NPASS Compound

Natural Product: NPC477530

Natural Product ID	NPC477530
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Mundulone
IUPAC Name	3-hydroxy-7-(5-methoxy-2,2-dimethylchromen-6-yl)-2,2-dimethyl-3,4-dihydropyrano[3,2-g]chromen-6-one
Synonyms	Mundulone
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	4587968
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0002506] Isoflavonoids [CHEMONTID:0001612] Isoflavans [CHEMONTID:0001827] Isoflavanones [CHEMONTID:0003526] 6-prenylated isoflavanones

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 58 62 0 0 0 0 0 0 0 0999 V2000 8.1569 0.0053 -0.0783 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9113 0.7717 -0.5150 C 0 0 0 0 0 0 0 0 0 0 0 0 6.1755 1.2671 0.6550 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9265 1.0078 0.9159 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1356 0.1672 0.0205 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8003 -0.3124 -1.0867 C 0 0 0 0 0 0 0 0 0 0 0 0 6.1160 -0.0241 -1.3378 O 0 0 0 0 0 0 0 0 0 0 0 0 4.0418 -1.1165 -1.9423 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7199 -1.4124 -1.6997 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0756 -0.9217 -0.5860 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8133 -0.1279 0.2645 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2144 0.3913 1.3989 O 0 0 0 0 0 0 0 0 0 0 0 0 1.5812 1.6457 1.3195 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6838 -1.1923 -0.2664 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2893 -2.2695 0.4999 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9671 -2.5059 0.7835 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.9216 -1.7219 0.3483 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6287 -0.6193 -0.4251 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3050 -0.3560 -0.7335 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0659 0.6541 -1.4393 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6376 0.2161 -0.8897 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9433 -0.0668 -0.5698 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9961 0.8563 -1.0888 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3496 0.2348 -0.9549 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.5032 -0.3474 0.4462 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6106 -1.4422 0.5234 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.2651 -1.1691 0.2063 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2565 -1.9697 0.6473 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1683 0.7044 1.4942 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.9066 -0.8262 0.6162 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.4742 -0.8307 -1.8419 O 0 0 0 0 0 0 0 0 0 0 0 0 7.3484 1.9628 -1.3957 C 0 0 0 0 0 0 0 0 0 0 0 0 8.7626 0.6833 0.5601 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8168 -0.8748 0.4825 H 0 0 0 0 0 0 0 0 0 0 0 0 8.7583 -0.2394 -0.9646 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7157 1.8982 1.3558 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4031 1.3879 1.7916 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5529 -1.5014 -2.8189 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1874 -2.0288 -2.3816 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5423 1.5417 1.7072 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6145 1.9964 0.2717 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1297 2.4012 1.9207 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0863 -2.9318 0.8684 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3433 1.0652 -1.4920 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9112 1.8648 -0.6630 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7769 0.9731 -2.1878 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1449 0.9493 -1.1913 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4931 -2.8323 1.2532 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2506 1.2633 1.2558 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0445 0.1979 2.4722 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0589 1.3735 1.5435 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.9203 -1.9110 0.8111 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.3523 -0.3366 1.5003 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.5323 -0.5989 -0.2722 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9209 -1.6142 -1.4269 H 0 0 0 0 0 0 0 0 0 0 0 0 7.6116 1.5295 -2.3767 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1518 2.5316 -0.9169 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4260 2.5600 -1.5472 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 2 0 6 7 1 0 6 8 1 0 8 9 2 0 9 10 1 0 10 11 2 0 11 12 1 0 12 13 1 0 10 14 1 0 14 15 2 0 15 16 1 0 16 17 1 0 17 18 2 0 18 19 1 0 19 20 2 0 18 21 1 0 21 22 2 0 22 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 26 27 1 0 27 28 2 0 25 29 1 0 25 30 1 0 24 31 1 0 2 32 1 0 7 2 1 0 11 5 1 0 19 14 1 0 28 17 1 0 27 22 1 0 1 33 1 0 1 34 1 0 1 35 1 0 3 36 1 0 4 37 1 0 8 38 1 0 9 39 1 0 13 40 1 0 13 41 1 0 13 42 1 0 15 43 1 0 21 44 1 0 23 45 1 0 23 46 1 0 24 47 1 0 28 48 1 0 29 49 1 0 29 50 1 0 29 51 1 0 30 52 1 0 30 53 1 0 30 54 1 0 31 55 1 0 32 56 1 0 32 57 1 0 32 58 1 0 M END

