NPASS Compound

Natural Product: NPC31296

Natural Product ID	NPC31296
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	24-Exomethylenecalicoferol E
IUPAC Name	(1R,3aS,4S,7aR)-4-[2-(5-hydroxy-2-methylphenyl)ethyl]-7a-methyl-1-[(2R)-6-methyl-5-methylideneheptan-2-yl]-2,3,3a,4,6,7-hexahydro-1H-inden-5-one
Synonyms	24-Exomethylenecalicoferol E
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1922225
PubChem CID	10047202
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001550] Sesquiterpenoids

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 72 74 0 0 0 0 0 0 0 0999 V2000 -4.6634 -1.0638 -1.9791 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2817 -0.2688 -1.1218 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6958 -0.6363 -0.7559 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.6115 0.5566 -1.0247 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.7271 -0.8766 0.7304 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6119 0.9019 -0.5682 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1526 0.9878 -0.5854 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3322 0.1279 0.3127 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.9043 0.4454 0.0083 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.7104 1.9316 0.2832 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7093 2.1061 0.7372 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3247 0.7572 0.4559 C 0 0 2 0 0 0 0 0 0 0 0 0 0.1466 -0.1823 0.8315 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.0455 -0.1778 2.3024 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5748 -1.5253 0.2814 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8943 -2.0131 0.7505 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8754 -0.9759 1.1198 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0211 -1.3083 1.3219 O 0 0 0 0 0 0 0 0 0 0 0 0 2.5277 0.4636 1.2588 C 0 0 1 0 0 0 0 0 0 0 0 0 3.6271 1.4138 1.1045 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3624 1.6838 -0.1275 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1840 0.6025 -0.7105 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5049 0.4904 -0.1963 C 0 0 0 0 0 0 0 0 0 0 0 0 7.3641 -0.4923 -0.5863 C 0 0 0 0 0 0 0 0 0 0 0 0 8.6489 -0.5816 -0.0706 O 0 0 0 0 0 0 0 0 0 0 0 0 6.8974 -1.3999 -1.5223 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6454 -1.3361 -2.0451 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7778 -0.3119 -1.6275 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4316 -0.2315 -2.2828 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7355 -1.2670 0.3965 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1824 -1.9207 -2.3715 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6523 -0.9154 -2.3310 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0289 -1.5384 -1.2644 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.6584 0.1982 -0.8460 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4176 1.2860 -0.2018 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4861 0.9635 -2.0297 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.7697 -1.0331 1.0984 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3337 -0.0408 1.3375 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1549 -1.7910 1.0306 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0056 1.1812 0.4497 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9924 1.7824 -1.1987 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8626 2.0764 -0.3500 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7619 0.8882 -1.6563 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5150 0.5738 1.3666 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6681 0.2438 -1.0614 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9398 2.5331 -0.6238 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3769 2.2729 1.0979 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8392 2.3736 1.7777 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1925 2.8199 0.0283 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4233 0.6650 -0.6039 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3077 0.7504 2.8237 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5224 -1.0119 2.8148 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1261 -0.2249 2.5882 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1696 -2.3277 0.4475 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6138 -1.4025 -0.8293 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3733 -2.6680 -0.0307 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7838 -2.6807 1.6508 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2527 0.5329 2.3901 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2892 2.3937 1.6051 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4375 1.0889 1.8723 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7357 2.1502 -0.9399 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0945 2.5284 0.1083 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8138 1.2239 0.5285 H 0 0 0 0 0 0 0 0 0 0 0 0 8.7944 -0.8805 0.8972 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5884 -2.1802 -1.8273 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2685 -2.0476 -2.7839 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5444 -0.5524 -3.3698 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0756 0.8000 -2.2574 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7491 -0.9095 -1.7562 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3226 -1.7992 1.3205 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4970 -1.8813 -0.4931 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8239 -1.3410 0.5863 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 1 0 3 5 1 0 2 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 1 13 15 1 0 15 16 1 0 16 17 1 0 17 18 2 0 17 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 2 0 23 24 1 0 24 25 1 0 24 26 2 0 26 27 1 0 27 28 2 0 28 29 1 0 8 30 1 0 13 9 1 0 28 22 1 0 19 12 1 0 1 31 1 0 1 32 1 0 3 33 1 0 4 34 1 0 4 35 1 0 4 36 1 0 5 37 1 0 5 38 1 0 5 39 1 0 6 40 1 0 6 41 1 0 7 42 1 0 7 43 1 0 8 44 1 1 9 45 1 6 10 46 1 0 10 47 1 0 11 48 1 0 11 49 1 0 12 50 1 6 14 51 1 0 14 52 1 0 14 53 1 0 15 54 1 0 15 55 1 0 16 56 1 0 16 57 1 0 19 58 1 1 20 59 1 0 20 60 1 0 21 61 1 0 21 62 1 0 23 63 1 0 25 64 1 0 26 65 1 0 27 66 1 0 29 67 1 0 29 68 1 0 29 69 1 0 30 70 1 0 30 71 1 0 30 72 1 0 M END

Standard InCHIKey	HEUHMWCGNUTYFR-SOVKOMHZSA-N
Standard InCHI	InChI=1S/C28H42O2/c1-18(2)19(3)7-8-21(5)25-13-14-26-24(27(30)15-16-28(25,26)6)12-10-22-17-23(29)11-9-20(22)4/h9,11,17-18,21,24-26,29H,3,7-8,10,12-16H2,1-2,4-6H3/t21-,24+,25-,26+,28-/m1/s1
SMILES	C=C(C(C)C)CC[C@H]([C@H]1CC[C@@H]2[C@]1(C)CCC(=O)[C@H]2CCc1cc(O)ccc1C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	410.32	Volume:	471.573 ? Van der Waals volume.
Dense:	0.87	LogP:	6.074 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.47 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.751 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	8.0	Rigid Bonds:	18.0
TPSA:	37.3 ? Topological Polar Surface Area.	H-Bond Acceptor:	2.0
H-Bond Donor:	1.0	Rings:	3.0
Heavy Atoms:	2.0

