NPASS Compound

Natural Product: NPC559378

Natural Product ID	NPC559378
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(2~{R},3~{R},4~{S},5~{R},6~{S})-6-[2-[3-[(2~{S},3~{S},4~{S},5~{R},6~{R})-6-carboxy-3,4,5-trihydroxy-tetrahydropyran-2-yl]oxy-4-hydroxy-phenyl]-5-hydroxy-4-oxo-chromen-7-yl]oxy-3,4,5-trihydroxy-tetrahydropyran-2-carboxylic acid
IUPAC Name	(2~{R},3~{R},4~{S},5~{R},6~{S})-6-[2-[3-[(2~{S},3~{S},4~{S},5~{R},6~{R})-6-carboxy-3,4,5-trihydroxy-tetrahydropyran-2-yl]oxy-4-hydroxy-phenyl]-5-hydroxy-4-oxo-chromen-7-yl]oxy-3,4,5-trihydroxy-tetrahydropyran-2-carboxylic acid
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 71 75 0 0 0 0 0 0 0 0999 V2000 -8.4347 1.7211 -3.2180 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.6304 0.9376 -2.6833 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.4102 -0.3057 -3.2437 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.9150 1.3542 -1.4408 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.0857 0.3541 -1.0073 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.7767 0.2917 0.3192 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.5358 -0.2388 0.4912 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.9678 -1.3277 0.9927 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5704 -1.4615 0.9655 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9041 -2.5574 1.4631 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4283 -2.5768 1.3786 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2994 -3.6333 1.8323 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6871 -3.6794 1.7659 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3689 -4.6463 2.1803 O 0 0 0 0 0 0 0 0 0 0 0 0 2.3286 -2.5902 1.2096 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6982 -2.5394 1.0988 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4042 -3.6403 1.5744 O 0 0 0 0 0 0 0 0 0 0 0 0 4.3087 -1.4452 0.5429 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5713 -0.3774 0.0847 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1542 0.7253 -0.4728 O 0 0 0 0 0 0 0 0 0 0 0 0 5.4862 1.0147 -0.6977 C 0 0 2 0 0 0 0 0 0 0 0 0 5.8763 2.1550 -0.0161 O 0 0 0 0 0 0 0 0 0 0 0 0 7.2383 2.2928 -0.0461 C 0 0 1 0 0 0 0 0 0 0 0 0 7.9486 1.3089 0.8135 C 0 0 0 0 0 0 0 0 0 0 0 0 7.2999 0.5010 1.5122 O 0 0 0 0 0 0 0 0 0 0 0 0 9.3404 1.3166 0.8148 O 0 0 0 0 0 0 0 0 0 0 0 0 7.7572 2.4031 -1.4300 C 0 0 2 0 0 0 0 0 0 0 0 0 7.7459 3.7525 -1.8195 O 0 0 0 0 0 0 0 0 0 0 0 0 7.1529 1.5396 -2.4727 C 0 0 2 0 0 0 0 0 0 0 0 0 7.1473 2.2416 -3.6908 O 0 0 0 0 0 0 0 0 0 0 0 0 5.7139 1.1729 -2.1981 C 0 0 1 0 0 0 0 0 0 0 0 0 5.4784 -0.0703 -2.7789 O 0 0 0 0 0 0 0 0 0 0 0 0 2.1860 -0.4528 0.2079 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5564 -1.5416 0.7624 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2244 -1.5703 0.8607 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6214 -3.5890 2.0218 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9933 -3.4947 2.0673 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6393 -2.3731 1.5555 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0046 -2.3665 1.6441 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.8263 1.6227 1.0440 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.7236 2.4063 0.7479 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.0933 2.3748 0.7420 C 0 0 1 0 0 0 0 0 0 0 0 0 -6.8002 3.6445 0.2651 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.8971 1.6706 -0.3359 C 0 0 1 0 0 0 0 0 0 0 0 0 -8.9735 2.4172 -0.7473 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.1358 -0.7718 -3.7922 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3599 2.3223 -1.6257 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5553 -0.3868 0.7792 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9941 -0.6593 0.5300 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1865 -4.4984 2.2736 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3361 -3.5087 1.9161 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4066 -1.4575 0.4796 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1124 0.1587 -0.3826 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4771 3.2924 0.4497 H 0 0 0 0 0 0 0 0 0 0 0 0 9.8812 0.6929 1.4006 H 0 0 0 0 0 0 0 0 0 0 0 0 8.8573 2.1255 -1.3797 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1768 3.8222 -2.6057 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7709 0.6326 -2.6667 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4591 1.7001 -4.4415 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0059 1.8890 -2.6236 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2418 -0.6947 -2.6951 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5817 0.3842 -0.1504 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1436 -4.4593 2.4211 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5358 -4.3189 2.5116 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5148 -2.9131 2.3401 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8081 1.4065 2.1260 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4453 2.2657 -0.1949 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.7405 2.4837 1.6262 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2638 3.8902 -0.5593 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.2520 0.7064 0.0915 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.1119 3.1553 -0.0757 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 2 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 2 0 9 10 1 0 10 11 1 0 11 12 2 0 12 13 1 0 13 14 2 0 13 15 1 0 15 16 2 0 16 17 1 0 16 18 1 0 18 19 2 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 24 25 2 0 24 26 1 0 23 27 1 0 27 28 1 0 27 29 1 0 29 30 1 0 29 31 1 0 31 32 1 0 19 33 1 0 33 34 2 0 34 35 1 0 10 36 2 0 36 37 1 0 37 38 2 0 38 39 1 0 6 40 1 0 40 41 1 0 40 42 1 0 42 43 1 0 42 44 1 0 44 45 1 0 44 4 1 0 38 8 1 0 35 11 1 0 34 15 1 0 31 21 1 0 3 46 1 0 4 47 1 6 6 48 1 1 9 49 1 0 12 50 1 0 17 51 1 0 18 52 1 0 21 53 1 1 23 54 1 1 26 55 1 0 27 56 1 1 28 57 1 0 29 58 1 6 30 59 1 0 31 60 1 6 32 61 1 0 33 62 1 0 36 63 1 0 37 64 1 0 39 65 1 0 40 66 1 1 41 67 1 0 42 68 1 1 43 69 1 0 44 70 1 1 45 71 1 0 M END

