NPASS Compound

Natural Product: NPC277974

Natural Product ID	NPC277974
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	JHKNAYGQYUKKDQ-YUMQZZPRSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	90472998
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0000050] Lactones [CHEMONTID:0001245] Gamma butyrolactones

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 26 27 0 0 0 0 0 0 0 0999 V2000 2.7915 -0.9154 -0.1566 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4704 -0.2871 0.0575 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3705 -0.9527 -0.2633 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9791 -0.3673 -0.1924 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7214 -1.0291 0.9480 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7091 -0.6257 -1.4761 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8913 1.1112 0.1190 C 0 0 1 0 0 0 0 0 0 0 0 0 0.0448 1.2343 1.3288 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3958 1.0662 0.6226 C 0 0 2 0 0 0 0 0 0 0 0 0 1.2037 1.9637 -0.4766 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.1140 1.8565 -0.9009 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5334 2.3300 -1.9813 O 0 0 0 0 0 0 0 0 0 0 0 0 3.4486 -0.2113 -0.7248 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7229 -1.8255 -0.8141 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2913 -1.2378 0.7643 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4742 -1.9798 -0.5940 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0040 -1.4733 1.6674 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3643 -1.8514 0.5817 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3827 -0.2857 1.4555 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7556 -0.2446 -1.4135 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7223 -1.7079 -1.6517 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1976 -0.0868 -2.2912 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8696 1.5481 0.3134 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1578 0.4068 2.0137 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0392 2.2092 1.8051 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2276 1.3553 1.2594 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 3 4 1 0 4 5 1 0 4 6 1 0 4 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 2 0 9 2 1 0 11 7 1 0 1 13 1 0 1 14 1 0 1 15 1 0 3 16 1 0 5 17 1 0 5 18 1 0 5 19 1 0 6 20 1 0 6 21 1 0 6 22 1 0 7 23 1 1 8 24 1 0 8 25 1 0 9 26 1 1 M END

Standard InCHIKey	JHKNAYGQYUKKDQ-YUMQZZPRSA-N
Standard InCHI	InChI=1S/C10H14O2/c1-6-5-10(2,3)7-4-8(6)12-9(7)11/h5,7-8H,4H2,1-3H3/t7-,8-/m0/s1
SMILES	CC1=CC(C)(C)[C@H]2C[C@@H]1OC2=O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	166.1	Volume:	176.711 ? Van der Waals volume.
Dense:	0.94	LogP:	2.068 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.255 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.116 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	0.0	Rigid Bonds:	10.0
TPSA:	26.3 ? Topological Polar Surface Area.	H-Bond Acceptor:	2.0
H-Bond Donor:	0.0	Rings:	2.0
Heavy Atoms:	2.0

MedChem Properties

QED Drug-Likeness Score:	0.406	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.846	Fsp³:	0.7
MCE-18:	32.118 ? 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:	0.225	Fluc inhibitor:	0.046 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.032 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.0 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.843	Promiscuous compounds:	0.532

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.464	MDCK Permeability:	-4.43
Pgp-inhibitor:	0.105	Pgp-substrate:	0.697
PAMPA:	0.705 ? 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):	0.002
20% Bioavailability (F20%):	0.015	30% Bioavailability (F30%):	0.007
50% Bioavailability (F50%):	0.095

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.702	MRP1:	0.815
Plasma Protein Binding (PPB):	50.273%	Volume Distribution (VD):	0.036
Fu:	48.585% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.411
OATP1B3 inhibitor:	0.13	BCRP inhibitor:	0.014
BSEP inhibitor:	0.38

ADMET: Metabolism

CYP1A2-inhibitor:	0.523	CYP1A2-substrate:	0.198
CYP2C19-inhibitor:	0.7	CYP2C19-substrate:	0.009
CYP2C9-inhibitor:	0.121	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.004	CYP2D6-substrate:	0.852
CYP3A4-inhibitor:	0.998	CYP3A4-substrate:	0.78
CYP2B6-substrate:	0.045	CYP2C8-inhibitor:	0.844
HLM stability:	0.82 ? 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):

10.786

Half-life (T1/2):

