NPASS Compound

Natural Product: NPC277042

Natural Product ID	NPC277042
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	5-(1,3-Benzodioxol-5-Yl)-1-Piperidin-1-Ylpenta-2,4-Dien-1-One
IUPAC Name	5-(1,3-benzodioxol-5-yl)-1-piperidin-1-ylpenta-2,4-dien-1-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL3188765
PubChem CID	4840
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000279] Alkaloids and derivatives

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 40 42 0 0 0 0 0 0 0 0999 V2000 -5.8474 1.4132 0.1726 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5597 0.6857 -1.1174 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0923 0.5157 -1.3074 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2993 0.4176 -0.1311 N 0 0 0 0 0 0 0 0 0 0 0 0 -3.8456 0.5219 1.1889 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3304 0.4814 1.2755 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8923 0.2081 -0.2561 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1787 0.1162 0.7934 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.3239 0.1071 -1.5770 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1006 -0.0784 -1.8964 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9864 -0.2281 -0.9653 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2339 -0.4193 -1.4496 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4053 -0.5830 -0.6429 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3264 -0.5541 0.7286 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5053 -0.7196 1.4737 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7098 -0.9061 0.8530 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7760 -0.9334 -0.5336 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6274 -0.7723 -1.2759 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1237 -1.1370 -0.8236 O 0 0 0 0 0 0 0 0 0 0 0 0 7.9114 -0.7929 0.3049 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9871 -1.0892 1.3635 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.9052 1.6372 0.3166 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1933 2.3200 0.1781 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0273 -0.3244 -1.1273 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9453 1.2903 -1.9706 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6536 1.3300 -1.9321 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8886 -0.4229 -1.9081 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5074 1.4855 1.6801 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3867 -0.3298 1.7732 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6302 0.8635 2.2732 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7029 -0.5167 1.0508 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0486 0.2053 -2.4155 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1427 -0.1281 -2.9739 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8595 -0.1960 0.0866 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3451 -0.4496 -2.5467 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4104 -0.4113 1.2739 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4055 -0.6912 2.5610 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6826 -0.7942 -2.3678 H 0 0 0 0 0 0 0 0 0 0 0 0 8.8080 -1.4056 0.4090 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1127 0.2843 0.3791 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 4 7 1 0 7 8 2 0 7 9 1 0 9 10 2 3 10 11 1 0 11 12 2 3 12 13 1 0 13 14 2 0 14 15 1 0 15 16 2 0 16 17 1 0 17 18 2 0 17 19 1 0 19 20 1 0 20 21 1 0 6 1 1 0 18 13 1 0 21 16 1 0 1 22 1 0 1 23 1 0 2 24 1 0 2 25 1 0 3 26 1 0 3 27 1 0 5 28 1 0 5 29 1 0 6 30 1 0 6 31 1 0 9 32 1 0 10 33 1 0 11 34 1 0 12 35 1 0 14 36 1 0 15 37 1 0 18 38 1 0 20 39 1 0 20 40 1 0 M END

Standard InCHIKey	MXXWOMGUGJBKIW-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C17H19NO3/c19-17(18-10-4-1-5-11-18)7-3-2-6-14-8-9-15-16(12-14)21-13-20-15/h2-3,6-9,12H,1,4-5,10-11,13H2
SMILES	C1CCN(CC1)C(=O)C=CC=Cc1ccc2c(c1)OCO2

Calculated Properties

Physi-Chem Properties

Molecular Weight:	285.14	Volume:	298.468 ? Van der Waals volume.
Dense:	0.955	LogP:	2.905 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.877 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.736 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	19.0
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:	0.633	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.344	Fsp³:	0.353
MCE-18:	35.304 ? 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:	0.658	Fluc inhibitor:	1.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.679 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.794 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.015	Promiscuous compounds:	0.066

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.714	MDCK Permeability:	-4.666
Pgp-inhibitor:	0.72	Pgp-substrate:	0.024
PAMPA:	0.035 ? 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%):	0.021	30% Bioavailability (F30%):	0.001
50% Bioavailability (F50%):	0.132

