NPASS Compound

Natural Product: NPC260474

Natural Product ID	NPC260474
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Avarone
IUPAC Name	2-[[(1R,2S,4aS,8aS)-1,2,4a,5-tetramethyl-2,3,4,7,8,8a-hexahydronaphthalen-1-yl]methyl]cyclohexa-2,5-diene-1,4-dione
Synonyms	Avarone; Avrone
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL464645
PubChem CID	72186
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001534] Quinone and hydroquinone lipids [CHEMONTID:0002802] Prenylquinones

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 51 53 0 0 0 0 0 0 0 0999 V2000 -3.5829 0.6407 -1.8927 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4644 1.0413 -0.9997 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9963 2.2644 -1.0791 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8826 2.8151 -0.2552 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4895 1.8020 0.8391 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4867 0.4564 0.2064 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.9001 0.0230 -0.0253 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.8104 0.0118 1.1405 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0094 -1.3087 -0.7137 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2641 -2.3021 0.0993 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2279 -1.8833 0.2449 C 0 0 2 0 0 0 0 0 0 0 0 0 0.8432 -3.0620 0.9034 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3883 -0.5769 0.8885 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.1465 -0.7570 2.3526 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7735 -0.1266 1.0844 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6524 0.2528 -0.0049 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0429 1.5472 -0.0706 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9270 2.0442 -1.1121 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2868 3.2511 -1.1779 O 0 0 0 0 0 0 0 0 0 0 0 0 4.4416 1.1533 -2.1390 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0827 -0.1106 -2.0925 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1782 -0.6068 -1.0258 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9395 -1.8333 -1.1140 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.2721 -0.0754 -1.4011 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2059 0.1111 -2.8113 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2099 1.5090 -2.1917 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4399 2.9476 -1.7947 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1804 3.7553 0.2325 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0027 3.0140 -0.8871 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4414 2.1659 1.2559 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2597 1.9606 1.6258 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0323 0.5802 -0.8204 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1622 -1.0316 1.4128 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4684 0.4405 2.0738 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7942 0.5319 0.9249 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5553 -1.2374 -1.7207 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0485 -1.6199 -0.7934 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1811 -3.2370 -0.5385 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6914 -2.6235 1.0267 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4982 -1.7661 -0.8481 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1764 -3.5330 1.6663 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8182 -2.9384 1.3542 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9673 -3.8544 0.1066 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2086 0.2124 2.8436 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0059 -1.4040 2.3939 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6873 -1.3219 2.8653 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2704 -0.9888 1.6918 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8346 0.6746 1.9167 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6915 2.2355 0.6856 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1118 1.5243 -2.9329 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4704 -0.7674 -2.8565 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 5 6 1 0 6 7 1 0 7 8 1 1 7 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 11 13 1 0 13 14 1 1 13 15 1 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 2 0 18 20 1 0 20 21 2 0 21 22 1 0 22 23 2 0 7 2 1 0 22 16 1 0 13 6 1 0 1 24 1 0 1 25 1 0 1 26 1 0 3 27 1 0 4 28 1 0 4 29 1 0 5 30 1 0 5 31 1 0 6 32 1 6 8 33 1 0 8 34 1 0 8 35 1 0 9 36 1 0 9 37 1 0 10 38 1 0 10 39 1 0 11 40 1 6 12 41 1 0 12 42 1 0 12 43 1 0 14 44 1 0 14 45 1 0 14 46 1 0 15 47 1 0 15 48 1 0 17 49 1 0 20 50 1 0 21 51 1 0 M END

Standard InCHIKey	VPRHEJGLNUDEEH-LWILDLIXSA-N
Standard InCHI	InChI=1S/C21H28O2/c1-14-6-5-7-19-20(14,3)11-10-15(2)21(19,4)13-16-12-17(22)8-9-18(16)23/h6,8-9,12,15,19H,5,7,10-11,13H2,1-4H3/t15-,19+,20+,21+/m0/s1
SMILES	CC1=CCC[C@@H]2[C@]1(C)CC[C@H](C)[C@@]2(C)CC1=CC(=O)C=CC1=O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	312.21	Volume:	350.501 ? Van der Waals volume.
Dense:	0.891	LogP:	3.663 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.422 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.117 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	19.0
TPSA:	34.14 ? Topological Polar Surface Area.	H-Bond Acceptor:	2.0
H-Bond Donor:	0.0	Rings:	3.0
Heavy Atoms:	2.0

MedChem Properties

QED Drug-Likeness Score:	0.541	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.25	Fsp³:	0.619
MCE-18:	51.882 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted	GSK Rule:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	1
Chelating Alert:	0	PAINS Alert:	1
Colloidal aggregators:	0.719	Fluc inhibitor:	0.959 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.035 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.003 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.895	Promiscuous compounds:	0.281

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.804	MDCK Permeability:	-4.665
Pgp-inhibitor:	0.279	Pgp-substrate:	0.002
PAMPA:	0.545 ? 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):	0.001
20% Bioavailability (F20%):	0.018	30% Bioavailability (F30%):	0.027
50% Bioavailability (F50%):	0.413

