NPASS Compound

Structure

Physi-Chem Properties

Molecular Weight:	306.15
Volume:	322.164
LogP:	2.152
LogD:	1.467
LogS:	-2.46
# Rotatable Bonds:	7
TPSA:	69.67
# H-Bond Aceptor:	5
# H-Bond Donor:	0
# Rings:	1
# Heavy Atoms:	5

MedChem Properties

QED Drug-Likeness Score:	0.428
Synthetic Accessibility Score:	4.286
Fsp3:	0.471
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
GSK Rule:	Accepted
BMS Rule:	2
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.579
MDCK Permeability:	3.60636186087504e-05
Pgp-inhibitor:	0.006
Pgp-substrate:	0.003
Human Intestinal Absorption (HIA):	0.051
20% Bioavailability (F20%):	0.913
30% Bioavailability (F30%):	0.453

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.185
Plasma Protein Binding (PPB):	59.03022003173828%
Volume Distribution (VD):	0.844
Pgp-substrate:	49.791053771972656%

ADMET: Metabolism

CYP1A2-inhibitor:	0.502
CYP1A2-substrate:	0.097
CYP2C19-inhibitor:	0.542
CYP2C19-substrate:	0.419
CYP2C9-inhibitor:	0.433
CYP2C9-substrate:	0.083
CYP2D6-inhibitor:	0.018
CYP2D6-substrate:	0.111
CYP3A4-inhibitor:	0.113
CYP3A4-substrate:	0.232

ADMET: Excretion

Clearance (CL):	6.026
Half-life (T1/2):	0.877

ADMET: Toxicity

hERG Blockers:	0.009
Human Hepatotoxicity (H-HT):	0.31
Drug-inuced Liver Injury (DILI):	0.919
AMES Toxicity:	0.519
Rat Oral Acute Toxicity:	0.937
Maximum Recommended Daily Dose:	0.397
Skin Sensitization:	0.916
Carcinogencity:	0.539
Eye Corrosion:	0.931
Eye Irritation:	0.956
Respiratory Toxicity:	0.966

Download Data

Data Type	Select
General Info & Identifiers & Properties
Structure MOL file
Source Organisms
Biological Activities
Similar NPs/Drugs

Natural Product: NPC476590

Natural Product ID:	NPC476590
*Common Name:**	(4S)-4-[(1R,2E)-1-hydroxy-3,7-dimethyl-5-oxoocta-2,6-dienyl]-3-methylideneoxolan-2-one
IUPAC Name:	(4S)-4-[(1R,2E)-1-hydroxy-3,7-dimethyl-5-oxoocta-2,6-dienyl]-3-methylideneoxolan-2-one
Synonyms:
Standard InCHIKey:	FQUMNEMBNIZUPZ-JRNZPDHYSA-N
Standard InCHI:	InChI=1S/C15H20O4/c1-9(2)5-12(16)6-10(3)7-14(17)13-8-19-15(18)11(13)4/h5,7,13-14,17H,4,6,8H2,1-3H3/b10-7+/t13-,14-/m1/s1
SMILES:	CC(=CC(=O)C/C(=C/[C@H]([C@@H]1COC(=O)C1=C)O)/C)C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	n.a.
PubChem CID:	49799789
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001283] Terpene lactones

*Note: the InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
**Note: the Chemical Classification was calculated by NPClassifier Version 1.5. Reference: PMID:34662515.

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO20111	Anthemis auriculata	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[16643047]
NPO20111	Anthemis auriculata	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19299148]
NPO20111	Anthemis auriculata	Species	Asteraceae	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	NP ID	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
Others	2

Activity Type	# Activity
Others	2

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT2	Others	Unspecified		Inhibition	=	25	%	PMID[19299148]
NPT2	Others	Unspecified		FC	=	5	n.a.	PMID[19299148]

☑ Note for Activity Records:
☉ The quantitative biological activities were primarily integrated from ChEMBL (Version-30) database and were also directly collected from PubMed literature. PubMed PMID was provided as the reference link for each activity record.

