NPASS Compound

Natural Product: NPC206737

Natural Product ID	NPC206737
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Schisanhenol
IUPAC Name	n.a.
Synonyms	(+)-Gomisin K3; Schisanhenol
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL490125
PubChem CID	73057
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000238] Tannins [CHEMONTID:0001710] Hydrolyzable tannins

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 59 61 0 0 0 0 0 0 0 0999 V2000 -5.2267 -2.0367 0.9434 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0955 -2.4671 0.2230 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.9523 -1.6944 0.1858 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9022 -0.4742 0.8629 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7567 0.2589 0.8060 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9169 1.5472 1.5185 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5814 2.6873 0.5261 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.1187 2.3610 -0.8474 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1633 3.1043 0.5457 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.0575 4.6294 0.6846 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6132 2.7813 -0.7475 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2454 1.4545 -0.5478 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7088 0.2186 -0.1527 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6593 -0.2406 0.0666 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7033 -1.4341 -0.6070 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8630 -2.1553 -0.5347 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8916 -3.3585 -1.2123 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.4784 -4.5220 -0.5204 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3944 -1.8208 -1.3188 O 0 0 0 0 0 0 0 0 0 0 0 0 1.4608 -0.9044 0.0604 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8282 -2.0395 0.4722 O 0 0 0 0 0 0 0 0 0 0 0 0 0.6175 -2.3899 1.8305 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8100 -0.7998 -0.1394 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3866 0.4169 -0.5398 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5955 1.5347 -0.7388 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7502 0.4695 -0.7285 O 0 0 0 0 0 0 0 0 0 0 0 0 5.3231 1.6973 -1.1316 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5802 -1.9328 0.0674 O 0 0 0 0 0 0 0 0 0 0 0 0 3.7810 -2.7852 -1.0574 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1234 -2.2088 2.0431 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4594 -0.9668 0.8038 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1362 -2.6222 0.6418 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7278 -0.0808 1.4310 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9241 1.6603 1.9121 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1990 1.6249 2.3636 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2110 3.5477 0.9005 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6081 1.5417 -1.3469 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1846 2.0504 -0.6989 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1426 3.3052 -1.4283 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4183 2.6493 1.3695 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9526 5.0371 0.1673 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1575 4.9301 1.7526 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8480 5.0230 0.2198 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0447 2.8230 -1.6217 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4147 3.5381 -0.9116 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4472 -4.4116 -0.1185 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4998 -5.4164 -1.1858 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1282 -4.7594 0.3440 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6450 -1.5275 -2.2468 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1805 -3.3107 2.0133 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0433 -1.5879 2.4412 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4565 -2.5985 2.0446 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9993 2.4897 -1.0444 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9796 1.9842 -2.1401 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4303 1.6401 -1.1813 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0897 2.4734 -0.3642 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3381 -3.7036 -0.7922 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4310 -2.2116 -1.7540 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8567 -3.0181 -1.5827 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 1 0 6 7 1 0 7 8 1 0 7 9 1 0 9 10 1 0 9 11 1 0 11 12 1 0 12 13 2 0 13 14 1 0 14 15 1 0 15 16 2 0 16 17 1 0 17 18 1 0 15 19 1 0 13 20 1 0 20 21 1 0 21 22 1 0 20 23 2 0 23 24 1 0 24 25 2 0 24 26 1 0 26 27 1 0 23 28 1 0 28 29 1 0 16 3 1 0 14 5 2 0 25 12 1 0 1 30 1 0 1 31 1 0 1 32 1 0 4 33 1 0 6 34 1 0 6 35 1 0 7 36 1 1 8 37 1 0 8 38 1 0 8 39 1 0 9 40 1 1 10 41 1 0 10 42 1 0 10 43 1 0 11 44 1 0 11 45 1 0 18 46 1 0 18 47 1 0 18 48 1 0 19 49 1 0 22 50 1 0 22 51 1 0 22 52 1 0 25 53 1 0 27 54 1 0 27 55 1 0 27 56 1 0 29 57 1 0 29 58 1 0 29 59 1 0 M END

Standard InCHIKey	FYSHYFPJBONYCQ-QWHCGFSZSA-N
Standard InCHI	InChI=1S/C23H30O6/c1-12-8-14-10-16(25-3)21(27-5)20(24)18(14)19-15(9-13(12)2)11-17(26-4)22(28-6)23(19)29-7/h10-13,24H,8-9H2,1-7H3/t12-,13+/m0/s1
SMILES	COc1cc2C[C@H](C)[C@H](C)Cc3c(c2c(c1OC)O)c(OC)c(c(c3)OC)OC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	402.2	Volume:	417.617 ? Van der Waals volume.
Dense:	0.963	LogP:	2.998 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.017 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.129 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	18.0
TPSA:	66.38 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	1.0	Rings:	3.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.796	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.429	Fsp³:	0.478
MCE-18:	67.941 ? 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:	1	PAINS Alert:	0
Colloidal aggregators:	0.503	Fluc inhibitor:	0.342 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.169 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.195 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.328	Promiscuous compounds:	0.547

