NPASS Compound

Natural Product: NPC190286

Natural Product ID	NPC190286
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Withanolide G
IUPAC Name	(2R)-2-[(1R)-1-hydroxy-1-[(8R,9S,10R,13R,14R,17S)-14-hydroxy-10,13-dimethyl-1-oxo-7,8,9,11,12,15,16,17-octahydro-4H-cyclopenta[a]phenanthren-17-yl]ethyl]-4,5-dimethyl-2,3-dihydropyran-6-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL2333678
PubChem CID	21679023
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0001125] Steroid lactones [CHEMONTID:0001560] Withanolides 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 71 75 0 0 0 0 0 0 0 0999 V2000 6.5476 1.0126 1.4097 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3178 1.0440 0.5753 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9282 2.1712 0.0371 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7402 3.3917 0.2823 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7147 2.1879 -0.7691 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3349 3.2650 -1.2897 O 0 0 0 0 0 0 0 0 0 0 0 0 2.9963 0.9818 -0.9422 O 0 0 0 0 0 0 0 0 0 0 0 0 3.0800 0.0029 0.1116 C 0 0 2 0 0 0 0 0 0 0 0 0 4.5522 -0.1952 0.3510 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5238 -1.3294 -0.3499 C 0 0 1 0 0 0 0 0 0 0 0 0 2.8534 -2.3245 0.7014 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1738 -1.3006 -0.9112 C 0 0 1 0 0 0 0 0 0 0 0 0 0.7352 -2.6672 -1.3496 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7180 -2.7769 -0.9111 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1167 -1.3333 -0.8989 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.4350 -1.0252 -0.3440 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.5227 -1.7316 -1.1799 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8060 -1.2207 -0.6299 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9456 -0.0891 0.0369 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3093 0.2984 0.5333 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6758 1.6510 -0.0150 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7293 2.5100 -0.3000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3197 2.1987 -0.1025 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5029 3.1244 -0.3256 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.8431 0.8552 0.3426 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.5662 0.8580 1.8239 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6512 0.4573 -0.4977 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.4760 1.3279 -0.3437 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1189 0.7858 -0.3837 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0362 -0.6941 -0.1562 C 0 0 2 0 0 0 0 0 0 0 0 0 0.0341 -0.9728 1.3038 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0622 -0.8340 -2.2121 O 0 0 0 0 0 0 0 0 0 0 0 0 3.3582 -1.6539 -1.4610 O 0 0 0 0 0 0 0 0 0 0 0 0 7.3910 1.5319 0.9502 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8850 -0.0536 1.5633 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3435 1.3828 2.4499 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7902 3.6421 1.3731 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8059 3.2515 -0.0284 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2826 4.2770 -0.2087 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6472 0.4125 1.0099 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9708 -0.6837 -0.5603 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7528 -0.8604 1.2204 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2815 -3.2402 0.7519 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8773 -1.9007 1.7332 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9295 -2.6453 0.5536 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2417 -0.6805 -1.8617 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3013 -3.5096 -0.9701 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8040 -2.7847 -2.4768 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3129 -3.3826 -1.6161 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7169 -3.1620 0.1160 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6478 -1.3984 0.6698 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3938 -1.5432 -2.2487 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4882 -2.8315 -0.9331 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6938 -1.8514 -0.8045 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3735 0.3453 1.6278 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0930 -0.4034 0.1461 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.6960 1.9306 -0.1791 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0223 3.4941 -0.7005 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5693 0.9897 2.3155 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1904 -0.1134 2.1294 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9810 1.7276 2.1291 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0186 0.5895 -1.5643 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5210 2.1908 -1.0797 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5997 1.8649 0.6480 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3083 0.9557 -1.4201 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5646 1.3502 0.2844 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9946 -0.9997 1.7478 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4940 -1.9102 1.6159 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4676 -0.0628 1.8175 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9621 -1.5519 -2.8763 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0084 -2.3419 -1.2545 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 3 4 1 0 3 5 1 0 5 6 2 0 5 7 1 0 7 8 1 0 8 9 1 0 8 10 1 0 10 11 1 0 10 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 2 0 19 20 1 0 20 21 1 0 21 22 2 0 22 23 1 0 23 24 2 0 23 25 1 0 25 26 1 1 25 27 1 0 27 28 1 0 28 29 1 0 29 30 1 0 30 31 1 1 15 32 1 6 10 33 1 6 9 2 1 0 30 12 1 0 30 15 1 0 27 16 1 0 25 19 1 0 1 34 1 0 1 35 1 0 1 36 1 0 4 37 1 0 4 38 1 0 4 39 1 0 8 40 1 1 9 41 1 0 9 42 1 0 11 43 1 0 11 44 1 0 11 45 1 0 12 46 1 6 13 47 1 0 13 48 1 0 14 49 1 0 14 50 1 0 16 51 1 1 17 52 1 0 17 53 1 0 18 54 1 0 20 55 1 0 20 56 1 0 21 57 1 0 22 58 1 0 26 59 1 0 26 60 1 0 26 61 1 0 27 62 1 6 28 63 1 0 28 64 1 0 29 65 1 0 29 66 1 0 31 67 1 0 31 68 1 0 31 69 1 0 32 70 1 0 33 71 1 0 M END

