NPASS Compound

Natural Product: NPC106668

Natural Product ID	NPC106668
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Verbenalin
IUPAC Name	methyl (1S,4aS,7S,7aR)-7-methyl-5-oxo-1-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-4a,6,7,7a-tetrahydro-1H-cyclopenta[c]pyran-4-carboxylate
Synonyms	Verbenalin
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1080178
PubChem CID	73467
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0002049] Terpene glycosides [CHEMONTID:0004081] Iridoid O-glycosides

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 51 53 0 0 0 0 0 0 0 0999 V2000 0.4529 -1.2837 -2.9879 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0418 -1.1212 -1.6189 C 0 0 1 0 0 0 0 0 0 0 0 0 2.4410 -1.7330 -1.6154 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1387 -0.8392 -0.6417 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9273 -1.1493 0.2169 O 0 0 0 0 0 0 0 0 0 0 0 0 2.6568 0.5460 -0.9473 C 0 0 2 0 0 0 0 0 0 0 0 0 2.9616 1.4992 0.1435 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0256 2.1669 0.8072 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7107 1.9365 0.4355 O 0 0 0 0 0 0 0 0 0 0 0 0 0.4136 0.5916 0.0382 C 0 0 2 0 0 0 0 0 0 0 0 0 1.2071 0.3305 -1.2167 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.9443 0.3973 -0.0947 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.5169 -0.5577 0.7063 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.4277 0.1597 1.6654 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.5129 -0.7765 2.0896 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.3418 -1.0476 0.8386 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.4136 -1.3685 -0.3187 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.5786 -0.3553 -1.4204 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9119 -0.1917 -1.7810 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.1287 -1.5804 0.0911 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.3055 -2.0242 1.0347 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.2669 -0.2825 3.1207 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.6853 0.6255 2.7562 O 0 0 0 0 0 0 0 0 0 0 0 0 4.3915 1.6855 0.4743 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2970 1.0687 -0.1360 O 0 0 0 0 0 0 0 0 0 0 0 0 4.7572 2.5549 1.4756 O 0 0 0 0 0 0 0 0 0 0 0 0 6.0639 2.8224 1.8864 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3589 -2.0623 -3.0044 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1946 -1.6267 -3.7386 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0244 -0.3510 -3.3423 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3916 -1.6724 -0.9097 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8673 -1.6741 -2.6234 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4332 -2.7860 -1.2969 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1172 0.8752 -1.9150 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3293 2.8539 1.6000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7650 -0.1301 0.8049 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8257 0.9995 -2.0192 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6556 -0.9912 1.3108 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8235 1.0683 1.1472 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0418 -1.7420 2.3673 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8582 -0.1053 0.5945 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7894 -2.3425 -0.7391 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0652 -0.6889 -2.3648 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1072 0.6176 -1.1799 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0388 0.7086 -2.2043 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3339 -2.6555 0.2761 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6519 0.0966 3.7982 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7593 0.7487 2.4345 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7541 2.0853 1.4494 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2996 3.8743 1.5511 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0779 2.8259 3.0024 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 4 5 2 0 4 6 1 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 1 0 10 11 1 0 10 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 1 0 17 20 1 0 16 21 1 0 15 22 1 0 14 23 1 0 7 24 1 0 24 25 2 0 24 26 1 0 26 27 1 0 11 2 1 0 20 13 1 0 11 6 1 0 1 28 1 0 1 29 1 0 1 30 1 0 2 31 1 1 3 32 1 0 3 33 1 0 6 34 1 6 8 35 1 0 10 36 1 1 11 37 1 6 13 38 1 1 14 39 1 6 15 40 1 1 16 41 1 6 17 42 1 6 18 43 1 0 18 44 1 0 19 45 1 0 21 46 1 0 22 47 1 0 23 48 1 0 27 49 1 0 27 50 1 0 27 51 1 0 M END

Standard InCHIKey	HLXRWTJXGMHOFN-XJSNKYLASA-N
Standard InCHI	InChI=1S/C17H24O10/c1-6-3-8(19)11-7(15(23)24-2)5-25-16(10(6)11)27-17-14(22)13(21)12(20)9(4-18)26-17/h5-6,9-14,16-18,20-22H,3-4H2,1-2H3/t6-,9+,10+,11-,12+,13-,14+,16-,17-/m0/s1
SMILES	C[C@H]1CC(=O)[C@@H]2C(=CO[C@H]([C@H]12)O[C@H]1[C@@H]([C@H]([C@@H]([C@@H](CO)O1)O)O)O)C(=O)OC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	388.14	Volume:	356.912 ? Van der Waals volume.
Dense:	1.087	LogP:	-0.378 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	-0.198 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-0.782 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	18.0
TPSA:	151.98 ? Topological Polar Surface Area.	H-Bond Acceptor:	10.0
H-Bond Donor:	4.0	Rings:	3.0
Heavy Atoms:	10.0