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.983	MRP1:	0.49
Plasma Protein Binding (PPB):	95.353%	Volume Distribution (VD):	0.453
Fu:	4.486% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.966
OATP1B3 inhibitor:	0.966	BCRP inhibitor:	0.036
BSEP inhibitor:	0.996

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.339
CYP2C19-inhibitor:	0.279	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.002	CYP2C9-substrate:	0.004
CYP2D6-inhibitor:	0.002	CYP2D6-substrate:	0.832
CYP3A4-inhibitor:	0.886	CYP3A4-substrate:	0.999
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.997
HLM stability:	0.995 ? 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):

10.81

Half-life (T1/2):

0.586

ADMET: Toxicity

hERG Blockers:	0.053	hERG Blockers (10um):	0.445
Human Hepatotoxicity (H-HT):	0.703	Drug-induced Liver Injury (DILI):	0.239
AMES Toxicity:	0.316	Rat Oral Acute Toxicity:	0.652
Maximum Recommended Daily Dose:	0.922	Skin Sensitization:	0.984
Carcinogencity:	0.931	Eye Corrosion:	0.972
Eye Irritation:	0.997	Respiratory Toxicity:	0.932
Drug-induced Neurotoxicity:	0.635	Ototoxicity:	0.126
Hematotoxicity:	0.549	Drug-induced Nephrotoxicity:	0.14
Genotoxicity:	0.717	RPMI-8226 Immunitoxicity:	0.05
A549 Cytotoxicity:	0.082	Hek293 Cytotoxicity:	0.752
BCF:	2.125 ? 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:	5.214 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.638 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	6.351 ? 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
NPO5563	Dysidea avara	Species	Dysideidae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1021/jo00050a043]
NPO26203	Dysidea villosa	Species	Dysideidae	Eukaryota	n.a.	Hainan, China	n.a.	PMID[19091557]
NPO5563	Dysidea avara	Species	Dysideidae	Eukaryota	n.a.	South China Sea	n.a.	PMID[24547794]
NPO5563	Dysidea avara	Species	Dysideidae	Eukaryota	n.a.	n.a.	n.a.	PMID[2778453]
NPO5563	Dysidea avara	Species	Dysideidae	Eukaryota	n.a.	Bay of Naples, Italy	n.a.	PMID[7714539]
NPO26203	Dysidea villosa	Species	Dysideidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO5563	Dysidea avara	Species	Dysideidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO26203	Dysidea villosa	Species	Dysideidae	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	15
IC50	23
Inhibition	2
IC30	3
Selectivity ratio	1
Activity	14

Activity Type	# Activity
Individual protein	1
Cell line	38
Organism	16
Others	1
Non-molecular	2

