NPASS Compound

Natural Product: NPC46679

Natural Product ID	NPC46679
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Aristolochic Acid Ii
IUPAC Name	6-nitronaphtho[2,1-g][1,3]benzodioxole-5-carboxylic acid
Synonyms	Aristolochic acid II
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL602280
PubChem CID	108168
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0002448] Benzenoids [CHEMONTID:0000025] Phenanthrenes and derivatives [CHEMONTID:0002664] Aristolochic acids 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 31 34 0 0 0 0 0 0 0 0999 V2000 3.5921 -1.8602 -0.1721 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5024 -2.6388 -0.4996 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2075 -2.1318 -0.5025 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0082 -0.8167 -0.1689 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1047 -0.0114 0.1670 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3992 -0.5371 0.1644 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9304 1.2941 0.5088 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6629 1.8814 0.5341 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4140 1.1169 0.1919 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6544 1.6656 0.2032 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7689 0.8344 -0.1069 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5700 -0.4867 -0.4239 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3261 -1.0636 -0.4633 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2354 -0.2467 -0.1547 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5276 -2.3841 -0.8240 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.8723 -2.6955 -0.5359 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5556 -1.4495 -0.7516 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.9217 3.0870 0.0873 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0757 3.5057 0.4652 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0942 4.0484 -0.4031 O 0 0 0 0 0 1 0 0 0 0 0 0 0.6177 3.1674 1.1120 N 0 0 0 0 0 0 0 0 0 0 0 0 1.6438 4.0691 0.8747 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.2403 3.4472 1.9708 O 0 0 0 0 0 0 0 0 0 0 0 0 4.5821 -2.2390 -0.1680 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6070 -3.6873 -0.7714 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4101 -2.7798 -0.7640 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2347 0.1103 0.4292 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8089 1.8870 0.7669 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7205 1.3012 -0.0701 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0103 -2.9651 0.5303 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3249 -3.4224 -1.2259 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 2 0 5 7 1 0 7 8 2 0 8 9 1 0 9 10 2 0 10 11 1 0 11 12 2 0 12 13 1 0 13 14 2 0 13 15 1 0 15 16 1 0 16 17 1 0 10 18 1 0 18 19 2 0 18 20 1 0 8 21 1 0 21 22 1 0 21 23 2 0 6 1 1 0 14 9 1 0 14 4 1 0 17 12 1 0 1 24 1 0 2 25 1 0 3 26 1 0 6 27 1 0 7 28 1 0 11 29 1 0 16 30 1 0 16 31 1 0 M CHG 3 20 -1 21 1 22 -1 M END

Standard InCHIKey	MEEXETVZNQYRSP-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C16H9NO6/c18-16(19)10-6-12-15(23-7-22-12)14-9-4-2-1-3-8(9)5-11(13(10)14)17(20)21/h1-6H,7H2,(H,18,19)/p-1
SMILES	c1ccc2c(c1)cc(c1c(cc3c(c21)OCO3)C(=O)[O-])N(=O)=O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	311.04	Volume:	291.076 ? Van der Waals volume.
Dense:	1.069	LogP:	3.244 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.339 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.247 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	22.0
TPSA:	98.9 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	1.0	Rings:	4.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.443	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.508	Fsp³:	0.062
MCE-18:	46.588 ? 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:	0.945	Fluc inhibitor:	0.033 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.256 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.68 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.307	Promiscuous compounds:	0.405

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.988	MDCK Permeability:	-4.675
Pgp-inhibitor:	0.0	Pgp-substrate:	0.002
PAMPA:	0.999 ? 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%):	0.004	30% Bioavailability (F30%):	0.003
50% Bioavailability (F50%):	0.049

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.024	MRP1:	1.0
Plasma Protein Binding (PPB):	98.862%	Volume Distribution (VD):	-0.654
Fu:	0.667% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.379
OATP1B3 inhibitor:	0.852	BCRP inhibitor:	0.002
BSEP inhibitor:	0.266

ADMET: Metabolism

CYP1A2-inhibitor:	0.058	CYP1A2-substrate:	0.061
CYP2C19-inhibitor:	0.005	CYP2C19-substrate:	0.606
CYP2C9-inhibitor:	0.87	CYP2C9-substrate:	0.477
CYP2D6-inhibitor:	0.024	CYP2D6-substrate:	0.049
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.984
CYP2B6-substrate:	0.008	CYP2C8-inhibitor:	0.147
HLM stability:	0.007 ? 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):

1.195

Half-life (T1/2):

