NPASS Compound

Natural Product: NPC147568

Natural Product ID	NPC147568
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	CCFQLQIYEHITNK-SSORVZQWSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	11697907
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001553] Triterpenoids

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 80 83 0 0 0 0 0 0 0 0999 V2000 8.3454 -0.2921 0.0354 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1259 -0.4924 0.8552 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9181 -0.3571 0.3257 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6589 -0.5354 1.0572 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7490 0.6079 1.1694 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1624 1.2886 0.0383 C 0 0 1 0 0 0 0 0 0 0 0 0 4.2172 1.8858 -0.8737 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1052 0.7199 -0.7939 C 0 0 1 0 0 0 0 0 0 0 0 0 2.2938 -0.5394 -1.5426 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8569 -0.8595 -2.0093 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.0165 0.2124 -1.4373 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.0216 1.3527 -2.4077 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3621 -0.1937 -1.0068 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1621 -0.9487 -1.7407 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5271 -1.3764 -1.3380 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0527 -0.3060 -0.4066 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.5019 -0.3440 -0.1527 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0552 -1.6454 0.3336 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1782 -0.0944 -1.5158 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8859 0.8432 0.6930 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.6563 1.5342 1.2975 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8080 0.4329 1.8881 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1377 -0.2881 0.7794 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.8270 -1.6835 1.2951 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8476 0.2683 0.3147 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1461 1.1204 1.0332 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1684 1.6651 0.5648 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7755 0.5139 -0.1735 C 0 0 2 0 0 0 0 0 0 0 0 0 0.6627 -0.7101 0.6959 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6860 0.4576 1.7874 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8552 -0.7514 -3.4018 O 0 0 0 0 0 0 0 0 0 0 0 0 7.2901 -0.8529 2.3020 C 0 0 0 0 0 0 0 0 0 0 0 0 8.2111 0.5604 -0.6865 H 0 0 0 0 0 0 0 0 0 0 0 0 9.2399 -0.1046 0.6593 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4595 -1.2165 -0.5980 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8757 -0.1056 -0.7218 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1547 -1.5147 0.7896 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9781 -0.7806 2.1266 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9864 0.3351 1.9582 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3430 1.4012 1.7395 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6603 2.2144 0.4945 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1528 2.1280 -0.3752 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3221 1.2971 -1.8244 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8428 2.8855 -1.2644 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9163 1.5005 -1.6065 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6174 -1.4215 -1.0095 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9761 -0.4268 -2.4245 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5509 -1.8730 -1.7635 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7114 1.2344 -3.2378 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1007 2.3440 -1.9932 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0291 1.3361 -2.9170 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7773 -1.2714 -2.7062 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1563 -1.3170 -2.2704 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6037 -2.3931 -0.9656 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8502 0.6664 -0.9560 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3768 -2.5101 0.1108 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3441 -1.5964 1.4038 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0166 -1.9306 -0.1911 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1802 0.3620 -1.3677 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5582 0.6710 -2.0274 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1798 -0.9975 -2.1294 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4373 1.6232 0.1629 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0924 2.0975 0.5315 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9985 2.1842 2.1182 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5513 -0.3096 2.3225 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2139 0.7224 2.7482 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7046 -2.1524 1.7856 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0996 -1.5136 2.1456 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2966 -2.3151 0.5869 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5245 1.4307 1.9726 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8434 1.8708 1.4470 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0837 2.6013 0.0232 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3331 -0.4568 1.7296 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0758 -1.4503 0.3179 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6147 -1.2600 0.8049 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0586 1.3174 2.1434 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8225 -1.6472 -3.8346 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7675 -0.1085 2.9173 H 0 0 0 0 0 0 0 0 0 0 0 0 8.3413 -0.8549 2.5864 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9072 -1.8882 2.4394 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 3 3 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 6 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 6 11 13 1 0 13 14 2 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 17 19 1 0 17 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 1 1 23 25 1 0 25 26 2 0 26 27 1 0 27 28 1 0 28 29 1 1 20 30 1 0 10 31 1 0 2 32 1 0 28 8 1 0 28 11 1 0 25 13 1 0 23 16 1 0 1 33 1 0 1 34 1 0 1 35 1 0 3 36 1 0 4 37 1 0 4 38 1 0 5 39 1 0 5 40 1 0 6 41 1 1 7 42 1 0 7 43 1 0 7 44 1 0 8 45 1 6 9 46 1 0 9 47 1 0 10 48 1 6 12 49 1 0 12 50 1 0 12 51 1 0 14 52 1 0 15 53 1 0 15 54 1 0 16 55 1 6 18 56 1 0 18 57 1 0 18 58 1 0 19 59 1 0 19 60 1 0 19 61 1 0 20 62 1 6 21 63 1 0 21 64 1 0 22 65 1 0 22 66 1 0 24 67 1 0 24 68 1 0 24 69 1 0 26 70 1 0 27 71 1 0 27 72 1 0 29 73 1 0 29 74 1 0 29 75 1 0 30 76 1 0 31 77 1 0 32 78 1 0 32 79 1 0 32 80 1 0 M END