Standard InCHIKey	ZRJOVYPUBHQEES-HZRISEJCSA-N
Standard InCHI	InChI=1S/C28H38O5/c1-16-15-23(33-24(30)17(16)2)27(5,31)21-12-14-28(32)20-10-9-18-7-6-8-22(29)26(18,4)19(20)11-13-25(21,28)3/h6,8-9,19-21,23,31-32H,7,10-15H2,1-5H3/t19-,20+,21-,23+,25+,26-,27+,28+/m0/s1
SMILES	CC1=C(C)C(=O)O[C@H](C1)[C@@](C)([C@H]1CC[C@]2([C@@H]3CC=C4CC=CC(=O)[C@]4(C)[C@H]3CC[C@]12C)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	454.27	Volume:	480.831 ? Van der Waals volume.
Dense:	0.945	LogP:	1.79 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.203 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.686 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	28.0
TPSA:	83.83 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	2.0	Rings:	5.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.476	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.151	Fsp³:	0.714
MCE-18:	93.0 ? 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:	0.521	Fluc inhibitor:	0.122 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.011 ? 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:	0.469	Promiscuous compounds:	0.33

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.751	MDCK Permeability:	-4.679
Pgp-inhibitor:	0.042	Pgp-substrate:	0.105
PAMPA:	0.831 ? 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):	0.006
20% Bioavailability (F20%):	0.238	30% Bioavailability (F30%):	0.435
50% Bioavailability (F50%):	0.932

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.634	MRP1:	0.87
Plasma Protein Binding (PPB):	96.653%	Volume Distribution (VD):	0.151
Fu:	3.137% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.998	BCRP inhibitor:	0.374
BSEP inhibitor:	0.997

ADMET: Metabolism

CYP1A2-inhibitor:	0.999	CYP1A2-substrate:	0.422
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.959	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.866	CYP2D6-substrate:	0.033
CYP3A4-inhibitor:	0.365	CYP3A4-substrate:	0.989
CYP2B6-substrate:	0.002	CYP2C8-inhibitor:	0.999
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):

6.507

Half-life (T1/2):

2.126

ADMET: Toxicity

hERG Blockers:	0.032	hERG Blockers (10um):	0.133
Human Hepatotoxicity (H-HT):	0.718	Drug-induced Liver Injury (DILI):	0.279
AMES Toxicity:	0.294	Rat Oral Acute Toxicity:	0.337
Maximum Recommended Daily Dose:	0.648	Skin Sensitization:	0.994
Carcinogencity:	0.91	Eye Corrosion:	0.014
Eye Irritation:	0.604	Respiratory Toxicity:	0.425
Drug-induced Neurotoxicity:	0.134	Ototoxicity:	0.306
Hematotoxicity:	0.259	Drug-induced Nephrotoxicity:	0.74
Genotoxicity:	0.873	RPMI-8226 Immunitoxicity:	0.094
A549 Cytotoxicity:	0.186	Hek293 Cytotoxicity:	0.516
BCF:	0.811 ? 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:	3.473 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.064 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.438 ? 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
NPO13927	Withania coagulans	Species	Solanaceae	Eukaryota	fruits	n.a.	n.a.	PMID[18952419]
NPO13927	Withania coagulans	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[23316950]
NPO13927	Withania coagulans	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13927	Withania coagulans	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO13927	Withania coagulans	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO13927	Withania coagulans	Species	Solanaceae	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
IC50	4
Inhibition	2
Survival	2

Activity Type	# Activity
Individual protein	1
Cell line	4
Others	3

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT2601	Individual protein	NF-kappaB inhibitor alpha	Homo sapiens	IC50	>	50000.0	nM	PMID[18302334]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT113	Cell line	RAW264.7	Mus musculus	IC50	=	37500.0	nM	PMID[23398362]
NPT113	Cell line	RAW264.7	Mus musculus	Inhibition	=	88.5	%	PMID[17428663]
NPT2	Others	Unspecified	n.a.	IC50	=	12300.0	nM	PMID[16933872]
NPT2	Others	Unspecified	n.a.	Inhibition	=	86.9	%	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	IC50	=	20700.0	nM	PMID[20349977]

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT71	Cell line	HEK293	Homo sapiens	Survival	=	71.9	%	PMID[10560729]
NPT113	Cell line	RAW264.7	Mus musculus	Survival	=	100.0	%	PMID[19114678]

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 NPC190286 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	19622
0.1-0.2	26254
0.2-0.3	3804
0.3-0.4	117
0.4-0.5	39
0.5-0.6	12
0.6-0.7	5
0.7-0.8	0
0.8-0.85	0
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8769	High Similarity	NPC46570
0.7246	Intermediate Similarity	NPC153440
0.6901	Remote Similarity	NPC176840
0.6579	Remote Similarity	NPC5292
0.6351	Remote Similarity	NPC79579
0.6351	Remote Similarity	NPC107493
0.6267	Remote Similarity	NPC103045
0.5875	Remote Similarity	NPC484717
0.5844	Remote Similarity	NPC29133
0.5802	Remote Similarity	NPC484718
0.5789	Remote Similarity	NPC486565
0.5714	Remote Similarity	NPC191620
0.5584	Remote Similarity	NPC484742
0.5385	Remote Similarity	NPC225826
0.5185	Remote Similarity	NPC470961
0.5176	Remote Similarity	NPC484725
0.5062	Remote Similarity	NPC44428
0.5062	Remote Similarity	NPC78691
0.506	Remote Similarity	NPC474585

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC190286 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6926
0.1-0.2	2062
0.2-0.3	162
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