NPASS Compound

Natural Product: NPC216312

Natural Product ID	NPC216312
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Acetylalkannin
IUPAC Name	[(1S)-1-(5,8-dihydroxy-1,4-dioxonaphthalen-2-yl)-4-methylpent-3-enyl] acetate
Synonyms	11-O-Acetylalkannin; Acetylalkannin
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL112415
PubChem CID	9967285
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0002448] Benzenoids [CHEMONTID:0000023] Naphthalenes [CHEMONTID:0000153] Naphthoquinones

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 42 43 0 0 0 0 0 0 0 0999 V2000 -1.5329 4.4627 -0.8294 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4005 3.1513 -0.1725 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7198 2.9720 1.0163 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.9138 2.0751 -0.8649 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.7298 0.7843 -0.3931 C 0 0 2 0 0 0 0 0 0 0 0 0 0.7116 0.3981 -0.3009 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6523 1.1040 -0.9340 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0698 0.7693 -0.8764 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9541 1.4401 -1.4766 O 0 0 0 0 0 0 0 0 0 0 0 0 3.5139 -0.3976 -0.0903 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5744 -1.1460 0.5733 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1812 -0.7489 0.4676 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3434 -1.4621 1.0932 O 0 0 0 0 0 0 0 0 0 0 0 0 2.9151 -2.2633 1.3369 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9209 -3.0034 2.0017 O 0 0 0 0 0 0 0 0 0 0 0 0 4.2456 -2.6017 1.4084 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1962 -1.8524 0.7427 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8348 -0.7516 -0.0063 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7932 -0.0103 -0.6672 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.5481 -0.2830 -1.0111 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0140 0.0056 -0.8088 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8166 -0.8150 -0.1616 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3344 -2.0936 0.4204 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2483 -0.4444 -0.0127 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2653 5.2810 -0.1126 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6021 4.6745 -1.1178 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8633 4.5825 -1.7023 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0737 0.8301 0.6891 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3621 1.9469 -1.5060 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6323 -2.5914 2.9025 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5011 -3.4682 2.0018 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2488 -2.1378 0.8120 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0109 0.9273 -0.3642 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3531 -1.2288 -0.4646 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3284 -0.4966 -2.0705 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3621 0.9293 -1.2293 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6579 -1.9405 1.2875 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8335 -2.6802 -0.3922 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1777 -2.7040 0.7626 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5427 0.3616 -0.7088 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8467 -1.3566 -0.2904 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4972 -0.2185 1.0484 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 2 4 1 0 4 5 1 0 5 6 1 0 6 7 2 0 7 8 1 0 8 9 2 0 8 10 1 0 10 11 2 0 11 12 1 0 12 13 2 0 11 14 1 0 14 15 1 0 14 16 2 0 16 17 1 0 17 18 2 0 18 19 1 0 5 20 1 0 20 21 1 0 21 22 2 3 22 23 1 0 22 24 1 0 12 6 1 0 18 10 1 0 1 25 1 0 1 26 1 0 1 27 1 0 5 28 1 1 7 29 1 0 15 30 1 0 16 31 1 0 17 32 1 0 19 33 1 0 20 34 1 0 20 35 1 0 21 36 1 0 23 37 1 0 23 38 1 0 23 39 1 0 24 40 1 0 24 41 1 0 24 42 1 0 M END

Standard InCHIKey	WNFXUXZJJKTDOZ-HNNXBMFYSA-N
Standard InCHI	InChI=1S/C18H18O6/c1-9(2)4-7-15(24-10(3)19)11-8-14(22)16-12(20)5-6-13(21)17(16)18(11)23/h4-6,8,15,20-21H,7H2,1-3H3/t15-/m0/s1
SMILES	CC(=O)O[C@H](C1=CC(=O)c2c(C1=O)c(O)ccc2O)CC=C(C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	330.11	Volume:	334.421 ? Van der Waals volume.
Dense:	0.987	LogP:	3.261 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.111 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.311 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	15.0
TPSA:	100.9 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	2.0	Rings:	2.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.5	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.403	Fsp³:	0.278
MCE-18:	48.0 ? 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:	0	PAINS Alert:	1
Colloidal aggregators:	0.295	Fluc inhibitor:	0.68 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.838 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.454 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.463	Promiscuous compounds:	0.308

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.714	MDCK Permeability:	-4.574
Pgp-inhibitor:	0.005	Pgp-substrate:	0.011
PAMPA:	0.996 ? 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):	0.044
20% Bioavailability (F20%):	0.013	30% Bioavailability (F30%):	0.153
50% Bioavailability (F50%):	0.57

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.932
Plasma Protein Binding (PPB):	91.067%	Volume Distribution (VD):	0.296
Fu:	7.968% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.954
OATP1B3 inhibitor:	0.992	BCRP inhibitor:	0.0
BSEP inhibitor:	0.086

