NPASS Compound

Natural Product: NPC204848

Natural Product ID	NPC204848
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(R)-N-Trans-Feruloyloctopamine
IUPAC Name	(E)-N-[(2R)-2-hydroxy-2-(4-hydroxyphenyl)ethyl]-3-(4-hydroxy-3-methoxyphenyl)prop-2-enamide
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1802149
PubChem CID	11151622
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000476] Cinnamic acids and derivatives [CHEMONTID:0001391] Hydroxycinnamic 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 43 44 0 0 0 0 0 0 0 0999 V2000 -5.5594 1.0791 -3.0942 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8265 1.4145 -1.7460 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.8491 1.0788 -0.8070 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6822 0.4558 -1.1493 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7187 0.1299 -0.1905 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9328 0.4343 1.1245 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1216 1.0706 1.4844 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0568 1.3828 0.5267 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2523 2.0189 0.8632 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.5162 -0.5264 -0.6362 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5723 -0.8580 0.2209 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6192 -1.5298 -0.3618 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5442 -1.8571 0.4582 N 0 0 0 0 0 0 0 0 0 0 0 0 2.7318 -2.5137 -0.0393 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5705 -1.4315 -0.7304 C 0 0 1 0 0 0 0 0 0 0 0 0 3.8416 -0.4029 0.2906 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7694 -0.6321 1.2656 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0154 0.3281 2.2100 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3188 1.5187 2.1624 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3812 1.7769 1.1950 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1568 0.7855 0.2557 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5846 2.4828 3.1336 O 0 0 0 0 0 0 0 0 0 0 0 0 4.7423 -1.9888 -1.2420 O 0 0 0 0 0 0 0 0 0 0 0 0 0.7351 -1.7911 -1.7021 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.4642 1.2892 -3.7054 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3294 0.0027 -3.1252 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6854 1.6952 -3.4215 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5179 0.2156 -2.2026 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2143 0.2044 1.9260 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2999 1.3174 2.5354 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9177 1.5420 1.4576 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3886 -0.7516 -1.7068 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6214 -0.6728 1.2810 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5439 -3.3778 -0.6848 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3275 -2.9003 0.8229 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9494 -1.0449 -1.5596 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3287 -1.5582 1.3239 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7635 0.1377 2.9924 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8226 2.6792 1.1215 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4313 0.9337 -0.5275 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5530 3.4441 2.8708 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5752 -2.9468 -1.4274 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2208 -2.6346 -2.0261 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 5 10 1 0 10 11 2 0 11 12 1 0 12 13 2 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 2 0 19 20 1 0 20 21 2 0 19 22 1 0 15 23 1 0 12 24 1 0 8 3 1 0 21 16 1 0 1 25 1 0 1 26 1 0 1 27 1 0 4 28 1 0 6 29 1 0 7 30 1 0 9 31 1 0 10 32 1 0 11 33 1 0 14 34 1 0 14 35 1 0 15 36 1 6 17 37 1 0 18 38 1 0 20 39 1 0 21 40 1 0 22 41 1 0 23 42 1 0 24 43 1 0 M END

Standard InCHIKey	VJSCHQMOTSXAKB-CFZDNBDDSA-N
Standard InCHI	InChI=1S/C18H19NO5/c1-24-17-10-12(2-8-15(17)21)3-9-18(23)19-11-16(22)13-4-6-14(20)7-5-13/h2-10,16,20-22H,11H2,1H3,(H,19,23)/b9-3+/t16-/m0/s1
SMILES	COc1cc(ccc1O)/C=C/C(=NC[C@@H](c1ccc(cc1)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	329.13	Volume:	336.627 ? Van der Waals volume.
Dense:	0.978	LogP:	1.646 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.816 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.227 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	14.0
TPSA:	102.51 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	4.0	Rings:	2.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.482	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.068	Fsp³:	0.167
MCE-18:	26.0 ? 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:	1	PAINS Alert:	0
Colloidal aggregators:	0.881	Fluc inhibitor:	1.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.108 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.505 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.02	Promiscuous compounds:	0.333

