NPASS Compound

Natural Product: NPC3218

Natural Product ID	NPC3218
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Euroabienol
IUPAC Name	methyl (1R,4S,4aS,9S,10S,10aR)-4,10-diacetyloxy-5,9-dihydroxy-1,4a-dimethyl-7-propan-2-yl-2,3,4,9,10,10a-hexahydrophenanthrene-1-carboxylate
Synonyms	Euroabienol
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1223332
PubChem CID	46933232
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001551] Diterpenoids

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 67 69 0 0 0 0 0 0 0 0999 V2000 -3.8256 -0.1644 4.2957 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6555 -0.1986 2.8892 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.4217 0.0320 2.2937 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4546 0.2735 3.0490 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.2866 -0.0152 0.7744 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.3057 1.0126 0.3280 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8170 -1.3830 0.4511 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7664 -2.1398 -0.3156 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2625 -1.1898 -1.3908 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.3213 -0.2188 -0.8660 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.8903 0.2660 0.4699 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.4672 1.6650 0.7434 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.9120 2.5720 -0.2424 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.6429 3.7141 -0.0003 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9529 4.0085 1.1641 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.0668 4.5995 -1.1057 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0510 1.6373 0.8040 C 0 0 1 0 0 0 0 0 0 0 0 0 1.4072 1.7733 2.1638 O 0 0 0 0 0 0 0 0 0 0 0 0 1.6765 0.3979 0.3174 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0698 -0.5741 -0.5109 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7449 -1.6840 -0.8942 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1197 -2.6158 -1.7043 O 0 0 0 0 0 0 0 0 0 0 0 0 3.0526 -1.8753 -0.4709 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6525 -0.9330 0.3366 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9887 0.1997 0.7386 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0474 -1.1456 0.7830 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1601 -1.2241 2.2922 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9640 -0.0296 0.3314 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1877 0.9145 -1.8816 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0512 -1.9066 -2.5365 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.8300 -1.8395 -3.6804 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8145 -1.0478 -3.6534 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.5632 -2.6357 -4.8999 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4721 -1.0486 4.5521 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8834 -0.3115 4.8478 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3986 0.7231 4.6274 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4930 1.7825 1.1058 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2973 0.4584 0.2882 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1783 1.3925 -0.6808 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1650 -1.9699 1.3188 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7115 -1.2923 -0.2154 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2589 -3.0068 -0.7994 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9388 -2.4912 0.3379 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2061 -0.5561 -1.6256 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3098 -0.3447 1.2546 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8685 2.0079 1.7091 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2228 5.2454 -1.4494 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3985 4.0385 -2.0064 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8727 5.2881 -0.7945 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4724 2.5687 0.3283 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2501 2.2496 2.2407 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6492 -2.9242 -2.5272 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5453 -2.7742 -0.8038 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5051 0.9022 1.3690 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4589 -2.0964 0.3861 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9294 -0.2502 2.7706 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5205 -2.0313 2.7008 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2348 -1.4306 2.5118 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5350 0.9505 0.6273 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9066 -0.1311 0.9448 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1952 -0.0881 -0.7506 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1278 1.3611 -2.1818 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6463 1.6020 -1.6587 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1643 0.3808 -2.8240 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1726 -3.5653 -4.8224 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9684 -2.0617 -5.7593 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5080 -2.8224 -5.0940 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 3 5 1 0 5 6 1 6 5 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 2 0 14 16 1 0 12 17 1 0 17 18 1 0 17 19 1 0 19 20 2 0 20 21 1 0 21 22 1 0 21 23 2 0 23 24 1 0 24 25 2 0 24 26 1 0 26 27 1 0 26 28 1 0 10 29 1 6 9 30 1 0 30 31 1 0 31 32 2 0 31 33 1 0 11 5 1 0 25 19 1 0 20 10 1 0 1 34 1 0 1 35 1 0 1 36 1 0 6 37 1 0 6 38 1 0 6 39 1 0 7 40 1 0 7 41 1 0 8 42 1 0 8 43 1 0 9 44 1 6 11 45 1 1 12 46 1 1 16 47 1 0 16 48 1 0 16 49 1 0 17 50 1 6 18 51 1 0 22 52 1 0 23 53 1 0 25 54 1 0 26 55 1 0 27 56 1 0 27 57 1 0 27 58 1 0 28 59 1 0 28 60 1 0 28 61 1 0 29 62 1 0 29 63 1 0 29 64 1 0 33 65 1 0 33 66 1 0 33 67 1 0 M END

