NPASS Compound

Natural Product: NPC121783

Natural Product ID	NPC121783
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(+)-Epieudesmin
IUPAC Name	(3R,3aR,6S,6aR)-3,6-bis(3,4-dimethoxyphenyl)-1,3,3a,4,6,6a-hexahydrofuro[3,4-c]furan
Synonyms	(+)-Epieudesmin
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL512865
PubChem CID	7000209
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0001392] Lignans, neolignans and related compounds [CHEMONTID:0003686] Furanoid lignans

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 54 57 0 0 0 0 0 0 0 0999 V2000 7.4945 0.4985 1.5674 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6312 -0.4190 0.9612 O 0 0 0 0 0 0 0 0 0 0 0 0 5.3567 -0.0660 0.4921 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8886 1.2269 0.6099 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6341 1.5474 0.1419 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8000 0.6156 -0.4545 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2890 -0.6557 -0.5588 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5634 -1.0115 -0.0905 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0387 -2.3176 -0.2085 O 0 0 0 0 0 0 0 0 0 0 0 0 4.1947 -3.2735 -0.8158 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4921 1.0397 -0.9555 C 0 0 1 0 0 0 0 0 0 0 0 0 0.3366 0.1453 -0.7637 C 0 0 1 0 0 0 0 0 0 0 0 0 0.4874 -1.0617 0.0726 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7559 -1.2098 0.7032 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.2505 0.0282 1.0138 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.7207 0.1142 0.8428 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4843 0.7237 1.8119 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8613 0.8315 1.7027 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4792 0.3129 0.5917 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7441 -0.3111 -0.4111 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3569 -0.3952 -0.2552 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3976 -0.8241 -1.5196 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.6929 -1.4574 -2.5467 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.8511 0.4141 0.4713 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.6021 1.0412 1.4764 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6300 0.9996 0.0621 C 0 0 1 0 0 0 0 0 0 0 0 0 0.3824 1.9025 0.7596 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1595 2.2729 -0.3255 O 0 0 0 0 0 0 0 0 0 0 0 0 7.2555 0.7247 2.6190 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5279 1.4777 1.0163 H 0 0 0 0 0 0 0 0 0 0 0 0 8.5378 0.1120 1.5206 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5458 1.9555 1.0786 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3053 2.5674 0.2526 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7203 -1.4480 -1.0267 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9366 -2.9911 -1.8455 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2363 -3.2504 -0.2218 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5732 -4.3005 -0.7208 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5840 1.2799 -2.0434 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1832 -0.0620 -1.7283 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5320 -1.9645 -0.6160 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2800 -1.0328 0.8137 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0275 0.2742 2.0793 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0442 1.1546 2.7184 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4708 1.3051 2.4522 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7991 -0.8809 -1.0389 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9363 -2.1740 -2.1564 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4052 -2.0338 -3.1785 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1686 -0.6946 -3.1317 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2799 2.1156 1.5972 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.6882 0.9804 1.2459 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4459 0.5748 2.4796 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3343 1.5646 -0.5567 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1208 2.7594 1.2116 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9470 1.2748 1.4514 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 2 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 1 0 6 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 2 0 19 20 1 0 20 21 2 0 20 22 1 0 22 23 1 0 19 24 1 0 24 25 1 0 15 26 1 0 26 27 1 0 27 28 1 0 8 3 1 0 28 11 1 0 26 12 1 0 21 16 1 0 1 29 1 0 1 30 1 0 1 31 1 0 4 32 1 0 5 33 1 0 7 34 1 0 10 35 1 0 10 36 1 0 10 37 1 0 11 38 1 6 12 39 1 6 13 40 1 0 13 41 1 0 15 42 1 1 17 43 1 0 18 44 1 0 21 45 1 0 23 46 1 0 23 47 1 0 23 48 1 0 25 49 1 0 25 50 1 0 25 51 1 0 26 52 1 6 27 53 1 0 27 54 1 0 M END

Standard InCHIKey	PEUUVVGQIVMSAW-WWLNLUSPSA-N
Standard InCHI	InChI=1S/C22H26O6/c1-23-17-7-5-13(9-19(17)25-3)21-15-11-28-22(16(15)12-27-21)14-6-8-18(24-2)20(10-14)26-4/h5-10,15-16,21-22H,11-12H2,1-4H3/t15-,16-,21-,22+/m0/s1
SMILES	COc1ccc(cc1OC)[C@H]1[C@H]2CO[C@H](c3ccc(c(c3)OC)OC)[C@H]2CO1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	386.17	Volume:	391.765 ? Van der Waals volume.
Dense:	0.986	LogP:	1.787 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.212 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.631 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	21.0
TPSA:	55.38 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	0.0	Rings:	4.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.753	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.488	Fsp³:	0.455
MCE-18:	74.25 ? 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:	0.361	Fluc inhibitor:	0.485 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.036 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.038 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.306	Promiscuous compounds:	0.27

