NPASS Compound

Natural Product: NPC177476

Natural Product ID	NPC177476
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Austrobailignan 1
IUPAC Name	(5R,5aR,8aR)-5-(7-methoxy-1,3-benzodioxol-5-yl)-5a,8,8a,9-tetrahydro-5H-[2]benzofuro[5,6-f][1,3]benzodioxol-6-one
Synonyms	NSC-294826
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL509850
PubChem CID	325700
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0001392] Lignans, neolignans and related compounds [CHEMONTID:0001510] Lignan 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 46 51 0 0 0 0 0 0 0 0999 V2000 4.1884 -2.3597 0.3766 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2027 -0.9735 0.5580 O 0 0 0 0 0 0 0 0 0 0 0 0 3.1214 -0.1669 0.1868 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9837 -0.6849 -0.3764 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8758 0.0429 -0.7690 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9589 1.4031 -0.5609 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1061 1.9739 0.0131 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1790 1.1955 0.3841 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1922 1.9736 0.9258 O 0 0 0 0 0 0 0 0 0 0 0 0 3.8157 3.3112 0.7737 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4659 3.2789 0.3352 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.3246 -0.5261 -1.3566 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.5182 0.2344 -0.8829 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9356 1.3437 -1.5818 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0458 2.0191 -1.1289 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7637 1.6455 -0.0131 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3494 0.5352 0.6887 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2216 -0.1657 0.2433 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8860 -1.3533 1.0637 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6460 -1.9896 0.5567 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.5987 -3.4953 0.7224 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1387 -3.9715 -0.4016 O 0 0 0 0 0 0 0 0 0 0 0 0 0.1210 -3.0173 -1.4401 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7132 -3.2275 -2.5219 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.6562 -1.9190 -0.9497 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.8291 2.5484 0.1636 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.4361 3.7100 -0.5456 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6827 3.1496 -1.6235 O 0 0 0 0 0 0 0 0 0 0 0 0 3.2215 -2.7816 0.7102 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0415 -2.7787 0.9546 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4142 -2.5862 -0.6914 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9694 -1.7451 -0.5227 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1871 2.1209 -0.8067 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9072 3.8028 1.7795 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4709 3.7988 0.0176 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2556 -0.4803 -2.4704 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4278 1.7094 -2.4851 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9071 0.2362 1.5642 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8597 -1.0959 2.1414 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7309 -2.0834 0.9062 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2033 -1.4902 1.0413 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5768 -3.9581 0.8256 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0039 -3.6907 1.6333 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7248 -2.1012 -1.2826 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8118 4.3163 0.1166 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2935 4.2925 -0.9262 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 10 11 1 0 5 12 1 0 12 13 1 0 13 14 2 0 14 15 1 0 15 16 2 0 16 17 1 0 17 18 2 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 2 0 23 25 1 0 16 26 1 0 26 27 1 0 27 28 1 0 8 3 1 0 25 12 1 0 11 7 1 0 18 13 1 0 25 20 1 0 28 15 1 0 1 29 1 0 1 30 1 0 1 31 1 0 4 32 1 0 6 33 1 0 10 34 1 0 10 35 1 0 12 36 1 6 14 37 1 0 17 38 1 0 19 39 1 0 19 40 1 0 20 41 1 1 21 42 1 0 21 43 1 0 25 44 1 6 27 45 1 0 27 46 1 0 M END

Standard InCHIKey	GROYKMASYUMFER-RQUSPXKASA-N
Standard InCHI	InChI=1S/C21H18O7/c1-23-16-4-11(5-17-20(16)28-9-27-17)18-13-6-15-14(25-8-26-15)3-10(13)2-12-7-24-21(22)19(12)18/h3-6,12,18-19H,2,7-9H2,1H3/t12-,18+,19-/m0/s1
SMILES	COc1cc(cc2c1OCO2)[C@@H]1c2cc3c(cc2C[C@H]2COC(=O)[C@H]12)OCO3

Calculated Properties

Physi-Chem Properties

Molecular Weight:	382.11	Volume:	363.51 ? Van der Waals volume.
Dense:	1.051	LogP:	2.244 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.448 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.503 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	30.0
TPSA:	72.45 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	0.0	Rings:	6.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.74	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.735	Fsp³:	0.381
MCE-18:	104.483 ? 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:	0.559	Fluc inhibitor:	0.593 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.361 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.029 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.231	Promiscuous compounds:	0.471

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.95	MDCK Permeability:	-4.707
Pgp-inhibitor:	0.066	Pgp-substrate:	0.002
PAMPA:	0.059 ? 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%):	0.002	30% Bioavailability (F30%):	0.0
50% Bioavailability (F50%):	0.013

