NPASS Compound

Natural Product: NPC284960

Natural Product ID	NPC284960
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Lethedoside C
IUPAC Name	2-(3-hydroxy-4,5-dimethoxyphenyl)-7-methoxy-5-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxychromen-4-one
Synonyms	Lethedoside C
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL455082
PubChem CID	10391471
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0001111] Flavonoid glycosides [CHEMONTID:0001583] Flavonoid O-glycosides

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 62 65 0 0 0 0 0 0 0 0999 V2000 -5.0042 -2.1163 -3.6897 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.9884 -1.9450 -2.7213 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3672 -1.6076 -1.3833 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.6233 -0.4529 -1.4191 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.7689 -0.4452 -0.2659 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.7579 0.3216 -0.3212 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7040 1.0490 -0.3655 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8005 2.4478 -0.6278 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7292 3.2589 -0.6854 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8655 4.6385 -0.9477 O 0 0 0 0 0 0 0 0 0 0 0 0 0.2698 5.4474 -0.9995 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5462 2.7795 -0.4912 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7000 1.4443 -0.2357 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3865 0.6071 -0.1749 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1366 -0.7093 0.0848 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0713 -1.5135 0.1524 O 0 0 0 0 0 0 0 0 0 0 0 0 1.1812 -1.1486 0.2746 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2013 -0.2432 0.1962 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9364 1.0095 -0.0532 O 0 0 0 0 0 0 0 0 0 0 0 0 3.5970 -0.6515 0.3885 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9566 -1.9386 0.6242 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2868 -2.2759 0.8093 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6678 -3.6039 1.0534 O 0 0 0 0 0 0 0 0 0 0 0 0 6.2770 -1.3238 0.7604 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9019 -0.0127 0.5194 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5858 0.3346 0.3340 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9089 0.9533 0.4699 O 0 0 0 0 0 0 0 0 0 0 0 0 6.5644 2.3012 0.2246 C 0 0 0 0 0 0 0 0 0 0 0 0 7.6095 -1.6478 0.9433 O 0 0 0 0 0 0 0 0 0 0 0 0 8.0866 -1.6231 2.2897 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7975 -0.1050 0.8625 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.6597 -1.3349 0.9974 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.4402 -1.4514 -0.3104 C 0 0 2 0 0 0 0 0 0 0 0 0 -7.3278 -2.5034 -0.3079 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.4790 -1.3187 2.1037 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.1489 0.2606 2.0121 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.8430 -1.2894 -4.2087 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4767 -2.9429 -2.5994 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6982 -1.1955 -3.0786 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7035 -2.4492 -1.1003 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6038 -1.5542 -0.1061 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7963 2.8540 -0.7851 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8419 5.4474 -0.0408 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0307 6.4892 -1.2318 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9857 5.0590 -1.7684 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4034 3.4368 -0.5381 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3363 -2.2031 0.4788 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2368 -2.7366 0.6750 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8180 -4.1874 0.2218 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3290 1.3545 0.1497 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4794 2.9226 0.4360 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7669 2.6094 0.9336 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2156 2.4563 -0.8346 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5023 -0.8985 2.8925 H 0 0 0 0 0 0 0 0 0 0 0 0 9.1389 -1.3230 2.2959 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9283 -2.6683 2.6728 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4570 0.7196 0.5170 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9579 -2.2080 0.9924 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9021 -0.4578 -0.4881 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.1602 -2.1981 0.1293 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4638 -2.2439 2.4866 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1713 0.3261 1.7982 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 1 0 10 11 1 0 9 12 2 0 12 13 1 0 13 14 2 0 14 15 1 0 15 16 2 0 15 17 1 0 17 18 2 0 18 19 1 0 18 20 1 0 20 21 2 0 21 22 1 0 22 23 1 0 22 24 2 0 24 25 1 0 25 26 2 0 25 27 1 0 27 28 1 0 24 29 1 0 29 30 1 0 5 31 1 0 31 32 1 0 32 33 1 0 33 34 1 0 32 35 1 0 31 36 1 0 33 3 1 0 14 7 1 0 26 20 1 0 19 13 1 0 1 37 1 0 2 38 1 0 2 39 1 0 3 40 1 1 5 41 1 1 8 42 1 0 11 43 1 0 11 44 1 0 11 45 1 0 12 46 1 0 17 47 1 0 21 48 1 0 23 49 1 0 26 50 1 0 28 51 1 0 28 52 1 0 28 53 1 0 30 54 1 0 30 55 1 0 30 56 1 0 31 57 1 6 32 58 1 1 33 59 1 6 34 60 1 0 35 61 1 0 36 62 1 0 M END

