NPASS Compound

Natural Product: NPC87448

Natural Product ID	NPC87448
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Reissantin E
IUPAC Name	n.a.
Synonyms	Reissantin E
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL467201
PubChem CID	10323282
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 69 72 0 0 0 0 0 0 0 0999 V2000 -0.2904 5.4541 -0.9840 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2499 4.1343 -0.5853 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4792 3.9325 -0.7205 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.5434 3.1511 -0.0839 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0912 1.8625 0.3182 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.2933 1.8556 1.8245 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7781 2.1082 1.9336 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5161 0.8527 1.4989 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.8799 1.2867 1.0848 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7575 -0.0138 0.5775 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.5599 -0.8913 -0.3172 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.5328 -2.0332 -0.4739 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.4978 -1.4831 -1.4321 C 0 0 1 0 0 0 0 0 0 0 0 0 0.1398 -0.2162 -1.0596 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.8256 0.7393 -0.3780 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.6090 1.4288 -1.4825 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3446 -0.2616 -0.3492 O 0 0 0 0 0 0 0 0 0 0 0 0 2.5612 0.2377 -0.8207 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5119 0.7534 -1.9760 O 0 0 0 0 0 0 0 0 0 0 0 0 3.7665 0.1625 -0.0389 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7862 -0.3880 1.2015 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9227 -0.4793 1.9790 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0953 0.0155 1.4649 C 0 0 0 0 0 0 0 0 0 0 0 0 6.1061 0.5809 0.2069 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9516 0.6559 -0.5434 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2225 -2.5118 -1.9473 O 0 0 0 0 0 0 0 0 0 0 0 0 0.2123 -3.1184 -3.1371 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6161 -2.6424 -3.9069 O 0 0 0 0 0 0 0 0 0 0 0 0 1.0808 -4.2263 -3.5028 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0865 -2.1658 0.9454 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2335 -2.9243 1.0945 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1166 -3.0127 1.6649 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9908 -0.8789 1.3641 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.7130 -1.4027 0.1284 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6831 0.1975 2.7508 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.9803 5.8773 -0.2250 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4774 6.1562 -1.3075 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9399 5.2598 -1.8864 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9883 1.8749 0.1289 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0450 0.9617 2.3272 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2923 2.7101 2.2237 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0550 2.4650 2.9250 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0844 2.9014 1.2116 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9452 2.4091 0.9226 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6642 1.1298 1.8880 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3048 0.8564 0.1856 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7094 -0.5062 -1.3472 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9848 -2.9187 -0.9086 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1766 -1.2254 -2.3182 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4185 0.3025 -2.0322 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0704 2.3731 -1.8155 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6372 0.8387 -2.4183 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5971 1.7705 -1.1947 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8702 -0.7782 1.6157 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8503 -0.9318 2.9538 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9751 -0.0665 2.0923 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0425 0.9688 -0.1874 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9669 1.0950 -1.5171 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0476 -3.7977 -3.8729 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3741 -4.8269 -2.5929 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6339 -4.9197 -4.2453 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4018 -3.4588 0.1648 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0426 -2.2970 1.4583 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1534 -3.7403 1.8793 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6678 -3.9605 2.1025 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8776 -3.4457 0.9484 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5660 -2.5310 2.5368 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9913 -1.3380 1.0370 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6108 0.0329 2.9692 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 8 9 1 0 8 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 6 14 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 13 26 1 0 26 27 1 0 27 28 2 0 27 29 1 0 12 30 1 0 30 31 1 0 30 32 1 0 30 33 1 0 11 34 1 0 8 35 1 1 15 5 1 0 25 20 1 0 15 10 1 0 10 33 1 1 1 36 1 0 1 37 1 0 1 38 1 0 5 39 1 1 6 40 1 0 6 41 1 0 7 42 1 0 7 43 1 0 9 44 1 0 9 45 1 0 9 46 1 0 11 47 1 6 12 48 1 6 13 49 1 6 14 50 1 6 16 51 1 0 16 52 1 0 16 53 1 0 21 54 1 0 22 55 1 0 23 56 1 0 24 57 1 0 25 58 1 0 29 59 1 0 29 60 1 0 29 61 1 0 31 62 1 0 31 63 1 0 31 64 1 0 32 65 1 0 32 66 1 0 32 67 1 0 34 68 1 0 35 69 1 0 M END

Standard InCHIKey	VDMRSWTYKXKIDN-SWHFUDTGSA-N
Standard InCHI	InChI=1S/C26H34O9/c1-14(27)32-17-12-13-24(5,31)26-20(29)18(23(3,4)35-26)19(33-15(2)28)21(25(17,26)6)34-22(30)16-10-8-7-9-11-16/h7-11,17-21,29,31H,12-13H2,1-6H3/t17-,18+,19-,20+,21-,24-,25-,26-/m0/s1
SMILES	CC(=O)O[C@H]1CC[C@@](C)([C@@]23[C@@H]([C@@H]([C@@H]([C@@H]([C@]12C)OC(=O)c1ccccc1)OC(=O)C)C(C)(C)O3)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	490.22	Volume:	487.32 ? Van der Waals volume.
Dense:	1.006	LogP:	1.726 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.031 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.462 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	7.0	Rigid Bonds:	23.0
TPSA:	128.59 ? Topological Polar Surface Area.	H-Bond Acceptor:	9.0
H-Bond Donor:	2.0	Rings:	4.0
Heavy Atoms:	9.0