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.059	MDCK Permeability:	-4.729
Pgp-inhibitor:	0.142	Pgp-substrate:	0.143
PAMPA:	0.022 ? 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):	0.0
20% Bioavailability (F20%):	0.022	30% Bioavailability (F30%):	0.025
50% Bioavailability (F50%):	0.782

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.1	MRP1:	0.993
Plasma Protein Binding (PPB):	89.122%	Volume Distribution (VD):	-0.188
Fu:	9.195% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.973
OATP1B3 inhibitor:	0.985	BCRP inhibitor:	0.261
BSEP inhibitor:	0.99

ADMET: Metabolism

CYP1A2-inhibitor:	0.939	CYP1A2-substrate:	0.047
CYP2C19-inhibitor:	0.997	CYP2C19-substrate:	0.398
CYP2C9-inhibitor:	0.877	CYP2C9-substrate:	0.002
CYP2D6-inhibitor:	0.42	CYP2D6-substrate:	0.219
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	0.038
CYP2B6-substrate:	0.055	CYP2C8-inhibitor:	0.988
HLM stability:	0.699 ? 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):

5.563

Half-life (T1/2):

0.929

ADMET: Toxicity

hERG Blockers:	0.114	hERG Blockers (10um):	0.479
Human Hepatotoxicity (H-HT):	0.526	Drug-induced Liver Injury (DILI):	0.569
AMES Toxicity:	0.491	Rat Oral Acute Toxicity:	0.3
Maximum Recommended Daily Dose:	0.382	Skin Sensitization:	0.612
Carcinogencity:	0.763	Eye Corrosion:	0.033
Eye Irritation:	0.875	Respiratory Toxicity:	0.877
Drug-induced Neurotoxicity:	0.485	Ototoxicity:	0.51
Hematotoxicity:	0.608	Drug-induced Nephrotoxicity:	0.446
Genotoxicity:	0.01	RPMI-8226 Immunitoxicity:	0.178
A549 Cytotoxicity:	0.561	Hek293 Cytotoxicity:	0.446
BCF:	2.187 ? 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:	4.375 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.995 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.187 ? 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
NPO24804	Schisandra rubriflora	Species	Schisandraceae	Eukaryota	n.a.	leaf	n.a.	PMID[16494492]
NPO24804	Schisandra rubriflora	Species	Schisandraceae	Eukaryota	n.a.	stem	n.a.	PMID[16494492]
NPO8187	Schisandra chinensis	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[16562834]
NPO24804	Schisandra rubriflora	Species	Schisandraceae	Eukaryota	fruits	n.a.	n.a.	PMID[17190445]
NPO24804	Schisandra rubriflora	Species	Schisandraceae	Eukaryota	n.a.	fruit	n.a.	PMID[17190445]
NPO24804	Schisandra rubriflora	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17489633]
NPO8584	Schisandra arisanensis	Species	Schisandraceae	Eukaryota	fruits	n.a.	n.a.	PMID[19673515]
NPO24804	Schisandra rubriflora	Species	Schisandraceae	Eukaryota	leaves and stems	n.a.	n.a.	PMID[20146529]
NPO8584	Schisandra arisanensis	Species	Schisandraceae	Eukaryota	fruits	n.a.	n.a.	PMID[20536188]
NPO8584	Schisandra arisanensis	Species	Schisandraceae	Eukaryota	fruits	n.a.	n.a.	PMID[23265871]
NPO7385	Schisandra sphenanthera	Species	Schisandraceae	Eukaryota	fruits	n.a.	n.a.	PMID[23265871]
NPO29191	Schisandra neglecta	Species	Schisandraceae	Eukaryota	Stems	Luoji Mountain Village, Xichang County, Sicuan Province, China	2011-Sep	PMID[23738539]
NPO8187	Schisandra chinensis	Species	Schisandraceae	Eukaryota	n.a.	fruit	n.a.	PMID[24155209]
NPO8187	Schisandra chinensis	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[24959987]
NPO8187	Schisandra chinensis	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[25302569]
NPO24804	Schisandra rubriflora	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7385	Schisandra sphenanthera	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8584	Schisandra arisanensis	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8187	Schisandra chinensis	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8187	Schisandra chinensis	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO7385	Schisandra sphenanthera	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO8584	Schisandra arisanensis	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO24804	Schisandra rubriflora	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO8584	Schisandra arisanensis	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO7385	Schisandra sphenanthera	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO8187	Schisandra chinensis	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO24804	Schisandra rubriflora	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO24804	Schisandra rubriflora	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO7385	Schisandra sphenanthera	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO8187	Schisandra chinensis	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO8187	Schisandra chinensis	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO7385	Schisandra sphenanthera	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO8187	Schisandra chinensis	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8584	Schisandra arisanensis	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO29191	Schisandra neglecta	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO24804	Schisandra rubriflora	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO7385	Schisandra sphenanthera	Species	Schisandraceae	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
EC50	1
IC50	1
Inhibition	6
Potency	12
Survival	1