MedChem Properties

QED Drug-Likeness Score:	0.457	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.093	Fsp³:	0.679
MCE-18:	73.489 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted	GSK Rule:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.689	Fluc inhibitor:	0.031 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.005 ? 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:	0.51	Promiscuous compounds:	0.076

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.296	MDCK Permeability:	-4.888
Pgp-inhibitor:	0.339	Pgp-substrate:	0.0
PAMPA:	0.003 ? 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):	0.0
20% Bioavailability (F20%):	0.204	30% Bioavailability (F30%):	0.931
50% Bioavailability (F50%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.015	MRP1:	0.479
Plasma Protein Binding (PPB):	96.16%	Volume Distribution (VD):	0.276
Fu:	4.025% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.314
BSEP inhibitor:	0.981

ADMET: Metabolism

CYP1A2-inhibitor:	0.021	CYP1A2-substrate:	1.0
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.997
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.037
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.999
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.064	CYP2C8-inhibitor:	1.0
HLM stability:	0.998 ? 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):

8.889

Half-life (T1/2):

0.448

ADMET: Toxicity

hERG Blockers:	0.157	hERG Blockers (10um):	0.599
Human Hepatotoxicity (H-HT):	0.631	Drug-induced Liver Injury (DILI):	0.125
AMES Toxicity:	0.266	Rat Oral Acute Toxicity:	0.25
Maximum Recommended Daily Dose:	0.42	Skin Sensitization:	0.898
Carcinogencity:	0.519	Eye Corrosion:	0.344
Eye Irritation:	0.913	Respiratory Toxicity:	0.7
Drug-induced Neurotoxicity:	0.316	Ototoxicity:	0.551
Hematotoxicity:	0.626	Drug-induced Nephrotoxicity:	0.45
Genotoxicity:	0.445	RPMI-8226 Immunitoxicity:	0.072
A549 Cytotoxicity:	0.212	Hek293 Cytotoxicity:	0.409
BCF:	2.434 ? 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:	5.142 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.094 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.845 ? 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
NPO32924	gorgonian astrogorgia sp.	Species	n.a.	n.a.	n.a.	Chinese	n.a.	PMID[21982797]

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	16

Activity Type	# Activity
Individual protein	16

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1661	Individual protein	ALK tyrosine kinase receptor	Homo sapiens	IC50	=	4360.0	nM	PubChem BioAssay data set
NPT1660	Individual protein	NUAK family SNF1-like kinase 1	Homo sapiens	IC50	>	100000.0	nM	PMID[8984156]
NPT1433	Individual protein	Serine/threonine-protein kinase Aurora-B	Homo sapiens	IC50	>	100000.0	nM	PMID[15679325]
NPT1659	Individual protein	Tyrosine-protein kinase receptor UFO	Homo sapiens	IC50	=	20200.0	nM	PMID[19319825]
NPT1436	Individual protein	Focal adhesion kinase 1	Homo sapiens	IC50	=	10700.0	nM	PMID[23347584]
NPT1438	Individual protein	Insulin-like growth factor I receptor	Homo sapiens	IC50	=	2300.0	nM	PMID[23411074]
NPT1337	Individual protein	Hepatocyte growth factor receptor	Homo sapiens	IC50	=	27500.0	nM	PMID[21142112]
NPT1658	Individual protein	Serine/threonine-protein kinase NEK2	Homo sapiens	IC50	>	100000.0	nM	PMID[20713679]
NPT1657	Individual protein	Serine/threonine-protein kinase NEK6	Homo sapiens	IC50	>	100000.0	nM	PMID[15104487]
NPT1265	Individual protein	Serine/threonine-protein kinase PIM1	Homo sapiens	IC50	>	100000.0	nM	PMID[15104487]
NPT1656	Individual protein	Protein kinase N1	Homo sapiens	IC50	>	100000.0	nM	PMID[18442289]
NPT1478	Individual protein	Vascular endothelial growth factor receptor 2	Homo sapiens	IC50	=	4850.0	nM	PMID[20044260]
NPT491	Individual protein	Dual specificity mitogen-activated protein kinase kinase 1	Homo sapiens	IC50	>	100000.0	nM	PMID[23434131]
NPT831	Individual protein	Serine/threonine-protein kinase PLK1	Homo sapiens	IC50	=	100000.0	nM	PubChem BioAssay data set
NPT36	Individual protein	Tyrosine-protein kinase SRC	Homo sapiens	IC50	=	1480.0	nM	PMID[12358729]
NPT728	Individual protein	Serine/threonine-protein kinase AKT	Homo sapiens	IC50	>	100000.0	nM	PubChem BioAssay data set

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

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 NPC31296 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	9776
0.1-0.2	36583
0.2-0.3	3396
0.3-0.4	78
0.4-0.5	16
0.5-0.6	3
0.6-0.7	3
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
0.8103	Intermediate Similarity	NPC79933
0.75	Intermediate Similarity	NPC473974
0.7143	Intermediate Similarity	NPC258366
0.6935	Remote Similarity	NPC247858
0.6324	Remote Similarity	NPC269598
0.6	Remote Similarity	NPC609139
0.5373	Remote Similarity	NPC137496
0.5362	Remote Similarity	NPC257540
0.5067	Remote Similarity	NPC609225

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC31296 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3357
0.1-0.2	5524
0.2-0.3	255
0.3-0.4	13
0.4-0.5	1
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