NPASS Compound

Natural Product: NPC205034

Natural Product ID	NPC205034
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	4-[(E)-2-[(1R,4As,5R,6R,8Ar)-6-Hydroxy-5-(Hydroxymethyl)-5,8A-Dimethyl-2-Methylidene-3,4,4A,6,7,8-Hexahydro-1H-Naphthalen-1-Yl]Ethenyl]-2H-Furan-5-One
IUPAC Name	4-[(E)-2-[(1R,4aS,5R,6R,8aR)-6-hydroxy-5-(hydroxymethyl)-5,8a-dimethyl-2-methylidene-3,4,4a,6,7,8-hexahydro-1H-naphthalen-1-yl]ethenyl]-2H-furan-5-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL361568
PubChem CID	5708351
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001283] Terpene lactones [CHEMONTID:0001538] Diterpene lactones

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 52 54 0 0 0 0 0 0 0 0999 V2000 1.4308 -3.0488 -0.0196 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4120 -2.2677 0.3093 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9214 -2.8419 0.4684 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0612 -1.9411 0.1459 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6826 -0.5109 0.4393 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.4349 -0.1233 -0.2792 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.3390 -0.7570 -1.6708 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2157 1.3366 -0.4365 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0209 2.2439 0.3921 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3069 1.7571 0.9201 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.8027 0.4546 0.3325 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.9113 -0.0209 1.2806 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3958 0.6278 -1.0221 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4336 1.5822 -0.8928 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.3366 2.6901 0.7722 O 0 0 0 0 0 0 0 0 0 0 0 0 0.7009 -0.7936 0.5042 C 0 0 2 0 0 0 0 0 0 0 0 0 2.0239 -0.4457 -0.0551 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9334 0.0531 0.7638 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2510 0.4170 0.2873 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2122 0.9240 1.0593 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4407 1.1918 0.2837 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0987 0.7892 -1.0213 O 0 0 0 0 0 0 0 0 0 0 0 0 4.7926 0.3222 -1.0416 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2120 -0.1084 -2.0843 O 0 0 0 0 0 0 0 0 0 0 0 0 1.2595 -4.1053 -0.1662 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4446 -2.6899 -0.1538 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9887 -3.2616 1.5086 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0087 -3.7432 -0.2028 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4939 -2.0805 -0.8568 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8930 -2.1918 0.8672 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4526 -0.5232 1.5494 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3320 -0.8611 -2.1415 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2678 -0.1267 -2.3584 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1210 -1.7450 -1.6505 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8822 1.5234 -0.2320 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3190 1.6472 -1.5194 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2329 3.2013 -0.1755 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3992 2.6122 1.2629 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2277 1.5665 2.0302 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5012 0.9057 1.5245 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4898 -0.3597 2.2426 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5950 -0.7179 0.8004 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8511 -0.2577 -1.4498 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6479 1.1020 -1.6836 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7074 1.9387 -1.7617 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0164 3.6192 0.8717 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5692 -0.5082 1.5510 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1877 -0.6106 -1.0886 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6696 0.1882 1.8234 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0978 1.1137 2.1266 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2790 0.5724 0.6751 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7325 2.2616 0.3363 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 1 0 4 5 1 0 5 6 1 0 6 7 1 6 6 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 1 11 13 1 0 13 14 1 0 10 15 1 0 6 16 1 0 16 17 1 0 17 18 2 0 18 19 1 0 19 20 2 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 2 0 16 2 1 0 23 19 1 0 11 5 1 0 1 25 1 0 1 26 1 0 3 27 1 0 3 28 1 0 4 29 1 0 4 30 1 0 5 31 1 1 7 32 1 0 7 33 1 0 7 34 1 0 8 35 1 0 8 36 1 0 9 37 1 0 9 38 1 0 10 39 1 1 12 40 1 0 12 41 1 0 12 42 1 0 13 43 1 0 13 44 1 0 14 45 1 0 15 46 1 0 16 47 1 1 17 48 1 0 18 49 1 0 20 50 1 0 21 51 1 0 21 52 1 0 M END