Standard InCHIKey	FEMTVABTBAWCEK-YTBAPPOLSA-N
Standard InCHI	InChI=1S/C25H34O8/c1-12(2)15-10-16-19(17(28)11-15)25(6)18(32-13(3)26)8-9-24(5,23(30)31-7)22(25)21(20(16)29)33-14(4)27/h10-12,18,20-22,28-29H,8-9H2,1-7H3/t18-,20-,21+,22-,24+,25+/m0/s1
SMILES	COC(=O)[C@]1(C)CC[C@@H]([C@]2([C@H]1[C@H](OC(=O)C)[C@@H](O)c1c2c(O)cc(c1)C(C)C)C)OC(=O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	462.23	Volume:	469.79 ? Van der Waals volume.
Dense:	0.984	LogP:	2.727 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.575 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.648 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	7.0	Rigid Bonds:	19.0
TPSA:	119.36 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	2.0	Rings:	3.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.517	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.606	Fsp³:	0.64
MCE-18:	91.537 ? 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:	0.634	Fluc inhibitor:	0.003 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.064 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.025 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.089	Promiscuous compounds:	0.223

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.14	MDCK Permeability:	-4.891
Pgp-inhibitor:	0.769	Pgp-substrate:	0.175
PAMPA:	0.555 ? 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):	0.016
20% Bioavailability (F20%):	0.794	30% Bioavailability (F30%):	0.982
50% Bioavailability (F50%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.003	MRP1:	0.999
Plasma Protein Binding (PPB):	83.787%	Volume Distribution (VD):	-0.275
Fu:	16.973% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.176
BSEP inhibitor:	0.916

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.325
CYP2C19-inhibitor:	0.006	CYP2C19-substrate:	0.416
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.002
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.002
CYP3A4-inhibitor:	0.812	CYP3A4-substrate:	0.967
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.97 ? 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):

8.371

Half-life (T1/2):

0.835

ADMET: Toxicity

hERG Blockers:	0.029	hERG Blockers (10um):	0.439
Human Hepatotoxicity (H-HT):	0.605	Drug-induced Liver Injury (DILI):	0.767
AMES Toxicity:	0.288	Rat Oral Acute Toxicity:	0.578
Maximum Recommended Daily Dose:	0.616	Skin Sensitization:	0.933
Carcinogencity:	0.351	Eye Corrosion:	0.021
Eye Irritation:	0.591	Respiratory Toxicity:	0.626
Drug-induced Neurotoxicity:	0.138	Ototoxicity:	0.471
Hematotoxicity:	0.568	Drug-induced Nephrotoxicity:	0.56
Genotoxicity:	0.392	RPMI-8226 Immunitoxicity:	0.063
A549 Cytotoxicity:	0.625	Hek293 Cytotoxicity:	0.227
BCF:	0.621 ? 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:	3.506 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.048 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.459 ? 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
NPO12357	Lycopus europaeus	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[20674349]
NPO12357	Lycopus europaeus	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12357	Lycopus europaeus	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO12357	Lycopus europaeus	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO12357	Lycopus europaeus	Species	Lamiaceae	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
MIC	21
MBC	15
MFC	6