1.641

ADMET: Toxicity

hERG Blockers:	0.04	hERG Blockers (10um):	0.113
Human Hepatotoxicity (H-HT):	0.455	Drug-induced Liver Injury (DILI):	0.993
AMES Toxicity:	0.89	Rat Oral Acute Toxicity:	0.473
Maximum Recommended Daily Dose:	0.364	Skin Sensitization:	0.901
Carcinogencity:	0.736	Eye Corrosion:	0.007
Eye Irritation:	0.974	Respiratory Toxicity:	0.9
Drug-induced Neurotoxicity:	0.128	Ototoxicity:	0.352
Hematotoxicity:	0.831	Drug-induced Nephrotoxicity:	0.678
Genotoxicity:	0.999	RPMI-8226 Immunitoxicity:	0.053
A549 Cytotoxicity:	0.044	Hek293 Cytotoxicity:	0.231
BCF:	0.593 ? 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:	3.317 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.489 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.0 ? 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
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.3987/COM-96-7609.]
NPO14814	Aristolochia contorta	Species	Aristolochiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[1431939]
NPO267	Couepia polyandra	Species	Chrysobalanaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[14640519]
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[16038566]
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	stem	n.a.	PMID[16964757]
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[18081254]
NPO12773	Stephania tetrandra	Species	Menispermaceae	Eukaryota	n.a.	root	n.a.	PMID[20030508]
NPO6336	Asarum sieboldii	Species	Aristolochiaceae	Eukaryota	roots	n.a.	n.a.	PMID[22381047]
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	rhizome	n.a.	PMID[23059629]
NPO12773	Stephania tetrandra	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[3728032]
NPO3961	Lavandula hybrida	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[39147955]
NPO12773	Stephania tetrandra	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[Article]
NPO19649	Akebia quinata	Species	Lardizabalaceae	Eukaryota	n.a.	n.a.	n.a.	Database[Article]
NPO19649	Akebia quinata	Species	Lardizabalaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO11170	Akebia trifoliata	Species	Lardizabalaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO6336	Asarum sieboldii	Species	Aristolochiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO29078	Asiasarum sieboldii	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12468	Asarum heterotropoides	Species	Aristolochiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO4659	Asiasarum heterotropoides	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12773	Stephania tetrandra	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO24916	Aristolochia debilis	Species	Aristolochiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO14814	Aristolochia contorta	Species	Aristolochiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO5606	Dimerostemma asperatum	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO267	Couepia polyandra	Species	Chrysobalanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO4533	Spatoglossum schmittii	Species	Dictyotaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO19649	Akebia quinata	Species	Lardizabalaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO24916	Aristolochia debilis	Species	Aristolochiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO14814	Aristolochia contorta	Species	Aristolochiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO6336	Asarum sieboldii	Species	Aristolochiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO12773	Stephania tetrandra	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO11170	Akebia trifoliata	Species	Lardizabalaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO11170	Akebia trifoliata	Species	Lardizabalaceae	Eukaryota	n.a.	pericarp	n.a.	PMID[p25172756]
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO14814	Aristolochia contorta	Species	Aristolochiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO24916	Aristolochia debilis	Species	Aristolochiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO6336	Asarum sieboldii	Species	Aristolochiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO19649	Akebia quinata	Species	Lardizabalaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO11170	Akebia trifoliata	Species	Lardizabalaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO12773	Stephania tetrandra	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO6336	Asarum sieboldii	Species	Aristolochiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO19649	Akebia quinata	Species	Lardizabalaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO24916	Aristolochia debilis	Species	Aristolochiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO11170	Akebia trifoliata	Species	Lardizabalaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO12468	Asarum heterotropoides	Species	Aristolochiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO14814	Aristolochia contorta	Species	Aristolochiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO12773	Stephania tetrandra	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO14814	Aristolochia contorta	Species	Aristolochiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO24916	Aristolochia debilis	Species	Aristolochiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO12468	Asarum heterotropoides	Species	Aristolochiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO4659	Asiasarum heterotropoides	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[TM-MC]
NPO6336	Asarum sieboldii	Species	Aristolochiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO11170	Akebia trifoliata	Species	Lardizabalaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO19649	Akebia quinata	Species	Lardizabalaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO12773	Stephania tetrandra	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO29078	Asiasarum sieboldii	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[TM-MC]
NPO11170	Akebia trifoliata	Species	Lardizabalaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO5606	Dimerostemma asperatum	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12773	Stephania tetrandra	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO29078	Asiasarum sieboldii	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[UNPD]
NPO4533	Spatoglossum schmittii	Species	Dictyotaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO3961	Lavandula hybrida	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO6336	Asarum sieboldii	Species	Aristolochiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO267	Couepia polyandra	Species	Chrysobalanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO10846	Aristolochia rotunda	Species	Aristolochiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12468	Asarum heterotropoides	Species	Aristolochiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1315	Sinomenium acutum	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO4659	Asiasarum heterotropoides	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[UNPD]
NPO19649	Akebia quinata	Species	Lardizabalaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO23841	Dysophylla verticillata	n.a.	n.a.	n.a.	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
IC50	1

Activity Type	# Activity
Individual protein	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1371	Individual protein	Cyclin-dependent kinase 2	Homo sapiens	IC50	>	20000.0	nM	PMID[20097066]

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 NPC46679 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	40439
0.1-0.2	9153
0.2-0.3	239
0.3-0.4	18
0.4-0.5	3
0.5-0.6	4
0.6-0.7	1
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
0.7586	Intermediate Similarity	NPC85661
0.6	Remote Similarity	NPC604080
0.5909	Remote Similarity	NPC171882
0.5522	Remote Similarity	NPC121510
0.5294	Remote Similarity	NPC91234
0.5072	Remote Similarity	NPC290227

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC46679 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6651
0.1-0.2	2482
0.2-0.3	17
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