NPASS Compound

Natural Product: NPC480913

Natural Product ID	NPC480913
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	DFJGFVMDWLNMQU-CZJBNPPGSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds]

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 63 67 0 0 0 0 0 0 0 0999 V2000 2.4465 1.3492 1.4570 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1314 0.6452 0.1769 C 0 0 2 0 0 0 0 0 0 0 0 0 1.2890 1.6455 -0.6293 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1057 1.8102 -0.0616 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8101 0.4888 -0.2796 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.0467 -0.4419 0.6213 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.8128 -1.7109 0.7588 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9695 -1.3028 1.6643 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8908 -0.3045 0.9578 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.1289 -1.0888 0.6407 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0120 -0.5879 -0.4245 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.2986 -0.0889 -1.6076 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.8431 0.0766 -1.5277 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2789 0.4564 -0.1513 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.7337 1.9257 -0.0175 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2052 2.5612 1.0710 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.6070 -0.8864 -2.7148 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.0074 0.3053 0.0519 O 0 0 0 0 0 0 0 0 0 0 0 0 1.3926 -0.6252 0.2474 C 0 0 1 0 0 0 0 0 0 0 0 0 1.6333 -1.2966 -1.0488 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8383 -0.6395 -1.6703 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3279 0.3594 -0.6419 C 0 0 2 0 0 0 0 0 0 0 0 0 4.5193 -0.1703 -0.0307 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8520 -0.5181 1.1919 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2127 -1.0047 1.2683 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7656 -1.4022 2.3492 O 0 0 0 0 0 0 0 0 0 0 0 0 6.7315 -0.9447 0.0075 O 0 0 0 0 0 0 0 0 0 0 0 0 5.7608 -0.4109 -0.8485 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8658 -1.5241 1.2370 O 0 0 0 0 0 0 0 0 0 0 0 0 3.5136 1.7170 1.3724 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9135 2.3428 1.5747 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2223 0.8134 2.3734 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8086 2.6276 -0.6755 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1643 1.3080 -1.6736 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5602 2.6515 -0.5816 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0168 1.9323 1.0259 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4824 0.2007 -1.3277 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0008 0.0818 1.6262 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2082 -2.4262 1.3673 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1378 -2.1288 -0.1917 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4721 -0.8254 2.5589 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4887 -2.1788 2.0395 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1745 0.4092 1.7647 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7465 -1.2404 1.5545 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8270 -2.1392 0.3544 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6649 -1.4562 -0.7428 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7639 0.9136 -1.8661 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5036 0.8306 -2.2707 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3404 -0.8651 -1.8370 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5465 2.4588 -0.9885 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8406 1.9816 0.1091 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2141 3.5198 0.9253 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0222 -1.7062 -2.7027 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6756 0.5907 0.9467 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8877 -2.3952 -0.9495 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8146 -1.2825 -1.7804 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5952 -0.1450 -2.6374 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6237 -1.3779 -1.9333 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6335 1.3125 -1.1796 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2037 -0.4492 2.0224 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5522 -1.0844 -1.6780 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1690 0.5581 -1.2175 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5336 -1.2251 2.1093 H 0 0 0 0 0 0 0 0 0 0 0 0 2 1 1 1 2 3 1 0 3 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 1 1 15 16 1 0 12 17 1 0 11 18 1 0 6 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 2 0 24 25 1 0 25 26 2 0 25 27 1 0 27 28 1 0 19 29 1 1 22 2 1 0 28 23 1 0 19 2 1 0 14 5 1 0 14 9 1 0 1 30 1 0 1 31 1 0 1 32 1 0 3 33 1 0 3 34 1 0 4 35 1 0 4 36 1 0 5 37 1 6 6 38 1 1 7 39 1 0 7 40 1 0 8 41 1 0 8 42 1 0 9 43 1 1 10 44 1 0 10 45 1 0 11 46 1 6 12 47 1 6 13 48 1 0 13 49 1 0 15 50 1 0 15 51 1 0 16 52 1 0 17 53 1 0 18 54 1 0 20 55 1 0 20 56 1 0 21 57 1 0 21 58 1 0 22 59 1 6 24 60 1 0 28 61 1 0 28 62 1 0 29 63 1 0 M END

Standard InCHIKey	DFJGFVMDWLNMQU-CZJBNPPGSA-N
Standard InCHI	InChI=1S/C23H34O6/c1-21-6-4-16-17(3-2-14-9-18(25)19(26)10-22(14,16)12-24)23(21,28)7-5-15(21)13-8-20(27)29-11-13/h8,14-19,24-26,28H,2-7,9-12H2,1H3/t14-,15-,16+,17-,18-,19-,21-,22-,23+/m1/s1
SMILES	C[C@@]12CC[C@H]3[C@@H](CC[C@@H]4C[C@H]([C@@H](C[C@]34CO)O)O)[C@]2(CC[C@@H]1C1=CC(=O)OC1)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	406.24	Volume:	411.05 ? Van der Waals volume.
Dense:	0.988	LogP:	1.254 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.824 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.504 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	26.0
TPSA:	107.22 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	4.0	Rings:	5.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.519	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.858	Fsp³:	0.87
MCE-18:	90.791 ? 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:	0.512	Fluc inhibitor:	0.158 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.019 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.0 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.266	Promiscuous compounds:	0.532

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.219	MDCK Permeability:	-4.806
Pgp-inhibitor:	0.008	Pgp-substrate:	0.912
PAMPA:	0.97 ? 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):	0.031
20% Bioavailability (F20%):	0.645	30% Bioavailability (F30%):	0.506
50% Bioavailability (F50%):	0.883

