NPASS Compound

Natural Product: NPC200592

Natural Product ID	NPC200592
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Orbiculin A
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL500894
PubChem CID	10627032
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001550] Sesquiterpenoids [CHEMONTID:0002051] Agarofurans

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 80 84 0 0 0 0 0 0 0 0999 V2000 2.7592 1.2787 -0.9086 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2791 1.0133 -0.9980 C 0 0 2 0 0 0 0 0 0 0 0 0 0.5819 2.3602 -1.1661 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9153 2.0063 -1.1429 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.1661 1.8256 0.3526 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.3317 0.7302 0.9549 C 0 0 1 0 0 0 0 0 0 0 0 0 0.4684 1.4323 2.0505 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1306 -0.3284 1.6201 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.2862 -1.5150 2.0204 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7785 -1.9099 1.0716 C 0 0 2 0 0 0 0 0 0 0 0 0 1.6463 -0.6403 0.8544 C 0 0 2 0 0 0 0 0 0 0 0 0 0.6885 0.1123 -0.0015 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.0668 -0.8464 -0.7117 O 0 0 0 0 0 0 0 0 0 0 0 0 0.3197 -2.0885 -0.3423 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7235 -3.1654 -0.4982 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4789 -2.5168 -1.2293 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8165 -1.0987 0.2799 O 0 0 0 0 0 0 0 0 0 0 0 0 4.0223 -0.9853 0.9582 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0102 -0.4567 2.1007 O 0 0 0 0 0 0 0 0 0 0 0 0 5.2648 -1.4573 0.3801 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4422 -1.3338 1.0706 C 0 0 0 0 0 0 0 0 0 0 0 0 7.6560 -1.7656 0.5689 C 0 0 0 0 0 0 0 0 0 0 0 0 7.6940 -2.3454 -0.6759 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5084 -2.4767 -1.3863 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2954 -2.0323 -0.8571 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2554 -0.8470 1.1162 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.5188 -0.9453 1.4859 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6621 -0.4130 2.5816 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.5835 -1.5570 0.7717 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4507 -2.1564 -0.4649 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4846 -2.7479 -1.1505 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.7328 -2.7620 -0.6051 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9229 -2.1779 0.6277 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8795 -1.5886 1.3046 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8590 3.1249 0.8434 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7423 3.9789 1.4359 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9372 3.6026 1.5690 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.3870 5.3314 1.9379 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5936 3.1146 -1.6208 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.3898 3.1728 -2.7327 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5370 2.1215 -3.4089 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.0554 4.4417 -3.1212 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9510 2.1706 -1.5881 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3549 0.4756 -1.4204 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1377 1.5897 0.0549 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1819 0.5843 -2.0513 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8314 2.8033 -2.1314 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8449 3.0721 -0.3784 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0301 1.0916 -1.7120 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2477 1.7125 0.5722 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4328 1.8159 1.7013 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5388 0.8256 2.9713 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0776 2.3568 2.4240 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4391 0.1250 2.6231 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9151 -2.4472 2.1808 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1724 -1.3892 3.0274 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3566 -2.7237 1.4900 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8775 -0.1907 1.8354 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3542 -3.3266 0.3945 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2345 -4.1765 -0.6615 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3125 -3.0277 -1.4407 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1176 -3.2080 -2.0522 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2212 -3.1342 -0.6818 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9296 -1.6730 -1.7910 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4645 -0.8843 2.0544 H 0 0 0 0 0 0 0 0 0 0 0 0 8.5784 -1.6661 1.1159 H 0 0 0 0 0 0 0 0 0 0 0 0 8.5946 -2.6972 -1.1163 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5585 -2.9355 -2.3642 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3880 -2.1404 -1.4174 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4549 -2.1372 -0.8872 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3192 -3.2018 -2.1166 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.5334 -3.2349 -1.1649 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.9227 -2.2023 1.0388 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0789 -1.1355 2.2848 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3258 5.4037 2.2580 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0027 5.6261 2.8129 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6269 6.1013 1.1478 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0498 4.1909 -3.5919 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4932 4.9813 -3.9181 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2126 5.1161 -2.2683 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 4 5 1 0 5 6 1 0 6 7 1 1 6 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 6 13 14 1 0 14 15 1 0 14 16 1 0 11 17 1 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 23 24 1 0 24 25 2 0 8 26 1 0 26 27 1 0 27 28 2 0 27 29 1 0 29 30 2 0 30 31 1 0 31 32 2 0 32 33 1 0 33 34 2 0 5 35 1 0 35 36 1 0 36 37 2 0 36 38 1 0 4 39 1 0 39 40 1 0 40 41 2 0 40 42 1 0 12 2 1 0 25 20 1 0 34 29 1 0 12 6 1 0 14 10 1 0 1 43 1 0 1 44 1 0 1 45 1 0 2 46 1 6 3 47 1 0 3 48 1 0 4 49 1 6 5 50 1 6 7 51 1 0 7 52 1 0 7 53 1 0 8 54 1 1 9 55 1 0 9 56 1 0 10 57 1 1 11 58 1 1 15 59 1 0 15 60 1 0 15 61 1 0 16 62 1 0 16 63 1 0 16 64 1 0 21 65 1 0 22 66 1 0 23 67 1 0 24 68 1 0 25 69 1 0 30 70 1 0 31 71 1 0 32 72 1 0 33 73 1 0 34 74 1 0 38 75 1 0 38 76 1 0 38 77 1 0 42 78 1 0 42 79 1 0 42 80 1 0 M END