ADMET: Metabolism

CYP1A2-inhibitor:	0.016	CYP1A2-substrate:	0.588
CYP2C19-inhibitor:	0.001	CYP2C19-substrate:	0.017
CYP2C9-inhibitor:	0.001	CYP2C9-substrate:	0.01
CYP2D6-inhibitor:	0.006	CYP2D6-substrate:	0.032
CYP3A4-inhibitor:	0.001	CYP3A4-substrate:	0.941
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.99
HLM stability:	0.8 ? 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):

12.201

Half-life (T1/2):

1.412

ADMET: Toxicity

hERG Blockers:	0.024	hERG Blockers (10um):	0.313
Human Hepatotoxicity (H-HT):	0.661	Drug-induced Liver Injury (DILI):	0.884
AMES Toxicity:	0.891	Rat Oral Acute Toxicity:	0.489
Maximum Recommended Daily Dose:	0.346	Skin Sensitization:	0.964
Carcinogencity:	0.732	Eye Corrosion:	0.002
Eye Irritation:	0.935	Respiratory Toxicity:	0.682
Drug-induced Neurotoxicity:	0.165	Ototoxicity:	0.329
Hematotoxicity:	0.726	Drug-induced Nephrotoxicity:	0.608
Genotoxicity:	0.955	RPMI-8226 Immunitoxicity:	0.261
A549 Cytotoxicity:	0.688	Hek293 Cytotoxicity:	0.245
BCF:	1.638 ? 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:	4.472 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.621 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.2 ? 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
NPO11776	Lithospermum erythrorhizon	Species	Boraginaceae	Eukaryota	n.a.	root	n.a.	DOI[10.1007/s11418-007-0221-0]
NPO11776	Lithospermum erythrorhizon	Species	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1016/0031-9422(83)80138-1]
NPO11421	Arnebia euchroma	Species	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[12502328]
NPO11776	Lithospermum erythrorhizon	Species	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17157006]
NPO26982	Callyspongia siphonella	Species	Callyspongiidae	Eukaryota	n.a.	n.a.	n.a.	PMID[17488128]
NPO11776	Lithospermum erythrorhizon	Species	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19217780]
NPO26982	Callyspongia siphonella	Species	Callyspongiidae	Eukaryota	n.a.	n.a.	n.a.	PMID[19534474]
NPO12855	Alkanna cappadocica	Species	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[20405844]
NPO17855	Onosma paniculata	Species	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[22530779]
NPO11776	Lithospermum erythrorhizon	Species	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[3373224]
NPO11421	Arnebia euchroma	Species	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[7775984]
NPO12855	Alkanna cappadocica	Species	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO11421	Arnebia euchroma	Species	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO26982	Callyspongia siphonella	Species	Callyspongiidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO11300	Eucalyptus coccifera	Species	Myrtaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO9209	Rhizomnium magnifolium	Species	Mniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO11776	Lithospermum erythrorhizon	Species	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO20297	Arnebia guttata	Species	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO17855	Onosma paniculata	Species	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO11776	Lithospermum erythrorhizon	Species	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO30958	Onosma paniculatum	Species	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO29800	Onosma hookeri	Species	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO20297	Arnebia guttata	Species	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO11421	Arnebia euchroma	Species	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO11421	Arnebia euchroma	Species	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO20297	Arnebia guttata	Species	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO11776	Lithospermum erythrorhizon	Species	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO19450	Onosma hookerii	Species	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO17855	Onosma paniculata	Species	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO11776	Lithospermum erythrorhizon	Species	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO11421	Arnebia euchroma	Species	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO30958	Onosma paniculatum	Species	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO20297	Arnebia guttata	Species	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO20297	Arnebia guttata	Species	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO11776	Lithospermum erythrorhizon	Species	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO11421	Arnebia euchroma	Species	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO11776	Lithospermum erythrorhizon	Species	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO20297	Arnebia guttata	Species	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO17855	Onosma paniculata	Species	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO11421	Arnebia euchroma	Species	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO11300	Eucalyptus coccifera	Species	Myrtaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO9209	Rhizomnium magnifolium	Species	Mniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12855	Alkanna cappadocica	Species	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO26982	Callyspongia siphonella	Species	Callyspongiidae	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	6
Ratio	5
CD50	3
MBC	5
Activity	1
IC50	16

