NPASS Compound

Natural Product: NPC66515

Natural Product ID	NPC66515
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Lespedezaflavanone B
IUPAC Name	(2S)-5,7-dihydroxy-2-[4-hydroxy-3-(3-methylbut-2-enyl)phenyl]-8-(3-methylbut-2-enyl)-2,3-dihydrochromen-4-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL256340
PubChem CID	484588
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0000337] Flavans [CHEMONTID:0003642] 8-prenylated flavans [CHEMONTID:0003508] 8-prenylated flavanones

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 60 0 0 0 0 0 0 0 0999 V2000 -7.5061 -0.6653 0.1470 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3088 0.1518 0.4727 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2195 0.0942 -0.3185 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0319 0.8861 -0.0205 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8040 0.0823 0.2491 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6122 0.7665 0.4665 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4098 0.1483 0.7272 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4483 -1.2375 0.7636 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6259 -1.9429 0.5498 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8116 -1.2946 0.2914 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9903 -2.0077 0.0784 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8598 0.8806 0.9605 C 0 0 2 0 0 0 0 0 0 0 0 0 0.7047 2.3267 0.5058 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6247 2.2974 -0.9719 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2703 2.8418 -1.6505 O 0 0 0 0 0 0 0 0 0 0 0 0 1.6843 1.5717 -1.6634 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0414 1.8320 -2.9538 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0520 1.1224 -3.5712 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7036 0.1378 -2.8608 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3658 -0.1586 -1.5348 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1142 -1.1969 -0.8391 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7738 -1.4308 0.5641 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6895 -1.2353 1.4991 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0493 -0.7822 1.1203 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3353 -1.4739 2.9190 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3623 0.5626 -0.9617 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9811 0.3260 0.3243 O 0 0 0 0 0 0 0 0 0 0 0 0 4.7237 -0.5930 -3.4512 O 0 0 0 0 0 0 0 0 0 0 0 0 1.3372 2.8506 -3.6232 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.3119 1.0303 1.6731 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.9585 -1.0929 1.0892 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2410 -1.4651 -0.5498 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.2818 0.0283 -0.2526 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2277 -0.5431 -1.1928 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1551 1.6117 0.7986 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7674 1.5162 -0.9205 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6698 1.8237 0.4274 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4608 -1.7884 0.9670 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6719 -3.0277 0.5758 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2649 -2.7261 0.7313 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9925 0.8866 2.0816 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7016 2.7990 0.7811 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0846 2.8755 1.0108 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2877 1.3761 -4.5953 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9503 -2.1875 -1.3668 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2321 -1.0579 -0.9385 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7897 -1.7703 0.8772 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6730 -0.5381 2.0036 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0067 0.1567 0.4960 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5782 -1.5584 0.5474 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5142 -2.2325 2.9440 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2036 -1.7558 3.5359 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8753 -0.5212 3.2847 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0168 -1.5143 -3.1657 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9567 3.5284 -4.0933 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4662 2.1062 1.4116 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1312 0.7524 2.3487 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3712 0.9021 2.2723 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 3 3 4 1 0 4 5 1 0 5 6 2 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 2 0 10 11 1 0 7 12 1 0 12 13 1 0 13 14 1 0 14 15 2 0 14 16 1 0 16 17 2 0 17 18 1 0 18 19 2 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 2 3 23 24 1 0 23 25 1 0 20 26 2 0 26 27 1 0 19 28 1 0 17 29 1 0 2 30 1 0 10 5 1 0 27 12 1 0 26 16 1 0 1 31 1 0 1 32 1 0 1 33 1 0 3 34 1 0 4 35 1 0 4 36 1 0 6 37 1 0 8 38 1 0 9 39 1 0 11 40 1 0 12 41 1 1 13 42 1 0 13 43 1 0 18 44 1 0 21 45 1 0 21 46 1 0 22 47 1 0 24 48 1 0 24 49 1 0 24 50 1 0 25 51 1 0 25 52 1 0 25 53 1 0 28 54 1 0 29 55 1 0 30 56 1 0 30 57 1 0 30 58 1 0 M END