Standard InCHIKey	KYEKMLQQOXNBSD-HJJCBLRASA-N
Standard InCHI	InChI=1S/C33H38O9/c1-19-17-25(38-20(2)34)28(39-21(3)35)32(6)26(40-29(36)22-13-9-7-10-14-22)18-24-27(33(19,32)42-31(24,4)5)41-30(37)23-15-11-8-12-16-23/h7-16,19,24-28H,17-18H2,1-6H3/t19-,24-,25+,26+,27-,28+,32-,33-/m1/s1
SMILES	C[C@@H]1C[C@@H]([C@@H]([C@@]2(C)[C@H](C[C@@H]3[C@H]([C@]12OC3(C)C)OC(=O)c1ccccc1)OC(=O)c1ccccc1)OC(=O)C)OC(=O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	578.25	Volume:	589.289 ? Van der Waals volume.
Dense:	0.981	LogP:	3.688 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.347 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.177 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	10.0	Rigid Bonds:	30.0
TPSA:	114.43 ? Topological Polar Surface Area.	H-Bond Acceptor:	9.0
H-Bond Donor:	0.0	Rings:	5.0
Heavy Atoms:	9.0

MedChem Properties

QED Drug-Likeness Score:	0.348	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.624	Fsp³:	0.515
MCE-18:	159.84 ? 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:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.649	Fluc inhibitor:	0.146 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.008 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.029 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.3	Promiscuous compounds:	0.069

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.218	MDCK Permeability:	-4.795
Pgp-inhibitor:	0.997	Pgp-substrate:	0.089
PAMPA:	0.139 ? 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%):	0.042	30% Bioavailability (F30%):	0.165
50% Bioavailability (F50%):	0.965

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.695	MRP1:	1.0
Plasma Protein Binding (PPB):	94.52%	Volume Distribution (VD):	-0.342
Fu:	5.681% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.996
OATP1B3 inhibitor:	0.957	BCRP inhibitor:	0.09
BSEP inhibitor:	0.99

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.999
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.151
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.042
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.01	CYP3A4-substrate:	0.001
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.999 ? 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):

4.324

Half-life (T1/2):

