NPASS Compound

Natural Product: NPC179309

Natural Product ID	NPC179309
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	3,4-Dimethoxy Cinnamaldehyde
IUPAC Name	(E)-3-(3,4-dimethoxyphenyl)prop-2-enal
Synonyms	3,4-Dimethoxy Cinnamaldehyde
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL465888
PubChem CID	5375268
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000029] Cinnamaldehydes

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 26 0 0 0 0 0 0 0 0999 V2000 -3.3316 -2.4357 0.1262 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9864 -1.0721 0.1368 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.6313 -0.7010 0.0748 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6482 -1.6591 0.0044 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6785 -1.2450 -0.0552 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0422 0.0777 -0.0464 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4195 0.5529 -0.1074 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4823 -0.2319 -0.1782 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8311 0.3145 -0.2362 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7948 -0.4891 -0.3024 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0318 1.0126 0.0249 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3017 0.6447 0.0858 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3127 1.6209 0.1581 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.9421 2.9755 0.1671 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7583 -3.0528 0.8225 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4302 -2.4967 0.3406 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1950 -2.9010 -0.8935 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9256 -2.7037 -0.0030 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4361 -2.0079 -0.1100 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6560 1.6196 -0.0974 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3225 -1.2980 -0.1921 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0382 1.3747 -0.2249 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2757 2.0815 0.0346 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3849 3.2574 1.1053 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8753 3.5990 0.0760 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2854 3.1629 -0.7105 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 2 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 2 0 6 11 1 0 11 12 2 0 12 13 1 0 13 14 1 0 12 3 1 0 1 15 1 0 1 16 1 0 1 17 1 0 4 18 1 0 5 19 1 0 7 20 1 0 8 21 1 0 9 22 1 0 11 23 1 0 14 24 1 0 14 25 1 0 14 26 1 0 M END

Standard InCHIKey	KNUFNLWDGZQKKJ-ONEGZZNKSA-N
Standard InCHI	InChI=1S/C11H12O3/c1-13-10-6-5-9(4-3-7-12)8-11(10)14-2/h3-8H,1-2H3/b4-3+
SMILES	COc1ccc(/C=C/C=O)cc1OC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	192.08	Volume:	203.444 ? Van der Waals volume.
Dense:	0.944	LogP:	2.087 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.113 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.67 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	8.0
TPSA:	35.53 ? Topological Polar Surface Area.	H-Bond Acceptor:	3.0
H-Bond Donor:	0.0	Rings:	1.0
Heavy Atoms:	3.0

MedChem Properties

QED Drug-Likeness Score:	0.54	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	1.977	Fsp³:	0.182
MCE-18:	6.0 ? 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:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.348	Fluc inhibitor:	0.747 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.09 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.445 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.994	Promiscuous compounds:	0.055

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.744	MDCK Permeability:	-4.648
Pgp-inhibitor:	0.981	Pgp-substrate:	0.024
PAMPA:	0.036 ? 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):	0.22
20% Bioavailability (F20%):	0.688	30% Bioavailability (F30%):	0.42
50% Bioavailability (F50%):	0.826

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.013	MRP1:	0.032
Plasma Protein Binding (PPB):	88.105%	Volume Distribution (VD):	-0.374
Fu:	10.757% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.98
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.978
BSEP inhibitor:	0.999

ADMET: Metabolism

CYP1A2-inhibitor:	0.147	CYP1A2-substrate:	0.375
CYP2C19-inhibitor:	0.536	CYP2C19-substrate:	0.477
CYP2C9-inhibitor:	0.31	CYP2C9-substrate:	0.013
CYP2D6-inhibitor:	0.982	CYP2D6-substrate:	0.191
CYP3A4-inhibitor:	0.847	CYP3A4-substrate:	0.614
CYP2B6-substrate:	0.003	CYP2C8-inhibitor:	0.999
HLM stability:	0.377 ? 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):

8.297

Half-life (T1/2):

