NPASS Compound

Natural Product: NPC605721

Natural Product ID	NPC605721
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	BLPUOQGPBJPXRL-UHFFFAOYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL4303457
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0000296] Benzodioxoles

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 36 38 0 0 0 0 0 0 0 0999 V2000 -1.6417 2.9819 0.5604 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.2656 1.7914 0.1905 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0975 1.4303 0.4591 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7139 0.3243 0.1975 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1152 0.0584 0.5163 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9396 0.9611 1.1342 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2731 0.6728 1.4233 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7990 -0.5325 1.0938 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0031 -1.4699 0.4705 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6995 -1.1703 0.1951 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7692 -2.6110 0.2403 O 0 0 0 0 0 0 0 0 0 0 0 0 6.1374 -2.2113 0.2998 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0585 -1.1295 1.2349 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.2762 1.0472 -0.4204 N 0 0 0 0 0 0 0 0 0 0 0 0 -3.6029 1.6894 -0.5612 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5755 0.8212 0.1998 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7317 -0.4536 -0.6382 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5927 -0.6412 -1.5777 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2307 -0.2888 -0.9526 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7187 2.2007 0.9613 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1927 -0.4807 -0.2879 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5812 1.9311 1.4191 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9003 1.4101 1.9138 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0618 -1.8905 -0.2917 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4835 -1.8640 -0.6928 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7301 -3.0411 0.7132 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8658 1.6415 -1.6259 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5849 2.7319 -0.1707 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5430 1.3011 0.3832 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0701 0.4870 1.1471 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6596 -0.3025 -1.2267 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8511 -1.3200 0.0395 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5266 -1.7430 -1.7906 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7026 -0.1419 -2.5575 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0277 -1.0695 -0.1912 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5259 -0.3334 -1.8079 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 2 3 4 5 1 0 5 6 2 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 2 0 9 11 1 0 11 12 1 0 12 13 1 0 2 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 1 0 10 5 1 0 19 14 1 0 13 8 1 0 3 20 1 0 4 21 1 0 6 22 1 0 7 23 1 0 10 24 1 0 12 25 1 0 12 26 1 0 15 27 1 0 15 28 1 0 16 29 1 0 16 30 1 0 17 31 1 0 17 32 1 0 18 33 1 0 18 34 1 0 19 35 1 0 19 36 1 0 M END

Standard InCHIKey	BLPUOQGPBJPXRL-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C15H17NO3/c17-15(16-8-2-1-3-9-16)7-5-12-4-6-13-14(10-12)19-11-18-13/h4-7,10H,1-3,8-9,11H2
SMILES	O=C(C=Cc1ccc2c(c1)OCO2)N1CCCCC1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	259.12	Volume:	266.512 ? Van der Waals volume.
Dense:	0.972	LogP:	2.778 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.802 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.418 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	18.0
TPSA:	38.77 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	0.0	Rings:	3.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.766	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.054	Fsp³:	0.4
MCE-18:	36.0 ? 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:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.611	Fluc inhibitor:	1.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.544 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.809 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.011	Promiscuous compounds:	0.032

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.594	MDCK Permeability:	-4.686
Pgp-inhibitor:	0.865	Pgp-substrate:	0.014
PAMPA:	0.031 ? 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):	0.001
20% Bioavailability (F20%):	0.036	30% Bioavailability (F30%):	0.001
50% Bioavailability (F50%):	0.064

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.965	MRP1:	0.511
Plasma Protein Binding (PPB):	93.796%	Volume Distribution (VD):	0.154
Fu:	6.399% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.288
OATP1B3 inhibitor:	0.403	BCRP inhibitor:	0.01
BSEP inhibitor:	0.998

ADMET: Metabolism

CYP1A2-inhibitor:	0.067	CYP1A2-substrate:	0.656
CYP2C19-inhibitor:	0.215	CYP2C19-substrate:	0.651
CYP2C9-inhibitor:	0.648	CYP2C9-substrate:	0.302
CYP2D6-inhibitor:	1.0	CYP2D6-substrate:	0.988
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.99
CYP2B6-substrate:	0.031	CYP2C8-inhibitor:	0.867
HLM stability:	0.642 ? 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):

4.496

Half-life (T1/2):