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.961	MRP1:	0.268
Plasma Protein Binding (PPB):	95.854%	Volume Distribution (VD):	0.288
Fu:	3.796% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.843
OATP1B3 inhibitor:	0.827	BCRP inhibitor:	0.015
BSEP inhibitor:	0.997

ADMET: Metabolism

CYP1A2-inhibitor:	0.198	CYP1A2-substrate:	0.003
CYP2C19-inhibitor:	0.956	CYP2C19-substrate:	0.001
CYP2C9-inhibitor:	0.186	CYP2C9-substrate:	0.813
CYP2D6-inhibitor:	1.0	CYP2D6-substrate:	1.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.948
CYP2B6-substrate:	0.291	CYP2C8-inhibitor:	0.335
HLM stability:	0.878 ? 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):

4.649

Half-life (T1/2):

0.386

ADMET: Toxicity

hERG Blockers:	0.371	hERG Blockers (10um):	0.517
Human Hepatotoxicity (H-HT):	0.557	Drug-induced Liver Injury (DILI):	0.407
AMES Toxicity:	0.784	Rat Oral Acute Toxicity:	0.346
Maximum Recommended Daily Dose:	0.762	Skin Sensitization:	0.948
Carcinogencity:	0.693	Eye Corrosion:	0.017
Eye Irritation:	0.78	Respiratory Toxicity:	0.67
Drug-induced Neurotoxicity:	0.728	Ototoxicity:	0.37
Hematotoxicity:	0.254	Drug-induced Nephrotoxicity:	0.524
Genotoxicity:	0.243	RPMI-8226 Immunitoxicity:	0.126
A549 Cytotoxicity:	0.206	Hek293 Cytotoxicity:	0.557
BCF:	0.899 ? 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:	3.477 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.145 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.522 ? 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]
NPO876	Didymosphaeria enalia	Species	Didymosphaeriaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO11137	Dichotomanthes tristaniicarpa	Species	Rosaceae	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]
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]
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

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

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	=	3.821898767	mg/kg	TOXRIC

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 NPC277042 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	20806
0.1-0.2	27387
0.2-0.3	1436
0.3-0.4	161
0.4-0.5	28
0.5-0.6	14
0.6-0.7	6
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	2
0.95-1	3

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC255817
1.0	High Similarity	NPC136330
0.9778	High Similarity	NPC94280
0.9167	High Similarity	NPC205178
0.9167	High Similarity	NPC227218
0.7778	Intermediate Similarity	NPC73883
0.7778	Intermediate Similarity	NPC251454
0.7593	Intermediate Similarity	NPC103947
0.7593	Intermediate Similarity	NPC45783
0.7551	Intermediate Similarity	NPC167096
0.7551	Intermediate Similarity	NPC605721
0.7358	Intermediate Similarity	NPC159150
0.7347	Intermediate Similarity	NPC217574
0.7321	Intermediate Similarity	NPC220923
0.7321	Intermediate Similarity	NPC196609
0.7143	Intermediate Similarity	NPC328419
0.7091	Intermediate Similarity	NPC230698
0.7091	Intermediate Similarity	NPC99078
0.7091	Intermediate Similarity	NPC96406
0.6909	Remote Similarity	NPC193673
0.6415	Remote Similarity	NPC470707
0.614	Remote Similarity	NPC194359
0.614	Remote Similarity	NPC28641
0.614	Remote Similarity	NPC180647
0.614	Remote Similarity	NPC225745
0.5862	Remote Similarity	NPC145446
0.5862	Remote Similarity	NPC137172
0.5789	Remote Similarity	NPC252107
0.5667	Remote Similarity	NPC318862
0.5645	Remote Similarity	NPC95366
0.5556	Remote Similarity	NPC199209
0.5439	Remote Similarity	NPC469808
0.5417	Remote Similarity	NPC127326
0.5333	Remote Similarity	NPC248505
0.5323	Remote Similarity	NPC251466
0.52	Remote Similarity	NPC111225
0.5082	Remote Similarity	NPC182147
0.5082	Remote Similarity	NPC207541
0.5082	Remote Similarity	NPC246133

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC277042 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3992
0.1-0.2	5034
0.2-0.3	114
0.3-0.4	8
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	1

Similarity Score	Similarity Level	Drug ID	Developmental Stage
1.0	High Similarity	NPD2492	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