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.998	MRP1:	0.963
Plasma Protein Binding (PPB):	97.766%	Volume Distribution (VD):	0.035
Fu:	2.238% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.577
OATP1B3 inhibitor:	0.089	BCRP inhibitor:	0.0
BSEP inhibitor:	0.998

ADMET: Metabolism

CYP1A2-inhibitor:	0.961	CYP1A2-substrate:	0.993
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.862
CYP2C9-inhibitor:	0.049	CYP2C9-substrate:	0.975
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.999
CYP3A4-inhibitor:	0.996	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.002
HLM stability:	0.217 ? 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):

3.51

Half-life (T1/2):

1.593

ADMET: Toxicity

hERG Blockers:	0.24	hERG Blockers (10um):	0.561
Human Hepatotoxicity (H-HT):	0.938	Drug-induced Liver Injury (DILI):	0.998
AMES Toxicity:	0.885	Rat Oral Acute Toxicity:	0.889
Maximum Recommended Daily Dose:	0.851	Skin Sensitization:	0.983
Carcinogencity:	0.95	Eye Corrosion:	0.001
Eye Irritation:	0.369	Respiratory Toxicity:	0.958
Drug-induced Neurotoxicity:	0.959	Ototoxicity:	0.751
Hematotoxicity:	0.958	Drug-induced Nephrotoxicity:	0.989
Genotoxicity:	0.998	RPMI-8226 Immunitoxicity:	0.635
A549 Cytotoxicity:	0.904	Hek293 Cytotoxicity:	0.854
BCF:	1.633 ? 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:	4.152 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.139 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.201 ? 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
NPO8247	Austrobaileya scandens	Species	Austrobaileyaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[27214307]
NPO4224	Koelreuteria henryi	Species	Sapindaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[7714533]
NPO8247	Austrobaileya scandens	Species	Austrobaileyaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO4224	Koelreuteria henryi	Species	Sapindaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO4224	Koelreuteria henryi	Species	Sapindaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8247	Austrobaileya scandens	Species	Austrobaileyaceae	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	9
T/C	1
IC50	3
GI50	58

