NPASS Compound

Natural Product: NPC234494

Natural Product ID	NPC234494
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Nimonol
IUPAC Name	[(5R,6R,7S,8R,9R,10R,13S,17R)-17-(furan-3-yl)-6-hydroxy-4,4,8,10,13-pentamethyl-3-oxo-5,6,7,9,11,12,16,17-octahydrocyclopenta[a]phenanthren-7-yl] acetate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL2386304
PubChem CID	73356511
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001553] Triterpenoids [CHEMONTID:0002380] Limonoids

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 73 0 0 0 0 0 0 0 0999 V2000 -0.2020 -3.5921 3.6941 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7988 -2.3314 3.1535 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5753 -1.6203 3.8356 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.5087 -1.9014 1.8617 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0513 -0.7221 1.3210 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.0384 -1.1186 0.2721 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.4348 -0.0616 -0.6836 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.8850 -0.0089 -1.0481 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8314 0.4270 -0.0092 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2677 -1.4420 -1.4522 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9966 0.8089 -2.2894 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9109 0.6450 -3.1210 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.9987 1.8408 -2.5424 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9843 2.0639 -1.7194 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7764 1.2858 -0.4759 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.3001 2.1094 0.6383 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2927 0.9418 -0.3701 C 0 0 1 0 0 0 0 0 0 0 0 0 0.6304 2.0454 -0.6902 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0630 1.5839 -0.5927 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2257 0.1305 -0.3817 C 0 0 1 0 0 0 0 0 0 0 0 0 2.0830 -0.7537 -1.5617 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6153 -0.0765 0.2613 C 0 0 1 0 0 0 0 0 0 0 0 0 3.4336 -1.4974 0.7299 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0620 -1.3375 1.3637 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3689 -0.3995 0.7250 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0171 0.2009 0.9149 C 0 0 2 0 0 0 0 0 0 0 0 0 0.2321 1.2125 2.0651 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7283 0.1820 -0.6222 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3263 1.4498 -0.7095 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3583 1.3618 -1.6103 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4189 0.1431 -2.0629 O 0 0 0 0 0 0 0 0 0 0 0 0 5.4706 -0.5751 -1.4981 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5675 -2.2689 -0.3655 O 0 0 0 0 0 0 0 0 0 0 0 0 0.4825 -3.3239 4.5388 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3225 -4.1117 2.8740 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0482 -4.1993 4.0834 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6589 -0.2829 2.1747 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9757 -1.4669 0.8002 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9569 -0.3723 -1.6789 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6242 0.1114 1.0088 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8419 -0.0175 -0.2624 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0329 1.5381 -0.0522 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3960 -1.9075 -1.9372 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5287 -1.9458 -0.4919 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1256 -1.4095 -2.1406 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0558 2.4722 -3.4312 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3017 2.8511 -1.9568 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4681 2.8035 0.9628 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0530 2.8573 0.2289 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8113 1.6113 1.4506 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1482 0.1768 -1.1923 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4390 3.0038 -0.1827 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4976 2.2679 -1.7992 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5404 2.1521 0.2307 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6606 1.8573 -1.5004 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3691 -1.6180 -1.4020 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7705 -0.2373 -2.5009 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0416 -1.2844 -1.8157 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6303 0.5865 1.1773 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1996 -1.6902 1.5092 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4301 -2.2430 -0.0716 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7952 -1.9432 2.2070 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7032 1.3159 2.6547 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9355 0.7132 2.7650 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6905 2.1381 1.7343 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0511 2.3506 -0.1802 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0282 2.1777 -1.9076 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3327 -1.6093 -1.7201 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1001 -2.0476 -1.2068 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 8 11 1 0 11 12 2 0 11 13 1 0 13 14 2 0 14 15 1 0 15 16 1 1 15 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 1 6 20 22 1 0 22 23 1 0 23 24 1 0 24 25 2 0 25 26 1 0 26 27 1 1 22 28 1 0 28 29 1 0 29 30 2 0 30 31 1 0 31 32 1 0 6 33 1 0 26 5 1 0 32 28 2 0 15 7 1 0 26 17 1 0 25 20 1 0 1 34 1 0 1 35 1 0 1 36 1 0 5 37 1 1 6 38 1 1 7 39 1 6 9 40 1 0 9 41 1 0 9 42 1 0 10 43 1 0 10 44 1 0 10 45 1 0 13 46 1 0 14 47 1 0 16 48 1 0 16 49 1 0 16 50 1 0 17 51 1 6 18 52 1 0 18 53 1 0 19 54 1 0 19 55 1 0 21 56 1 0 21 57 1 0 21 58 1 0 22 59 1 1 23 60 1 0 23 61 1 0 24 62 1 0 27 63 1 0 27 64 1 0 27 65 1 0 29 66 1 0 30 67 1 0 32 68 1 0 33 69 1 0 M END

Standard InCHIKey	GDMYRVKWBYREMU-XMLHTYRRSA-N
Standard InCHI	InChI=1S/C28H36O5/c1-16(29)33-24-22(31)23-25(2,3)21(30)10-13-27(23,5)20-9-12-26(4)18(17-11-14-32-15-17)7-8-19(26)28(20,24)6/h8,10-11,13-15,18,20,22-24,31H,7,9,12H2,1-6H3/t18-,20+,22+,23-,24+,26-,27+,28-/m0/s1
SMILES	CC(=O)O[C@@H]1[C@@H]([C@H]2C(C)(C)C(=O)C=C[C@]2(C)[C@H]2CC[C@@]3(C)[C@@H](CC=C3[C@]12C)c1ccoc1)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	452.26	Volume:	478.194 ? Van der Waals volume.
Dense:	0.946	LogP:	3.157 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.103 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.702 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	27.0
TPSA:	76.74 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	1.0	Rings:	5.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.492	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.018	Fsp³:	0.643
MCE-18:	126.783 ? 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:	0.813	Fluc inhibitor:	0.008 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.064 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.002 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.044	Promiscuous compounds:	0.109