Standard InCHIKey	WGZGLIQYUYIVRX-BKSKZGTRSA-N
Standard InCHI	InChI=1S/C24H26O12/c1-31-11-6-15-19(16(7-11)35-24-22(30)21(29)20(28)18(9-25)36-24)12(26)8-14(34-15)10-4-13(27)23(33-3)17(5-10)32-2/h4-8,18,20-22,24-25,27-30H,9H2,1-3H3/t18-,20-,21+,22-,24-/m1/s1
SMILES	OC[C@H]1O[C@@H](Oc2cc(OC)cc3c2c(=O)cc(o3)c2cc(O)c(c(c2)OC)OC)[C@@H]([C@H]([C@@H]1O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	506.14	Volume:	473.825 ? Van der Waals volume.
Dense:	1.068	LogP:	1.133 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.619 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.22 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	7.0	Rigid Bonds:	24.0
TPSA:	177.51 ? Topological Polar Surface Area.	H-Bond Acceptor:	12.0
H-Bond Donor:	5.0	Rings:	4.0
Heavy Atoms:	12.0

MedChem Properties

QED Drug-Likeness Score:	0.298	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.983	Fsp³:	0.375
MCE-18:	89.182 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.595	Fluc inhibitor:	0.169 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.953 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.906 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.09	Promiscuous compounds:	0.574

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.931	MDCK Permeability:	-5.156
Pgp-inhibitor:	0.009	Pgp-substrate:	0.205
PAMPA:	0.619 ? 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):	0.545
20% Bioavailability (F20%):	0.095	30% Bioavailability (F30%):	0.867
50% Bioavailability (F50%):	0.981

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.002	MRP1:	0.415
Plasma Protein Binding (PPB):	79.13%	Volume Distribution (VD):	-0.131
Fu:	20.997% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.967
BSEP inhibitor:	0.112

ADMET: Metabolism

CYP1A2-inhibitor:	0.202	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.009	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.037	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.194	CYP2D6-substrate:	0.806
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.995
HLM stability:	0.293 ? 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):

2.904

Half-life (T1/2):

3.391

ADMET: Toxicity

hERG Blockers:	0.03	hERG Blockers (10um):	0.118
Human Hepatotoxicity (H-HT):	0.651	Drug-induced Liver Injury (DILI):	0.956
AMES Toxicity:	0.86	Rat Oral Acute Toxicity:	0.044
Maximum Recommended Daily Dose:	0.095	Skin Sensitization:	0.988
Carcinogencity:	0.467	Eye Corrosion:	0.0
Eye Irritation:	0.406	Respiratory Toxicity:	0.057
Drug-induced Neurotoxicity:	0.02	Ototoxicity:	0.837
Hematotoxicity:	0.366	Drug-induced Nephrotoxicity:	0.522
Genotoxicity:	0.569	RPMI-8226 Immunitoxicity:	0.126
A549 Cytotoxicity:	0.264	Hek293 Cytotoxicity:	0.353
BCF:	0.4 ? 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:	3.002 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.507 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.742 ? 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
NPO33004	lethedon tannaensis	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[10075750]
NPO33004	lethedon tannaensis	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[8759170]

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	1

Activity Type	# Activity
Cell line	1

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
NPT91	Cell line	KB	Homo sapiens	IC50	=	43.0	ug.mL-1	PMID[19880317]