Standard InCHIKey	OPANBGHBBMSMQC-TYBBTENRSA-N
Standard InCHI	InChI=1S/C27H26O18/c28-9-2-1-7(3-13(9)43-27-21(36)17(32)19(34)23(45-27)25(39)40)12-6-11(30)15-10(29)4-8(5-14(15)42-12)41-26-20(35)16(31)18(33)22(44-26)24(37)38/h1-6,16-23,26-29,31-36H,(H,37,38)(H,39,40)/t16-,17-,18+,19+,20+,21-,22+,23+,26+,27+/m0/s1
SMILES	O=C(O)[C@@H]1O[C@@H](OC2=CC(C3=CC(=O)C4=C(O)C=C(O[C@@H]5O[C@@H](C(=O)O)[C@H](O)[C@H](O)[C@H]5O)C=C4O3)=CC=C2O)[C@@H](O)[C@@H](O)[C@H]1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	638.11	Volume:	564.625 ? Van der Waals volume.
Dense:	1.13	LogP:	0.186 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	0.762 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-1.92 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	7.0	Rigid Bonds:	32.0
TPSA:	303.57 ? Topological Polar Surface Area.	H-Bond Acceptor:	18.0
H-Bond Donor:	10.0	Rings:	5.0
Heavy Atoms:	18.0

MedChem Properties

QED Drug-Likeness Score:	0.127	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.818	Fsp³:	0.37
MCE-18:	127.459 ? 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:	1
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.476	Fluc inhibitor:	0.34 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.915 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.888 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.374	Promiscuous compounds:	0.515

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.454	MDCK Permeability:	-5.038
Pgp-inhibitor:	0.0	Pgp-substrate:	0.962
PAMPA:	1.0 ? 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):	0.309
20% Bioavailability (F20%):	0.143	30% Bioavailability (F30%):	0.62
50% Bioavailability (F50%):	0.989