0.496

ADMET: Toxicity

hERG Blockers:	0.06	hERG Blockers (10um):	0.621
Human Hepatotoxicity (H-HT):	0.102	Drug-induced Liver Injury (DILI):	0.909
AMES Toxicity:	0.344	Rat Oral Acute Toxicity:	0.133
Maximum Recommended Daily Dose:	0.172	Skin Sensitization:	0.987
Carcinogencity:	0.602	Eye Corrosion:	0.001
Eye Irritation:	0.337	Respiratory Toxicity:	0.045
Drug-induced Neurotoxicity:	0.592	Ototoxicity:	0.195
Hematotoxicity:	0.044	Drug-induced Nephrotoxicity:	0.401
Genotoxicity:	0.258	RPMI-8226 Immunitoxicity:	0.037
A549 Cytotoxicity:	0.395	Hek293 Cytotoxicity:	0.482
BCF:	0.781 ? 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:	3.847 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.184 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.889 ? 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
NPO6349	Celastrus orbiculatus	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[10346948]
NPO6349	Celastrus orbiculatus	Species	Celastraceae	Eukaryota	n.a.	root	n.a.	PMID[10346948]
NPO6349	Celastrus orbiculatus	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[11170672]
NPO6349	Celastrus orbiculatus	Species	Celastraceae	Eukaryota	n.a.	root	n.a.	PMID[11809076]
NPO6349	Celastrus orbiculatus	Species	Celastraceae	Eukaryota	Seeds	n.a.	n.a.	PMID[18507472]
NPO6349	Celastrus orbiculatus	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[23421714]
NPO6349	Celastrus orbiculatus	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[27791375]
NPO6349	Celastrus orbiculatus	Species	Celastraceae	Eukaryota	n.a.	root	n.a.	PMID[9461657]
NPO6349	Celastrus orbiculatus	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[9461657]
NPO6349	Celastrus orbiculatus	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO6349	Celastrus orbiculatus	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO6349	Celastrus orbiculatus	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO6349	Celastrus orbiculatus	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO6349	Celastrus orbiculatus	Species	Celastraceae	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	17
Ratio IC50	7
Activity	5

Activity Type	# Activity
Cell line	9
Others	13
Non-molecular	7

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
NPT83	Cell line	MCF7	Homo sapiens	IC50	=	53160.0	nM	PMID[9461657]
NPT383	Cell line	SNB-19	Homo sapiens	IC50	=	40780.0	nM	PMID[9461657]
NPT146	Cell line	SK-OV-3	Homo sapiens	IC50	=	48420.0	nM	PMID[9461657]
NPT370	Cell line	NCI-H23	Homo sapiens	IC50	=	41940.0	nM	PMID[9461657]
NPT398	Cell line	UACC-62	Homo sapiens	IC50	=	38770.0	nM	PMID[9461657]
NPT386	Cell line	KM12	Homo sapiens	IC50	=	38560.0	nM	PMID[9461657]
NPT113	Cell line	RAW264.7	Mus musculus	IC50	>	300000.0	nM	PMID[11809076]
NPT80	Cell line	Raji	Homo sapiens	Activity	=	60.0	%	PMID[26854381]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	49020.0	nM	PMID[9461657]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	64900.0	nM	PMID[9461657]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	800.0	nM	PMID[9461657]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	7330.0	nM	PMID[9461657]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	31600.0	nM	PMID[10346948]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	32000.0	nM	PMID[10346948]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	400.0	nM	PMID[10346948]
NPT2	Others	Unspecified	n.a.	IC50	=	61910	nM	PMID[9461657]
NPT2	Others	Unspecified	n.a.	IC50	=	1150	nM	PMID[9461657]
NPT2	Others	Unspecified	n.a.	Ratio IC50	=	1.11	n.a.	PMID[9461657]
NPT2	Others	Unspecified	n.a.	Ratio IC50	=	1.6	n.a.	PMID[9461657]
NPT2	Others	Unspecified	n.a.	Ratio IC50	=	0.95	n.a.	PMID[9461657]
NPT2	Others	Unspecified	n.a.	Ratio IC50	=	80.0	n.a.	PMID[10346948]
NPT2	Others	Unspecified	n.a.	Ratio IC50	=	3.0	n.a.	PMID[10346948]
NPT2	Others	Unspecified	n.a.	Ratio IC50	=	0.9	n.a.	PMID[10346948]
NPT2	Others	Unspecified	n.a.	Ratio IC50	=	1.2	n.a.	PMID[10346948]
NPT2	Others	Unspecified	n.a.	Activity	=	5.1	%	PMID[26854381]
NPT2	Others	Unspecified	n.a.	Activity	=	35.2	%	PMID[26854381]
NPT2	Others	Unspecified	n.a.	Activity	=	76.6	%	PMID[26854381]
NPT2	Others	Unspecified	n.a.	Activity	=	100.0	%	PMID[26854381]