Chemically structural similarity: I. Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes 4,3285 NPs with experimentally-derived bioactivity available in NPASS)

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules. Tc lies between [0, 1] where '1' indicates the highest similarity. What is Tanimoto coefficient

● The left chart: Distribution of similarity level between NPC476590 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	155
0.1-0.2	1445
0.2-0.3	6792
0.3-0.4	16763
0.4-0.5	9634
0.5-0.6	5382
0.6-0.7	1979
0.7-0.8	472
0.8-0.85	61
0.85-0.9	8
0.9-0.95	4
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC114727
0.9167	High Similarity	NPC68819
0.913	High Similarity	NPC88877
0.913	High Similarity	NPC476591
0.859	High Similarity	NPC116543
0.859	High Similarity	NPC169575
0.859	High Similarity	NPC40746
0.8571	High Similarity	NPC24417
0.8529	High Similarity	NPC474658
0.8481	Intermediate Similarity	NPC96259
0.8481	Intermediate Similarity	NPC141193
0.8462	Intermediate Similarity	NPC229825
0.8451	Intermediate Similarity	NPC470256
0.8421	Intermediate Similarity	NPC93763
0.8421	Intermediate Similarity	NPC108816
0.8375	Intermediate Similarity	NPC470755
0.8375	Intermediate Similarity	NPC165162
0.8354	Intermediate Similarity	NPC473390
0.8354	Intermediate Similarity	NPC131669
0.8354	Intermediate Similarity	NPC59097
0.8312	Intermediate Similarity	NPC167881
0.8312	Intermediate Similarity	NPC98557
0.831	Intermediate Similarity	NPC194871
0.8289	Intermediate Similarity	NPC116177
0.8289	Intermediate Similarity	NPC320630
0.8289	Intermediate Similarity	NPC7563
0.8272	Intermediate Similarity	NPC475461
0.8272	Intermediate Similarity	NPC305475
0.8267	Intermediate Similarity	NPC478196
0.8267	Intermediate Similarity	NPC478193
0.8267	Intermediate Similarity	NPC478192
0.8267	Intermediate Similarity	NPC478194
0.8267	Intermediate Similarity	NPC478191
0.8267	Intermediate Similarity	NPC478195
0.825	Intermediate Similarity	NPC191476
0.825	Intermediate Similarity	NPC476804
0.825	Intermediate Similarity	NPC114979
0.825	Intermediate Similarity	NPC158756
0.8219	Intermediate Similarity	NPC202011
0.8182	Intermediate Similarity	NPC196653
0.8182	Intermediate Similarity	NPC471465
0.8148	Intermediate Similarity	NPC255307
0.8101	Intermediate Similarity	NPC52861
0.8095	Intermediate Similarity	NPC129419
0.8082	Intermediate Similarity	NPC475982
0.8077	Intermediate Similarity	NPC270126
0.8077	Intermediate Similarity	NPC99651
0.8072	Intermediate Similarity	NPC475819
0.8072	Intermediate Similarity	NPC476805
0.8049	Intermediate Similarity	NPC469910
0.8028	Intermediate Similarity	NPC282760
0.8028	Intermediate Similarity	NPC470123
0.8026	Intermediate Similarity	NPC161038
0.8	Intermediate Similarity	NPC474959
0.8	Intermediate Similarity	NPC475046
0.8	Intermediate Similarity	NPC11383
0.8	Intermediate Similarity	NPC68110
0.8	Intermediate Similarity	NPC310450