Standard InCHIKey	XMJAJFVLHDIEHF-CRBRZBHVSA-N
Standard InCHI	InChI=1S/C20H28O4/c1-13-4-7-16-19(2,10-8-17(22)20(16,3)12-21)15(13)6-5-14-9-11-24-18(14)23/h5-6,9,15-17,21-22H,1,4,7-8,10-12H2,2-3H3/b6-5+/t15-,16+,17-,19+,20+/m1/s1
SMILES	C=C1CC[C@H]2[C@@](C)(CC[C@H]([C@@]2(C)CO)O)[C@@H]1/C=C/C1=CCOC1=O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	332.2	Volume:	353.422 ? Van der Waals volume.
Dense:	0.94	LogP:	2.453 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.551 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.109 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	19.0
TPSA:	66.76 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	2.0	Rings:	3.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.616	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.681	Fsp³:	0.65
MCE-18:	54.727 ? 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:	0.458	Fluc inhibitor:	0.366 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.009 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.003 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.538	Promiscuous compounds:	0.268

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.045	MDCK Permeability:	-4.882
Pgp-inhibitor:	0.121	Pgp-substrate:	0.017
PAMPA:	0.498 ? 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):	0.062
20% Bioavailability (F20%):	0.912	30% Bioavailability (F30%):	0.849
50% Bioavailability (F50%):	0.995

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.616	MRP1:	0.38
Plasma Protein Binding (PPB):	83.288%	Volume Distribution (VD):	-0.334
Fu:	9.88% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.938
OATP1B3 inhibitor:	0.938	BCRP inhibitor:	0.407
BSEP inhibitor:	0.882

ADMET: Metabolism

CYP1A2-inhibitor:	0.337	CYP1A2-substrate:	0.393
CYP2C19-inhibitor:	0.477	CYP2C19-substrate:	0.062
CYP2C9-inhibitor:	0.204	CYP2C9-substrate:	0.047
CYP2D6-inhibitor:	0.596	CYP2D6-substrate:	0.008
CYP3A4-inhibitor:	0.005	CYP3A4-substrate:	0.949
CYP2B6-substrate:	0.002	CYP2C8-inhibitor:	0.999
HLM stability:	0.197 ? 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):

6.353

Half-life (T1/2):

1.439

ADMET: Toxicity

hERG Blockers:	0.04	hERG Blockers (10um):	0.257
Human Hepatotoxicity (H-HT):	0.793	Drug-induced Liver Injury (DILI):	0.662
AMES Toxicity:	0.818	Rat Oral Acute Toxicity:	0.728
Maximum Recommended Daily Dose:	0.716	Skin Sensitization:	0.995
Carcinogencity:	0.991	Eye Corrosion:	0.004
Eye Irritation:	0.833	Respiratory Toxicity:	0.689
Drug-induced Neurotoxicity:	0.49	Ototoxicity:	0.478
Hematotoxicity:	0.72	Drug-induced Nephrotoxicity:	0.898
Genotoxicity:	0.964	RPMI-8226 Immunitoxicity:	0.163
A549 Cytotoxicity:	0.501	Hek293 Cytotoxicity:	0.571
BCF:	0.793 ? 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:	3.552 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.231 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.597 ? 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
NPO3578	Andrographis paniculata	Species	Acanthaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1111/ppl.12252]
NPO30573	Antrodia camphorata	Species	Fomitopsidaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[14738384]
NPO3578	Andrographis paniculata	Species	Acanthaceae	Eukaryota	n.a.	root	n.a.	PMID[15894448]
NPO3578	Andrographis paniculata	Species	Acanthaceae	Eukaryota	n.a.	leaf	n.a.	PMID[15894448]
NPO3578	Andrographis paniculata	Species	Acanthaceae	Eukaryota	aerial parts	purchased in Juhuacun herbal market, Kunming, Yunnan Province, China	2002-Oct	PMID[16562826]
NPO30573	Antrodia camphorata	Species	Fomitopsidaceae	Eukaryota	fruiting bodies	n.a.	n.a.	PMID[16643055]
NPO30573	Antrodia camphorata	Species	Fomitopsidaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17559265]
NPO3578	Andrographis paniculata	Species	Acanthaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[18357994]
NPO3578	Andrographis paniculata	Species	Acanthaceae	Eukaryota	n.a.	leaf	n.a.	PMID[21598983]
NPO3578	Andrographis paniculata	Species	Acanthaceae	Eukaryota	n.a.	leaf	n.a.	PMID[22026410]
NPO30573	Antrodia camphorata	Species	Fomitopsidaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[24387703]
NPO3578	Andrographis paniculata	Species	Acanthaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[8377022]
NPO3578	Andrographis paniculata	Species	Acanthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO30573	Antrodia camphorata	Species	Fomitopsidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO30573	Antrodia camphorata	Species	Fomitopsidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO3578	Andrographis paniculata	Species	Acanthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO3578	Andrographis paniculata	Species	Acanthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO3578	Andrographis paniculata	Species	Acanthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO3578	Andrographis paniculata	Species	Acanthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO3578	Andrographis paniculata	Species	Acanthaceae	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
Inhibition	3
Potency	11
IG50	5
GI50	1
Activity	6
IZ	1
IC50	8
Ratio CC50/IC50	1
ED50	7
EC50	1
CC50	2