Standard InCHIKey	BMIMEYWWZBBDCM-QHCPKHFHSA-N
Standard InCHI	InChI=1S/C25H28O5/c1-14(2)5-7-16-11-17(8-10-19(16)26)23-13-22(29)24-21(28)12-20(27)18(25(24)30-23)9-6-15(3)4/h5-6,8,10-12,23,26-28H,7,9,13H2,1-4H3/t23-/m0/s1
SMILES	CC(=CCc1cc(ccc1O)[C@@H]1CC(=O)c2c(cc(c(CC=C(C)C)c2O1)O)O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	408.19	Volume:	435.51 ? Van der Waals volume.
Dense:	0.937	LogP:	5.74 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.014 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.886 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	20.0
TPSA:	86.99 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	3.0	Rings:	3.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.567	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.526	Fsp³:	0.32
MCE-18:	65.545 ? 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:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.982	Fluc inhibitor:	0.904 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.486 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.618 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.462	Promiscuous compounds:	0.156

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.898	MDCK Permeability:	-4.685
Pgp-inhibitor:	0.773	Pgp-substrate:	0.058
PAMPA:	0.132 ? 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):	0.053
20% Bioavailability (F20%):	0.998	30% Bioavailability (F30%):	1.0
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.962
Plasma Protein Binding (PPB):	94.955%	Volume Distribution (VD):	0.478
Fu:	4.68% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.928
OATP1B3 inhibitor:	0.974	BCRP inhibitor:	1.0
BSEP inhibitor:	0.494

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	1.0
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	1.0
CYP2C9-inhibitor:	0.018	CYP2C9-substrate:	0.043
CYP2D6-inhibitor:	0.425	CYP2D6-substrate:	0.204
CYP3A4-inhibitor:	0.001	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	1.0 ? 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):

6.373

Half-life (T1/2):

1.269

ADMET: Toxicity

hERG Blockers:	0.049	hERG Blockers (10um):	0.492
Human Hepatotoxicity (H-HT):	0.824	Drug-induced Liver Injury (DILI):	0.843
AMES Toxicity:	0.865	Rat Oral Acute Toxicity:	0.947
Maximum Recommended Daily Dose:	0.711	Skin Sensitization:	0.992
Carcinogencity:	0.336	Eye Corrosion:	0.0
Eye Irritation:	0.6	Respiratory Toxicity:	0.99
Drug-induced Neurotoxicity:	0.807	Ototoxicity:	0.702
Hematotoxicity:	0.248	Drug-induced Nephrotoxicity:	0.969
Genotoxicity:	0.997	RPMI-8226 Immunitoxicity:	0.18
A549 Cytotoxicity:	0.931	Hek293 Cytotoxicity:	0.767
BCF:	2.109 ? 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:	5.28 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.755 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	6.174 ? 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
NPO7154	Glycyrrhiza uralensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1007/s11164-015-2099-x]
NPO7154	Glycyrrhiza uralensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1134/S1021443711030101]
NPO32948	propolis	Genus	Rhytismataceae	Eukaryota	n.a.	n.a.	n.a.	PMID[10757720]
NPO32948	propolis	Genus	Rhytismataceae	Eukaryota	n.a.	n.a.	n.a.	PMID[1593279]
NPO7154	Glycyrrhiza uralensis	Species	Fabaceae	Eukaryota	n.a.	root	n.a.	PMID[16441081]
NPO7154	Glycyrrhiza uralensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[16675659]
NPO32948	propolis	Genus	Rhytismataceae	Eukaryota	n.a.	China	n.a.	PMID[19278239]
NPO32948	propolis	Genus	Rhytismataceae	Eukaryota	n.a.	Ywar Taw village, Shan State of Myanmar	2006-Dec	PMID[19572611]
NPO1698	Glycyrrhiza inflata	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21123068]
NPO7154	Glycyrrhiza uralensis	Species	Fabaceae	Eukaryota	n.a.	root	n.a.	PMID[22074222]
NPO7154	Glycyrrhiza uralensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[22074222]
NPO7154	Glycyrrhiza uralensis	Species	Fabaceae	Eukaryota	n.a.	root	n.a.	PMID[23867078]
NPO7154	Glycyrrhiza uralensis	Species	Fabaceae	Eukaryota	n.a.	rhizome	n.a.	PMID[23867078]
NPO7154	Glycyrrhiza uralensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[24479468]
NPO7154	Glycyrrhiza uralensis	Species	Fabaceae	Eukaryota	roots	n.a.	n.a.	PMID[24957203]
NPO7154	Glycyrrhiza uralensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[25445757]
NPO7154	Glycyrrhiza uralensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[25744461]
NPO7154	Glycyrrhiza uralensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[26841168]
NPO1698	Glycyrrhiza inflata	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[28522265]
NPO1698	Glycyrrhiza inflata	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[29641206]
NPO7154	Glycyrrhiza uralensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[32196343]
NPO32948	propolis	Genus	Rhytismataceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7154	Glycyrrhiza uralensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO1698	Glycyrrhiza inflata	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO1698	Glycyrrhiza inflata	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO7154	Glycyrrhiza uralensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO1698	Glycyrrhiza inflata	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO7154	Glycyrrhiza uralensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO1698	Glycyrrhiza inflata	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO7154	Glycyrrhiza uralensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO7154	Glycyrrhiza uralensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO1698	Glycyrrhiza inflata	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO7154	Glycyrrhiza uralensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1698	Glycyrrhiza inflata	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
IC50	8
Inhibition	3
FC	1
MIC	1
CD100	1
PC50	1
GI	5
Activity	1