0.7976	Intermediate Similarity	NPC268298
0.7949	Intermediate Similarity	NPC267231
0.7907	Intermediate Similarity	NPC295204
0.7907	Intermediate Similarity	NPC162205
0.7907	Intermediate Similarity	NPC288240
0.7907	Intermediate Similarity	NPC273579
0.7901	Intermediate Similarity	NPC284472
0.7901	Intermediate Similarity	NPC229799
0.7901	Intermediate Similarity	NPC286770
0.7895	Intermediate Similarity	NPC476355
0.7882	Intermediate Similarity	NPC144133
0.7882	Intermediate Similarity	NPC179394
0.7882	Intermediate Similarity	NPC475855
0.7867	Intermediate Similarity	NPC316185
0.7857	Intermediate Similarity	NPC151648
0.7857	Intermediate Similarity	NPC287089
0.7857	Intermediate Similarity	NPC476803
0.7857	Intermediate Similarity	NPC473715
0.7831	Intermediate Similarity	NPC150755
0.7821	Intermediate Similarity	NPC97516
0.7821	Intermediate Similarity	NPC476028
0.7821	Intermediate Similarity	NPC275530
0.7821	Intermediate Similarity	NPC141789
0.7821	Intermediate Similarity	NPC171204
0.7808	Intermediate Similarity	NPC122627
0.7792	Intermediate Similarity	NPC329852
0.7791	Intermediate Similarity	NPC473321
0.7778	Intermediate Similarity	NPC89555
0.7778	Intermediate Similarity	NPC26624
0.7763	Intermediate Similarity	NPC284006
0.775	Intermediate Similarity	NPC281132
0.7711	Intermediate Similarity	NPC21469
0.7701	Intermediate Similarity	NPC475838
0.7701	Intermediate Similarity	NPC228451
0.7701	Intermediate Similarity	NPC469692
0.7701	Intermediate Similarity	NPC469645
0.7701	Intermediate Similarity	NPC125674
0.7692	Intermediate Similarity	NPC301207
0.7692	Intermediate Similarity	NPC205615
0.7692	Intermediate Similarity	NPC123360
0.7692	Intermediate Similarity	NPC256640
0.7692	Intermediate Similarity	NPC16279
0.7674	Intermediate Similarity	NPC473619
0.7674	Intermediate Similarity	NPC469368
0.7674	Intermediate Similarity	NPC474232
0.7671	Intermediate Similarity	NPC248125
0.7662	Intermediate Similarity	NPC117746
0.7662	Intermediate Similarity	NPC140287
0.7662	Intermediate Similarity	NPC15499
0.7662	Intermediate Similarity	NPC315843
0.7662	Intermediate Similarity	NPC259599
0.7662	Intermediate Similarity	NPC294434
0.7654	Intermediate Similarity	NPC281949
0.7654	Intermediate Similarity	NPC150502
0.7654	Intermediate Similarity	NPC301477
0.7654	Intermediate Similarity	NPC25684
0.7654	Intermediate Similarity	NPC470241
0.7647	Intermediate Similarity	NPC136879
0.7632	Intermediate Similarity	NPC319163
0.7632	Intermediate Similarity	NPC67076
0.7632	Intermediate Similarity	NPC163003
0.7625	Intermediate Similarity	NPC470239
0.7625	Intermediate Similarity	NPC470244
0.7625	Intermediate Similarity	NPC475210
0.7625	Intermediate Similarity	NPC178277
0.7614	Intermediate Similarity	NPC121825
0.7614	Intermediate Similarity	NPC474247
0.7606	Intermediate Similarity	NPC26810
0.7595	Intermediate Similarity	NPC176329
0.7595	Intermediate Similarity	NPC49302
0.7595	Intermediate Similarity	NPC474818