Activity Type	# Activity
Individual protein	11
Cell line	25
Organism	3
Non-molecular	4
Others	3

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT3	Individual protein	Thioredoxin glutathione reductase	Schistosoma mansoni	Potency	=	39810.7	nM	PubChem BioAssay data set
NPT152	Individual protein	Nuclear factor erythroid 2-related factor 2	Homo sapiens	Potency	n.a.	20596.2	nM	PubChem BioAssay data set
NPT199	Individual protein	DNA polymerase kappa	Homo sapiens	Potency	n.a.	89125.1	nM	PubChem BioAssay data set
NPT497	Individual protein	Maltase-glucoamylase	Homo sapiens	Inhibition	=	16.5	%	PMID[17428667]
NPT50	Individual protein	Tyrosyl-DNA phosphodiesterase 1	Homo sapiens	Potency	=	63095.7	nM	PubChem BioAssay data set
NPT50	Individual protein	Tyrosyl-DNA phosphodiesterase 1	Homo sapiens	Potency	n.a.	44668.4	nM	PubChem BioAssay data set
NPT8	Individual protein	DNA polymerase iota	Homo sapiens	Potency	n.a.	89125.1	nM	PubChem BioAssay data set
NPT535	Individual protein	Parathyroid hormone receptor	Homo sapiens	Potency	n.a.	50118.7	nM	PubChem BioAssay data set
NPT532	Individual protein	Lysine-specific demethylase 4A	Homo sapiens	Potency	n.a.	89125.1	nM	PubChem BioAssay data set
NPT49	Individual protein	DNA-(apurinic or apyrimidinic site) lyase	Homo sapiens	Potency	n.a.	31622.8	nM	PubChem BioAssay data set