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.757	MDCK Permeability:	-4.739
Pgp-inhibitor:	0.558	Pgp-substrate:	0.053
PAMPA:	0.003 ? 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):	0.002
20% Bioavailability (F20%):	0.061	30% Bioavailability (F30%):	0.164
50% Bioavailability (F50%):	0.793

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.011	MRP1:	0.641
Plasma Protein Binding (PPB):	86.495%	Volume Distribution (VD):	0.155
Fu:	12.515% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.99
OATP1B3 inhibitor:	0.994	BCRP inhibitor:	0.271
BSEP inhibitor:	0.951

ADMET: Metabolism

CYP1A2-inhibitor:	0.999	CYP1A2-substrate:	0.258
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.462
CYP2C9-inhibitor:	0.07	CYP2C9-substrate:	0.038
CYP2D6-inhibitor:	0.999	CYP2D6-substrate:	0.413
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	0.192
CYP2B6-substrate:	0.001	CYP2C8-inhibitor:	0.595
HLM stability:	0.45 ? 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):

7.544

Half-life (T1/2):

2.839

ADMET: Toxicity

hERG Blockers:	0.135	hERG Blockers (10um):	0.49
Human Hepatotoxicity (H-HT):	0.695	Drug-induced Liver Injury (DILI):	0.843
AMES Toxicity:	0.714	Rat Oral Acute Toxicity:	0.22
Maximum Recommended Daily Dose:	0.299	Skin Sensitization:	0.632
Carcinogencity:	0.561	Eye Corrosion:	0.138
Eye Irritation:	0.978	Respiratory Toxicity:	0.526
Drug-induced Neurotoxicity:	0.5	Ototoxicity:	0.236
Hematotoxicity:	0.522	Drug-induced Nephrotoxicity:	0.597
Genotoxicity:	0.57	RPMI-8226 Immunitoxicity:	0.103
A549 Cytotoxicity:	0.08	Hek293 Cytotoxicity:	0.208
BCF:	2.026 ? 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:	3.84 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.377 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.664 ? 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
NPO14144	Hernandia peltata	Species	Hernandiaceae	Eukaryota	n.a.	stem	n.a.	DOI[10.1021/np960034d]
NPO14144	Hernandia peltata	Species	Hernandiaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.3987/R-1980-04-0397]
NPO14144	Hernandia peltata	Species	Hernandiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[14987061]
NPO4756	Mesua elegans	Species	Calophyllaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[20943395]
NPO8211	Artocarpus odoratissimus	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21275386]
NPO5710	Michelia rajaniana	Species	Magnoliaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[3236012]
NPO6557	Lotus villosus	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO1319	Zanthoxylum culantrillo	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO24791	Smyrnium perfoliatum	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO10466	Commiphora kua	Species	Burseraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8211	Artocarpus odoratissimus	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO81	Erythrina orientalis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO4442	Artemisia austriaca	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO11244	Chrysolaena propinqua	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO25530	Daphne blagayana	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO9469	Digitalis obscura	Species	Plantaginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8378	Fagara heitzii	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[COCONUT]
NPO28383	Vernonia tufnellae	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO4756	Mesua elegans	Species	Calophyllaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO5710	Michelia rajaniana	Species	Magnoliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO5060	Onychopetalum amazonicum	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO3215	Phora atra	Species	Phoridae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO924	Russula subnigricans	Species	Russulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO29440	Sarcomyxa serotina	Species	Tricholomataceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO14144	Hernandia peltata	Species	Hernandiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO9318	Stevia serrata	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12990	Umbelopsis vinacea	Species	Umbelopsidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO14144	Hernandia peltata	Species	Hernandiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO216	Leontodon filii	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO4756	Mesua elegans	Species	Calophyllaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28383	Vernonia tufnellae	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO11244	Chrysolaena propinqua	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12990	Umbelopsis vinacea	Species	Umbelopsidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8378	Fagara heitzii	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[UNPD]
NPO24791	Smyrnium perfoliatum	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO15809	Solenostemon sylvaticus	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO6557	Lotus villosus	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1319	Zanthoxylum culantrillo	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO5060	Onychopetalum amazonicum	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO9469	Digitalis obscura	Species	Plantaginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO25530	Daphne blagayana	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28588	Lindera praecox	Species	Lauraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO10466	Commiphora kua	Species	Burseraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO29440	Sarcomyxa serotina	Species	Tricholomataceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO4442	Artemisia austriaca	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO9414	Tuberolachnus salignus	Species	Lachnidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO81	Erythrina orientalis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO3215	Phora atra	Species	Phoridae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8211	Artocarpus odoratissimus	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO5710	Michelia rajaniana	Species	Magnoliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO9318	Stevia serrata	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO924	Russula subnigricans	Species	Russulaceae	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
ED50	7