1.259

ADMET: Toxicity

hERG Blockers:	0.049	hERG Blockers (10um):	0.435
Human Hepatotoxicity (H-HT):	0.576	Drug-induced Liver Injury (DILI):	0.655
AMES Toxicity:	0.811	Rat Oral Acute Toxicity:	0.616
Maximum Recommended Daily Dose:	0.633	Skin Sensitization:	0.99
Carcinogencity:	0.856	Eye Corrosion:	0.723
Eye Irritation:	0.938	Respiratory Toxicity:	0.632
Drug-induced Neurotoxicity:	0.907	Ototoxicity:	0.168
Hematotoxicity:	0.343	Drug-induced Nephrotoxicity:	0.88
Genotoxicity:	0.814	RPMI-8226 Immunitoxicity:	0.094
A549 Cytotoxicity:	0.249	Hek293 Cytotoxicity:	0.14
BCF:	1.669 ? 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:	3.932 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.892 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.235 ? 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
NPO19178	Justicia hyssopifolia	Species	Acanthaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[11312930]
NPO14250	Schisandra henryi	Species	Schisandraceae	Eukaryota	n.a.	stem	n.a.	PMID[14661856]
NPO15563	Valeriana prionophylla	Species	Caprifoliaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[15270567]
NPO4513	Commiphora africana	Species	Burseraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[15679332]
NPO2890	Scrophularia lepidota	Species	Scrophulariaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19299148]
NPO16646	Artemisia campestris	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[32372353]
NPO16646	Artemisia campestris	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[33588649]
NPO57430	Artemisia khorassanica	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[35508595]
NPO4513	Commiphora africana	Species	Burseraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[37653941]
NPO16646	Artemisia campestris	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[37849964]
NPO16933	Halichondria cylindrata	Species	Halichondriidae	Eukaryota	n.a.	n.a.	n.a.	PMID[8991950]
NPO13812	Illicium floridanum	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[9548851]
NPO11474	Ligusticum jeholense	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO23695	Setosphaeria turcica	Species	Pleosporaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO17818	Acrantophis dumerili	Species	Boidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO18226	Ajuga chia	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO18294	Anacyclus clavatus	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO21638	Attalea cohune	Species	Arecaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO16268	Blattella germanica	Species	Ectobiidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO16046	Buchnerodendron speciosum	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[COCONUT]
NPO15831	Panicum dichotomiflorum	Species	Poaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO16646	Artemisia campestris	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO14245.1	Veratrum album subsp. lobelianum	Subspecies	Melanthiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO15563	Valeriana prionophylla	Species	Caprifoliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO2890	Scrophularia lepidota	Species	Scrophulariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO10635	Schkuhria pusilla	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO14250	Schisandra henryi	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO18501	Salvia carduacea	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO18565	Penicillium striatisporum	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12395	Cardamine impatiens	Species	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO27137	Ocotea usambarensis	Species	Lauraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO26926	Montanoa frutescens	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO19178	Justicia hyssopifolia	Species	Acanthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13812	Illicium floridanum	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO22448	Helichrysum nanum	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO16933	Halichondria cylindrata	Species	Halichondriidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO18776	Erlangea fusca	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO18969	Dysidea etheria	Species	Dysideidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO18627	Cardamine komarovii	Species	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO11474	Ligusticum jeholense	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO16646	Artemisia campestris	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO19178	Justicia hyssopifolia	Species	Acanthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO2890	Scrophularia lepidota	Species	Scrophulariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO11474	Ligusticum jeholense	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO2890	Scrophularia lepidota	Species	Scrophulariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO16646	Artemisia campestris	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO14250	Schisandra henryi	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO19178	Justicia hyssopifolia	Species	Acanthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO11474	Ligusticum jeholense	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO14250	Schisandra henryi	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO16646	Artemisia campestris	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO11474	Ligusticum jeholense	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO17818	Acrantophis dumerili	Species	Boidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO27137	Ocotea usambarensis	Species	Lauraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO18776	Erlangea fusca	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO16268	Blattella germanica	Species	Ectobiidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO18969	Dysidea etheria	Species	Dysideidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO18501	Salvia carduacea	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO27171	Euphorbia sessiliflora	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO16933	Halichondria cylindrata	Species	Halichondriidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO18565	Penicillium striatisporum	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO10635	Schkuhria pusilla	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12395	Cardamine impatiens	Species	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO18226	Ajuga chia	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO23695	Setosphaeria turcica	Species	Pleosporaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO15563	Valeriana prionophylla	Species	Caprifoliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO11474	Ligusticum jeholense	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO18627	Cardamine komarovii	Species	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO2890	Scrophularia lepidota	Species	Scrophulariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO14250	Schisandra henryi	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO18294	Anacyclus clavatus	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO15831	Panicum dichotomiflorum	Species	Poaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO16046	Buchnerodendron speciosum	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[UNPD]
NPO14245.1	Veratrum album subsp. lobelianum	Subspecies	Melanthiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO26926	Montanoa frutescens	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO21638	Attalea cohune	Species	Arecaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13812	Illicium floridanum	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO16646	Artemisia campestris	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO27462	Webera corymbosa	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[UNPD]
NPO4513	Commiphora africana	Species	Burseraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO17229	Catha cassinoides	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO22448	Helichrysum nanum	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO19178	Justicia hyssopifolia	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
NPO16646	Artemisia campestris	Oil	Aerial parts	2.14Â±0.05	n.a.	n.a.	%	PMID[37849964]
NPO4513	Commiphora africana	Oil	n.a.	0.1	n.a.	n.a.	%	PMID[37653941]
NPO57430	Artemisia khorassanica	Oil	n.a.	1.921	n.a.	n.a.	%	PMID[35508595]

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

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 NPC277974 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	19696
0.1-0.2	26585
0.2-0.3	3550
0.3-0.4	27
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	0

Similarity Score	Similarity Level	Natural Product ID
		NPC

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC277974 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6730
0.1-0.2	2350
0.2-0.3	70
0.3-0.4	0
0.4-0.5	0
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	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
		NPD

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