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT378	Cell line	NCI/ADR-RES	Homo sapiens	IG50	>	100.0	uM	PMID[15324893]
NPT380	Cell line	U-251	Homo sapiens	IG50	=	81.0	uM	PMID[15324893]
NPT323	Cell line	SW-620	Homo sapiens	IG50	>	100.0	uM	PMID[15324893]
NPT455	Cell line	NCI-H522	Homo sapiens	IG50	>	100.0	uM	PMID[15324893]
NPT90	Cell line	DU-145	Homo sapiens	IG50	=	2.0	uM	PMID[15324893]
NPT116	Cell line	HL-60	Homo sapiens	GI50	=	25620.0	nM	PMID[18357994]
NPT2295	Cell line	5637	Homo sapiens	Inhibition	=	44.7	%	PMID[24120543]
NPT165	Cell line	HeLa	Homo sapiens	IC50	=	149.09	ug.mL-1	DOI[10.1039/C4MD00566J]
NPT369	Cell line	ACHN	Homo sapiens	IC50	=	327.77	ug.mL-1	DOI[10.1039/C4MD00566J]
NPT319	Cell line	B16	Mus musculus	IC50	=	25.17	ug.mL-1	DOI[10.1039/C4MD00566J]
NPT81	Cell line	A549	Homo sapiens	IC50	=	117.4	ug.mL-1	DOI[10.1039/C4MD00566J]
NPT168	Cell line	P388	Mus musculus	ED50	=	35.01	uM	PMID[29097170]
NPT91	Cell line	KB	Homo sapiens	ED50	=	5.07	uM	PMID[29097170]
NPT139	Cell line	HT-29	Homo sapiens	ED50	=	28.55	uM	PMID[29097170]
NPT83	Cell line	MCF7	Homo sapiens	ED50	=	18.67	uM	PMID[29097170]
NPT81	Cell line	A549	Homo sapiens	ED50	=	28.15	uM	PMID[29097170]
NPT71	Cell line	HEK293	Homo sapiens	ED50	=	7.53	uM	PMID[29097170]
NPT886	Cell line	NIH3T3	Mus musculus	IC50	=	64270.0	nM	PMID[30144698]
NPT681	Cell line	PC-12	Rattus norvegicus	Activity	<=	16.1	%	PMID[31014564]
NPT681	Cell line	PC-12	Rattus norvegicus	Activity	=	18.6	%	PMID[31014564]
NPT25412	Cell line	HuCC-A1	Homo sapiens	ED50	=	35.83	uM	PMID[29097170]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Activity	=	40.7	%	PMID[16643055]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Activity	=	35.7	%	PMID[16643055]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Activity	=	30.8	%	PMID[16643055]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Activity	=	29.5	%	PMID[16643055]
NPT79	Organism	Bacillus subtilis	Bacillus subtilis	IZ	=	7.0	mm	PMID[16562826]
NPT22368	Organism	Zika virus	Zika virus	EC50	=	30570.0	nM	PMID[36055002]
NPT963	Organism	Hepatitis B virus	Hepatitis B virus	IC50	=	22600.0	nM	PMID[24731274]
NPT30043	Cell line	Vero	Chlorocebus sabaeus	CC50	>	200000.0	nM	PMID[36055002]
NPT2	Others	Unspecified	n.a.	Potency	n.a.	22387.2	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Ratio CC50/IC50	=	8.7	n.a.	PMID[24731274]
NPT2	Others	Unspecified	n.a.	Potency	n.a.	25118.9	nM	PubChem BioAssay data set
NPT28795	Cell line	BMMC	n.a.	IC50	=	8340.0	nM	PMID[33485256]
NPT28795	Cell line	BMMC	n.a.	CC50	>	30000.0	nM	PMID[33485256]

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 NPC205034 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	16653
0.1-0.2	25903
0.2-0.3	6916
0.3-0.4	328
0.4-0.5	32
0.5-0.6	14
0.6-0.7	6
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC152778
0.8235	Intermediate Similarity	NPC310479
0.7636	Intermediate Similarity	NPC162615
0.7321	Intermediate Similarity	NPC474440
0.7193	Intermediate Similarity	NPC16967
0.6964	Remote Similarity	NPC139692
0.6964	Remote Similarity	NPC209355
0.6786	Remote Similarity	NPC476602
0.661	Remote Similarity	NPC242848
0.6364	Remote Similarity	NPC4509
0.614	Remote Similarity	NPC94200
0.5902	Remote Similarity	NPC159763
0.5902	Remote Similarity	NPC278386
0.5902	Remote Similarity	NPC124512
0.5833	Remote Similarity	NPC131813
0.5806	Remote Similarity	NPC72845
0.5806	Remote Similarity	NPC234993
0.5806	Remote Similarity	NPC134072
0.5593	Remote Similarity	NPC608380
0.5574	Remote Similarity	NPC77001
0.5574	Remote Similarity	NPC253618
0.5556	Remote Similarity	NPC191521
0.5333	Remote Similarity	NPC79945
0.5294	Remote Similarity	NPC73911
0.5254	Remote Similarity	NPC476949

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC205034 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6516
0.1-0.2	2461
0.2-0.3	169
0.3-0.4	3
0.4-0.5	0
0.5-0.6	1
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
0.5902	Remote Similarity	NPD4225	Phase 3

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