Activity Type	# Activity
Cell line	7

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
NPT168	Cell line	P388	Mus musculus	ED50	=	1.7	ug ml-1	PMID[14987061]
NPT575	Cell line	KM-20L2	Homo sapiens	ED50	=	3.0	ug ml-1	PMID[14987061]
NPT90	Cell line	DU-145	Homo sapiens	ED50	=	3.1	ug ml-1	PMID[14987061]
NPT1081	Cell line	BXPC-3	Homo sapiens	ED50	=	3.4	ug ml-1	PMID[14987061]
NPT83	Cell line	MCF7	Homo sapiens	ED50	=	3.5	ug ml-1	PMID[14987061]
NPT395	Cell line	SF-268	Homo sapiens	ED50	=	3.8	ug ml-1	PMID[14987061]
NPT397	Cell line	NCI-H460	Homo sapiens	ED50	=	3.8	ug ml-1	PMID[14987061]

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 NPC121783 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	26142
0.1-0.2	21116
0.2-0.3	2199
0.3-0.4	232
0.4-0.5	84
0.5-0.6	37
0.6-0.7	22
0.7-0.8	0
0.8-0.85	3
0.85-0.9	2
0.9-0.95	0
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC34902
1.0	High Similarity	NPC18449
0.8889	High Similarity	NPC222127
0.8889	High Similarity	NPC82862
0.8205	Intermediate Similarity	NPC227160
0.8205	Intermediate Similarity	NPC82111
0.8158	Intermediate Similarity	NPC606146
0.7442	Intermediate Similarity	NPC27843
0.7442	Intermediate Similarity	NPC7171
0.7179	Intermediate Similarity	NPC171928
0.7179	Intermediate Similarity	NPC158526
0.7179	Intermediate Similarity	NPC129687
0.7179	Intermediate Similarity	NPC33611
0.7179	Intermediate Similarity	NPC16830
0.7179	Intermediate Similarity	NPC100223
0.7143	Intermediate Similarity	NPC488505
0.6977	Remote Similarity	NPC189474
0.6944	Remote Similarity	NPC281864
0.6944	Remote Similarity	NPC328682
0.6944	Remote Similarity	NPC54321
0.6809	Remote Similarity	NPC474139
0.6316	Remote Similarity	NPC216929
0.6316	Remote Similarity	NPC312713
0.6316	Remote Similarity	NPC126935
0.6316	Remote Similarity	NPC65933
0.6316	Remote Similarity	NPC57268
0.6316	Remote Similarity	NPC172676
0.625	Remote Similarity	NPC298317
0.625	Remote Similarity	NPC255566
0.6122	Remote Similarity	NPC483653
0.6098	Remote Similarity	NPC473092
0.6098	Remote Similarity	NPC473093
0.6098	Remote Similarity	NPC8050
0.6	Remote Similarity	NPC88640
0.6	Remote Similarity	NPC101153
0.6	Remote Similarity	NPC193666
0.6	Remote Similarity	NPC123526
0.6	Remote Similarity	NPC608725
0.5926	Remote Similarity	NPC246947
0.5814	Remote Similarity	NPC148893
0.5814	Remote Similarity	NPC115207
0.5814	Remote Similarity	NPC158079
0.5814	Remote Similarity	NPC228346
0.5814	Remote Similarity	NPC40432
0.5814	Remote Similarity	NPC25333
0.5814	Remote Similarity	NPC161557
0.5814	Remote Similarity	NPC49235
0.5741	Remote Similarity	NPC276753
0.5741	Remote Similarity	NPC205796
0.5714	Remote Similarity	NPC50683
0.5714	Remote Similarity	NPC30890
0.5714	Remote Similarity	NPC112571
0.5714	Remote Similarity	NPC285725
0.5714	Remote Similarity	NPC206882
0.5682	Remote Similarity	NPC165155
0.5682	Remote Similarity	NPC24490
0.561	Remote Similarity	NPC141765
0.561	Remote Similarity	NPC34103
0.5556	Remote Similarity	NPC40094
0.5333	Remote Similarity	NPC57119
0.5333	Remote Similarity	NPC158471
0.5333	Remote Similarity	NPC226862
0.5319	Remote Similarity	NPC126409
0.5319	Remote Similarity	NPC99572
0.5306	Remote Similarity	NPC14022
0.5306	Remote Similarity	NPC601703
0.5217	Remote Similarity	NPC312199
0.5217	Remote Similarity	NPC209229
0.5185	Remote Similarity	NPC488545
0.5185	Remote Similarity	NPC488546
0.5106	Remote Similarity	NPC158331
0.5106	Remote Similarity	NPC483654
0.5106	Remote Similarity	NPC254120
0.5098	Remote Similarity	NPC469981
0.5091	Remote Similarity	NPC55793

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC121783 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4208
0.1-0.2	4671
0.2-0.3	264
0.3-0.4	6
0.4-0.5	1
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