Activity Type	# Activity
Individual protein	1
Cell line	18
Organism	16
Non-molecular	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT143	Individual protein	DNA topoisomerase I	Homo sapiens	MIC	=	5000.0	nM	PMID[9873739]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT377	Cell line	OVCAR-3	Homo sapiens	CD50	=	1.5	ug ml-1	PMID[12502328]
NPT165	Cell line	HeLa	Homo sapiens	CD50	=	1.5	ug ml-1	PMID[12502328]
NPT65	Cell line	HepG2	Homo sapiens	CD50	=	2.0	ug ml-1	PMID[12502328]
NPT393	Cell line	HCT-116	Homo sapiens	IC50	=	340.0	nM	PMID[17949858]
NPT65	Cell line	HepG2	Homo sapiens	IC50	=	390.0	nM	PMID[17949858]
NPT139	Cell line	HT-29	Homo sapiens	IC50	=	10460.0	nM	PMID[20405844]
NPT82	Cell line	MDA-MB-231	Homo sapiens	IC50	=	8470.0	nM	PMID[20405844]
NPT306	Cell line	PC-3	Homo sapiens	IC50	=	11030.0	nM	PMID[20405844]
NPT2296	Cell line	AU565	Homo sapiens	IC50	=	880.0	nM	PMID[20405844]
NPT65	Cell line	HepG2	Homo sapiens	IC50	=	7410.0	nM	PMID[20405844]
NPT858	Cell line	LNCaP	Homo sapiens	IC50	=	11530.0	nM	PMID[20405844]
NPT83	Cell line	MCF7	Homo sapiens	IC50	=	7050.0	nM	PMID[20405844]
NPT165	Cell line	HeLa	Homo sapiens	IC50	=	6750.0	nM	PMID[20405844]
NPT134	Cell line	SK-BR-3	Homo sapiens	IC50	=	1660.0	nM	PMID[20405844]
NPT90	Cell line	DU-145	Homo sapiens	IC50	=	6650.0	nM	PMID[20405844]
NPT2405	Cell line	SAOS-2	Homo sapiens	IC50	=	4930.0	nM	PMID[20405844]
NPT189	Cell line	Vero	Chlorocebus aethiops	IC50	=	760.0	nM	PMID[20405844]
NPT886	Cell line	NIH3T3	Mus musculus	IC50	=	7730.0	nM	PMID[20405844]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	6060.0	nM	PMID[20405844]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	Ratio	<=	2.0	n.a.	PMID[12502328]
NPT175	Organism	Enterococcus faecalis	Enterococcus faecalis	MBC	=	6.25	ug ml-1	PMID[12502328]
NPT175	Organism	Enterococcus faecalis	Enterococcus faecalis	MIC	=	6.25	ug.mL-1	PMID[12502328]
NPT175	Organism	Enterococcus faecalis	Enterococcus faecalis	MBC	=	3.13	ug ml-1	PMID[12502328]
NPT175	Organism	Enterococcus faecalis	Enterococcus faecalis	MIC	=	3.13	ug.mL-1	PMID[12502328]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	MBC	=	1.56	ug ml-1	PMID[12502328]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	MIC	=	1.56	ug.mL-1	PMID[12502328]
NPT175	Organism	Enterococcus faecalis	Enterococcus faecalis	Ratio	<=	2.0	n.a.	PMID[12502328]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	Activity	>=	99.9	%	PMID[12502328]
NPT1531	Organism	Enterococcus faecium	Enterococcus faecium	MBC	=	6.25	ug ml-1	PMID[12502328]
NPT1531	Organism	Enterococcus faecium	Enterococcus faecium	MIC	=	6.25	ug.mL-1	PMID[12502328]
NPT1531	Organism	Enterococcus faecium	Enterococcus faecium	Ratio	<=	2.0	n.a.	PMID[12502328]

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 NPC216312 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	7841
0.1-0.2	37991
0.2-0.3	3940
0.3-0.4	56
0.4-0.5	4
0.5-0.6	6
0.6-0.7	3
0.7-0.8	0
0.8-0.85	8
0.85-0.9	6
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC299405
0.8889	High Similarity	NPC256463
0.8511	High Similarity	NPC111422
0.8511	High Similarity	NPC241349
0.8511	High Similarity	NPC306835
0.8511	High Similarity	NPC37992
0.8511	High Similarity	NPC29771
0.8333	Intermediate Similarity	NPC32749
0.8333	Intermediate Similarity	NPC42262
0.8163	Intermediate Similarity	NPC147542
0.8163	Intermediate Similarity	NPC220496
0.8163	Intermediate Similarity	NPC327916
0.8163	Intermediate Similarity	NPC257003
0.8163	Intermediate Similarity	NPC476477
0.8	Intermediate Similarity	NPC471602
0.717	Intermediate Similarity	NPC89664
0.7143	Intermediate Similarity	NPC474300
0.678	Remote Similarity	NPC471444
0.6727	Remote Similarity	NPC476473
0.6207	Remote Similarity	NPC274085
0.597	Remote Similarity	NPC474301
0.5294	Remote Similarity	NPC246693
0.5294	Remote Similarity	NPC242358
0.5294	Remote Similarity	NPC306765
0.5294	Remote Similarity	NPC110609
0.5217	Remote Similarity	NPC609532

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC216312 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3856
0.1-0.2	5164
0.2-0.3	129
0.3-0.4	1
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