NPASS Compound

Natural Product: NPC209614

Natural Product ID	NPC209614
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	3'-O-Methyl-5'-Methoxydiplacone
IUPAC Name	(2S)-6-[(2E)-3,7-dimethylocta-2,6-dienyl]-5,7-dihydroxy-2-(4-hydroxy-3,5-dimethoxyphenyl)-2,3-dihydrochromen-4-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL463842
PubChem CID	24854123
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0000337] Flavans [CHEMONTID:0003646] 6-prenylated flavans [CHEMONTID:0003507] 6-prenylated flavanones

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 66 68 0 0 0 0 0 0 0 0999 V2000 -5.4846 -3.6988 -0.2151 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6447 -2.9311 0.0271 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.5020 -1.5674 0.2223 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2563 -0.9851 0.1787 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0863 0.3685 0.3696 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2068 1.1179 0.6054 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.4848 0.6097 0.6639 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.6102 -0.7505 0.4672 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.8551 -1.3590 0.5068 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.6215 1.3706 0.9034 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.4331 2.7601 1.0981 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7732 1.0365 0.3296 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.4296 1.3327 -1.0916 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9709 1.3104 -1.3605 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5621 1.6450 -2.4896 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.9774 0.9175 -0.3757 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4257 0.4167 0.8271 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7796 0.3165 1.0295 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.4847 0.0404 1.7693 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8828 0.1372 1.5746 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3201 0.6373 0.3728 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3761 1.0208 -0.5865 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8161 1.5255 -1.7994 O 0 0 0 0 0 0 0 0 0 0 0 0 2.7626 0.7627 0.0994 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3567 -0.5422 -0.2146 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3786 -1.0235 0.4761 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8985 -2.3538 0.0719 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3416 -2.2301 -0.3485 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5314 -1.3269 -1.4875 C 0 0 0 0 0 0 0 0 0 0 0 0 7.3478 -0.2928 -1.4133 C 0 0 0 0 0 0 0 0 0 0 0 0 7.4912 0.5986 -2.6335 C 0 0 0 0 0 0 0 0 0 0 0 0 8.1599 0.0673 -0.2163 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0045 -0.3152 1.5969 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7346 -0.2726 2.5957 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.7166 -4.7395 -0.4994 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8113 -3.7202 0.6839 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8811 -3.2695 -1.0615 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3503 -1.5613 -0.0074 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1147 2.1909 0.7613 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.6846 -0.7623 0.4448 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8332 3.1470 0.2257 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.3957 3.3093 1.1297 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8394 2.9958 1.9995 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8761 2.0018 0.9063 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9671 0.7012 -1.8361 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7609 2.3825 -1.3165 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8487 -0.3448 2.6943 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8198 1.0160 -2.6570 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3053 1.3164 0.8906 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8759 1.4038 -0.8220 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9367 -1.1328 -1.0492 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3373 -2.7938 -0.7833 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8494 -3.1020 0.8890 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6509 -3.2577 -0.6830 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9903 -1.9461 0.4771 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0040 -1.4709 -2.4490 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4853 1.0640 -2.6435 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6690 1.3678 -2.5681 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3358 -0.0013 -3.5535 H 0 0 0 0 0 0 0 0 0 0 0 0 8.6482 -0.8687 0.1500 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5922 0.4936 0.6097 H 0 0 0 0 0 0 0 0 0 0 0 0 8.9925 0.7366 -0.5412 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0071 -0.7856 1.8351 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2279 0.7501 1.3937 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4415 -0.4248 2.5458 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0970 0.3627 3.2808 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 7 10 1 0 10 11 1 0 5 12 1 0 12 13 1 0 13 14 1 0 14 15 2 0 14 16 1 0 16 17 2 0 17 18 1 0 17 19 1 0 19 20 2 0 20 21 1 0 21 22 2 0 22 23 1 0 21 24 1 0 24 25 1 0 25 26 2 0 26 27 1 0 27 28 1 0 28 29 1 0 29 30 2 3 30 31 1 0 30 32 1 0 26 33 1 0 20 34 1 0 8 3 1 0 18 12 1 0 22 16 1 0 1 35 1 0 1 36 1 0 1 37 1 0 4 38 1 0 6 39 1 0 9 40 1 0 11 41 1 0 11 42 1 0 11 43 1 0 12 44 1 1 13 45 1 0 13 46 1 0 19 47 1 0 23 48 1 0 24 49 1 0 24 50 1 0 25 51 1 0 27 52 1 0 27 53 1 0 28 54 1 0 28 55 1 0 29 56 1 0 31 57 1 0 31 58 1 0 31 59 1 0 32 60 1 0 32 61 1 0 32 62 1 0 33 63 1 0 33 64 1 0 33 65 1 0 34 66 1 0 M END

