NPASS Compound

Natural Product: NPC481066

Natural Product ID	NPC481066
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	QZBHYGQMPZZAOD-FXFUGHCXSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	132487993
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001550] Sesquiterpenoids [CHEMONTID:0002051] Agarofurans

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 74 78 0 0 0 0 0 0 0 0999 V2000 0.5036 -4.2076 -2.0979 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4326 -3.5105 -1.1155 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.5250 -2.7555 -1.7738 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5491 -1.2974 -1.6641 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.8148 -0.7121 -0.4394 C 0 0 1 0 0 0 0 0 0 0 0 0 0.5457 -1.2840 -0.4908 C 0 0 1 0 0 0 0 0 0 0 0 0 1.0607 -1.1821 -1.9046 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5971 -0.7212 0.3913 C 0 0 2 0 0 0 0 0 0 0 0 0 1.5778 -1.2591 1.8137 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6045 -2.7545 1.8053 C 0 0 2 0 0 0 0 0 0 0 0 0 1.5840 -3.3234 0.3752 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3161 -2.7461 -0.0759 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.5121 -2.7026 1.0673 O 0 0 0 0 0 0 0 0 0 0 0 0 0.1622 -3.1756 2.1469 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0489 -4.6332 2.4101 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3119 -2.4327 3.3850 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7714 0.6643 0.3502 O 0 0 0 0 0 0 0 0 0 0 0 0 2.9154 1.2888 -0.1187 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8325 0.5243 -0.5294 O 0 0 0 0 0 0 0 0 0 0 0 0 3.1186 2.7283 -0.1651 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2882 3.2519 -0.6702 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5067 4.6332 -0.7197 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5538 5.4971 -0.2631 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3840 4.9964 0.2429 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1714 3.6192 0.2900 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9613 0.6606 -0.4350 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7414 1.2867 0.5254 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3010 0.5294 1.3940 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.9719 2.6877 0.6263 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7471 3.2322 1.6175 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9628 4.6171 1.6877 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3987 5.4530 0.7612 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6215 4.9159 -0.2342 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4196 3.5541 -0.2889 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8918 -0.8009 -1.5200 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4377 0.1636 -2.3340 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6797 0.6182 -3.2562 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.8279 0.6649 -2.1702 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5550 -5.3200 -1.9210 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1632 -4.1085 -3.1455 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5669 -3.8752 -1.9531 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9313 -4.3631 -0.5541 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4735 -3.0170 -2.8770 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5553 -3.1422 -1.4974 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1364 -0.7295 -2.5330 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4074 -1.1381 0.4204 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1714 -1.3444 -1.8979 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5809 -1.8057 -2.6400 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9291 -0.1215 -2.2142 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5710 -1.1416 -0.0207 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7019 -0.8174 2.3072 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4723 -0.8876 2.3290 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3417 -3.2265 2.4387 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4552 -4.4352 0.5492 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4846 -3.1478 -0.1851 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3506 -5.2400 1.6024 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5914 -4.8420 3.3167 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0710 -5.0045 2.7082 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9292 -3.1239 4.0296 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5348 -2.1236 4.0280 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9970 -1.5939 3.1329 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0449 2.5957 -1.0317 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4271 5.0462 -1.1172 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7582 6.5769 -0.3170 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6487 5.6990 0.5965 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2655 3.2189 0.6852 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2129 2.6285 2.3683 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5804 5.0150 2.4835 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5559 6.5408 0.7991 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1819 5.5751 -0.9576 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7924 3.1470 -1.0965 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4703 0.0601 -2.8623 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8352 1.7405 -2.4630 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1771 0.6168 -1.1339 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 1 0 5 6 1 0 6 7 1 6 6 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 1 13 14 1 0 14 15 1 0 14 16 1 0 8 17 1 0 17 18 1 0 18 19 2 0 18 20 1 0 20 21 2 0 21 22 1 0 22 23 2 0 23 24 1 0 24 25 2 0 5 26 1 0 26 27 1 0 27 28 2 0 27 29 1 0 29 30 2 0 30 31 1 0 31 32 2 0 32 33 1 0 33 34 2 0 4 35 1 0 35 36 1 0 36 37 2 0 36 38 1 0 12 2 1 0 25 20 1 0 34 29 1 0 12 6 1 0 14 10 1 0 1 39 1 0 1 40 1 0 1 41 1 0 2 42 1 1 3 43 1 0 3 44 1 0 4 45 1 6 5 46 1 1 7 47 1 0 7 48 1 0 7 49 1 0 8 50 1 6 9 51 1 0 9 52 1 0 10 53 1 1 11 54 1 0 11 55 1 0 15 56 1 0 15 57 1 0 15 58 1 0 16 59 1 0 16 60 1 0 16 61 1 0 21 62 1 0 22 63 1 0 23 64 1 0 24 65 1 0 25 66 1 0 30 67 1 0 31 68 1 0 32 69 1 0 33 70 1 0 34 71 1 0 38 72 1 0 38 73 1 0 38 74 1 0 M END