0.7595	Intermediate Similarity	NPC474278
0.7595	Intermediate Similarity	NPC125365
0.7595	Intermediate Similarity	NPC51809
0.759	Intermediate Similarity	NPC31086
0.759	Intermediate Similarity	NPC474865
0.7586	Intermediate Similarity	NPC300312
0.7586	Intermediate Similarity	NPC261607
0.7586	Intermediate Similarity	NPC111114
0.7568	Intermediate Similarity	NPC203335
0.7558	Intermediate Similarity	NPC295312
0.7558	Intermediate Similarity	NPC206001
0.7558	Intermediate Similarity	NPC87306
0.7558	Intermediate Similarity	NPC218927
0.7536	Intermediate Similarity	NPC135863
0.7534	Intermediate Similarity	NPC19769
0.7532	Intermediate Similarity	NPC295633
0.7532	Intermediate Similarity	NPC58956
0.7532	Intermediate Similarity	NPC269206
0.7529	Intermediate Similarity	NPC160138
0.7529	Intermediate Similarity	NPC237540
0.7528	Intermediate Similarity	NPC304886
0.7528	Intermediate Similarity	NPC471142
0.7528	Intermediate Similarity	NPC477922
0.75	Intermediate Similarity	NPC318766
0.75	Intermediate Similarity	NPC28049
0.75	Intermediate Similarity	NPC279214
0.75	Intermediate Similarity	NPC221095
0.75	Intermediate Similarity	NPC473471
0.75	Intermediate Similarity	NPC475302
0.75	Intermediate Similarity	NPC473737
0.75	Intermediate Similarity	NPC475912
0.7473	Intermediate Similarity	NPC141191
0.7471	Intermediate Similarity	NPC71533
0.7471	Intermediate Similarity	NPC106510
0.7471	Intermediate Similarity	NPC473455
0.747	Intermediate Similarity	NPC16488
0.747	Intermediate Similarity	NPC52923
0.747	Intermediate Similarity	NPC44261
0.747	Intermediate Similarity	NPC250315
0.7468	Intermediate Similarity	NPC203277
0.7468	Intermediate Similarity	NPC127118
0.7468	Intermediate Similarity	NPC209113
0.7444	Intermediate Similarity	NPC477921
0.7444	Intermediate Similarity	NPC230800
0.7444	Intermediate Similarity	NPC279621
0.7442	Intermediate Similarity	NPC477302
0.7439	Intermediate Similarity	NPC141810
0.7439	Intermediate Similarity	NPC112868
0.7439	Intermediate Similarity	NPC325031
0.7439	Intermediate Similarity	NPC471325
0.7436	Intermediate Similarity	NPC474758
0.7436	Intermediate Similarity	NPC48641
0.7436	Intermediate Similarity	NPC107654
0.7432	Intermediate Similarity	NPC146811
0.7432	Intermediate Similarity	NPC276299
0.7429	Intermediate Similarity	NPC471619
0.7416	Intermediate Similarity	NPC303942
0.7416	Intermediate Similarity	NPC474338
0.7416	Intermediate Similarity	NPC167219
0.7416	Intermediate Similarity	NPC57405
0.7412	Intermediate Similarity	NPC107787
0.7412	Intermediate Similarity	NPC134885
0.7412	Intermediate Similarity	NPC469483
0.7412	Intermediate Similarity	NPC210218
0.7412	Intermediate Similarity	NPC315395
0.7412	Intermediate Similarity	NPC134807
0.7412	Intermediate Similarity	NPC219498
0.7412	Intermediate Similarity	NPC308412
0.7412	Intermediate Similarity	NPC204686
0.7412	Intermediate Similarity	NPC473687
0.7412	Intermediate Similarity	NPC261721

