NPASS Compound

Structure

NPC259476 OpenBabel07101719142D 26 28 0 0 1 0 0 0 0 0999 V2000 -2.8147 -3.2024 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.7788 -2.0685 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.2788 -1.2024 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6808 -0.7024 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5468 -3.2024 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1691 -1.6092 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8147 -1.2024 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2788 -0.2024 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5468 -0.2024 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6808 -2.7024 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4128 0.2976 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.0827 -1.2024 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.6808 -1.7024 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.9487 -1.7024 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.4128 -2.7024 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5000 -0.8660 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4128 -1.7024 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.9781 -0.2079 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2788 -1.2024 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5468 -1.2024 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.4128 1.2976 0.0000 Cl 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 0.0000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -1.9487 -2.7024 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.2788 -3.2024 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.4945 -0.9706 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7213 0.4612 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 10 2 0 0 0 0 2 19 1 0 0 0 0 3 19 1 0 0 0 0 5 10 1 0 0 0 0 5 15 1 0 0 0 0 6 12 1 0 0 0 0 6 16 1 0 0 0 0 7 13 1 0 0 0 0 7 14 1 0 0 0 0 8 11 1 0 0 0 0 8 19 1 0 0 0 0 9 11 1 0 0 0 0 9 20 1 0 0 0 0 10 13 1 0 0 0 0 11 21 1 6 0 0 0 12 14 1 6 0 0 0 12 18 1 0 0 0 0 13 20 1 1 0 0 0 14 23 1 1 0 0 0 15 17 1 0 0 0 0 15 24 2 0 0 0 0 16 22 2 0 0 0 0 16 25 1 0 0 0 0 17 19 1 0 0 0 0 17 20 1 1 0 0 0 18 22 1 0 0 0 0 18 26 2 0 0 0 0 20 4 1 1 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	381.17
Volume:	379.63
LogP:	3.225
LogD:	2.459
LogS:	-3.318
# Rotatable Bonds:	3
TPSA:	93.55
# H-Bond Aceptor:	5
# H-Bond Donor:	4
# Rings:	3
# Heavy Atoms:	6

MedChem Properties

QED Drug-Likeness Score:	0.466
Synthetic Accessibility Score:	5.047
Fsp3:	0.65
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
GSK Rule:	Accepted
BMS Rule:	1
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-5.427
MDCK Permeability:	1.3475391824613325e-05
Pgp-inhibitor:	0.103
Pgp-substrate:	0.974
Human Intestinal Absorption (HIA):	0.007
20% Bioavailability (F20%):	0.912
30% Bioavailability (F30%):	0.011

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.379
Plasma Protein Binding (PPB):	59.94560241699219%
Volume Distribution (VD):	1.872
Pgp-substrate:	30.251047134399414%

ADMET: Metabolism

CYP1A2-inhibitor:	0.007
CYP1A2-substrate:	0.412
CYP2C19-inhibitor:	0.027
CYP2C19-substrate:	0.208
CYP2C9-inhibitor:	0.095
CYP2C9-substrate:	0.943
CYP2D6-inhibitor:	0.015
CYP2D6-substrate:	0.199
CYP3A4-inhibitor:	0.213
CYP3A4-substrate:	0.261

ADMET: Excretion

Clearance (CL):	14.715
Half-life (T1/2):	0.585

ADMET: Toxicity

hERG Blockers:	0.011
Human Hepatotoxicity (H-HT):	0.195
Drug-inuced Liver Injury (DILI):	0.75
AMES Toxicity:	0.038
Rat Oral Acute Toxicity:	0.894
Maximum Recommended Daily Dose:	0.98
Skin Sensitization:	0.298
Carcinogencity:	0.939
Eye Corrosion:	0.005
Eye Irritation:	0.025
Respiratory Toxicity:	0.977

Download Data

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

Natural Product: NPC259476

Natural Product ID:	NPC259476
*Common Name:**	Haterumaimide G
IUPAC Name:	(3R)-3-[(1S)-2-[(1S,4aS,7S,8aR)-7-chloro-5,5,8a-trimethyl-2-methylidene-4-oxo-4a,6,7,8-tetrahydro-1H-naphthalen-1-yl]-1-hydroxyethyl]pyrrolidine-2,5-dione
Synonyms:	Haterumaimide G
Standard InCHIKey:	NWRSNRSZAJAFCO-KHVISUPTSA-N
Standard InCHI:	InChI=1S/C20H28ClNO4/c1-10-5-15(24)17-19(2,3)8-11(21)9-20(17,4)13(10)7-14(23)12-6-16(25)22-18(12)26/h11-14,17,23H,1,5-9H2,2-4H3,(H,22,25,26)/t11-,12+,13-,14-,17-,20+/m0/s1
SMILES:	Cl[C@H]1CC(C)(C)[C@H]2[C@@](C1)(C)[C@@H](C[C@@H]([C@H]1CC(=NC1=O)O)O)C(=C)CC2=O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL518723
PubChem CID:	10937812
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0000218] Pyrrolidines [CHEMONTID:0001158] Pyrrolidones [CHEMONTID:0003031] Pyrrolidine-2-ones