MedChem Properties

QED Drug-Likeness Score:	0.4	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.641	Fsp³:	0.765
MCE-18:	56.0 ? 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:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.503	Fluc inhibitor:	0.002 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.247 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.001 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.215	Promiscuous compounds:	0.27

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.677	MDCK Permeability:	-5.093
Pgp-inhibitor:	0.002	Pgp-substrate:	0.154
PAMPA:	0.961 ? 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):	0.291
20% Bioavailability (F20%):	0.114	30% Bioavailability (F30%):	0.869
50% Bioavailability (F50%):	0.804

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.027	MRP1:	0.882
Plasma Protein Binding (PPB):	38.4%	Volume Distribution (VD):	-0.532
Fu:	58.698% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.995
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.016
BSEP inhibitor:	0.016

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.002	CYP2C19-substrate:	0.002
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.008
CYP3A4-inhibitor:	0.014	CYP3A4-substrate:	0.004
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.853
HLM stability:	0.129 ? 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):

1.863

Half-life (T1/2):

2.756

ADMET: Toxicity

hERG Blockers:	0.016	hERG Blockers (10um):	0.135
Human Hepatotoxicity (H-HT):	0.744	Drug-induced Liver Injury (DILI):	0.965
AMES Toxicity:	0.826	Rat Oral Acute Toxicity:	0.057
Maximum Recommended Daily Dose:	0.044	Skin Sensitization:	0.995
Carcinogencity:	0.302	Eye Corrosion:	0.0
Eye Irritation:	0.155	Respiratory Toxicity:	0.028
Drug-induced Neurotoxicity:	0.069	Ototoxicity:	0.957
Hematotoxicity:	0.717	Drug-induced Nephrotoxicity:	0.751
Genotoxicity:	0.48	RPMI-8226 Immunitoxicity:	0.088
A549 Cytotoxicity:	0.123	Hek293 Cytotoxicity:	0.116
BCF:	0.287 ? 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:	2.756 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.29 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.525 ? 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
NPO23142	Lamium album	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19904996]
NPO23218	Viscum coloratum	Species	Viscaceae	Eukaryota	n.a.	aerial part	n.a.	PMID[2082684]
NPO23218	Viscum coloratum	Species	Viscaceae	Eukaryota	n.a.	aerial part	n.a.	PMID[21922656]
NPO12588	Cornus officinalis	Species	Cornaceae	Eukaryota	Fruits	n.a.	n.a.	PMID[29140705]
NPO23218	Viscum coloratum	Species	Viscaceae	Eukaryota	n.a.	aerial part	n.a.	PMID[3254039]
NPO23218	Viscum coloratum	Species	Viscaceae	Eukaryota	n.a.	aerial part	n.a.	PMID[3256207]
NPO7808	Viscum album	Species	Viscaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[35357239]
NPO7808	Viscum album	Species	Viscaceae	Eukaryota	n.a.	twig	n.a.	PMID[9179367]
NPO1458	Burkholderia gladioli	Species	Burkholderiaceae	Bacteria	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12588	Cornus officinalis	Species	Cornaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO2838	Verbena officinalis	Species	Verbenaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO23218	Viscum coloratum	Species	Viscaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO26236	Artocarpus incisus	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7268	Ipomoea violacea	Species	Convolvulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO11004	Cornus capitata	Species	Cornaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO10779	Lychnophora ericoides	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO23142	Lamium album	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7808	Viscum album	Species	Viscaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO2838	Verbena officinalis	Species	Verbenaceae	Eukaryota	Root	n.a.	n.a.	Database[FooDB]
NPO2838	Verbena officinalis	Species	Verbenaceae	Eukaryota	Flower	n.a.	n.a.	Database[FooDB]
NPO2838	Verbena officinalis	Species	Verbenaceae	Eukaryota	Leaf	n.a.	n.a.	Database[FooDB]
NPO2838	Verbena officinalis	Species	Verbenaceae	Eukaryota	Plant	n.a.	n.a.	Database[FooDB]
NPO2838	Verbena officinalis	Species	Verbenaceae	Eukaryota	Stem	n.a.	n.a.	Database[FooDB]
NPO2838	Verbena officinalis	Species	Verbenaceae	Eukaryota		n.a.	n.a.	Database[FooDB]
NPO23218	Viscum coloratum	Species	Viscaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO2838	Verbena officinalis	Species	Verbenaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO12588	Cornus officinalis	Species	Cornaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO7268	Ipomoea violacea	Species	Convolvulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO7808	Viscum album	Species	Viscaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO2838	Verbena officinalis	Species	Verbenaceae	Eukaryota	n.a.	n.a.		Database[Phenol-Explorer]
NPO23218	Viscum coloratum	Species	Viscaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO7808	Viscum album	Species	Viscaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO12588	Cornus officinalis	Species	Cornaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO7268	Ipomoea violacea	Species	Convolvulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO2838	Verbena officinalis	Species	Verbenaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO11004	Cornus capitata	Species	Cornaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO7268	Ipomoea violacea	Species	Convolvulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO12588	Cornus officinalis	Species	Cornaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO2838	Verbena officinalis	Species	Verbenaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO23218	Viscum coloratum	Species	Viscaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO7808	Viscum album	Species	Viscaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO2838	Verbena officinalis	Species	Verbenaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO12588	Cornus officinalis	Species	Cornaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO6227	Umbilicaria papulosa	Species	Umbilicariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO23218	Viscum coloratum	Species	Viscaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO26236	Artocarpus incisus	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO10411	Bauhinia uruguayensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO16022	Streptomyces aureomonopodiales	Species	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	Database[UNPD]
NPO7268	Ipomoea violacea	Species	Convolvulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12588	Cornus officinalis	Species	Cornaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO7808	Viscum album	Species	Viscaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO11004	Cornus capitata	Species	Cornaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1458	Burkholderia gladioli	Species	Burkholderiaceae	Bacteria	n.a.	n.a.	n.a.	Database[UNPD]
NPO10779	Lychnophora ericoides	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO23142	Lamium album	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO2838	Verbena officinalis	Species	Verbenaceae	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
NPO2838	Verbena officinalis	Other	Flower	500	500	500	mg/100g	Database [DUKE]
NPO2838	Verbena officinalis	Other	Plant	300	300	300	mg/100g	Database [DUKE]