Standard InCHIKey	UPBJEHBYZUPVDF-JUALLIRVSA-N
Standard InCHI	InChI=1S/C27H32O7/c1-15(2)7-6-8-16(3)9-10-18-19(28)13-22-25(26(18)30)20(29)14-21(34-22)17-11-23(32-4)27(31)24(12-17)33-5/h7,9,11-13,21,28,30-31H,6,8,10,14H2,1-5H3/b16-9+/t21-/m0/s1
SMILES	COc1cc(cc(c1O)OC)[C@@H]1CC(=O)c2c(O1)cc(c(c2O)C/C=C(/CCC=C(C)C)C)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	468.21	Volume:	487.682 ? Van der Waals volume.
Dense:	0.96	LogP:	5.918 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.972 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.721 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	8.0	Rigid Bonds:	20.0
TPSA:	105.45 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	3.0	Rings:	3.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.423	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.494	Fsp³:	0.37
MCE-18:	68.378 ? 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:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	1
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.825	Fluc inhibitor:	0.623 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.467 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.75 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.294	Promiscuous compounds:	0.166

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.099	MDCK Permeability:	-4.738
Pgp-inhibitor:	1.0	Pgp-substrate:	0.001
PAMPA:	0.001 ? 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):	0.004
20% Bioavailability (F20%):	0.01	30% Bioavailability (F30%):	0.197
50% Bioavailability (F50%):	0.994

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.898
Plasma Protein Binding (PPB):	97.418%	Volume Distribution (VD):	0.054
Fu:	2.15% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.945
BSEP inhibitor:	0.999

ADMET: Metabolism

CYP1A2-inhibitor:	0.109	CYP1A2-substrate:	0.997
CYP2C19-inhibitor:	0.998	CYP2C19-substrate:	0.748
CYP2C9-inhibitor:	0.742	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.143	CYP2D6-substrate:	0.912
CYP3A4-inhibitor:	0.04	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.996 ? 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):

5.38

Half-life (T1/2):