Activity Type	# Activity
Individual protein	5
Cell line	13
Organism	2
Non-molecular	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT178	Individual protein	Protein-tyrosine phosphatase 1B	Homo sapiens	IC50	=	62400.0	nM	PubChem BioAssay data set
NPT178	Individual protein	Protein-tyrosine phosphatase 1B	Homo sapiens	Inhibition	=	46.0	%	PMID[28522265]
NPT152	Individual protein	Nuclear factor erythroid 2-related factor 2	Homo sapiens	FC	=	1.41	n.a.	PMID[28835349]
NPT178	Individual protein	Protein-tyrosine phosphatase 1B	Homo sapiens	IC50	=	2100.0	nM	PMID[32196343]
NPT178	Individual protein	Protein-tyrosine phosphatase 1B	Homo sapiens	Inhibition	>	60.0	%	PMID[32196343]

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	=	7.6	ug.mL-1	PubChem BioAssay data set
NPT639	Cell line	NCI-H187	Homo sapiens	IC50	=	7.6	ug.mL-1	PubChem BioAssay data set
NPT461	Cell line	PANC-1	Homo sapiens	CD100	=	25.0	uM	DrugMatrix in vitro pharmacology data
NPT461	Cell line	PANC-1	Homo sapiens	PC50	=	19.8	uM	PMID[19572611]
NPT83	Cell line	MCF7	Homo sapiens	IC50	=	13130.0	nM	PMID[28522265]
NPT660	Cell line	SW480	Homo sapiens	IC50	=	12530.0	nM	PMID[28522265]
NPT83	Cell line	MCF7	Homo sapiens	GI	=	86.0	%	PMID[28522265]
NPT660	Cell line	SW480	Homo sapiens	GI	=	81.0	%	PMID[28522265]
NPT65	Cell line	HepG2	Homo sapiens	GI	=	24.0	%	PMID[28522265]
NPT2615	Cell line	HEK-293T	Homo sapiens	GI	=	6.0	%	PMID[28522265]
NPT113	Cell line	RAW264.7	Mus musculus	Inhibition	=	14.0	%	PMID[28522265]
NPT65	Cell line	HepG2	Homo sapiens	Activity	=	80.0	%	PMID[32196343]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	3.7	ug.mL-1	PMID[18211005]
NPT88	Organism	Mycobacterium tuberculosis	Mycobacterium tuberculosis	MIC	=	100.0	ug.mL-1	PubChem BioAssay data set
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	7.6	ug.mL-1	PMID[18171023]
NPT21742	Cell line	L02	Homo sapiens	GI	=	12.0	%	PMID[28522265]