Standard InCHIKey	KJTDZAHLWHEULN-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C26H26O6/c1-25(2)9-8-16-19(31-25)7-6-15(24(16)29-5)18-13-30-21-12-20-14(10-17(21)23(18)28)11-22(27)26(3,4)32-20/h6-10,12-13,22,27H,11H2,1-5H3
SMILES	CC1(C=CC2=C(O1)C=CC(=C2OC)C3=COC4=C(C3=O)C=C5CC(C(OC5=C4)(C)C)O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	434.17	Volume:	444.483 ? Van der Waals volume.
Dense:	0.977	LogP:	3.733 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.27 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.879 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	28.0
TPSA:	78.13 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	1.0	Rings:	5.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.628	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.675	Fsp³:	0.346
MCE-18:	103.314 ? 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:	0.654	Fluc inhibitor:	0.449 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.724 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.516 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.119	Promiscuous compounds:	0.368

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.869	MDCK Permeability:	-4.733
Pgp-inhibitor:	0.043	Pgp-substrate:	0.418
PAMPA:	0.788 ? 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):	0.116
20% Bioavailability (F20%):	0.684	30% Bioavailability (F30%):	0.78
50% Bioavailability (F50%):	0.996

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.123	MRP1:	0.947
Plasma Protein Binding (PPB):	91.607%	Volume Distribution (VD):	0.227
Fu:	7.685% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.28
OATP1B3 inhibitor:	0.975	BCRP inhibitor:	0.969
BSEP inhibitor:	0.977

ADMET: Metabolism

CYP1A2-inhibitor:	0.002	CYP1A2-substrate:	0.991
CYP2C19-inhibitor:	0.245	CYP2C19-substrate:	0.712
CYP2C9-inhibitor:	0.095	CYP2C9-substrate:	0.117
CYP2D6-inhibitor:	0.007	CYP2D6-substrate:	0.544
CYP3A4-inhibitor:	0.071	CYP3A4-substrate:	0.693
CYP2B6-substrate:	0.001	CYP2C8-inhibitor:	1.0
HLM stability:	0.267 ? 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):

7.076

Half-life (T1/2):

0.761

ADMET: Toxicity

hERG Blockers:	0.301	hERG Blockers (10um):	0.614
Human Hepatotoxicity (H-HT):	0.547	Drug-induced Liver Injury (DILI):	0.637
AMES Toxicity:	0.571	Rat Oral Acute Toxicity:	0.679
Maximum Recommended Daily Dose:	0.875	Skin Sensitization:	0.16
Carcinogencity:	0.862	Eye Corrosion:	0.0
Eye Irritation:	0.443	Respiratory Toxicity:	0.913
Drug-induced Neurotoxicity:	0.423	Ototoxicity:	0.726
Hematotoxicity:	0.197	Drug-induced Nephrotoxicity:	0.285
Genotoxicity:	0.333	RPMI-8226 Immunitoxicity:	0.077
A549 Cytotoxicity:	0.188	Hek293 Cytotoxicity:	0.532
BCF:	1.706 ? 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:	4.369 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.268 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.515 ? 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
NPO10386	Mundulea chapelieri	Species	Fabaceae	Eukaryota	bark	an elevation of 850 m (171725? S; 484030? E), Toamasina, Madagascar	2002-JAN	PMID[15043430]
NPO10386	Mundulea chapelieri	Species	Fabaceae	Eukaryota	n.a.	leaf	n.a.	PMID[15043430]
NPO10386	Mundulea chapelieri	Species	Fabaceae	Eukaryota	n.a.	flower	n.a.	PMID[15043430]
NPO10386	Mundulea chapelieri	Species	Fabaceae	Eukaryota	n.a.	bark	n.a.	PMID[15043430]
NPO10386	Mundulea chapelieri	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO10386	Mundulea chapelieri	Species	Fabaceae	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	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
Potency	26
Inhibition	2
IC50	1