Activity Type	# Activity
Cell line	5
Individual protein	8
Organism	6
Others	2

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT50	Individual protein	Tyrosyl-DNA phosphodiesterase 1	Homo sapiens	Potency	=	28.2	nM	PubChem BioAssay data set
NPT54	Individual protein	Nonstructural protein 1	Influenza A virus	Potency	=	19952.6	nM	PubChem BioAssay data set
NPT524	Individual protein	Serine-protein kinase ATM	Homo sapiens	Potency	=	19952.6	nM	PubChem BioAssay data set
NPT443	Individual protein	Histone acetyltransferase GCN5	Homo sapiens	Potency	n.a.	3548.1	nM	PubChem BioAssay data set
NPT10	Individual protein	Geminin	Homo sapiens	Potency	n.a.	6513.1	nM	PubChem BioAssay data set
NPT478	Individual protein	Ataxin-2	Homo sapiens	Potency	n.a.	35481.3	nM	PubChem BioAssay data set
NPT101	Individual protein	Glucagon-like peptide 1 receptor	Homo sapiens	Potency	n.a.	22387.2	nM	PubChem BioAssay data set
NPT11	Individual protein	Guanine nucleotide-binding protein G(s), subunit alpha	Homo sapiens	Potency	n.a.	11220.2	nM	PubChem BioAssay data set

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT759	Cell line	H9	Homo sapiens	IC50	=	42000.0	nM	PMID[17190445]
NPT927	Cell line	PBMC	Homo sapiens	Inhibition	=	60.8	%	PMID[19673515]
NPT927	Cell line	PBMC	Homo sapiens	Inhibition	=	80.1	%	PMID[19673515]
NPT927	Cell line	PBMC	Homo sapiens	Inhibition	=	76.0	%	PMID[19673515]
NPT24	Organism	Human immunodeficiency virus 1	Human immunodeficiency virus 1	EC50	=	5700.0	nM	PMID[17190445]
NPT963	Organism	Hepatitis B virus	Hepatitis B virus	Inhibition	=	45.0	%	PMID[19640714]
NPT963	Organism	Hepatitis B virus	Hepatitis B virus	Inhibition	=	0.0	%	PMID[19640714]
NPT312	Organism	Saccharomyces cerevisiae	Saccharomyces cerevisiae	Potency	=	4466.8	nM	PubChem BioAssay data set
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	Potency	n.a.	13115.4	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Inhibition	=	69.0	%	PMID[23265871]
NPT2	Others	Unspecified	n.a.	Potency	n.a.	28183.8	nM	PubChem BioAssay data set

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT21742	Cell line	L02	Homo sapiens	Survival	=	48.1	%	PMID[24602900]

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 NPC206737 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	23789
0.1-0.2	22660
0.2-0.3	3183
0.3-0.4	134
0.4-0.5	55
0.5-0.6	20
0.6-0.7	8
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC289258
1.0	High Similarity	NPC611061
0.7955	Intermediate Similarity	NPC555
0.7955	Intermediate Similarity	NPC7515
0.7917	Intermediate Similarity	NPC184684
0.7917	Intermediate Similarity	NPC184641
0.7917	Intermediate Similarity	NPC133934
0.72	Intermediate Similarity	NPC180602
0.6829	Remote Similarity	NPC283114
0.6829	Remote Similarity	NPC207702
0.6829	Remote Similarity	NPC149008
0.6809	Remote Similarity	NPC56764
0.6809	Remote Similarity	NPC188378
0.6078	Remote Similarity	NPC86605
0.6034	Remote Similarity	NPC73467
0.6	Remote Similarity	NPC3072
0.5932	Remote Similarity	NPC189239
0.5893	Remote Similarity	NPC470917
0.5833	Remote Similarity	NPC121661
0.5714	Remote Similarity	NPC469659
0.5714	Remote Similarity	NPC145722
0.5714	Remote Similarity	NPC256776
0.5714	Remote Similarity	NPC185680
0.5556	Remote Similarity	NPC276026
0.5455	Remote Similarity	NPC240279
0.5439	Remote Similarity	NPC55239
0.541	Remote Similarity	NPC252286
0.5357	Remote Similarity	NPC46277
0.5323	Remote Similarity	NPC154971
0.5306	Remote Similarity	NPC32189
0.5303	Remote Similarity	NPC475756
0.5224	Remote Similarity	NPC476065
0.5172	Remote Similarity	NPC301765
0.5147	Remote Similarity	NPC474606
0.5098	Remote Similarity	NPC102256
0.5094	Remote Similarity	NPC205442

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC206737 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4825
0.1-0.2	4218
0.2-0.3	102
0.3-0.4	5
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