*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
NPO33282	lissoclinum sp.	Species	Didemnidae	Eukaryota	n.a.	n.a.	n.a.	PMID[11575950]

☑ 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
IC50	1

Activity Type	# Activity
Cell Line	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT168	Cell Line	P388	Mus musculus	IC50	>	10.0	ug.mL-1	PMID[534525]

☑ 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 NPC259476 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	97
0.1-0.2	948
0.2-0.3	9786
0.3-0.4	17856
0.4-0.5	9750
0.5-0.6	4106
0.6-0.7	146
0.7-0.8	0
0.8-0.85	1
0.85-0.9	2
0.9-0.95	3
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
0.95	High Similarity	NPC168733
0.9314	High Similarity	NPC92829
0.9135	High Similarity	NPC7797
0.9048	High Similarity	NPC122404
0.8962	High Similarity	NPC24462
0.8796	High Similarity	NPC216335
0.8131	Intermediate Similarity	NPC42590
0.687	Remote Similarity	NPC475800
0.6838	Remote Similarity	NPC46764
0.6807	Remote Similarity	NPC106479
0.6752	Remote Similarity	NPC474725
0.6609	Remote Similarity	NPC474563
0.6555	Remote Similarity	NPC328052
0.6525	Remote Similarity	NPC307903
0.6525	Remote Similarity	NPC140251
0.65	Remote Similarity	NPC12270
0.6455	Remote Similarity	NPC314500
0.6417	Remote Similarity	NPC476290
0.64	Remote Similarity	NPC323532
0.6381	Remote Similarity	NPC46881
0.6381	Remote Similarity	NPC110780
0.6355	Remote Similarity	NPC102292
0.6321	Remote Similarity	NPC471036
0.6321	Remote Similarity	NPC291320
0.6311	Remote Similarity	NPC200085
0.6311	Remote Similarity	NPC253703
0.6311	Remote Similarity	NPC476269
0.6311	Remote Similarity	NPC51695
0.6311	Remote Similarity	NPC314858
0.6306	Remote Similarity	NPC278106
0.6286	Remote Similarity	NPC14151
0.6273	Remote Similarity	NPC253618
0.6273	Remote Similarity	NPC77001
0.6261	Remote Similarity	NPC234542
0.625	Remote Similarity	NPC59170
0.6239	Remote Similarity	NPC259009
0.6239	Remote Similarity	NPC476755
0.6239	Remote Similarity	NPC165895
0.6226	Remote Similarity	NPC476292
0.6226	Remote Similarity	NPC212083
0.6226	Remote Similarity	NPC474605
0.6226	Remote Similarity	NPC145143
0.6216	Remote Similarity	NPC80401
0.6216	Remote Similarity	NPC180849
0.6216	Remote Similarity	NPC470378
0.6216	Remote Similarity	NPC261994
0.6216	Remote Similarity	NPC149761
0.6214	Remote Similarity	NPC474433
0.6214	Remote Similarity	NPC469867
0.6214	Remote Similarity	NPC106078
0.621	Remote Similarity	NPC470540
0.6207	Remote Similarity	NPC473224
0.6204	Remote Similarity	NPC190704
0.6204	Remote Similarity	NPC201655
0.6204	Remote Similarity	NPC471034
0.6195	Remote Similarity	NPC191094
0.6195	Remote Similarity	NPC302008
0.619	Remote Similarity	NPC164999
0.6182	Remote Similarity	NPC56413
0.6174	Remote Similarity	NPC167380
0.6168	Remote Similarity	NPC118800
0.6168	Remote Similarity	NPC472498
0.6161	Remote Similarity	NPC299185
0.6161	Remote Similarity	NPC476168
0.6161	Remote Similarity	NPC250753
0.6154	Remote Similarity	NPC469492
0.6154	Remote Similarity	NPC476986
0.6154	Remote Similarity	NPC470905
0.6147	Remote Similarity	NPC470955
0.614	Remote Similarity	NPC84018
0.614	Remote Similarity	NPC29112
0.614	Remote Similarity	NPC138245
0.614	Remote Similarity	NPC231060
0.6136	Remote Similarity	NPC477352
0.6134	Remote Similarity	NPC119329
0.6132	Remote Similarity	NPC223330
0.6132	Remote Similarity	NPC209318
0.6117	Remote Similarity	NPC476601
0.6111	Remote Similarity	NPC146683
0.6111	Remote Similarity	NPC474482
0.6111	Remote Similarity	NPC475745
0.6111	Remote Similarity	NPC476190
0.6106	Remote Similarity	NPC82138
0.6106	Remote Similarity	NPC474807
0.6106	Remote Similarity	NPC226513
0.6106	Remote Similarity	NPC59350
0.6106	Remote Similarity	NPC199543
0.6106	Remote Similarity	NPC181594
0.6106	Remote Similarity	NPC144739
0.6102	Remote Similarity	NPC469598