1.404

ADMET: Toxicity

hERG Blockers:	0.163	hERG Blockers (10um):	0.428
Human Hepatotoxicity (H-HT):	0.525	Drug-induced Liver Injury (DILI):	0.455
AMES Toxicity:	0.767	Rat Oral Acute Toxicity:	0.421
Maximum Recommended Daily Dose:	0.312	Skin Sensitization:	0.752
Carcinogencity:	0.688	Eye Corrosion:	0.855
Eye Irritation:	0.987	Respiratory Toxicity:	0.654
Drug-induced Neurotoxicity:	0.785	Ototoxicity:	0.191
Hematotoxicity:	0.29	Drug-induced Nephrotoxicity:	0.437
Genotoxicity:	0.452	RPMI-8226 Immunitoxicity:	0.077
A549 Cytotoxicity:	0.063	Hek293 Cytotoxicity:	0.137
BCF:	1.024 ? 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:	3.627 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.994 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.583 ? 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
NPO15892	Euphorbia quinquecostata	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[12350147]
NPO12006	Apis mellifera	Species	Apidae	Eukaryota	n.a.	n.a.	n.a.	PMID[17548953]
NPO13379	Schizanthus tricolor	Species	Solanaceae	Eukaryota	Aerial parts	n.a.	n.a.	PMID[20166702]
NPO11266	Garcinia cambogia	Species	Clusiaceae	Eukaryota	n.a.	exocarp	n.a.	PMID[21114277]
NPO13379	Schizanthus tricolor	Species	Solanaceae	Eukaryota	n.a.	aerial part	n.a.	PMID[21171571]
NPO12006	Apis mellifera	Species	Apidae	Eukaryota	n.a.	n.a.	n.a.	PMID[24675423]
NPO12006	Apis mellifera	Species	Apidae	Eukaryota	n.a.	Bako, Ethiopia		PMID[24926420]
NPO12006	Apis mellifera	Species	Apidae	Eukaryota	n.a.	Enemore, Ethiopia		PMID[24926420]
NPO12006	Apis mellifera	Species	Apidae	Eukaryota	n.a.	Gedo, Ethiopia		PMID[24926420]
NPO12006	Apis mellifera	Species	Apidae	Eukaryota	n.a.	Holleta, Ethiopia		PMID[24926420]
NPO3013	Clathria basilana	Species	Microcionidae	Eukaryota	n.a.	n.a.	n.a.	PMID[29094598]
NPO15892	Euphorbia quinquecostata	Species	Euphorbiaceae	Eukaryota	stem wood	n.a.	n.a.	PMID[8946746]
NPO13178	Ornithoglossum viride	Species	Colchicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO26871	Volkameria inermis	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO15892	Euphorbia quinquecostata	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12521	Sphaeranthus confertifolius	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13379	Schizanthus tricolor	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO5280	Rubia tetragona	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO14470	Polypodium decumanum	Species	Polypodiidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO14369	Pocillopora eydouxi	Species	Pocilloporidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO11842	Petasites laevigatus	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO4700	Pertusaria truncata	Species	Pertusariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO9569	Licaria chrysophylla	Species	Lauraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO14169	Acrocarpia paniculata	Species	Sargassaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13473	Anodendron affine	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12006	Apis mellifera	Species	Apidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13876	Cedrela salvadorensis	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO3013	Clathria basilana	Species	Microcionidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7541	Ormosia hosiei	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO11266	Garcinia cambogia	Species	Clusiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13669	Hertia cheirifolia	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7541	Ormosia hosiei	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO11842	Petasites laevigatus	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO12006	Apis mellifera	Species	Apidae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO13473	Anodendron affine	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO11266	Garcinia cambogia	Species	Clusiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO11266	Garcinia cambogia	Species	Clusiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO13473	Anodendron affine	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO26871	Volkameria inermis	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO7541	Ormosia hosiei	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO11842	Petasites laevigatus	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO7541	Ormosia hosiei	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO12006	Apis mellifera	Species	Apidae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO14470	Polypodium decumanum	Species	Polypodiidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13379	Schizanthus tricolor	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO11842	Petasites laevigatus	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO15892	Euphorbia quinquecostata	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO3013	Clathria basilana	Species	Microcionidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12521	Sphaeranthus confertifolius	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO4700	Pertusaria truncata	Species	Pertusariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO14369	Pocillopora eydouxi	Species	Pocilloporidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12006	Apis mellifera	Species	Apidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO5280	Rubia tetragona	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO14169	Acrocarpia paniculata	Species	Sargassaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13178	Ornithoglossum viride	Species	Colchicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13876	Cedrela salvadorensis	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13473	Anodendron affine	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO9569	Licaria chrysophylla	Species	Lauraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO7541	Ormosia hosiei	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13669	Hertia cheirifolia	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO26871	Volkameria inermis	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO11266	Garcinia cambogia	Species	Clusiaceae	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

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
CD	1
Activity	1
IC50	2
EC50	1
MIC	14