1.324

ADMET: Toxicity

hERG Blockers:	0.074	hERG Blockers (10um):	0.538
Human Hepatotoxicity (H-HT):	0.862	Drug-induced Liver Injury (DILI):	0.937
AMES Toxicity:	0.361	Rat Oral Acute Toxicity:	0.763
Maximum Recommended Daily Dose:	0.67	Skin Sensitization:	0.966
Carcinogencity:	0.468	Eye Corrosion:	0.0
Eye Irritation:	0.697	Respiratory Toxicity:	0.986
Drug-induced Neurotoxicity:	0.61	Ototoxicity:	0.58
Hematotoxicity:	0.424	Drug-induced Nephrotoxicity:	0.847
Genotoxicity:	0.954	RPMI-8226 Immunitoxicity:	0.439
A549 Cytotoxicity:	0.902	Hek293 Cytotoxicity:	0.659
BCF:	2.106 ? 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:	5.033 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.473 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.932 ? 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
NPO22079	Paulownia tomentosa	Species	Paulowniaceae	Eukaryota	fruits	n.a.	n.a.	PMID[17625893]
NPO22079	Paulownia tomentosa	Species	Paulowniaceae	Eukaryota	Fruits	n.a.	n.a.	PMID[18293924]
NPO22079	Paulownia tomentosa	Species	Paulowniaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[20192247]
NPO22079	Paulownia tomentosa	Species	Paulowniaceae	Eukaryota	n.a.	fruit	n.a.	PMID[21319773]
NPO22079	Paulownia tomentosa	Species	Paulowniaceae	Eukaryota	fruits	n.a.	n.a.	PMID[22445674]
NPO22079	Paulownia tomentosa	Species	Paulowniaceae	Eukaryota	fruits	n.a.	n.a.	PMID[23623680]
NPO22079	Paulownia tomentosa	Species	Paulowniaceae	Eukaryota	fruits	n.a.	n.a.	PMID[25735399]
NPO22079	Paulownia tomentosa	Species	Paulowniaceae	Eukaryota	Fruits	n.a.	n.a.	PMID[28322565]
NPO22079	Paulownia tomentosa	Species	Paulowniaceae	Eukaryota	Fruits	n.a.	n.a.	PMID[28968119]
NPO22079	Paulownia tomentosa	Species	Paulowniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO22079	Paulownia tomentosa	Species	Paulowniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO22079	Paulownia tomentosa	Species	Paulowniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO22079	Paulownia tomentosa	Species	Paulowniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO22079	Paulownia tomentosa	Species	Paulowniaceae	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
IC50	4
MIC	10
EC50	7
Ki	1

Activity Type	# Activity
Individual protein	2
Cell line	8
Organism	10
Others	2

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT279	Individual protein	Leukocyte elastase	Homo sapiens	IC50	=	71300.0	nM	PMID[28968119]
NPT570	Individual protein	Arachidonate 5-lipoxygenase	Homo sapiens	IC50	=	380.0	nM	PMID[28322565]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT83	Cell line	MCF7	Homo sapiens	EC50	>	10000.0	nM	PMID[9358638]
NPT404	Cell line	CCRF-CEM	Homo sapiens	EC50	>	10000.0	nM	DrugMatrix in vitro pharmacology data
NPT389	Cell line	RPMI-8226	Homo sapiens	EC50	>	10000.0	nM	PMID[9461657]
NPT2015	Cell line	U-266	Homo sapiens	EC50	>	10000.0	nM	PubChem BioAssay data set
NPT165	Cell line	HeLa	Homo sapiens	EC50	>	10000.0	nM	PMID[23398362]
NPT1160	Cell line	BJ	Homo sapiens	EC50	>	10000.0	nM	PMID[22019188]
NPT1970	Cell line	THP-1	Homo sapiens	EC50	>	10000.0	nM	PMID[12408708]
NPT1970	Cell line	THP-1	Homo sapiens	IC50	<	10000.0	nM	PMID[1791472]
NPT20	Organism	Candida albicans	Candida albicans	MIC	>	32.0	ug.mL-1	PMID[8258833]
NPT79	Organism	Bacillus subtilis	Bacillus subtilis	MIC	=	4.0	ug.mL-1	PMID[16562846]
NPT564	Organism	Listeria monocytogenes	Listeria monocytogenes	MIC	=	4.0	ug.mL-1	PMID[25990761]
NPT19	Organism	Escherichia coli	Escherichia coli	MIC	>	32.0	ug.mL-1	PMID[20594858]
NPT18	Organism	Pseudomonas aeruginosa	Pseudomonas aeruginosa	MIC	>	32.0	ug.mL-1	DrugMatrix in vitro pharmacology data
NPT175	Organism	Enterococcus faecalis	Enterococcus faecalis	MIC	=	4.0	ug.mL-1	PMID[24261937]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	MIC	=	4.0	ug.mL-1	PMID[21761866]
NPT17	Organism	Staphylococcus epidermidis	Staphylococcus epidermidis	MIC	=	4.0	ug.mL-1	PMID[21761866]
NPT3608	Organism	Salmonella enteritidis	Salmonella enterica subsp. enterica serovar Enteritidis	MIC	>	32.0	ug.mL-1	DrugMatrix in vitro pharmacology data
NPT314	Organism	Bacillus cereus	Bacillus cereus	MIC	=	4.0	ug.mL-1	PMID[19651906]
NPT2	Others	Unspecified	n.a.	Ki	=	8400.0	nM	PMID[12088420]
NPT2	Others	Unspecified	n.a.	IC50	=	13900.0	nM	PMID[26147490]