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 NPC200592 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	16030
0.1-0.2	31876
0.2-0.3	1424
0.3-0.4	353
0.4-0.5	91
0.5-0.6	49
0.6-0.7	17
0.7-0.8	0
0.8-0.85	0
0.85-0.9	1
0.9-0.95	2
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC610542
0.9273	High Similarity	NPC195647
0.9273	High Similarity	NPC270498
0.8596	High Similarity	NPC473081
0.7937	Intermediate Similarity	NPC473673
0.7778	Intermediate Similarity	NPC177340
0.7727	Intermediate Similarity	NPC607428
0.7647	Intermediate Similarity	NPC14499
0.7538	Intermediate Similarity	NPC472574
0.7463	Intermediate Similarity	NPC473112
0.7231	Intermediate Similarity	NPC67777
0.7231	Intermediate Similarity	NPC43241
0.7213	Intermediate Similarity	NPC283375
0.7143	Intermediate Similarity	NPC88593
0.7077	Intermediate Similarity	NPC479047
0.7077	Intermediate Similarity	NPC191082
0.7077	Intermediate Similarity	NPC291638
0.6935	Remote Similarity	NPC183122
0.6719	Remote Similarity	NPC481047
0.6719	Remote Similarity	NPC481045
0.6716	Remote Similarity	NPC139067
0.6714	Remote Similarity	NPC473613
0.6714	Remote Similarity	NPC473085
0.6667	Remote Similarity	NPC474608
0.6567	Remote Similarity	NPC4341
0.6522	Remote Similarity	NPC479044
0.6418	Remote Similarity	NPC163087
0.6324	Remote Similarity	NPC483883
0.6324	Remote Similarity	NPC151585
0.6176	Remote Similarity	NPC70973
0.6154	Remote Similarity	NPC481066
0.6111	Remote Similarity	NPC184747
0.6087	Remote Similarity	NPC246480
0.6056	Remote Similarity	NPC92293
0.5972	Remote Similarity	NPC609924
0.5942	Remote Similarity	NPC473111
0.5897	Remote Similarity	NPC75600
0.5897	Remote Similarity	NPC483884
0.5789	Remote Similarity	NPC608007
0.5775	Remote Similarity	NPC147217
0.5775	Remote Similarity	NPC270590
0.5753	Remote Similarity	NPC266265
0.5733	Remote Similarity	NPC609221
0.5676	Remote Similarity	NPC210591
0.5676	Remote Similarity	NPC95265
0.5658	Remote Similarity	NPC475039
0.5658	Remote Similarity	NPC476035
0.5634	Remote Similarity	NPC48017
0.5634	Remote Similarity	NPC147880
0.56	Remote Similarity	NPC475652
0.557	Remote Similarity	NPC56953
0.5556	Remote Similarity	NPC27377
0.5556	Remote Similarity	NPC158663
0.5556	Remote Similarity	NPC148062
0.5526	Remote Similarity	NPC481050
0.5513	Remote Similarity	NPC605086
0.5507	Remote Similarity	NPC475429
0.5507	Remote Similarity	NPC476094
0.5493	Remote Similarity	NPC473060
0.5493	Remote Similarity	NPC17877
0.5493	Remote Similarity	NPC159520
0.5479	Remote Similarity	NPC471100
0.5479	Remote Similarity	NPC605884
0.5467	Remote Similarity	NPC97667
0.5352	Remote Similarity	NPC483879
0.5309	Remote Similarity	NPC483870
0.5286	Remote Similarity	NPC211137
0.5286	Remote Similarity	NPC66761
0.5286	Remote Similarity	NPC483843
0.5278	Remote Similarity	NPC483902
0.5278	Remote Similarity	NPC472577
0.527	Remote Similarity	NPC254558
0.527	Remote Similarity	NPC471107
0.5263	Remote Similarity	NPC70716
0.52	Remote Similarity	NPC41481
0.5195	Remote Similarity	NPC36021
0.5139	Remote Similarity	NPC481067
0.5135	Remote Similarity	NPC137718
0.5068	Remote Similarity	NPC51314
0.5067	Remote Similarity	NPC473758
0.5063	Remote Similarity	NPC483887
0.5063	Remote Similarity	NPC158020
0.5062	Remote Similarity	NPC483865

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC200592 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4085
0.1-0.2	4892
0.2-0.3	173
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