Activity Type	# Activity
Cell line	67
Non-molecular	2
Others	2

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	T/C	=	125.0	%	DOI[10.1021/np50015a016]
NPT762	Cell line	A-431	Homo sapiens	ED50	=	3.6	10'-6 ug/ml	PMID[15620238]
NPT376	Cell line	A498	Homo sapiens	ED50	=	3.2	10'-6 ug/ml	PMID[15620238]
NPT81	Cell line	A549	Homo sapiens	ED50	=	3.9	10'-6 ug/ml	PMID[15620238]
NPT139	Cell line	HT-29	Homo sapiens	ED50	=	3.7	10'-6 ug/ml	PMID[15620238]
NPT83	Cell line	MCF7	Homo sapiens	ED50	=	5.2	10'-5 ug/ml	PMID[15620238]
NPT306	Cell line	PC-3	Homo sapiens	ED50	=	3.3	10'-6 ug/ml	PMID[11754602]
NPT373	Cell line	SK-MEL-5	Homo sapiens	ED50	=	3.0	10'-7 ug/ml	PMID[11754602]
NPT146	Cell line	SK-OV-3	Homo sapiens	ED50	=	2.7	10'-6 ug/ml	PMID[20455578]
NPT367	Cell line	MDA-N	Homo sapiens	GI50	n.a.	10.0	nM	PMID[8699183]
NPT368	Cell line	SN12C	Homo sapiens	GI50	n.a.	10.0	nM	PMID[19506058]
NPT370	Cell line	NCI-H23	Homo sapiens	GI50	n.a.	10.0	nM	PMID[18341287]
NPT369	Cell line	ACHN	Homo sapiens	GI50	n.a.	12.08	nM	PubChem BioAssay data set
NPT371	Cell line	UO-31	Homo sapiens	GI50	n.a.	10.0	nM	DOI[10.6019/CHEMBL1201861]
NPT372	Cell line	HOP-92	Homo sapiens	GI50	n.a.	10.0	nM	PMID[15270579]
NPT116	Cell line	HL-60	Homo sapiens	GI50	n.a.	544.5	nM	PMID[18330976]
NPT90	Cell line	DU-145	Homo sapiens	GI50	n.a.	10.0	nM	PMID[25316316]
NPT374	Cell line	SF-539	Homo sapiens	GI50	n.a.	10.0	nM	PMID[11473426]
NPT373	Cell line	SK-MEL-5	Homo sapiens	GI50	n.a.	10.0	nM	PMID[19646870]
NPT375	Cell line	Malme-3M	Homo sapiens	GI50	n.a.	10.0	nM	PMID[17844994]
NPT376	Cell line	A498	Homo sapiens	GI50	n.a.	10.0	nM	PMID[24487236]
NPT111	Cell line	K562	Homo sapiens	GI50	n.a.	616.6	nM	PMID[8627602]
NPT377	Cell line	OVCAR-3	Homo sapiens	GI50	n.a.	10.0	nM	PMID[15332846]
NPT112	Cell line	MOLT-4	Homo sapiens	GI50	n.a.	10.0	nM	PMID[19721074]
NPT378	Cell line	NCI/ADR-RES	Homo sapiens	GI50	n.a.	10.0	nM	DOI[10.1007/s00044-012-0437-8]
NPT379	Cell line	HOP-62	Homo sapiens	GI50	n.a.	10.0	nM	PMID[21696174]
NPT380	Cell line	U-251	Homo sapiens	GI50	n.a.	10.0	nM	PMID[22676269]
NPT382	Cell line	OVCAR-5	Homo sapiens	GI50	n.a.	10.0	nM	PMID[2746258]
NPT381	Cell line	OVCAR-8	Homo sapiens	GI50	n.a.	10.0	nM	PMID[17315965]
NPT383	Cell line	SNB-19	Homo sapiens	GI50	n.a.	10.0	nM	PMID[19459694]
NPT82	Cell line	MDA-MB-231	Homo sapiens	GI50	n.a.	10.0	nM	DrugMatrix in vivo data: Pathology
NPT384	Cell line	TK-10	Homo sapiens	GI50	n.a.	1986.09	nM	PubChem BioAssay data set
NPT385	Cell line	SR	Homo sapiens	GI50	n.a.	10.0	nM	DOI[10.1016/j.cropro.2012.04.001]
NPT323	Cell line	SW-620	Homo sapiens	GI50	n.a.	10.0	nM	PMID[23819871]
NPT455	Cell line	NCI-H522	Homo sapiens	GI50	n.a.	10.0	nM	PMID[26110443]
NPT386	Cell line	KM12	Homo sapiens	GI50	n.a.	131.83	nM	PubChem BioAssay data set
NPT387	Cell line	M14	Homo sapiens	GI50	n.a.	10.0	nM	PMID[18077363]
NPT388	Cell line	NCI-H322M	Homo sapiens	GI50	n.a.	10.0	nM	PMID[12431049]
NPT389	Cell line	RPMI-8226	Homo sapiens	GI50	n.a.	10.0	nM	PMID[15214798]
NPT456	Cell line	OVCAR-4	Homo sapiens	GI50	n.a.	11376.27	nM	PMID[18232639]
NPT390	Cell line	LOX IMVI	Homo sapiens	GI50	n.a.	10.0	nM	DrugMatrix in vitro pharmacology data
NPT147	Cell line	SK-MEL-2	Homo sapiens	GI50	n.a.	10.0	nM	PMID[15646539]
NPT81	Cell line	A549	Homo sapiens	GI50	n.a.	10.0	nM	PMID[2550587]
NPT391	Cell line	HCC 2998	Homo sapiens	GI50	n.a.	10.0	nM	PMID[22758660]
NPT392	Cell line	SNB-75	Homo sapiens	GI50	n.a.	27.8	nM	PMID[23434418]
NPT148	Cell line	HCT-15	Homo sapiens	GI50	n.a.	10.0	nM	PMID[23317013]
NPT393	Cell line	HCT-116	Homo sapiens	GI50	n.a.	10.0	nM	PMID[17892263]
NPT395	Cell line	SF-268	Homo sapiens	GI50	n.a.	10.0	nM	PMID[13678412]
NPT394	Cell line	EKVX	Homo sapiens	GI50	n.a.	10.0	nM	PMID[20499851]
NPT306	Cell line	PC-3	Homo sapiens	GI50	n.a.	10.0	nM	PMID[12608857]
NPT83	Cell line	MCF7	Homo sapiens	GI50	n.a.	10.0	nM	PMID[6546590]
NPT146	Cell line	SK-OV-3	Homo sapiens	GI50	n.a.	10.0	nM	PMID[18950230]
NPT397	Cell line	NCI-H460	Homo sapiens	GI50	n.a.	10.0	nM	PMID[23398362]
NPT398	Cell line	UACC-62	Homo sapiens	GI50	n.a.	10.0	nM	PubChem BioAssay data set
NPT308	Cell line	CAKI-1	Homo sapiens	GI50	n.a.	10.0	nM	PMID[16190773]
NPT400	Cell line	MDA-MB-435	Homo sapiens	GI50	n.a.	10.0	nM	PMID[10780915]
NPT458	Cell line	IGROV-1	Homo sapiens	GI50	n.a.	10.0	nM	PMID[8893847]
NPT399	Cell line	SF-295	Homo sapiens	GI50	n.a.	10.0	nM	PMID[19489598]
NPT401	Cell line	786-0	Homo sapiens	GI50	n.a.	10.0	nM	PMID[16643028]
NPT402	Cell line	Hs-578T	Homo sapiens	GI50	n.a.	10.0	nM	PMID[17261619]
NPT403	Cell line	UACC-257	Homo sapiens	GI50	n.a.	124.74	nM	PMID[26034885]
NPT404	Cell line	CCRF-CEM	Homo sapiens	GI50	n.a.	663.74	nM	PMID[18327911]
NPT405	Cell line	NCI-H226	Homo sapiens	GI50	n.a.	10.0	nM	PMID[18513974]
NPT139	Cell line	HT-29	Homo sapiens	GI50	n.a.	10.0	nM	PMID[15646539]
NPT170	Cell line	SK-MEL-28	Homo sapiens	GI50	n.a.	10.0	nM	PMID[26034885]
NPT406	Cell line	RXF 393	Homo sapiens	GI50	n.a.	10.0	nM	PMID[16933872]
NPT407	Cell line	COLO 205	Homo sapiens	GI50	n.a.	10.79	nM	PMID[17958396]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	ED50	=	0.027	ug ml-1	DOI[10.1021/np50015a016]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	50.0	nM	PMID[27214307]
NPT2	Others	Unspecified	n.a.	IC50	=	800.0	nM	PMID[20413315]
NPT2	Others	Unspecified	n.a.	IC50	=	1000.0	nM	PMID[20413315]