Activity Type	# Activity
Organism	38
Non-molecular	4

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
NPT1190	Organism	Salmonella enterica	Salmonella enterica	MIC	=	179.0	ug.mL-1	PMID[20405847]
NPT5743	Organism	Arcanobacterium pyogenes	Arcanobacterium pyogenes	MIC	=	179.0	ug.mL-1	PMID[1479376]
NPT729	Organism	Micrococcus luteus	Micrococcus luteus	MIC	=	45.0	ug.mL-1	PMID[15921404]
NPT2242	Organism	Penicillium chrysogenum	Penicillium chrysogenum	MIC	=	1433.0	ug.mL-1	PMID[22705001]
NPT1190	Organism	Salmonella enterica	Salmonella enterica	MBC	=	1.433	mg/ml	PMID[12828469]
NPT5743	Organism	Arcanobacterium pyogenes	Arcanobacterium pyogenes	MBC	=	1.433	mg/ml	PMID[26225905]
NPT729	Organism	Micrococcus luteus	Micrococcus luteus	MBC	=	0.179	mg/ml	PMID[26225905]
NPT2242	Organism	Penicillium chrysogenum	Penicillium chrysogenum	MFC	=	2.867	mg/ml	PMID[26191359]
NPT173	Organism	Klebsiella pneumoniae	Klebsiella pneumoniae	MIC	=	179.0	ug.mL-1	PMID[2691635]
NPT173	Organism	Klebsiella pneumoniae	Klebsiella pneumoniae	MIC	=	45.0	ug.mL-1	PMID[2691635]
NPT79	Organism	Bacillus subtilis	Bacillus subtilis	MIC	=	179.0	ug.mL-1	PMID[20405847]
NPT20	Organism	Candida albicans	Candida albicans	MIC	=	358.0	ug.mL-1	PMID[15921404]
NPT312	Organism	Saccharomyces cerevisiae	Saccharomyces cerevisiae	MIC	=	89.0	ug.mL-1	PMID[15921404]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	MIC	=	1433.0	ug.mL-1	PMID[20674349]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	MIC	>	5735.0	ug.mL-1	PMID[20674349]
NPT173	Organism	Klebsiella pneumoniae	Klebsiella pneumoniae	MBC	=	1.433	mg/ml	DrugMatrix in vivo data: Pathology
NPT173	Organism	Klebsiella pneumoniae	Klebsiella pneumoniae	MBC	=	0.716	mg/ml	DrugMatrix in vivo data: Pathology
NPT79	Organism	Bacillus subtilis	Bacillus subtilis	MBC	=	2.867	mg/ml	DrugMatrix in vivo data: Pathology
NPT20	Organism	Candida albicans	Candida albicans	MFC	=	1.433	mg/ml	PMID[26151487]
NPT312	Organism	Saccharomyces cerevisiae	Saccharomyces cerevisiae	MFC	=	0.089	mg/ml	PMID[26225905]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	MFC	=	2.867	mg/ml	PMID[20674349]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	MFC	>	5.735	mg/ml	PMID[20674349]
NPT19	Organism	Escherichia coli	Escherichia coli	MIC	=	358.0	ug.mL-1	PMID[16378364]
NPT19	Organism	Escherichia coli	Escherichia coli	MIC	=	716.0	ug.mL-1	PMID[2691635]
NPT19	Organism	Escherichia coli	Escherichia coli	MIC	=	179.0	ug.mL-1	PMID[26287401]
NPT18	Organism	Pseudomonas aeruginosa	Pseudomonas aeruginosa	MIC	=	358.0	ug.mL-1	PMID[20405847]
NPT766	Organism	Proteus vulgaris	Proteus vulgaris	MIC	=	179.0	ug.mL-1	PMID[2691635]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	MIC	=	179.0	ug.mL-1	PMID[15921404]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	MIC	=	22.0	ug.mL-1	PMID[15921404]
NPT87	Organism	Aspergillus fumigatus	Aspergillus fumigatus	MIC	=	89.0	ug.mL-1	PMID[22705001]
NPT19	Organism	Escherichia coli	Escherichia coli	MBC	=	0.716	mg/ml	DrugMatrix in vivo data: Pathology
NPT19	Organism	Escherichia coli	Escherichia coli	MBC	=	5.735	mg/ml	DrugMatrix in vivo data: Pathology
NPT19	Organism	Escherichia coli	Escherichia coli	MBC	=	2.867	mg/ml	DrugMatrix in vivo data: Pathology
NPT18	Organism	Pseudomonas aeruginosa	Pseudomonas aeruginosa	MBC	=	2.867	mg/ml	DrugMatrix in vivo data: Pathology
NPT766	Organism	Proteus vulgaris	Proteus vulgaris	MBC	=	5.735	mg/ml	DrugMatrix in vivo data: Pathology
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	MBC	=	5.735	mg/ml	PMID[26225905]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	MBC	=	2.867	mg/ml	PMID[26225905]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	MBC	=	0.716	mg/ml	PMID[26225905]
NPT87	Organism	Aspergillus fumigatus	Aspergillus fumigatus	MFC	=	0.358	mg/ml	PMID[26151487]
NPT314	Organism	Bacillus cereus	Bacillus cereus	MIC	=	89.0	ug.mL-1	PMID[1479376]
NPT314	Organism	Bacillus cereus	Bacillus cereus	MBC	=	0.716	mg/ml	DrugMatrix in vivo data: Pathology

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 NPC3218 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	8569
0.1-0.2	39323
0.2-0.3	1946
0.3-0.4	16
0.4-0.5	4
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	Natural Product ID
		NPC

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC3218 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4100
0.1-0.2	4989
0.2-0.3	61
0.3-0.4	0
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