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.211	MDCK Permeability:	-4.893
Pgp-inhibitor:	0.0	Pgp-substrate:	0.355
PAMPA:	0.851 ? 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):	0.0
20% Bioavailability (F20%):	0.925	30% Bioavailability (F30%):	0.987
50% Bioavailability (F50%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.097
Plasma Protein Binding (PPB):	67.39%	Volume Distribution (VD):	-0.092
Fu:	31.891% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.848
OATP1B3 inhibitor:	0.998	BCRP inhibitor:	0.398
BSEP inhibitor:	0.085

ADMET: Metabolism

CYP1A2-inhibitor:	0.001	CYP1A2-substrate:	0.08
CYP2C19-inhibitor:	0.008	CYP2C19-substrate:	0.761
CYP2C9-inhibitor:	0.001	CYP2C9-substrate:	0.398
CYP2D6-inhibitor:	0.996	CYP2D6-substrate:	0.583
CYP3A4-inhibitor:	0.014	CYP3A4-substrate:	0.492
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.544
HLM stability:	0.901 ? 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):

10.208

Half-life (T1/2):

1.689

ADMET: Toxicity

hERG Blockers:	0.121	hERG Blockers (10um):	0.308
Human Hepatotoxicity (H-HT):	0.834	Drug-induced Liver Injury (DILI):	0.27
AMES Toxicity:	0.699	Rat Oral Acute Toxicity:	0.424
Maximum Recommended Daily Dose:	0.744	Skin Sensitization:	0.993
Carcinogencity:	0.801	Eye Corrosion:	0.001
Eye Irritation:	0.822	Respiratory Toxicity:	0.804
Drug-induced Neurotoxicity:	0.553	Ototoxicity:	0.336
Hematotoxicity:	0.06	Drug-induced Nephrotoxicity:	0.507
Genotoxicity:	0.828	RPMI-8226 Immunitoxicity:	0.024
A549 Cytotoxicity:	0.235	Hek293 Cytotoxicity:	0.617
BCF:	0.511 ? 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:	2.889 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	3.83 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.24 ? 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
NPO28141	Colpomenia sinuosa	Species	Scytosiphonaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1021/np50097a033]
NPO28608	Olea europaea	Species	Oleaceae	Eukaryota	n.a.	fruit	n.a.	PMID[12802735]
NPO28608	Olea europaea	Species	Oleaceae	Eukaryota	n.a.	fruit	n.a.	PMID[18384095]
NPO25983	Pisonia aculeata	Species	Nyctaginaceae	Eukaryota	n.a.	root	n.a.	PMID[21542597]
NPO25983	Pisonia aculeata	Species	Nyctaginaceae	Eukaryota	n.a.	stem	n.a.	PMID[21542597]
NPO25983	Pisonia aculeata	Species	Nyctaginaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21542597]
NPO28608	Olea europaea	Species	Oleaceae	Eukaryota	n.a.	fruit	n.a.	PMID[22014120]
NPO28608	Olea europaea	Species	Oleaceae	Eukaryota	n.a.	leaf	n.a.	PMID[22014120]
NPO28608	Olea europaea	Species	Oleaceae	Eukaryota	n.a.	leaf	n.a.	PMID[22014168]
NPO28608	Olea europaea	Species	Oleaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[23540838]
NPO28608	Olea europaea	Species	Oleaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[24295708]
NPO28608	Olea europaea	Species	Oleaceae	Eukaryota	n.a.	leaf	n.a.	PMID[25102361]
NPO28608	Olea europaea	Species	Oleaceae	Eukaryota	n.a.	fruit	n.a.	PMID[25306330]
NPO21355	Elsholtzia ciliata	Species	Lamiaceae	Eukaryota	Aerial Parts	n.a.	n.a.	PMID[32991171]
NPO28608	Olea europaea	Species	Oleaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[35986990]
NPO28608	Olea europaea	Species	Oleaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[36770740]
NPO28608	Olea europaea	Species	Oleaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[36985747]
NPO28608	Olea europaea	Species	Oleaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[37087263]
NPO28608	Olea europaea	Species	Oleaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[37924762]
NPO28608	Olea europaea	Species	Oleaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[38306771]
NPO28608	Olea europaea	Species	Oleaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[38474614]
NPO21557	Woodsia manchuriensis	Species	Woodsiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO28556	Streptomyces pentaticus	Species	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	Database[COCONUT]
NPO28646	Streptomyces argenteolus	Species	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	Database[COCONUT]
NPO28422	Sabia japonica	Species	Sabiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO28195	Phlogacanthus tubiflorus	Species	Acanthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO20714	Lobophytum schoedei	Species	Alcyoniidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO27905	Eritrichium sericeum	Species	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO28141	Colpomenia sinuosa	Species	Scytosiphonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO28070	Chrysosplenium americanum	Species	Saxifragaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO23326	Bohadschia vitiensis	Species	Holothuriidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO27829	Aplophyllum pedicellatum	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[COCONUT]
NPO28263	Anemone tomentosa	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO21355	Elsholtzia ciliata	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO28608	Olea europaea	Species	Oleaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO25983	Pisonia aculeata	Species	Nyctaginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO28608	Olea europaea	Species	Oleaceae	Eukaryota	Fruit	n.a.	n.a.	Database[FooDB]
NPO28608	Olea europaea	Species	Oleaceae	Eukaryota	Oil	n.a.	n.a.	Database[FooDB]
NPO28608	Olea europaea	Species	Oleaceae	Eukaryota		n.a.	n.a.	Database[FooDB]
NPO28608	Olea europaea	Species	Oleaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO21355	Elsholtzia ciliata	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO28608	Olea europaea	Species	Oleaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO21355	Elsholtzia ciliata	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO28608	Olea europaea	Species	Oleaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO21355	Elsholtzia ciliata	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO21355	Elsholtzia ciliata	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO28646	Streptomyces argenteolus	Species	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	Database[UNPD]
NPO28070	Chrysosplenium americanum	Species	Saxifragaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28422	Sabia japonica	Species	Sabiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO23326	Bohadschia vitiensis	Species	Holothuriidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28608	Olea europaea	Species	Oleaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO20714	Lobophytum schoedei	Species	Alcyoniidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO21557	Woodsia manchuriensis	Species	Woodsiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28195	Phlogacanthus tubiflorus	Species	Acanthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28141	Colpomenia sinuosa	Species	Scytosiphonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO27829	Aplophyllum pedicellatum	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[UNPD]
NPO27905	Eritrichium sericeum	Species	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO25983	Pisonia aculeata	Species	Nyctaginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28556	Streptomyces pentaticus	Species	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	Database[UNPD]
NPO28263	Anemone tomentosa	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO21355	Elsholtzia ciliata	Species	Lamiaceae	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
MIC	1
EC50	1

