NPASS Compound

Natural Product: NPC233034

Natural Product ID	NPC233034
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Tridolgosir
IUPAC Name	(1S,2R,8R,8aR)-1,2,3,5,6,7,8,8a-octahydroindolizine-1,2,8-triol
Synonyms	Swainsonine; Tridolgosir
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL371197
PubChem CID	51683
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0000251] Indolizidines

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 27 28 0 0 0 0 0 0 0 0999 V2000 -3.4180 0.4056 0.3343 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.1031 0.3146 0.7312 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.2376 1.4109 0.1421 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0562 0.8178 -0.3694 N 0 0 0 0 0 0 0 0 0 0 0 0 0.0014 -0.5323 0.2155 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.4285 -0.9417 0.1580 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.8526 -1.0186 -1.1701 O 0 0 0 0 0 0 0 0 0 0 0 0 0.9260 -1.3024 -0.6547 C 0 0 2 0 0 0 0 0 0 0 0 0 0.9502 -2.6445 -0.3291 O 0 0 0 0 0 0 0 0 0 0 0 0 2.3173 -0.7297 -0.3951 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3684 0.7455 -0.4389 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1683 1.4697 0.0312 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0109 0.5115 1.1438 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9830 0.3014 1.8446 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8228 1.8127 -0.7365 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0829 2.2555 0.8391 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3716 -0.5106 1.2533 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6859 -1.8330 0.7363 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7919 -0.7273 -1.1908 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6986 -1.1314 -1.7334 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7453 -2.7087 0.6513 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6012 -1.0854 0.6312 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0571 -1.1451 -1.0906 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6840 1.0482 -1.4800 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2393 1.0775 0.2022 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1576 2.4816 -0.4526 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1870 1.6583 1.1272 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 1 0 5 6 1 0 6 7 1 0 5 8 1 0 8 9 1 0 8 10 1 0 10 11 1 0 11 12 1 0 6 2 1 0 12 4 1 0 1 13 1 0 2 14 1 1 3 15 1 0 3 16 1 0 5 17 1 1 6 18 1 1 7 19 1 0 8 20 1 6 9 21 1 0 10 22 1 0 10 23 1 0 11 24 1 0 11 25 1 0 12 26 1 0 12 27 1 0 M END

Standard InCHIKey	FXUAIOOAOAVCGD-WCTZXXKLSA-N
Standard InCHI	InChI=1S/C8H15NO3/c10-5-2-1-3-9-4-6(11)8(12)7(5)9/h5-8,10-12H,1-4H2/t5-,6-,7-,8-/m1/s1
SMILES	O[C@@H]1CN2[C@@H]([C@@H]1O)[C@H](O)CCC2

Calculated Properties

Physi-Chem Properties

Molecular Weight:	173.11	Volume:	167.179 ? Van der Waals volume.
Dense:	1.035	LogP:	-0.73 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	-0.301 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-0.24 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	0.0	Rigid Bonds:	10.0
TPSA:	63.93 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	3.0	Rings:	2.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.419	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.825	Fsp³:	1.0
MCE-18:	33.0 ? 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:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.191	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.116 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.005 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.021	Promiscuous compounds:	0.064

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.753	MDCK Permeability:	-5.039
Pgp-inhibitor:	0.007	Pgp-substrate:	0.896
PAMPA:	0.989 ? 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):	0.032
20% Bioavailability (F20%):	0.245	30% Bioavailability (F30%):	0.124
50% Bioavailability (F50%):	0.679

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.005	MRP1:	0.214
Plasma Protein Binding (PPB):	30.178%	Volume Distribution (VD):	-0.319
Fu:	70.613% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.425
OATP1B3 inhibitor:	0.2	BCRP inhibitor:	0.108
BSEP inhibitor:	0.381

ADMET: Metabolism

CYP1A2-inhibitor:	0.038	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.163	CYP2C19-substrate:	0.003
CYP2C9-inhibitor:	0.014	CYP2C9-substrate:	0.008
CYP2D6-inhibitor:	0.002	CYP2D6-substrate:	0.002
CYP3A4-inhibitor:	0.114	CYP3A4-substrate:	0.002
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.074
HLM stability:	0.111 ? 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):

4.08

Half-life (T1/2):