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.197	MDCK Permeability:	-4.867
Pgp-inhibitor:	0.97	Pgp-substrate:	0.007
PAMPA:	0.431 ? 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):	0.013
20% Bioavailability (F20%):	0.92	30% Bioavailability (F30%):	0.853
50% Bioavailability (F50%):	0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.699	MRP1:	0.925
Plasma Protein Binding (PPB):	93.725%	Volume Distribution (VD):	0.071
Fu:	6.827% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	0.995	BCRP inhibitor:	0.594
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.108	CYP1A2-substrate:	0.043
CYP2C19-inhibitor:	0.754	CYP2C19-substrate:	0.029
CYP2C9-inhibitor:	0.013	CYP2C9-substrate:	0.053
CYP2D6-inhibitor:	0.002	CYP2D6-substrate:	0.166
CYP3A4-inhibitor:	0.856	CYP3A4-substrate:	0.993
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.999
HLM stability:	0.942 ? 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):

10.529

Half-life (T1/2):

0.48

ADMET: Toxicity

hERG Blockers:	0.172	hERG Blockers (10um):	0.405
Human Hepatotoxicity (H-HT):	0.571	Drug-induced Liver Injury (DILI):	0.814
AMES Toxicity:	0.449	Rat Oral Acute Toxicity:	0.917
Maximum Recommended Daily Dose:	0.98	Skin Sensitization:	0.707
Carcinogencity:	0.886	Eye Corrosion:	0.0
Eye Irritation:	0.452	Respiratory Toxicity:	0.87
Drug-induced Neurotoxicity:	0.258	Ototoxicity:	0.322
Hematotoxicity:	0.399	Drug-induced Nephrotoxicity:	0.573
Genotoxicity:	0.993	RPMI-8226 Immunitoxicity:	0.121
A549 Cytotoxicity:	0.263	Hek293 Cytotoxicity:	0.704
BCF:	1.285 ? 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:	4.013 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.744 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.209 ? 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
NPO10033	Turraea pubescens	Species	Meliaceae	Eukaryota	twig	Dongfang, Hainan Province, China	2010-Mar	PMID[23734701]
NPO40792	Azaridachta indica	Species	n.a.	n.a.	Leaves	n.a.	n.a.	PMID[24499352]
NPO10033	Turraea pubescens	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO10033	Turraea pubescens	Species	Meliaceae	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
Activity	3
AFI	1
IC50	4

Activity Type	# Activity
Cell line	4
Organism	4

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
NPT113	Cell line	RAW264.7	Mus musculus	IC50	>	20000.0	nM	PMID[25437914]
NPT116	Cell line	HL-60	Homo sapiens	IC50	<	10000.0	nM	PMID[20619938]
NPT306	Cell line	PC-3	Homo sapiens	IC50	=	95000.0	nM	PMID[23795891]
NPT165	Cell line	HeLa	Homo sapiens	IC50	=	77000.0	nM	PMID[20624681]
NPT1175	Organism	Spodoptera litura	Spodoptera litura	Activity	=	32.5	%	PMID[23249297]
NPT1175	Organism	Spodoptera litura	Spodoptera litura	Activity	=	55.7	%	PMID[16038557]
NPT1175	Organism	Spodoptera litura	Spodoptera litura	Activity	=	32.2	%	PMID[19848434]
NPT1175	Organism	Spodoptera litura	Spodoptera litura	AFI	=	47.3	%	PMID[12137465]

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 NPC234494 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	9251
0.1-0.2	35872
0.2-0.3	4554
0.3-0.4	117
0.4-0.5	34
0.5-0.6	24
0.6-0.7	3
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
0.7297	Intermediate Similarity	NPC204365
0.7297	Intermediate Similarity	NPC56197
0.6753	Remote Similarity	NPC253201
0.6582	Remote Similarity	NPC302054
0.6173	Remote Similarity	NPC92979
0.5976	Remote Similarity	NPC33938
0.5976	Remote Similarity	NPC471001
0.5854	Remote Similarity	NPC470997
0.5854	Remote Similarity	NPC471174
0.5679	Remote Similarity	NPC302987
0.5529	Remote Similarity	NPC196846
0.5488	Remote Similarity	NPC238843
0.5488	Remote Similarity	NPC199044
0.5476	Remote Similarity	NPC470999
0.5476	Remote Similarity	NPC472672
0.5467	Remote Similarity	NPC264048
0.5455	Remote Similarity	NPC471002
0.5294	Remote Similarity	NPC272590
0.525	Remote Similarity	NPC488636
0.5185	Remote Similarity	NPC185456
0.5181	Remote Similarity	NPC470998
0.5169	Remote Similarity	NPC471004
0.5169	Remote Similarity	NPC471000
0.5122	Remote Similarity	NPC239097
0.5114	Remote Similarity	NPC34056
0.5059	Remote Similarity	NPC471006
0.5056	Remote Similarity	NPC34421
0.5056	Remote Similarity	NPC237259
0.5055	Remote Similarity	NPC470995

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC234494 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3377
0.1-0.2	5679
0.2-0.3	93
0.3-0.4	1
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