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.985
Plasma Protein Binding (PPB):	73.355%	Volume Distribution (VD):	-0.235
Fu:	22.84% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.001
OATP1B3 inhibitor:	0.057	BCRP inhibitor:	0.011
BSEP inhibitor:	0.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.368
HLM stability:	0.001 ? 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):

0.917

Half-life (T1/2):

6.087

ADMET: Toxicity

hERG Blockers:	0.001	hERG Blockers (10um):	0.009
Human Hepatotoxicity (H-HT):	0.36	Drug-induced Liver Injury (DILI):	0.983
AMES Toxicity:	0.637	Rat Oral Acute Toxicity:	0.016
Maximum Recommended Daily Dose:	0.013	Skin Sensitization:	0.992
Carcinogencity:	0.004	Eye Corrosion:	0.0
Eye Irritation:	0.212	Respiratory Toxicity:	0.007
Drug-induced Neurotoxicity:	0.0	Ototoxicity:	0.966
Hematotoxicity:	0.097	Drug-induced Nephrotoxicity:	0.784
Genotoxicity:	0.886	RPMI-8226 Immunitoxicity:	0.1
A549 Cytotoxicity:	0.022	Hek293 Cytotoxicity:	0.03
BCF:	0.144 ? 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:	2.63 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.272 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.336 ? 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
NPO25135	Marchantia berteroana	Species	Marchantiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO25135	Marchantia berteroana	Species	Marchantiaceae	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

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

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 NPC559378 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	26532
0.1-0.2	20974
0.2-0.3	1684
0.3-0.4	495
0.4-0.5	124
0.5-0.6	33
0.6-0.7	11
0.7-0.8	0
0.8-0.85	2
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8421	Intermediate Similarity	NPC282169
0.8421	Intermediate Similarity	NPC20505
0.7848	Intermediate Similarity	NPC608742
0.6988	Remote Similarity	NPC43211
0.6988	Remote Similarity	NPC601144
0.6667	Remote Similarity	NPC237435
0.6552	Remote Similarity	NPC600989
0.6512	Remote Similarity	NPC311830
0.6395	Remote Similarity	NPC115760
0.6279	Remote Similarity	NPC135277
0.6279	Remote Similarity	NPC210094
0.625	Remote Similarity	NPC253685
0.6053	Remote Similarity	NPC137062
0.6	Remote Similarity	NPC229409
0.5977	Remote Similarity	NPC101191
0.5957	Remote Similarity	NPC64051
0.5843	Remote Similarity	NPC610187
0.5814	Remote Similarity	NPC19709
0.5747	Remote Similarity	NPC189142
0.5747	Remote Similarity	NPC77660
0.5698	Remote Similarity	NPC331652
0.5632	Remote Similarity	NPC39360
0.5632	Remote Similarity	NPC29763
0.5632	Remote Similarity	NPC210003
0.5625	Remote Similarity	NPC46202
0.5495	Remote Similarity	NPC601710
0.5444	Remote Similarity	NPC27942
0.54	Remote Similarity	NPC195257
0.5385	Remote Similarity	NPC235260
0.5385	Remote Similarity	NPC49344
0.5385	Remote Similarity	NPC155763
0.5376	Remote Similarity	NPC190003
0.5341	Remote Similarity	NPC473043
0.5326	Remote Similarity	NPC22832
0.5326	Remote Similarity	NPC243930
0.5319	Remote Similarity	NPC4390
0.5263	Remote Similarity	NPC606546
0.5222	Remote Similarity	NPC95090
0.5222	Remote Similarity	NPC27408
0.5213	Remote Similarity	NPC601586
0.5165	Remote Similarity	NPC181712
0.5128	Remote Similarity	NPC48479
0.5111	Remote Similarity	NPC261866
0.5106	Remote Similarity	NPC602805
0.5106	Remote Similarity	NPC607707
0.5102	Remote Similarity	NPC210073
0.5063	Remote Similarity	NPC108406

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC559378 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4752
0.1-0.2	4327
0.2-0.3	61
0.3-0.4	8
0.4-0.5	1
0.5-0.6	0
0.6-0.7	1
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
0.6667	Remote Similarity	NPD4338	Clinical (unspecified phase)

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