3.255

ADMET: Toxicity

hERG Blockers:	0.073	hERG Blockers (10um):	0.384
Human Hepatotoxicity (H-HT):	0.372	Drug-induced Liver Injury (DILI):	0.064
AMES Toxicity:	0.387	Rat Oral Acute Toxicity:	0.106
Maximum Recommended Daily Dose:	0.092	Skin Sensitization:	0.604
Carcinogencity:	0.257	Eye Corrosion:	0.064
Eye Irritation:	0.859	Respiratory Toxicity:	0.131
Drug-induced Neurotoxicity:	0.11	Ototoxicity:	0.672
Hematotoxicity:	0.152	Drug-induced Nephrotoxicity:	0.362
Genotoxicity:	0.072	RPMI-8226 Immunitoxicity:	0.049
A549 Cytotoxicity:	0.028	Hek293 Cytotoxicity:	0.09
BCF:	0.128 ? 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:	1.618 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	2.779 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	1.873 ? 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
NPO64970	Oxytropis spp. + Embellisia sp. symbiont	Species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[ 18060459]
NPO64659	Swainsona canescens + Undifilum sp. symbiont	Species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[ 24053110]
NPO64691	Astragalus lentiginosus + Undifilum cinereum symbiont	Species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[ 24223679]
NPO64760	Astragalus lentiginosus + Undifilum fulvum symbiont	Species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[ 24223679]
NPO64656	Astragalus sp. + Embellisia sp. symbiont	Species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[ 24758700]
NPO64961	Astragalus spp. and Oxytropis spp. + Undifilum oxytropis symbiont	Species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[ 31151062]
NPO64845	Oxytropis deflexa + Fusarium tricinctum symbiont	Species	n.a.	n.a.	n.a.	n.a.	n.a.	DOI[10.5897/AJMR2024.9772]
NPO64930	Oxytropis kansuensis + Fusarium tricinctum symbiont	Species	n.a.	n.a.	n.a.	n.a.	n.a.	DOI[10.5897/AJMR2024.9772]
NPO40701	Ipomoea sp. Q6 [aff. calobra]	Strain	Convolvulaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[7673932]
NPO14272	Swainsona luteola	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO14272	Swainsona luteola	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO14272	Swainsona luteola	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO31538	Swailnsonia galegifolia	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO30725	Swailnsonia canescens	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO14272	Swainsona luteola	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]

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
IC50	11
Ki	3
Inhibition	9
Potency	3
GI50	58
Hepatotoxicity (acute)	1
Hepatotoxicity (moderate)	2
Hepatotoxicity (granulomatous hepatitis)	1
Hepatotoxicity (benign tumour)	1

Activity Type	# Activity
Individual protein	12
Cell line	58
Organism	4
Single protein	1
Others	9
Non-molecular	5