0.528

ADMET: Toxicity

hERG Blockers:	0.33	hERG Blockers (10um):	0.521
Human Hepatotoxicity (H-HT):	0.615	Drug-induced Liver Injury (DILI):	0.526
AMES Toxicity:	0.621	Rat Oral Acute Toxicity:	0.243
Maximum Recommended Daily Dose:	0.543	Skin Sensitization:	0.793
Carcinogencity:	0.614	Eye Corrosion:	0.027
Eye Irritation:	0.734	Respiratory Toxicity:	0.558
Drug-induced Neurotoxicity:	0.755	Ototoxicity:	0.25
Hematotoxicity:	0.366	Drug-induced Nephrotoxicity:	0.494
Genotoxicity:	0.617	RPMI-8226 Immunitoxicity:	0.102
A549 Cytotoxicity:	0.113	Hek293 Cytotoxicity:	0.487
BCF:	0.879 ? 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:	3.402 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.966 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.333 ? 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
NPO10274	Pothomorphe peltata	n.a.	n.a.	n.a.	n.a.	Dominican Republic	n.a.	PMID[11430019]
NPO6544	Carpesium longifolium	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[14695795]
NPO3968	Dracontium loretense	Species	Araceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19341262]
NPO3968	Dracontium loretense	Species	Araceae	Eukaryota	corms	Iquitos, Peru	2005-MAY	PMID[19341262]
NPO10666	Verbesina virginica	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19485332]
NPO4251	Photorhabdus luminescens	Species	Morganellaceae	Bacteria	n.a.	n.a.	n.a.	PMID[22909174]
NPO12125	Pseudomonas stutzeri	Species	Pseudomonadaceae	Bacteria	n.a.	n.a.	n.a.	PMID[23149469]
NPO6648	Piper retrofractum	Species	Piperaceae	Eukaryota	Fruits	n.a.	n.a.	PMID[23506561]
NPO6648	Piper retrofractum	Species	Piperaceae	Eukaryota	leaves	n.a.	n.a.	PMID[25127165]
NPO4251	Photorhabdus luminescens	Species	Morganellaceae	Bacteria	n.a.	n.a.	n.a.	PMID[25988621]
NPO13059	Abies webbiana	Species	Pinaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8639	Agaricus xanthodermus	Species	Agaricaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO10459	Brickellia longifolia	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12488	Bupleurum rigidum	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO6544	Carpesium longifolium	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO11511	Cochlearia officinalis	Species	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO9950	Coelogyne nitida	Species	Orchidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO6880	Crocus corsicus	Species	Iridaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO11137	Dichotomanthes tristaniicarpa	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO876	Didymosphaeria enalia	Species	Didymosphaeriaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO4251	Photorhabdus luminescens	Species	Morganellaceae	Bacteria	n.a.	n.a.	n.a.	Database[COCONUT]
NPO10666	Verbesina virginica	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO27487	Silene banksia	Species	Caryophyllaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7158	Schefflera venulosa	Species	Araliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12125	Pseudomonas stutzeri	Species	Pseudomonadaceae	Bacteria	n.a.	n.a.	n.a.	Database[COCONUT]
NPO10274	Pothomorphe peltata	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[COCONUT]
NPO2840	Podocarpus minor	Species	Podocarpaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO6648	Piper retrofractum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO26616	Piper novae-hollandiae	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO3968	Dracontium loretense	Species	Araceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO23642	Penicillium tardum	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO230	Palisota barteri	Species	Commelinaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7536	Mycoplasma mycoides	Species	Mycoplasmataceae	Bacteria	n.a.	n.a.	n.a.	Database[COCONUT]
NPO9166	Monascus rubropunctatus	Species	Fellodistomidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO2393	Matsumurella chinensis	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO43	Leifsonia aquatica	Species	Microbacteriaceae	Bacteria	n.a.	n.a.	n.a.	Database[COCONUT]
NPO964	Homalium laurifolium	Species	Salicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12383	Frullania brasiliensis	Species	Frullaniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO6428	Euphorbia wangii	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO6544	Carpesium longifolium	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO7158	Schefflera venulosa	Species	Araliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO7158	Schefflera venulosa	Species	Araliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO6544	Carpesium longifolium	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO12383	Frullania brasiliensis	Species	Frullaniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO27487	Silene banksia	Species	Caryophyllaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO6648	Piper retrofractum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO6428	Euphorbia wangii	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO4251	Photorhabdus luminescens	Species	Morganellaceae	Bacteria	n.a.	n.a.	n.a.	Database[UNPD]
NPO12383	Frullania brasiliensis	Species	Frullaniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12125	Pseudomonas stutzeri	Species	Pseudomonadaceae	Bacteria	n.a.	n.a.	n.a.	Database[UNPD]
NPO2393	Matsumurella chinensis	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO6544	Carpesium longifolium	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO23642	Penicillium tardum	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12488	Bupleurum rigidum	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO7158	Schefflera venulosa	Species	Araliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO876	Didymosphaeria enalia	Species	Didymosphaeriaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO9166	Monascus rubropunctatus	Species	Fellodistomidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO10274	Pothomorphe peltata	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[UNPD]
NPO3968	Dracontium loretense	Species	Araceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO10459	Brickellia longifolia	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8639	Agaricus xanthodermus	Species	Agaricaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO2840	Podocarpus minor	Species	Podocarpaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO964	Homalium laurifolium	Species	Salicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO9950	Coelogyne nitida	Species	Orchidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO230	Palisota barteri	Species	Commelinaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO11511	Cochlearia officinalis	Species	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO43	Leifsonia aquatica	Species	Microbacteriaceae	Bacteria	n.a.	n.a.	n.a.	Database[UNPD]
NPO26616	Piper novae-hollandiae	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO6880	Crocus corsicus	Species	Iridaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO6648	Piper retrofractum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13059	Abies webbiana	Species	Pinaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO10666	Verbesina virginica	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO27487	Silene banksia	Species	Caryophyllaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO11137	Dichotomanthes tristaniicarpa	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO7536	Mycoplasma mycoides	Species	Mycoplasmataceae	Bacteria	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	4