Chemically structural similarity: II. Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC476590 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	142
0.1-0.2	2122
0.2-0.3	4157
0.3-0.4	1989
0.4-0.5	522
0.5-0.6	170
0.6-0.7	43
0.7-0.8	5
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
0.7333	Intermediate Similarity	NPD1698	Clinical (unspecified phase)
0.7108	Intermediate Similarity	NPD5790	Clinical (unspecified phase)
0.7079	Intermediate Similarity	NPD5785	Approved
0.6915	Remote Similarity	NPD4225	Approved
0.6897	Remote Similarity	NPD5363	Approved
0.6889	Remote Similarity	NPD46	Approved
0.6889	Remote Similarity	NPD6698	Approved
0.6867	Remote Similarity	NPD4268	Approved
0.6867	Remote Similarity	NPD4271	Approved
0.686	Remote Similarity	NPD7154	Phase 3
0.6818	Remote Similarity	NPD4249	Approved
0.6782	Remote Similarity	NPD6400	Clinical (unspecified phase)
0.6744	Remote Similarity	NPD5209	Approved
0.6742	Remote Similarity	NPD4251	Approved
0.6742	Remote Similarity	NPD4250	Approved
0.6706	Remote Similarity	NPD4820	Approved
0.6706	Remote Similarity	NPD4821	Approved
0.6706	Remote Similarity	NPD4252	Approved
0.6706	Remote Similarity	NPD4822	Approved
0.6706	Remote Similarity	NPD4819	Approved
0.6705	Remote Similarity	NPD6082	Clinical (unspecified phase)
0.6703	Remote Similarity	NPD7838	Discovery
0.6569	Remote Similarity	NPD6371	Approved
0.6562	Remote Similarity	NPD8029	Clinical (unspecified phase)
0.6552	Remote Similarity	NPD4269	Approved
0.6552	Remote Similarity	NPD4270	Approved
0.6517	Remote Similarity	NPD1694	Approved
0.6517	Remote Similarity	NPD1733	Clinical (unspecified phase)
0.6477	Remote Similarity	NPD5362	Discontinued
0.6471	Remote Similarity	NPD5784	Clinical (unspecified phase)
0.6444	Remote Similarity	NPD5786	Approved
0.6436	Remote Similarity	NPD7899	Clinical (unspecified phase)
0.6429	Remote Similarity	NPD6927	Phase 3
0.6413	Remote Similarity	NPD1695	Approved
0.641	Remote Similarity	NPD2685	Clinical (unspecified phase)
0.6364	Remote Similarity	NPD6435	Approved
0.6353	Remote Similarity	NPD4756	Discovery
0.6316	Remote Similarity	NPD4246	Clinical (unspecified phase)
0.6292	Remote Similarity	NPD5332	Approved
0.6292	Remote Similarity	NPD5331	Approved
0.6292	Remote Similarity	NPD6110	Phase 1
0.6277	Remote Similarity	NPD7983	Approved
0.6267	Remote Similarity	NPD9119	Approved
0.6267	Remote Similarity	NPD69	Approved
0.625	Remote Similarity	NPD5369	Approved
0.625	Remote Similarity	NPD4247	Clinical (unspecified phase)
0.625	Remote Similarity	NPD4790	Discontinued
0.6237	Remote Similarity	NPD5370	Suspended
0.618	Remote Similarity	NPD4752	Clinical (unspecified phase)
0.6162	Remote Similarity	NPD7639	Approved
0.6162	Remote Similarity	NPD7640	Approved
0.6136	Remote Similarity	NPD5368	Approved
0.6133	Remote Similarity	NPD9118	Approved
0.6105	Remote Similarity	NPD4810	Clinical (unspecified phase)
0.6105	Remote Similarity	NPD7637	Suspended
0.61	Remote Similarity	NPD5344	Discontinued
0.6061	Remote Similarity	NPD7638	Approved
0.6058	Remote Similarity	NPD6686	Approved
0.6055	Remote Similarity	NPD7115	Discovery
0.6053	Remote Similarity	NPD585	Clinical (unspecified phase)
0.6042	Remote Similarity	NPD5778	Approved
0.6042	Remote Similarity	NPD5779	Approved
0.6038	Remote Similarity	NPD8413	Clinical (unspecified phase)
0.598	Remote Similarity	NPD6647	Phase 2
0.5979	Remote Similarity	NPD5282	Discontinued
0.5882	Remote Similarity	NPD9411	Phase 1
0.5876	Remote Similarity	NPD6399	Phase 3
0.5859	Remote Similarity	NPD7839	Suspended
0.5844	Remote Similarity	NPD6109	Phase 1
0.5842	Remote Similarity	NPD6648	Approved
0.5833	Remote Similarity	NPD6053	Discontinued
0.5823	Remote Similarity	NPD368	Approved
0.5775	Remote Similarity	NPD5343	Approved
0.5747	Remote Similarity	NPD1452	Discontinued
0.5741	Remote Similarity	NPD2204	Approved
0.5729	Remote Similarity	NPD5764	Clinical (unspecified phase)
0.5729	Remote Similarity	NPD6101	Approved
0.5714	Remote Similarity	NPD4265	Approved
0.5714	Remote Similarity	NPD4222	Approved
0.5694	Remote Similarity	NPD4220	Pre-registration
0.566	Remote Similarity	NPD5697	Approved
0.5644	Remote Similarity	NPD6083	Phase 2
0.5644	Remote Similarity	NPD6084	Phase 2
0.5644	Remote Similarity	NPD7902	Approved
0.5638	Remote Similarity	NPD1696	Phase 3
0.5612	Remote Similarity	NPD6411	Approved
0.5607	Remote Similarity	NPD6881	Approved
0.5607	Remote Similarity	NPD6899	Approved
0.5604	Remote Similarity	NPD8259	Clinical (unspecified phase)
0.56	Remote Similarity	NPD5695	Phase 3

Bioactivity similarity: Similar Natural Products in NPASS

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