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT204	Individual protein	Acetylcholinesterase	Homo sapiens	MIC	=	1.0	ug	PMID[18426901]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT168	Cell line	P388	Mus musculus	IC50	=	3200.0	nM	PMID[19785430]
NPT81	Cell line	A549	Homo sapiens	IC50	=	6400.0	nM	PMID[17536859]
NPT139	Cell line	HT-29	Homo sapiens	IC50	=	6400.0	nM	PMID[22194678]
NPT170	Cell line	SK-MEL-28	Homo sapiens	IC50	=	6400.0	nM	PMID[19785430]
NPT168	Cell line	P388	Mus musculus	IC50	=	3100.0	nM	DrugMatrix in vitro pharmacology data
NPT81	Cell line	A549	Homo sapiens	IC50	=	6000.0	nM	DrugMatrix in vitro pharmacology data
NPT139	Cell line	HT-29	Homo sapiens	IC50	=	6000.0	nM	PMID[15217297]
NPT170	Cell line	SK-MEL-28	Homo sapiens	IC50	=	6000.0	nM	Open TG-GATES in vivo data: Biochemistry
NPT111	Cell line	K562	Homo sapiens	IC50	=	4900.0	nM	DrugMatrix in vitro pharmacology data
NPT165	Cell line	HeLa	Homo sapiens	IC50	=	26800.0	nM	PMID[19013823]
NPT927	Cell line	PBMC	Homo sapiens	IC50	=	4800.0	nM	PMID[17536859]
NPT927	Cell line	PBMC	Homo sapiens	IC50	=	4500.0	nM	PMID[26222693]
NPT81	Cell line	A549	Homo sapiens	IC50	=	30030.0	nM	DrugMatrix in vitro pharmacology data
NPT165	Cell line	HeLa	Homo sapiens	IC50	=	18120.0	nM	PMID[21044847]
NPT111	Cell line	K562	Homo sapiens	IC50	=	17080.0	nM	PMID[11689078]
NPT2488	Cell line	MDA-MB-453	Homo sapiens	IC50	=	16710.0	nM	PubChem BioAssay data set
NPT171	Cell line	MRC5	Homo sapiens	IC50	>	200000.0	nM	PMID[20028108]
NPT397	Cell line	NCI-H460	Homo sapiens	IC50	=	24000.0	nM	PMID[16562825]
NPT941	Cell line	HaCaT	Homo sapiens	IC30	=	16.0	uM	PMID[23176597]
NPT941	Cell line	HaCaT	Homo sapiens	IC50	=	37000.0	nM	PMID[24070022]
NPT397	Cell line	NCI-H460	Homo sapiens	IC30	=	36.0	uM	PMID[24070022]
NPT397	Cell line	NCI-H460	Homo sapiens	Selectivity ratio	<=	1.5	n.a.	PMID[27128177]
NPT397	Cell line	NCI-H460	Homo sapiens	Activity	=	74.0	%	PMID[19223646]
NPT397	Cell line	NCI-H460	Homo sapiens	Activity	=	3.4	%	PMID[17542634]
NPT397	Cell line	NCI-H460	Homo sapiens	Activity	=	16.3	%	DrugMatrix in vivo data: Hematology
NPT397	Cell line	NCI-H460	Homo sapiens	Activity	=	6.3	%	PMID[12105963]
NPT397	Cell line	NCI-H460	Homo sapiens	Activity	=	65.8	%	PMID[25650896]
NPT397	Cell line	NCI-H460	Homo sapiens	Activity	=	2.6	%	PMID[18356045]
NPT397	Cell line	NCI-H460	Homo sapiens	Activity	=	22.7	%	PMID[18278870]
NPT397	Cell line	NCI-H460	Homo sapiens	Activity	=	8.9	%	PMID[226705]
NPT941	Cell line	HaCaT	Homo sapiens	Activity	=	78.3	%	PMID[3560159]
NPT941	Cell line	HaCaT	Homo sapiens	Activity	=	2.5	%	PMID[23527875]
NPT941	Cell line	HaCaT	Homo sapiens	Activity	=	10.1	%	PMID[17420206]
NPT941	Cell line	HaCaT	Homo sapiens	Activity	=	9.1	%	PMID[24210499]
NPT397	Cell line	NCI-H460	Homo sapiens	IC50	=	84000.0	nM	PMID[20149652]
NPT397	Cell line	NCI-H460	Homo sapiens	IC30	=	10.0	uM	PMID[11520222]
NPT22	Organism	Bacillus subtilis subsp. spizizenii	Bacillus subtilis subsp. spizizenii	MIC	=	10.0	ug.mL-1	PMID[10649984]
NPT729	Organism	Micrococcus luteus	Micrococcus luteus	MIC	=	1.0	ug.mL-1	PMID[15686950]
NPT729	Organism	Micrococcus luteus	Micrococcus luteus	MIC	=	2000380.0	nM	PMID[20558060]
NPT1824	Organism	Clostridium sporogenes	Clostridium sporogenes	MIC	=	20030.0	nM	PMID[24219991]
NPT1190	Organism	Salmonella enterica	Salmonella enterica	MIC	=	55120.0	nM	PMID[19459694]
NPT141	Organism	Agrobacterium tumefaciens	Agrobacterium tumefaciens	Inhibition	=	63.0	%	PMID[21316959]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	23900.0	nM	PMID[19995673]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	40330.0	nM	PMID[26476666]
NPT79	Organism	Bacillus subtilis	Bacillus subtilis	MIC	=	80130.0	nM	PMID[25137549]
NPT3888	Organism	Micrococcus flavus	Micrococcus flavus	MIC	=	20030.0	nM	PMID[12762801]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	MIC	=	1.56	ug.mL-1	PMID[17724159]
NPT1	Others	Radical scavenging activity	n.a.	IC50	=	32100.0	nM	PMID[11809072]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	MIC	=	6.25	ug.mL-1	PMID[18986200]
NPT19	Organism	Escherichia coli	Escherichia coli	MIC	=	25.0	ug.mL-1	PMID[11374943]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	MIC	=	40060.0	nM	DrugMatrix in vivo data: Biochemistry
NPT19	Organism	Escherichia coli	Escherichia coli	MIC	=	440960.0	nM	PMID[20727622]
NPT18	Organism	Pseudomonas aeruginosa	Pseudomonas aeruginosa	MIC	=	13780.0	nM	PMID[10924160]
NPT20972	Cell line	SU.86.86	Homo sapiens	Activity	>	20.0	%	PMID[31980363]
NPT3147	Organism	Kocuria rhizophila	Kocuria rhizophila	MIC	=	20030.0	nM	PubChem BioAssay data set

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
-	Artemia	LC50	=	0.14	ppm	PMID[21334900]
-	Artemia salina	LC50	=	170.0	ppm	PMID[24900630]
-	Artemia salina	LC50	=	0.14	ppm	PMID[11809072]

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 NPC260474 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	26407
0.1-0.2	22025
0.2-0.3	1301
0.3-0.4	82
0.4-0.5	32
0.5-0.6	4
0.6-0.7	5
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
0.6863	Remote Similarity	NPC302761
0.6731	Remote Similarity	NPC108955
0.6481	Remote Similarity	NPC602754
0.6481	Remote Similarity	NPC608337
0.6	Remote Similarity	NPC475833
0.5745	Remote Similarity	NPC606666
0.5357	Remote Similarity	NPC55869
0.5167	Remote Similarity	NPC99308
0.5147	Remote Similarity	NPC605940

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC260474 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7557
0.1-0.2	1533
0.2-0.3	60
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