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1053	Individual protein	Alpha-mannosidase 2C1	Rattus norvegicus	IC50	=	1750.0	nM	PMID[2504921]
NPT67	Individual protein	Cholinesterase	Equus caballus	Inhibition	=	-2.04	%	PMID[23062825]
NPT20556	Single protein	Replicase polyprotein 1ab	Severe acute respiratory syndrome coronavirus 2	Inhibition	=	13.48	%	DOI[10.6019/CHEMBL4495564]
NPT692	Individual protein	Histone deacetylase 6	Homo sapiens	Inhibition	=	-10.91	%	HDAC6 screening dataset using tau-based substrate in an enzymatic assay yields selective inhibitors and activators
NPT692	Individual protein	Histone deacetylase 6	Homo sapiens	Inhibition	=	-3.14	%	HDAC6 screening dataset using tau-based substrate in an enzymatic assay yields selective inhibitors and activators
NPT459	Individual protein	Human immunodeficiency virus type 1 reverse transcriptase	Human immunodeficiency virus 1	IC50	>	200.0	ug.mL-1	PMID[1710653]
NPT499	Individual protein	Lysosomal alpha-mannosidase	Homo sapiens	IC50	=	20000.0	nM	PMID[18599296]
NPT499	Individual protein	Lysosomal alpha-mannosidase	Homo sapiens	IC50	=	50.0	nM	PMID[18599296]
NPT499	Individual protein	Lysosomal alpha-mannosidase	Homo sapiens	IC50	=	10.0	nM	PMID[18599296]
NPT66	Individual protein	Acetylcholinesterase	Electrophorus electricus	Inhibition	=	5.09	%	PMID[23062825]
NPT504	Individual protein	Alpha-mannosidase	Glycine max	IC50	=	400.0	nM	PMID[15974577]
NPT5276	Individual protein	Mannosyl-oligosaccharide alpha-1,2-mannosidase isoform B	Drosophila melanogaster	IC50	=	5.0	nM	PMID[21295890]
NPT5276	Individual protein	Mannosyl-oligosaccharide alpha-1,2-mannosidase isoform B	Drosophila melanogaster	Ki	=	3.0	nM	PMID[21295890]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT368	Cell line	SN12C	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT369	Cell line	ACHN	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT370	Cell line	NCI-H23	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT371	Cell line	UO-31	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT372	Cell line	HOP-92	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT116	Cell line	HL-60	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT374	Cell line	SF-539	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT373	Cell line	SK-MEL-5	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT375	Cell line	Malme-3M	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT376	Cell line	A498	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT377	Cell line	OVCAR-3	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT112	Cell line	MOLT-4	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT379	Cell line	HOP-62	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT380	Cell line	U-251	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT381	Cell line	OVCAR-8	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT382	Cell line	OVCAR-5	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT383	Cell line	SNB-19	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT572	Cell line	DMS-273	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT384	Cell line	TK-10	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT323	Cell line	SW-620	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT573	Cell line	M19-MEL	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT455	Cell line	NCI-H522	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT386	Cell line	KM12	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT387	Cell line	M14	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT574	Cell line	XF498	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT388	Cell line	NCI-H322M	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT389	Cell line	RPMI-8226	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT456	Cell line	OVCAR-4	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT390	Cell line	LOX IMVI	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT147	Cell line	SK-MEL-2	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT81	Cell line	A549	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT575	Cell line	KM-20L2	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT392	Cell line	SNB-75	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT391	Cell line	HCC 2998	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT393	Cell line	HCT-116	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT148	Cell line	HCT-15	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT395	Cell line	SF-268	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT394	Cell line	EKVX	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT731	Cell line	LXFL 529	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT576	Cell line	DMS-114	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT146	Cell line	SK-OV-3	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT397	Cell line	NCI-H460	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT398	Cell line	UACC-62	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT308	Cell line	CAKI-1	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT399	Cell line	SF-295	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT458	Cell line	IGROV-1	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT577	Cell line	RXF 631	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT578	Cell line	SNB-78	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT403	Cell line	UACC-257	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT401	Cell line	786-0	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT404	Cell line	CCRF-CEM	Homo sapiens	GI50	n.a.	85310.01	nM	PubChem BioAssay data set
NPT579	Cell line	DLD-1	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT405	Cell line	NCI-H226	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT139	Cell line	HT-29	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT170	Cell line	SK-MEL-28	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT407	Cell line	COLO 205	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT406	Cell line	RXF 393	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT732	Cell line	HOP-18	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	Potency	n.a.	9528.3	nM	PubChem BioAssay data set
NPT20555	Organism	SARS-CoV-2	Severe acute respiratory syndrome coronavirus 2	Inhibition	=	-4.47	%	DOI[10.21203/rs.3.rs-23951/v1]
NPT20555	Organism	SARS-CoV-2	Severe acute respiratory syndrome coronavirus 2	Inhibition	=	0.05	%	DOI[10.6019/CHEMBL4495565]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Hepatotoxicity (acute)	=	10.5	%	PMID[15646539]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Hepatotoxicity (moderate)	=	2.0	n.a.	PMID[15646539]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Hepatotoxicity (moderate)	=	52.6	%	PMID[15646539]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Hepatotoxicity (granulomatous hepatitis)	=	0.0	n.a.	PMID[15646539]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Hepatotoxicity (benign tumour)	=	0.0	n.a.	PMID[15646539]
NPT2	Others	Unspecified	n.a.	Potency	n.a.	26603.2	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Inhibition	=	50.0	%	PMID[7673932]
NPT2	Others	Unspecified	n.a.	IC50	=	40.0	nM	PMID[18599296]
NPT2	Others	Unspecified	n.a.	Ki	=	155.0	nM	PMID[18599296]
NPT2	Others	Unspecified	n.a.	Ki	=	20.0	nM	PMID[18599296]
NPT2	Others	Unspecified	n.a.	IC50	=	11.0	nM	PMID[21295890]
NPT2	Others	Unspecified	n.a.	IC50	=	100.0	nM	PMID[22001328]
NPT2	Others	Unspecified	n.a.	Potency	n.a.	25118.9	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 NPC233034 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	44934
0.1-0.2	4809
0.2-0.3	96
0.3-0.4	11
0.4-0.5	4
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	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC481828
0.5294	Remote Similarity	NPC126664
0.5294	Remote Similarity	NPC34291
0.5294	Remote Similarity	NPC604626

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC233034 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7942
0.1-0.2	1183
0.2-0.3	20
0.3-0.4	1
0.4-0.5	2
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	1

Similarity Score	Similarity Level	Drug ID	Developmental Stage
1.0	High Similarity	NPD9440	Pre-clinical
0.5294	Remote Similarity	NPD9443	Pre-clinical

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