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 NPC284960 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	25128
0.1-0.2	21090
0.2-0.3	2457
0.3-0.4	871
0.4-0.5	233
0.5-0.6	53
0.6-0.7	16
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8219	Intermediate Similarity	NPC110349
0.7895	Intermediate Similarity	NPC182045
0.7308	Intermediate Similarity	NPC610763
0.6429	Remote Similarity	NPC22832
0.6429	Remote Similarity	NPC243930
0.6386	Remote Similarity	NPC222936
0.6235	Remote Similarity	NPC605067
0.622	Remote Similarity	NPC58053
0.6163	Remote Similarity	NPC311830
0.6163	Remote Similarity	NPC607707
0.6145	Remote Similarity	NPC95090
0.6145	Remote Similarity	NPC27408
0.6118	Remote Similarity	NPC609451
0.6071	Remote Similarity	NPC186807
0.6071	Remote Similarity	NPC45638
0.6024	Remote Similarity	NPC261866
0.6024	Remote Similarity	NPC83283
0.6	Remote Similarity	NPC15358
0.6	Remote Similarity	NPC201292
0.5977	Remote Similarity	NPC602805
0.5952	Remote Similarity	NPC93337
0.5952	Remote Similarity	NPC168822
0.5952	Remote Similarity	NPC189142
0.5952	Remote Similarity	NPC77660
0.5882	Remote Similarity	NPC105025
0.5862	Remote Similarity	NPC601144
0.5833	Remote Similarity	NPC39360
0.5833	Remote Similarity	NPC29763
0.5833	Remote Similarity	NPC210003
0.5806	Remote Similarity	NPC284277
0.5761	Remote Similarity	NPC129827
0.5714	Remote Similarity	NPC183357
0.5682	Remote Similarity	NPC486578
0.5618	Remote Similarity	NPC88023
0.5618	Remote Similarity	NPC309025
0.5568	Remote Similarity	NPC285197
0.5543	Remote Similarity	NPC295613
0.5474	Remote Similarity	NPC475366
0.5474	Remote Similarity	NPC475497
0.5455	Remote Similarity	NPC117260
0.5426	Remote Similarity	NPC473512
0.5402	Remote Similarity	NPC277205
0.5402	Remote Similarity	NPC37919
0.5393	Remote Similarity	NPC191306
0.5393	Remote Similarity	NPC224462
0.5385	Remote Similarity	NPC601586
0.5341	Remote Similarity	NPC58716
0.5341	Remote Similarity	NPC84362
0.5333	Remote Similarity	NPC21666
0.5287	Remote Similarity	NPC45618
0.5287	Remote Similarity	NPC143851
0.5275	Remote Similarity	NPC150442
0.5227	Remote Similarity	NPC146792
0.5227	Remote Similarity	NPC323593
0.5227	Remote Similarity	NPC203500
0.5227	Remote Similarity	NPC609879
0.5222	Remote Similarity	NPC169404
0.5222	Remote Similarity	NPC176186
0.5217	Remote Similarity	NPC479407
0.5213	Remote Similarity	NPC473657
0.5169	Remote Similarity	NPC603655
0.5165	Remote Similarity	NPC601710
0.5135	Remote Similarity	NPC29536
0.5128	Remote Similarity	NPC177298
0.5114	Remote Similarity	NPC289667
0.5111	Remote Similarity	NPC100720
0.5098	Remote Similarity	NPC244875
0.5056	Remote Similarity	NPC297987
0.5056	Remote Similarity	NPC136042
0.5055	Remote Similarity	NPC479402
0.5055	Remote Similarity	NPC488071
0.5054	Remote Similarity	NPC488072

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC284960 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5845
0.1-0.2	3231
0.2-0.3	57
0.3-0.4	12
0.4-0.5	4
0.5-0.6	1
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
0.55	Remote Similarity	NPD7472	Pre-clinical

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