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	3
Inhibition	2

Activity Type	# Activity
Individual protein	2
Organism	2
Others	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT154	Individual protein	Mothers against decapentaplegic homolog 3	Homo sapiens	Potency	n.a.	3548.1	nM	PubChem BioAssay data set
NPT64	Individual protein	ATPase family AAA domain-containing protein 5	Homo sapiens	Potency	n.a.	5802.4	nM	PubChem BioAssay data set

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT191	Organism	Hepatitis C virus	Hepatitis C virus	Inhibition	=	21.9	%	PMID[19904996]
NPT191	Organism	Hepatitis C virus	Hepatitis C virus	Inhibition	=	43.4	%	PMID[19904996]
NPT2	Others	Unspecified	n.a.	Potency	=	145.8	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 NPC106668 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	16656
0.1-0.2	28179
0.2-0.3	4431
0.3-0.4	439
0.4-0.5	96
0.5-0.6	32
0.6-0.7	21
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
0.7377	Intermediate Similarity	NPC27687
0.7049	Intermediate Similarity	NPC475928
0.6774	Remote Similarity	NPC35185
0.6774	Remote Similarity	NPC4899
0.6774	Remote Similarity	NPC177013
0.6613	Remote Similarity	NPC474730
0.6613	Remote Similarity	NPC170432
0.6349	Remote Similarity	NPC117596
0.6308	Remote Similarity	NPC37240
0.625	Remote Similarity	NPC255677
0.625	Remote Similarity	NPC22149
0.625	Remote Similarity	NPC306344
0.6212	Remote Similarity	NPC231710
0.6212	Remote Similarity	NPC470573
0.6212	Remote Similarity	NPC120021
0.6212	Remote Similarity	NPC216826
0.6212	Remote Similarity	NPC270908
0.6212	Remote Similarity	NPC65665
0.6154	Remote Similarity	NPC148270
0.6061	Remote Similarity	NPC61201
0.6029	Remote Similarity	NPC488472
0.6029	Remote Similarity	NPC257424
0.6	Remote Similarity	NPC307699
0.589	Remote Similarity	NPC488470
0.5882	Remote Similarity	NPC609500
0.5797	Remote Similarity	NPC222062
0.5758	Remote Similarity	NPC195510
0.5758	Remote Similarity	NPC298255
0.5758	Remote Similarity	NPC13171
0.5714	Remote Similarity	NPC41681
0.5652	Remote Similarity	NPC475851
0.5652	Remote Similarity	NPC475924
0.5606	Remote Similarity	NPC303451
0.5606	Remote Similarity	NPC72358
0.5588	Remote Similarity	NPC110701
0.5571	Remote Similarity	NPC254538
0.5541	Remote Similarity	NPC488456
0.5541	Remote Similarity	NPC488471
0.5541	Remote Similarity	NPC488466
0.5541	Remote Similarity	NPC488465
0.5541	Remote Similarity	NPC488460
0.5541	Remote Similarity	NPC488462
0.5538	Remote Similarity	NPC63897
0.5507	Remote Similarity	NPC193741
0.5479	Remote Similarity	NPC197541
0.5479	Remote Similarity	NPC234304
0.5479	Remote Similarity	NPC118761
0.5443	Remote Similarity	NPC488467
0.5395	Remote Similarity	NPC488457
0.5395	Remote Similarity	NPC488464
0.5395	Remote Similarity	NPC488463
0.5309	Remote Similarity	NPC488468
0.5072	Remote Similarity	NPC170204
0.5072	Remote Similarity	NPC250545
0.5062	Remote Similarity	NPC46641

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC106668 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6348
0.1-0.2	2694
0.2-0.3	89
0.3-0.4	19
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