Standard InCHIKey	CCFQLQIYEHITNK-SSORVZQWSA-N
Standard InCHI	InChI=1S/C30H48O2/c1-19(2)10-9-11-20(3)23-18-26(32)30(8)22-12-13-24-27(4,5)25(31)15-16-28(24,6)21(22)14-17-29(23,30)7/h10,12,14,20,23-26,31-32H,9,11,13,15-18H2,1-8H3/t20-,23-,24+,25+,26+,28-,29-,30-/m1/s1
SMILES	CC(=CCC[C@@H](C)[C@H]1C[C@@H]([C@@]2(C)C3=CC[C@H]4C(C)(C)[C@H](CC[C@]4(C)C3=CC[C@]12C)O)O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	440.37	Volume:	502.881 ? Van der Waals volume.
Dense:	0.876	LogP:	5.965 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.518 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.441 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	21.0
TPSA:	40.46 ? Topological Polar Surface Area.	H-Bond Acceptor:	2.0
H-Bond Donor:	2.0	Rings:	4.0
Heavy Atoms:	2.0

MedChem Properties

QED Drug-Likeness Score:	0.453	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.009	Fsp³:	0.8
MCE-18:	79.407 ? 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:	0.835	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.046 ? 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:	0.542	Promiscuous compounds:	0.138

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.863	MDCK Permeability:	-4.677
Pgp-inhibitor:	0.106	Pgp-substrate:	0.565
PAMPA:	0.85 ? 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):	0.002
20% Bioavailability (F20%):	0.365	30% Bioavailability (F30%):	0.225
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.444	MRP1:	0.549
Plasma Protein Binding (PPB):	91.321%	Volume Distribution (VD):	-0.069
Fu:	7.873% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.99	BCRP inhibitor:	0.86
BSEP inhibitor:	0.158

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.959
CYP2C19-inhibitor:	0.991	CYP2C19-substrate:	0.637
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.073
CYP2D6-inhibitor:	0.007	CYP2D6-substrate:	0.235
CYP3A4-inhibitor:	0.999	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.999
HLM stability:	0.998 ? 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):

14.902

Half-life (T1/2):

0.967

ADMET: Toxicity

hERG Blockers:	0.093	hERG Blockers (10um):	0.389
Human Hepatotoxicity (H-HT):	0.575	Drug-induced Liver Injury (DILI):	0.103
AMES Toxicity:	0.275	Rat Oral Acute Toxicity:	0.361
Maximum Recommended Daily Dose:	0.585	Skin Sensitization:	0.927
Carcinogencity:	0.672	Eye Corrosion:	0.009
Eye Irritation:	0.631	Respiratory Toxicity:	0.794
Drug-induced Neurotoxicity:	0.13	Ototoxicity:	0.667
Hematotoxicity:	0.231	Drug-induced Nephrotoxicity:	0.513
Genotoxicity:	0.09	RPMI-8226 Immunitoxicity:	0.133
A549 Cytotoxicity:	0.342	Hek293 Cytotoxicity:	0.259
BCF:	2.217 ? 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:	4.513 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.75 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.312 ? 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
NPO41040	Sphaerocoryne gracilis ssp. gracilis	Strain	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[32067457]

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
EC50	2
FC	1

Activity Type	# Activity
Individual protein	3

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1794	Individual protein	LXR-alpha	Homo sapiens	EC50	=	30.0	nM	PMID[16124770]
NPT1746	Individual protein	LXR-beta	Homo sapiens	EC50	>	50000.0	nM	PMID[16124770]
NPT1794	Individual protein	LXR-alpha	Homo sapiens	FC	=	8.0	n.a.	PMID[16124770]

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 NPC147568 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	24378
0.1-0.2	21781
0.2-0.3	3326
0.3-0.4	307
0.4-0.5	35
0.5-0.6	21
0.6-0.7	6
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
0.7857	Intermediate Similarity	NPC201852
0.7667	Intermediate Similarity	NPC138536
0.7321	Intermediate Similarity	NPC205455
0.6393	Remote Similarity	NPC202389
0.619	Remote Similarity	NPC475772
0.6154	Remote Similarity	NPC472942
0.6154	Remote Similarity	NPC69622
0.6154	Remote Similarity	NPC250575
0.6154	Remote Similarity	NPC607637
0.5833	Remote Similarity	NPC94393
0.5806	Remote Similarity	NPC6707
0.5738	Remote Similarity	NPC20853
0.5714	Remote Similarity	NPC285702
0.5714	Remote Similarity	NPC489791
0.5714	Remote Similarity	NPC166745
0.5714	Remote Similarity	NPC235464
0.5672	Remote Similarity	NPC212948
0.5522	Remote Similarity	NPC84271
0.5522	Remote Similarity	NPC102414
0.5484	Remote Similarity	NPC318136
0.5362	Remote Similarity	NPC203035
0.5278	Remote Similarity	NPC484797
0.5238	Remote Similarity	NPC46160
0.5238	Remote Similarity	NPC202642
0.5205	Remote Similarity	NPC39082
0.5205	Remote Similarity	NPC610107
0.5152	Remote Similarity	NPC231310
0.5072	Remote Similarity	NPC222845
0.5072	Remote Similarity	NPC296577
0.507	Remote Similarity	NPC214697

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC147568 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	8033
0.1-0.2	1063
0.2-0.3	51
0.3-0.4	3
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