761	Pgp-substrate:	0.001
PAMPA:	0.001 ? 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%):	0.028	30% Bioavailability (F30%):	0.469
50% Bioavailability (F50%):	0.924

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.136	MRP1:	0.423
Plasma Protein Binding (PPB):	96.04%	Volume Distribution (VD):	-0.218
Fu:	4.435% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.28
BSEP inhibitor:	0.995

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.972
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.036
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.982
CYP2D6-inhibitor:	0.028	CYP2D6-substrate:	1.0
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	1.0 ? 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):

10.946

Half-life (T1/2):

0.321

ADMET: Toxicity

hERG Blockers:	0.112	hERG Blockers (10um):	0.476
Human Hepatotoxicity (H-HT):	0.657	Drug-induced Liver Injury (DILI):	0.639
AMES Toxicity:	0.381	Rat Oral Acute Toxicity:	0.272
Maximum Recommended Daily Dose:	0.567	Skin Sensitization:	0.938
Carcinogencity:	0.877	Eye Corrosion:	0.134
Eye Irritation:	0.785	Respiratory Toxicity:	0.411
Drug-induced Neurotoxicity:	0.596	Ototoxicity:	0.357
Hematotoxicity:	0.5	Drug-induced Nephrotoxicity:	0.495
Genotoxicity:	0.679	RPMI-8226 Immunitoxicity:	0.06
A549 Cytotoxicity:	0.095	Hek293 Cytotoxicity:	0.56
BCF:	1.909 ? 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:	4.321 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.736 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.31 ? 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
NPO25775	Dasystenella acanthina	Species	Primnoidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO25775	Dasystenella acanthina	Species	Primnoidae	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

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

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 NPC580203 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	20346
0.1-0.2	24530
0.2-0.3	4732
0.3-0.4	186
0.4-0.5	39
0.5-0.6	17
0.6-0.7	8
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
0.6964	Remote Similarity	NPC159577
0.6786	Remote Similarity	NPC282593
0.6667	Remote Similarity	NPC35734
0.6667	Remote Similarity	NPC602429
0.6552	Remote Similarity	NPC149203
0.625	Remote Similarity	NPC307176
0.625	Remote Similarity	NPC321874
0.6102	Remote Similarity	NPC115023
0.5938	Remote Similarity	NPC320514
0.5932	Remote Similarity	NPC214043
0.5932	Remote Similarity	NPC85774
0.5902	Remote Similarity	NPC249312
0.5902	Remote Similarity	NPC323765
0.5738	Remote Similarity	NPC237712
0.5286	Remote Similarity	NPC187159
0.5254	Remote Similarity	NPC139397
0.5161	Remote Similarity	NPC227064
0.5161	Remote Similarity	NPC329043
0.5161	Remote Similarity	NPC58841
0.5161	Remote Similarity	NPC161423
0.5156	Remote Similarity	NPC303613
0.5147	Remote Similarity	NPC205860
0.5082	Remote Similarity	NPC2634
0.5082	Remote Similarity	NPC265782
0.5082	Remote Similarity	NPC251929

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC580203 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6426
0.1-0.2	2431
0.2-0.3	215
0.3-0.4	55
0.4-0.5	10
0.5-0.6	12
0.6-0.7	1
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
0.625	Remote Similarity	NPD4747	Phase 4
0.5968	Remote Similarity	NPD5737	Phase 4
0.5625	Remote Similarity	NPD6409	Approved
0.5556	Remote Similarity	NPD5330	Phase 4
0.5538	Remote Similarity	NPD6672	Phase 4
0.5161	Remote Similarity	NPD3666	Phase 4
0.5147	Remote Similarity	NPD6684	Phase 4
0.5147	Remote Similarity	NPD7334	Approved
0.5147	Remote Similarity	NPD7521	Phase 4
0.5082	Remote Similarity	NPD4691	Approved
0.5077	Remote Similarity	NPD6938	Clinical (unspecified phase)
0.5077	Remote Similarity	NPD6939	Phase 3
0.5072	Remote Similarity	NPD6903	Phase 4

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