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 NPC177476 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	28525
0.1-0.2	19779
0.2-0.3	1245
0.3-0.4	215
0.4-0.5	47
0.5-0.6	27
0.6-0.7	5
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	5
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC262455
0.9423	High Similarity	NPC80230
0.9423	High Similarity	NPC104024
0.9423	High Similarity	NPC101755
0.9423	High Similarity	NPC304687
0.9423	High Similarity	NPC65574
0.7857	Intermediate Similarity	NPC218092
0.7857	Intermediate Similarity	NPC246474
0.7857	Intermediate Similarity	NPC162851
0.7797	Intermediate Similarity	NPC30009
0.7797	Intermediate Similarity	NPC103197
0.7759	Intermediate Similarity	NPC480477
0.7458	Intermediate Similarity	NPC149505
0.6712	Remote Similarity	NPC115624
0.6615	Remote Similarity	NPC115281
0.6207	Remote Similarity	NPC23336
0.6129	Remote Similarity	NPC239890
0.6129	Remote Similarity	NPC209411
0.5846	Remote Similarity	NPC237946
0.5846	Remote Similarity	NPC32373
0.5797	Remote Similarity	NPC163527
0.5763	Remote Similarity	NPC92693
0.5738	Remote Similarity	NPC164082
0.569	Remote Similarity	NPC218841
0.5672	Remote Similarity	NPC210642
0.5672	Remote Similarity	NPC13985
0.5672	Remote Similarity	NPC207584
0.5672	Remote Similarity	NPC19947
0.5667	Remote Similarity	NPC40237
0.5645	Remote Similarity	NPC477698
0.5593	Remote Similarity	NPC151423
0.5593	Remote Similarity	NPC480480
0.5507	Remote Similarity	NPC119910
0.55	Remote Similarity	NPC222531
0.5469	Remote Similarity	NPC191158
0.5469	Remote Similarity	NPC177644
0.5333	Remote Similarity	NPC193779
0.5254	Remote Similarity	NPC11453
0.5246	Remote Similarity	NPC475000
0.5211	Remote Similarity	NPC288149
0.5211	Remote Similarity	NPC470637
0.5077	Remote Similarity	NPC176586
0.5077	Remote Similarity	NPC210354
0.5075	Remote Similarity	NPC293757
0.5075	Remote Similarity	NPC668

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC177476 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5375
0.1-0.2	3687
0.2-0.3	75
0.3-0.4	5
0.4-0.5	5
0.5-0.6	3
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
0.5846	Remote Similarity	NPD4965	Approved
0.5846	Remote Similarity	NPD4966	Phase 4
0.5846	Remote Similarity	NPD4967	Phase 2

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