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 NPC209614 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	18864
0.1-0.2	26509
0.2-0.3	3827
0.3-0.4	511
0.4-0.5	88
0.5-0.6	24
0.6-0.7	18
0.7-0.8	0
0.8-0.85	3
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC470328
0.8261	Intermediate Similarity	NPC45849
0.8261	Intermediate Similarity	NPC195796
0.806	Intermediate Similarity	NPC64915
0.7971	Intermediate Similarity	NPC226025
0.7971	Intermediate Similarity	NPC278778
0.7971	Intermediate Similarity	NPC488558
0.7941	Intermediate Similarity	NPC164272
0.7941	Intermediate Similarity	NPC470327
0.7857	Intermediate Similarity	NPC472630
0.7746	Intermediate Similarity	NPC472626
0.7746	Intermediate Similarity	NPC472631
0.7647	Intermediate Similarity	NPC290133
0.7647	Intermediate Similarity	NPC228504
0.7536	Intermediate Similarity	NPC213896
0.7324	Intermediate Similarity	NPC185276
0.7222	Intermediate Similarity	NPC298692
0.6857	Remote Similarity	NPC35038
0.6623	Remote Similarity	NPC488555
0.6623	Remote Similarity	NPC484418
0.6579	Remote Similarity	NPC210459
0.6538	Remote Similarity	NPC474055
0.6456	Remote Similarity	NPC472634
0.641	Remote Similarity	NPC287328
0.6364	Remote Similarity	NPC488557
0.6324	Remote Similarity	NPC1089
0.6282	Remote Similarity	NPC27337
0.6282	Remote Similarity	NPC472598
0.625	Remote Similarity	NPC223787
0.6234	Remote Similarity	NPC488554
0.6154	Remote Similarity	NPC282009
0.6104	Remote Similarity	NPC470326
0.6056	Remote Similarity	NPC125855
0.6053	Remote Similarity	NPC488556
0.6026	Remote Similarity	NPC472628
0.5974	Remote Similarity	NPC472627
0.5974	Remote Similarity	NPC58805
0.5974	Remote Similarity	NPC261063
0.5921	Remote Similarity	NPC279650
0.5897	Remote Similarity	NPC321779
0.5844	Remote Similarity	NPC262039
0.5783	Remote Similarity	NPC321399
0.5769	Remote Similarity	NPC22192
0.5714	Remote Similarity	NPC472629
0.5616	Remote Similarity	NPC223500
0.5616	Remote Similarity	NPC166689
0.557	Remote Similarity	NPC488549
0.5526	Remote Similarity	NPC477242
0.55	Remote Similarity	NPC201800
0.5385	Remote Similarity	NPC96408
0.5385	Remote Similarity	NPC610511
0.5375	Remote Similarity	NPC299436
0.5195	Remote Similarity	NPC200761
0.5176	Remote Similarity	NPC471499
0.5128	Remote Similarity	NPC24136
0.5122	Remote Similarity	NPC67396
0.5116	Remote Similarity	NPC293319
0.5063	Remote Similarity	NPC166934
0.5062	Remote Similarity	NPC267375

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC209614 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4335
0.1-0.2	4752
0.2-0.3	57
0.3-0.4	5
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