0.61	Remote Similarity	NPC91369
0.6095	Remote Similarity	NPC469517
0.6095	Remote Similarity	NPC476812
0.6095	Remote Similarity	NPC201459
0.6091	Remote Similarity	NPC174619
0.6091	Remote Similarity	NPC96496
0.6091	Remote Similarity	NPC153604
0.6091	Remote Similarity	NPC134197
0.6091	Remote Similarity	NPC57469
0.6091	Remote Similarity	NPC472495
0.6087	Remote Similarity	NPC121857
0.6078	Remote Similarity	NPC102313
0.6078	Remote Similarity	NPC199316
0.6077	Remote Similarity	NPC16709
0.6075	Remote Similarity	NPC477858
0.6075	Remote Similarity	NPC151519
0.6071	Remote Similarity	NPC100313
0.6071	Remote Similarity	NPC51486
0.6063	Remote Similarity	NPC476956
0.6058	Remote Similarity	NPC149249
0.6058	Remote Similarity	NPC476811
0.6058	Remote Similarity	NPC238227
0.6055	Remote Similarity	NPC474218
0.6053	Remote Similarity	NPC477290
0.6053	Remote Similarity	NPC153775
0.6053	Remote Similarity	NPC129004
0.6053	Remote Similarity	NPC91772
0.6053	Remote Similarity	NPC473314
0.6053	Remote Similarity	NPC29247
0.6053	Remote Similarity	NPC261333
0.6053	Remote Similarity	NPC292374
0.6053	Remote Similarity	NPC104371
0.6053	Remote Similarity	NPC101233
0.6053	Remote Similarity	NPC289539
0.6053	Remote Similarity	NPC111524
0.6053	Remote Similarity	NPC64006
0.6053	Remote Similarity	NPC215271
0.6038	Remote Similarity	NPC157895
0.6038	Remote Similarity	NPC104120
0.6038	Remote Similarity	NPC148685
0.6036	Remote Similarity	NPC470417
0.6036	Remote Similarity	NPC183374
0.6036	Remote Similarity	NPC474719
0.6036	Remote Similarity	NPC211162
0.6036	Remote Similarity	NPC328313
0.6034	Remote Similarity	NPC111187
0.6034	Remote Similarity	NPC190080
0.6033	Remote Similarity	NPC244982
0.6033	Remote Similarity	NPC476756
0.602	Remote Similarity	NPC103734
0.6019	Remote Similarity	NPC472743
0.6019	Remote Similarity	NPC475726
0.6019	Remote Similarity	NPC312480
0.6018	Remote Similarity	NPC198242
0.6018	Remote Similarity	NPC211403
0.6018	Remote Similarity	NPC154101
0.6	Remote Similarity	NPC34190
0.6	Remote Similarity	NPC269543
0.6	Remote Similarity	NPC472485
0.6	Remote Similarity	NPC142352
0.6	Remote Similarity	NPC70661
0.6	Remote Similarity	NPC476810
0.6	Remote Similarity	NPC41070
0.6	Remote Similarity	NPC76164
0.6	Remote Similarity	NPC247783
0.6	Remote Similarity	NPC194417
0.6	Remote Similarity	NPC263347
0.6	Remote Similarity	NPC185638
0.6	Remote Similarity	NPC153699
0.6	Remote Similarity	NPC14537
0.6	Remote Similarity	NPC96425
0.6	Remote Similarity	NPC472738
0.6	Remote Similarity	NPC210214
0.5984	Remote Similarity	NPC128210
0.5983	Remote Similarity	NPC288
0.5983	Remote Similarity	NPC26270
0.5983	Remote Similarity	NPC471038
0.5983	Remote Similarity	NPC109059
0.5982	Remote Similarity	NPC54689
0.5982	Remote Similarity	NPC213832
0.5982	Remote Similarity	NPC24772
0.5982	Remote Similarity	NPC116146
0.5982	Remote Similarity	NPC477943
0.5982	Remote Similarity	NPC57954
0.5981	Remote Similarity	NPC328264
0.5981	Remote Similarity	NPC474484
0.5981	Remote Similarity	NPC475951
0.5981	Remote Similarity	NPC116797
0.5981	Remote Similarity	NPC103754
0.5965	Remote Similarity	NPC472496
0.5963	Remote Similarity	NPC321187
0.5963	Remote Similarity	NPC214043
0.5963	Remote Similarity	NPC85774
0.5963	Remote Similarity	NPC329043
0.5963	Remote Similarity	NPC221758
0.5963	Remote Similarity	NPC474233
0.5963	Remote Similarity	NPC58841
0.5963	Remote Similarity	NPC161423
0.5963	Remote Similarity	NPC59453
0.5963	Remote Similarity	NPC227064
0.5963	Remote Similarity	NPC82902
0.5952	Remote Similarity	NPC476814
0.5952	Remote Similarity	NPC476813
0.595	Remote Similarity	NPC473252
0.5948	Remote Similarity	NPC247220
0.5948	Remote Similarity	NPC13949
0.5948	Remote Similarity	NPC135548
0.5948	Remote Similarity	NPC140242
0.5948	Remote Similarity	NPC165616
0.5948	Remote Similarity	NPC264979