MedChem Properties

QED Drug-Likeness Score:	0.482	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.662	Fsp³:	0.654
MCE-18:	148.884 ? 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:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.288	Fluc inhibitor:	0.012 ? 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:	0.008 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.069	Promiscuous compounds:	0.313

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.633	MDCK Permeability:	-4.851
Pgp-inhibitor:	0.999	Pgp-substrate:	0.472
PAMPA:	0.73 ? 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):	0.005
20% Bioavailability (F20%):	0.847	30% Bioavailability (F30%):	0.961
50% Bioavailability (F50%):	0.996

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.001	MRP1:	0.999
Plasma Protein Binding (PPB):	66.084%	Volume Distribution (VD):	-0.42
Fu:	31.885% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.96	BCRP inhibitor:	0.054
BSEP inhibitor:	0.999

ADMET: Metabolism

CYP1A2-inhibitor:	0.003	CYP1A2-substrate:	0.149
CYP2C19-inhibitor:	0.054	CYP2C19-substrate:	0.006
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.064
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.138
CYP3A4-inhibitor:	0.566	CYP3A4-substrate:	0.019
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.881
HLM stability:	0.829 ? 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):

5.502

Half-life (T1/2):

1.329

ADMET: Toxicity

hERG Blockers:	0.026	hERG Blockers (10um):	0.507
Human Hepatotoxicity (H-HT):	0.142	Drug-induced Liver Injury (DILI):	0.148
AMES Toxicity:	0.18	Rat Oral Acute Toxicity:	0.55
Maximum Recommended Daily Dose:	0.675	Skin Sensitization:	0.913
Carcinogencity:	0.171	Eye Corrosion:	0.012
Eye Irritation:	0.661	Respiratory Toxicity:	0.581
Drug-induced Neurotoxicity:	0.026	Ototoxicity:	0.488
Hematotoxicity:	0.076	Drug-induced Nephrotoxicity:	0.347
Genotoxicity:	0.707	RPMI-8226 Immunitoxicity:	0.052
A549 Cytotoxicity:	0.008	Hek293 Cytotoxicity:	0.049
BCF:	0.495 ? 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:	3.263 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.016 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.283 ? 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
NPO28607	Reissantia buchananii	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[14640511]
NPO28607	Reissantia buchananii	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO28607	Reissantia buchananii	Species	Celastraceae	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
ED50	9

Activity Type	# Activity
Cell line	8
Non-molecular	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
NPT81	Cell line	A549	Homo sapiens	ED50	>	20.0	ug ml-1	PMID[22276679]
NPT83	Cell line	MCF7	Homo sapiens	ED50	>	20.0	ug ml-1	PMID[26821820]
NPT180	Cell line	HCT-8	Homo sapiens	ED50	>	20.0	ug ml-1	PMID[26821820]
NPT91	Cell line	KB	Homo sapiens	ED50	=	14.4	ug ml-1	PMID[24617303]
NPT306	Cell line	PC-3	Homo sapiens	ED50	>	20.0	ug ml-1	PMID[24387703]
NPT309	Cell line	1A9	Homo sapiens	ED50	>	20.0	ug ml-1	PMID[23092389]
NPT310	Cell line	1A9/ptx-10	Homo sapiens	ED50	>	20.0	ug ml-1	PMID[12444694]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	ED50	=	16.5	ug ml-1	PMID[14640511]

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 NPC87448 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	10822
0.1-0.2	35683
0.2-0.3	2646
0.3-0.4	538
0.4-0.5	125
0.5-0.6	27
0.6-0.7	7
0.7-0.8	0
0.8-0.85	3
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8485	Intermediate Similarity	NPC470153
0.8116	Intermediate Similarity	NPC70403
0.8116	Intermediate Similarity	NPC177940
0.7231	Intermediate Similarity	NPC118080
0.7121	Intermediate Similarity	NPC97947
0.6667	Remote Similarity	NPC163719
0.6667	Remote Similarity	NPC95810
0.6429	Remote Similarity	NPC291599
0.6316	Remote Similarity	NPC470159
0.6111	Remote Similarity	NPC483846
0.6104	Remote Similarity	NPC472571
0.6087	Remote Similarity	NPC483863
0.5974	Remote Similarity	NPC29704
0.5974	Remote Similarity	NPC470157
0.5942	Remote Similarity	NPC301556
0.5921	Remote Similarity	NPC481490
0.5753	Remote Similarity	NPC200471
0.5753	Remote Similarity	NPC472575
0.5679	Remote Similarity	NPC301368
0.5679	Remote Similarity	NPC84815
0.5556	Remote Similarity	NPC125106
0.5556	Remote Similarity	NPC472573
0.5513	Remote Similarity	NPC147340
0.5493	Remote Similarity	NPC100913
0.5479	Remote Similarity	NPC483847
0.5479	Remote Similarity	NPC470152
0.5476	Remote Similarity	NPC253738
0.5455	Remote Similarity	NPC57628
0.5417	Remote Similarity	NPC66761
0.5417	Remote Similarity	NPC483843
0.5263	Remote Similarity	NPC471101
0.5222	Remote Similarity	NPC294579
0.5222	Remote Similarity	NPC144779
0.5205	Remote Similarity	NPC211137
0.52	Remote Similarity	NPC483886
0.5181	Remote Similarity	NPC611111
0.5067	Remote Similarity	NPC152440
0.5067	Remote Similarity	NPC475759
0.5067	Remote Similarity	NPC483888

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC87448 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3345
0.1-0.2	5607
0.2-0.3	198
0.3-0.4	0
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