Standard InCHIKey	QZBHYGQMPZZAOD-FXFUGHCXSA-N
Standard InCHI	InChI=1S/C31H36O7/c1-19-16-24(35-20(2)32)26(37-28(34)22-14-10-7-11-15-22)30(5)25(36-27(33)21-12-8-6-9-13-21)17-23-18-31(19,30)38-29(23,3)4/h6-15,19,23-26H,16-18H2,1-5H3/t19-,23-,24-,25+,26+,30-,31+/m1/s1
SMILES	C[C@@H]1C[C@H]([C@@H]([C@@]2(C)[C@H](C[C@@H]3C[C@]12OC3(C)C)OC(=O)c1ccccc1)OC(=O)c1ccccc1)OC(=O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	520.25	Volume:	539.753 ? Van der Waals volume.
Dense:	0.964	LogP:	3.955 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.718 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.266 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	8.0	Rigid Bonds:	29.0
TPSA:	88.13 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	0.0	Rings:	5.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.387	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.451	Fsp³:	0.516
MCE-18:	151.915 ? 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:	0.719	Fluc inhibitor:	0.341 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.012 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.054 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.307	Promiscuous compounds:	0.1

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.114	MDCK Permeability:	-4.691
Pgp-inhibitor:	0.994	Pgp-substrate:	0.477
PAMPA:	0.122 ? 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%):	0.022	30% Bioavailability (F30%):	0.037
50% Bioavailability (F50%):	0.871

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.948	MRP1:	1.0
Plasma Protein Binding (PPB):	96.062%	Volume Distribution (VD):	-0.052
Fu:	3.648% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.987
OATP1B3 inhibitor:	0.528	BCRP inhibitor:	0.357
BSEP inhibitor:	0.996

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.624
CYP2C19-inhibitor:	0.001	CYP2C19-substrate:	0.03
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.028
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.006
CYP3A4-inhibitor:	0.947	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.992 ? 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):

6.115

Half-life (T1/2):

0.427

ADMET: Toxicity

hERG Blockers:	0.135	hERG Blockers (10um):	0.806
Human Hepatotoxicity (H-HT):	0.094	Drug-induced Liver Injury (DILI):	0.838
AMES Toxicity:	0.29	Rat Oral Acute Toxicity:	0.164
Maximum Recommended Daily Dose:	0.462	Skin Sensitization:	0.97
Carcinogencity:	0.674	Eye Corrosion:	0.001
Eye Irritation:	0.458	Respiratory Toxicity:	0.143
Drug-induced Neurotoxicity:	0.767	Ototoxicity:	0.197
Hematotoxicity:	0.033	Drug-induced Nephrotoxicity:	0.546
Genotoxicity:	0.206	RPMI-8226 Immunitoxicity:	0.052
A549 Cytotoxicity:	0.31	Hek293 Cytotoxicity:	0.371
BCF:	1.075 ? 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:	4.22 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.531 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.196 ? 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
NPO40471	Celastrus subspicata	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[28548851]

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	1

Activity Type	# Activity
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
NPT2	Others	Unspecified	n.a.	IC50	=	7000.0	nM	PMID[28548851]

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 NPC481066 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	16355
0.1-0.2	31478
0.2-0.3	1475
0.3-0.4	375
0.4-0.5	118
0.5-0.6	36
0.6-0.7	12
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8125	Intermediate Similarity	NPC36021
0.7167	Intermediate Similarity	NPC147561
0.6949	Remote Similarity	NPC481065
0.6875	Remote Similarity	NPC483879
0.6875	Remote Similarity	NPC481070
0.6667	Remote Similarity	NPC214550
0.6615	Remote Similarity	NPC481067
0.6154	Remote Similarity	NPC195647
0.6154	Remote Similarity	NPC200592
0.6154	Remote Similarity	NPC610542
0.6119	Remote Similarity	NPC37641
0.6119	Remote Similarity	NPC473860
0.6081	Remote Similarity	NPC276735
0.6029	Remote Similarity	NPC472577
0.5972	Remote Similarity	NPC481071
0.5882	Remote Similarity	NPC114927
0.5811	Remote Similarity	NPC481068
0.5797	Remote Similarity	NPC483902
0.5775	Remote Similarity	NPC66985
0.5714	Remote Similarity	NPC483872
0.5672	Remote Similarity	NPC473081
0.5672	Remote Similarity	NPC270498
0.5588	Remote Similarity	NPC481047
0.5588	Remote Similarity	NPC481045
0.5584	Remote Similarity	NPC481069
0.5584	Remote Similarity	NPC473109
0.5513	Remote Similarity	NPC470231
0.5493	Remote Similarity	NPC479047
0.5493	Remote Similarity	NPC291638
0.5455	Remote Similarity	NPC483878
0.5443	Remote Similarity	NPC483874
0.5417	Remote Similarity	NPC43241
0.5417	Remote Similarity	NPC177340
0.5342	Remote Similarity	NPC473673
0.5333	Remote Similarity	NPC473082
0.5278	Remote Similarity	NPC483883
0.5278	Remote Similarity	NPC151585
0.527	Remote Similarity	NPC479044
0.5263	Remote Similarity	NPC607428
0.5244	Remote Similarity	NPC473214
0.5139	Remote Similarity	NPC473060
0.5072	Remote Similarity	NPC283375
0.5072	Remote Similarity	NPC474608
0.5068	Remote Similarity	NPC4341
0.5068	Remote Similarity	NPC191082
0.5068	Remote Similarity	NPC147880
0.5067	Remote Similarity	NPC472574
0.5065	Remote Similarity	NPC473112
0.5063	Remote Similarity	NPC14499
0.5062	Remote Similarity	NPC473089

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC481066 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3762
0.1-0.2	5206
0.2-0.3	180
0.3-0.4	2
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