Activity Type	# Activity
Organism	3
Single protein	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT20556	Single protein	Replicase polyprotein 1ab	Severe acute respiratory syndrome coronavirus 2	Inhibition	=	9.478	%	Identification of inhibitors of SARS-Cov2 M-Pro enzymatic activity using a small molecule repurposing screen

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT20555	Organism	SARS-CoV-2	Severe acute respiratory syndrome coronavirus 2	Inhibition	=	-4.69	%	Identification of inhibitors of SARS-CoV-2 in-vitro cellular toxicity in human (Caco-2) cells using a large scale drug repurposing collection
NPT20555	Organism	SARS-CoV-2	Severe acute respiratory syndrome coronavirus 2	Inhibition	=	-0.1	%	Cytopathic SARS-Cov2 screening on VERO-E6 cells in a large repurposing effort

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
-	Mus musculus	LD50	>	1000.0	mg/kg	ToxVal

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 NPC605721 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	19285
0.1-0.2	28565
0.2-0.3	1718
0.3-0.4	215
0.4-0.5	34
0.5-0.6	12
0.6-0.7	15
0.7-0.8	1
0.8-0.85	1
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	NPC167096
0.9756	High Similarity	NPC217574
0.8043	Intermediate Similarity	NPC470707
0.7551	Intermediate Similarity	NPC255817
0.7551	Intermediate Similarity	NPC136330
0.7347	Intermediate Similarity	NPC94280
0.7255	Intermediate Similarity	NPC205178
0.7255	Intermediate Similarity	NPC227218
0.7143	Intermediate Similarity	NPC469808
0.7037	Intermediate Similarity	NPC73883
0.7037	Intermediate Similarity	NPC251454
0.6981	Remote Similarity	NPC230698
0.6981	Remote Similarity	NPC99078
0.6981	Remote Similarity	NPC96406
0.6923	Remote Similarity	NPC159150
0.6909	Remote Similarity	NPC220923
0.6909	Remote Similarity	NPC196609
0.6852	Remote Similarity	NPC103947
0.6852	Remote Similarity	NPC45783
0.6792	Remote Similarity	NPC193673
0.6727	Remote Similarity	NPC328419
0.6604	Remote Similarity	NPC194359
0.6604	Remote Similarity	NPC28641
0.6604	Remote Similarity	NPC180647
0.6604	Remote Similarity	NPC225745
0.6071	Remote Similarity	NPC318862
0.5909	Remote Similarity	NPC127326
0.58	Remote Similarity	NPC76897
0.5652	Remote Similarity	NPC17497
0.5652	Remote Similarity	NPC111225
0.5652	Remote Similarity	NPC305602
0.5636	Remote Similarity	NPC252107
0.5439	Remote Similarity	NPC145446
0.5439	Remote Similarity	NPC137172
0.5246	Remote Similarity	NPC95366
0.52	Remote Similarity	NPC470708
0.52	Remote Similarity	NPC212643
0.5172	Remote Similarity	NPC248505

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC605721 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3646
0.1-0.2	5325
0.2-0.3	167
0.3-0.4	8
0.4-0.5	2
0.5-0.6	1
0.6-0.7	0
0.7-0.8	1
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
0.7551	Intermediate Similarity	NPD2492	Phase 2
0.56	Remote Similarity	NPD1357	Phase 4

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