Activity Type	# Activity
Individual protein	1
Cell line	1
Organism	15
Protein family	1
Others	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT440	Individual protein	Quinone oxidoreductase	Mus musculus	CD	=	9.5	ug ml-1	PMID[12350147]
NPT664	Protein family	Histone deacetylase	Homo sapiens	Activity	=	80.0	%	PMID[25042254]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT759	Cell line	H9	Homo sapiens	IC50	=	18.9	ug.mL-1	PMID[11678650]
NPT729	Organism	Micrococcus luteus	Micrococcus luteus	MIC	=	2600000.0	nM	DOI[10.1007/s00044-013-0484-9]
NPT21	Organism	Aspergillus niger	Aspergillus niger	MIC	=	5200000.0	nM	DOI[10.1007/s00044-013-0484-9]
NPT1264	Organism	Burkholderia cepacia	Burkholderia cepacia	MIC	=	5200000.0	nM	DOI[10.1007/s00044-013-0484-9]
NPT1033	Organism	Enterobacter cloacae	Enterobacter cloacae	MIC	=	10400000.0	nM	DOI[10.1007/s00044-013-0484-9]
NPT20	Organism	Candida albicans	Candida albicans	MIC	=	2600000.0	nM	DOI[10.1007/s00044-013-0484-9]
NPT79	Organism	Bacillus subtilis	Bacillus subtilis	MIC	=	5200000.0	nM	DOI[10.1007/s00044-013-0484-9]
NPT1262	Organism	Aspergillus parasiticus	Aspergillus parasiticus	MIC	=	2600000.0	nM	DOI[10.1007/s00044-013-0484-9]
NPT329	Organism	Trichophyton rubrum	Trichophyton rubrum	MIC	=	2600000.0	nM	DOI[10.1007/s00044-013-0484-9]
NPT173	Organism	Klebsiella pneumoniae	Klebsiella pneumoniae	MIC	=	10400000.0	nM	DOI[10.1007/s00044-013-0484-9]
NPT24	Organism	Human immunodeficiency virus 1	Human immunodeficiency virus 1	EC50	=	2.19	ug.mL-1	PMID[11678650]
NPT187	Organism	Issatchenkia orientalis	Pichia kudriavzevii	MIC	=	2600000.0	nM	DOI[10.1007/s00044-013-0484-9]
NPT1263	Organism	Aspergillus sydowii	Aspergillus sydowii	MIC	=	5200000.0	nM	DOI[10.1007/s00044-013-0484-9]
NPT18	Organism	Pseudomonas aeruginosa	Pseudomonas aeruginosa	MIC	=	2600000.0	nM	DOI[10.1007/s00044-013-0484-9]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	MIC	=	5200000.0	nM	DOI[10.1007/s00044-013-0484-9]
NPT19	Organism	Escherichia coli	Escherichia coli	MIC	=	10400000.0	nM	DOI[10.1007/s00044-013-0484-9]
NPT2	Others	Unspecified	n.a.	IC50	=	2.3	ug.mL-1	PMID[12350147]

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 NPC179309 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	28546
0.1-0.2	18073
0.2-0.3	2766
0.3-0.4	363
0.4-0.5	75
0.5-0.6	18
0.6-0.7	4
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
0.7419	Intermediate Similarity	NPC310905
0.7097	Intermediate Similarity	NPC13755
0.6857	Remote Similarity	NPC111225
0.6571	Remote Similarity	NPC227894
0.6571	Remote Similarity	NPC185738
0.6111	Remote Similarity	NPC245552
0.5833	Remote Similarity	NPC479110
0.5789	Remote Similarity	NPC294941
0.5641	Remote Similarity	NPC39793
0.5405	Remote Similarity	NPC123948
0.5405	Remote Similarity	NPC271985
0.5405	Remote Similarity	NPC96122
0.5385	Remote Similarity	NPC479111
0.5366	Remote Similarity	NPC258171
0.5349	Remote Similarity	NPC483672
0.5294	Remote Similarity	NPC55040
0.5238	Remote Similarity	NPC483674
0.5227	Remote Similarity	NPC38403
0.5227	Remote Similarity	NPC280001
0.5111	Remote Similarity	NPC607239
0.5094	Remote Similarity	NPC476387
0.5094	Remote Similarity	NPC249791
0.5094	Remote Similarity	NPC237594
0.5094	Remote Similarity	NPC119060

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC179309 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4386
0.1-0.2	4523
0.2-0.3	220
0.3-0.4	14
0.4-0.5	6
0.5-0.6	0
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	Drug ID	Developmental Stage
0.6571	Remote Similarity	NPD5536	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