Activity Type	# Activity
Individual protein	19
Cell line	1
Others	9

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT282	Individual protein	MAP kinase ERK2	Homo sapiens	Potency	=	3162.3	nM	PubChem BioAssay data set
NPT282	Individual protein	MAP kinase ERK2	Homo sapiens	Potency	=	12589.3	nM	PubChem BioAssay data set
NPT151	Individual protein	15-hydroxyprostaglandin dehydrogenase [NAD+]	Homo sapiens	Potency	=	15848.9	nM	PubChem BioAssay data set
NPT109	Individual protein	Cytochrome P450 3A4	Homo sapiens	Potency	=	2511.9	nM	PubChem BioAssay data set
NPT1139	Individual protein	Arachidonate 15-lipoxygenase, type II	Homo sapiens	Potency	n.a.	3981.1	nM	PubChem BioAssay data set
NPT531	Individual protein	Nuclear receptor ROR-gamma	Mus musculus	Potency	=	1122	nM	PubChem BioAssay data set
NPT72	Individual protein	Solute carrier organic anion transporter family member 1B3	Homo sapiens	Inhibition	=	45.15	%	PMID[23571415]
NPT791	Individual protein	Cruzipain	Trypanosoma cruzi	Potency	=	10000	nM	PubChem BioAssay data set
NPT94	Individual protein	Aldehyde dehydrogenase 1A1	Homo sapiens	Potency	=	12589.3	nM	PubChem BioAssay data set
NPT61	Individual protein	Beta-glucocerebrosidase	Homo sapiens	Potency	n.a.	5011.9	nM	PubChem BioAssay data set
NPT444	Individual protein	Ubiquitin carboxyl-terminal hydrolase 1	Homo sapiens	Potency	n.a.	35481.3	nM	PubChem BioAssay data set
NPT888	Individual protein	78 kDa glucose-regulated protein	Homo sapiens	Potency	n.a.	39810.7	nM	PubChem BioAssay data set
NPT73	Individual protein	Solute carrier organic anion transporter family member 1B1	Homo sapiens	Inhibition	=	31.23	%	PMID[23571415]
NPT93	Individual protein	Survival motor neuron protein	Homo sapiens	Potency	=	316.2	nM	PubChem BioAssay data set
NPT442	Individual protein	Ferritin light chain	Equus caballus	Potency	=	10000	nM	PubChem BioAssay data set
NPT45	Individual protein	Ubiquitin carboxyl-terminal hydrolase 2	Homo sapiens	Potency	=	10000	nM	PubChem BioAssay data set
NPT539	Individual protein	Cellular tumor antigen p53	Homo sapiens	Potency	=	25118.9	nM	PubChem BioAssay data set
NPT539	Individual protein	Cellular tumor antigen p53	Homo sapiens	Potency	=	19952.6	nM	PubChem BioAssay data set

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT179	Cell line	A2780	Homo sapiens	IC50	=	13	ug/ml	PMID[15043430]
NPT2	Others	Unspecified	n.a.	Potency	=	3162.3	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	=	70.8	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	20.6	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	46.1	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	11220.2	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	17782.8	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	10000	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	2238.7	nM	PubChem BioAssay data set

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 NPC477530 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	18913
0.1-0.2	28159
0.2-0.3	2476
0.3-0.4	274
0.4-0.5	32
0.5-0.6	3
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	Natural Product ID
0.7397	Intermediate Similarity	NPC179970
0.557	Remote Similarity	NPC488135
0.5341	Remote Similarity	NPC78071
0.5056	Remote Similarity	NPC5840

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC477530 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3770
0.1-0.2	5331
0.2-0.3	46
0.3-0.4	3
0.4-0.5	0
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