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.386	MRP1:	0.891
Plasma Protein Binding (PPB):	73.06%	Volume Distribution (VD):	0.092
Fu:	27.75% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.931
OATP1B3 inhibitor:	0.97	BCRP inhibitor:	0.006
BSEP inhibitor:	0.451

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.001	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.023	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.763
HLM stability:	0.065 ? 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):

4.794

Half-life (T1/2):

2.681

ADMET: Toxicity

hERG Blockers:	0.072	hERG Blockers (10um):	0.289
Human Hepatotoxicity (H-HT):	0.671	Drug-induced Liver Injury (DILI):	0.203
AMES Toxicity:	0.796	Rat Oral Acute Toxicity:	0.471
Maximum Recommended Daily Dose:	0.941	Skin Sensitization:	0.998
Carcinogencity:	0.939	Eye Corrosion:	0.0
Eye Irritation:	0.045	Respiratory Toxicity:	0.555
Drug-induced Neurotoxicity:	0.061	Ototoxicity:	0.808
Hematotoxicity:	0.682	Drug-induced Nephrotoxicity:	0.937
Genotoxicity:	0.762	RPMI-8226 Immunitoxicity:	0.324
A549 Cytotoxicity:	0.512	Hek293 Cytotoxicity:	0.712
BCF:	0.479 ? 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:	3.219 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.854 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.876 ? 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
NPO30295	Calotropis gigantea	Species	Apocynaceae	Eukaryota	leaves	n.a.	n.a.	PMID[16933890]
NPO30295	Calotropis gigantea	Species	Apocynaceae	Eukaryota	n.a.	root	n.a.	PMID[19052526]
NPO30295	Calotropis gigantea	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[28817274]
NPO30295	Calotropis gigantea	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[31967821]
NPO30295	Calotropis gigantea	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[32649211]
NPO30295	Calotropis gigantea	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[9548837]
NPO30295	Calotropis gigantea	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]

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	2

Activity Type	# Activity
Cell line	2

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
NPT461	Cell line	PANC-1	Homo sapiens	IC50	=	5100.0	nM	PMID[31967821]
NPT165	Cell line	HeLa	Homo sapiens	IC50	>	10000.0	nM	PMID[31967821]

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 NPC480913 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	11190
0.1-0.2	33379
0.2-0.3	5009
0.3-0.4	102
0.4-0.5	109
0.5-0.6	52
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	Natural Product ID
0.7869	Intermediate Similarity	NPC222875
0.7869	Intermediate Similarity	NPC25177
0.7705	Intermediate Similarity	NPC196931
0.6984	Remote Similarity	NPC187302
0.6719	Remote Similarity	NPC268829
0.6719	Remote Similarity	NPC295110
0.6119	Remote Similarity	NPC10232
0.6087	Remote Similarity	NPC196471
0.5974	Remote Similarity	NPC77299
0.5974	Remote Similarity	NPC480906
0.597	Remote Similarity	NPC186668
0.5897	Remote Similarity	NPC76572
0.5897	Remote Similarity	NPC193382
0.5821	Remote Similarity	NPC97487
0.5797	Remote Similarity	NPC480911
0.575	Remote Similarity	NPC483822
0.575	Remote Similarity	NPC305574
0.5652	Remote Similarity	NPC160583
0.561	Remote Similarity	NPC329905
0.5571	Remote Similarity	NPC72772
0.557	Remote Similarity	NPC5311
0.5513	Remote Similarity	NPC473852
0.5513	Remote Similarity	NPC471633
0.55	Remote Similarity	NPC480914
0.5429	Remote Similarity	NPC189588
0.5412	Remote Similarity	NPC32177
0.5412	Remote Similarity	NPC469756
0.5412	Remote Similarity	NPC275901
0.5362	Remote Similarity	NPC220217
0.5349	Remote Similarity	NPC480910
0.5349	Remote Similarity	NPC480909
0.5316	Remote Similarity	NPC99620
0.525	Remote Similarity	NPC196429
0.5238	Remote Similarity	NPC480907
0.5227	Remote Similarity	NPC486135
0.5227	Remote Similarity	NPC486137
0.5185	Remote Similarity	NPC469750
0.5185	Remote Similarity	NPC480915
0.5122	Remote Similarity	NPC199428
0.5122	Remote Similarity	NPC243196
0.5122	Remote Similarity	NPC84949
0.5122	Remote Similarity	NPC109448
0.5122	Remote Similarity	NPC480562
0.5122	Remote Similarity	NPC74945
0.5122	Remote Similarity	NPC310341
0.5122	Remote Similarity	NPC31354
0.5122	Remote Similarity	NPC69576
0.5116	Remote Similarity	NPC30483
0.5116	Remote Similarity	NPC470897
0.5067	Remote Similarity	NPC475030
0.5062	Remote Similarity	NPC84987
0.506	Remote Similarity	NPC253456
0.506	Remote Similarity	NPC159338
0.506	Remote Similarity	NPC88668
0.506	Remote Similarity	NPC250556
0.5059	Remote Similarity	NPC72260
0.5059	Remote Similarity	NPC488161
0.5059	Remote Similarity	NPC16569
0.5057	Remote Similarity	NPC236973
0.5057	Remote Similarity	NPC292467

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC480913 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5447
0.1-0.2	3499
0.2-0.3	189
0.3-0.4	3
0.4-0.5	9
0.5-0.6	2
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
0.506	Remote Similarity	NPD7507	Pre-clinical
0.5059	Remote Similarity	NPD8294	Phase 4

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