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 NPC259476 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	88
0.1-0.2	814
0.2-0.3	4315
0.3-0.4	3121
0.4-0.5	590
0.5-0.6	217
0.6-0.7	5
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
0.65	Remote Similarity	NPD1719	Phase 1
0.623	Remote Similarity	NPD5215	Approved
0.6142	Remote Similarity	NPD4522	Approved
0.608	Remote Similarity	NPD5167	Approved
0.6075	Remote Similarity	NPD3667	Approved
0.6016	Remote Similarity	NPD5169	Approved
0.6	Remote Similarity	NPD3618	Phase 1
0.5984	Remote Similarity	NPD5168	Approved
0.5971	Remote Similarity	NPD6333	Approved
0.5971	Remote Similarity	NPD6334	Approved
0.5968	Remote Similarity	NPD5216	Approved
0.5968	Remote Similarity	NPD5217	Approved
0.5968	Remote Similarity	NPD5127	Approved
0.5963	Remote Similarity	NPD3133	Approved
0.5963	Remote Similarity	NPD4786	Approved
0.5963	Remote Similarity	NPD3665	Phase 1
0.5963	Remote Similarity	NPD3666	Approved
0.5891	Remote Similarity	NPD7100	Approved
0.5887	Remote Similarity	NPD6420	Discontinued
0.5872	Remote Similarity	NPD4788	Approved
0.5833	Remote Similarity	NPD5091	Approved
0.5826	Remote Similarity	NPD6399	Phase 3
0.5766	Remote Similarity	NPD7520	Clinical (unspecified phase)
0.5739	Remote Similarity	NPD8034	Phase 2
0.5739	Remote Similarity	NPD8035	Phase 2
0.5726	Remote Similarity	NPD5128	Approved
0.5714	Remote Similarity	NPD3574	Clinical (unspecified phase)
0.5714	Remote Similarity	NPD5279	Phase 3
0.5702	Remote Similarity	NPD5328	Approved
0.5702	Remote Similarity	NPD4753	Phase 2
0.5693	Remote Similarity	NPD6914	Discontinued
0.5693	Remote Similarity	NPD5956	Approved
0.5692	Remote Similarity	NPD6314	Approved
0.5692	Remote Similarity	NPD6335	Approved
0.5692	Remote Similarity	NPD6313	Approved
0.569	Remote Similarity	NPD5781	Clinical (unspecified phase)
0.569	Remote Similarity	NPD4202	Approved
0.5678	Remote Similarity	NPD4697	Phase 3
0.5676	Remote Similarity	NPD3668	Phase 3
0.5667	Remote Similarity	NPD8418	Phase 2
0.5659	Remote Similarity	NPD6868	Approved
0.5649	Remote Similarity	NPD7101	Approved
0.563	Remote Similarity	NPD4755	Approved
0.5603	Remote Similarity	NPD6079	Approved
0.5603	Remote Similarity	NPD7515	Phase 2
0.56	Remote Similarity	NPD6415	Discontinued
0.56	Remote Similarity	NPD3171	Clinical (unspecified phase)

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