Activity Type	# Activity
Cell line	1
Organism	1

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
NPT804	Cell line	HT-22	Mus musculus	EC50	=	32300.0	nM	PMID[32991171]
NPT790	Organism	Mycobacterium tuberculosis H37Rv	Mycobacterium tuberculosis H37Rv	MIC	=	50.0	ug.mL-1	PMID[21542597]

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 NPC204848 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	24863
0.1-0.2	20848
0.2-0.3	3606
0.3-0.4	455
0.4-0.5	61
0.5-0.6	7
0.6-0.7	8
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	3

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC160607
1.0	High Similarity	NPC41473
1.0	High Similarity	NPC312770
0.7586	Intermediate Similarity	NPC14600
0.6949	Remote Similarity	NPC195749
0.6949	Remote Similarity	NPC35961
0.6721	Remote Similarity	NPC153644
0.6721	Remote Similarity	NPC299583
0.6667	Remote Similarity	NPC186898
0.6333	Remote Similarity	NPC214869
0.6129	Remote Similarity	NPC178571
0.6129	Remote Similarity	NPC155838
0.5738	Remote Similarity	NPC62101
0.5738	Remote Similarity	NPC95733
0.5556	Remote Similarity	NPC61879
0.5556	Remote Similarity	NPC296898
0.5152	Remote Similarity	NPC52029
0.5085	Remote Similarity	NPC14007
0.5065	Remote Similarity	NPC266931

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC204848 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3955
0.1-0.2	4989
0.2-0.3	196
0.3-0.4	9
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	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