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 NPC66515 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	14475
0.1-0.2	30200
0.2-0.3	4365
0.3-0.4	577
0.4-0.5	150
0.5-0.6	51
0.6-0.7	16
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
0.8214	Intermediate Similarity	NPC107572
0.8214	Intermediate Similarity	NPC32739
0.7719	Intermediate Similarity	NPC76372
0.7719	Intermediate Similarity	NPC37496
0.7667	Intermediate Similarity	NPC608140
0.7586	Intermediate Similarity	NPC150408
0.7541	Intermediate Similarity	NPC161506
0.7458	Intermediate Similarity	NPC148757
0.7288	Intermediate Similarity	NPC324436
0.7288	Intermediate Similarity	NPC78
0.7288	Intermediate Similarity	NPC306829
0.7097	Intermediate Similarity	NPC182852
0.7097	Intermediate Similarity	NPC291878
0.7049	Intermediate Similarity	NPC109223
0.7049	Intermediate Similarity	NPC480990
0.7049	Intermediate Similarity	NPC197252
0.7049	Intermediate Similarity	NPC10937
0.6923	Remote Similarity	NPC166934
0.6923	Remote Similarity	NPC300988
0.6825	Remote Similarity	NPC278476
0.6721	Remote Similarity	NPC236766
0.6562	Remote Similarity	NPC485610
0.6462	Remote Similarity	NPC10990
0.6462	Remote Similarity	NPC36217
0.6406	Remote Similarity	NPC125855
0.629	Remote Similarity	NPC164980
0.6269	Remote Similarity	NPC24136
0.6094	Remote Similarity	NPC221432
0.6094	Remote Similarity	NPC257097
0.6094	Remote Similarity	NPC265040
0.6032	Remote Similarity	NPC480991
0.6027	Remote Similarity	NPC218226
0.6	Remote Similarity	NPC610133
0.5942	Remote Similarity	NPC39752
0.5846	Remote Similarity	NPC149026
0.5846	Remote Similarity	NPC250214
0.5846	Remote Similarity	NPC75049
0.5781	Remote Similarity	NPC258630
0.5758	Remote Similarity	NPC220998
0.5758	Remote Similarity	NPC243171
0.5758	Remote Similarity	NPC482705
0.5692	Remote Similarity	NPC91560
0.5672	Remote Similarity	NPC285555
0.5672	Remote Similarity	NPC76338
0.5672	Remote Similarity	NPC250242
0.5652	Remote Similarity	NPC473078
0.5616	Remote Similarity	NPC185276
0.5606	Remote Similarity	NPC187282
0.5606	Remote Similarity	NPC262038
0.5606	Remote Similarity	NPC319910
0.5541	Remote Similarity	NPC101793
0.5507	Remote Similarity	NPC485620
0.55	Remote Similarity	NPC603284
0.5455	Remote Similarity	NPC39329
0.5455	Remote Similarity	NPC51032
0.5441	Remote Similarity	NPC106976
0.5429	Remote Similarity	NPC138288
0.5373	Remote Similarity	NPC69674
0.5362	Remote Similarity	NPC293286
0.5357	Remote Similarity	NPC28918
0.5352	Remote Similarity	NPC81697
0.5352	Remote Similarity	NPC278249
0.5352	Remote Similarity	NPC36275
0.5352	Remote Similarity	NPC223812
0.5352	Remote Similarity	NPC485615
0.5342	Remote Similarity	NPC477957
0.5325	Remote Similarity	NPC484417
0.5312	Remote Similarity	NPC246648
0.5294	Remote Similarity	NPC17170
0.5294	Remote Similarity	NPC310130
0.5278	Remote Similarity	NPC246948
0.527	Remote Similarity	NPC479215
0.527	Remote Similarity	NPC477958
0.5263	Remote Similarity	NPC132592
0.5211	Remote Similarity	NPC470890
0.5211	Remote Similarity	NPC200761
0.5211	Remote Similarity	NPC85162
0.5205	Remote Similarity	NPC484416
0.5152	Remote Similarity	NPC197351
0.5135	Remote Similarity	NPC485617
0.5082	Remote Similarity	NPC213322
0.5079	Remote Similarity	NPC221777
0.5075	Remote Similarity	NPC143896
0.5067	Remote Similarity	NPC214774

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC66515 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	2709
0.1-0.2	6318
0.2-0.3	116
0.3-0.4	4
0.4-0.5	3
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