NPASS Compound

Natural Product: NPC46912

Natural Product ID	NPC46912
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	3-Beta-Acetylolean-12-En-28-Methyl Ester
IUPAC Name	methyl (4aS,6aR,6aS,6bR,8aR,10S,12aR,14bS)-10-acetyloxy-2,2,6a,6b,9,9,12a-heptamethyl-1,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydropicene-4a-carboxylate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL2380326
PubChem CID	10255859
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001553] Triterpenoids

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 89 93 0 0 0 0 0 0 0 0999 V2000 -4.8877 3.6148 2.2097 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6836 2.4617 1.4477 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.1140 2.4370 0.1873 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7703 3.5612 -0.2642 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.9167 1.1535 -0.5934 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.3009 0.5852 -0.8041 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8187 -0.1161 0.4057 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9905 -1.2572 0.8979 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6262 -1.2303 0.1803 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1587 0.1685 0.2710 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.7412 0.4579 0.0806 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0605 0.7377 1.1592 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3883 1.0623 1.1818 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9554 0.1841 0.0857 C 0 0 1 0 0 0 0 0 0 0 0 0 0.4271 0.6462 -1.1996 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.0697 0.4605 -1.2302 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.7901 1.5829 -1.9770 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2548 1.5601 -1.8520 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4207 -0.7807 -2.0749 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8016 2.0489 -1.6083 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0936 -0.2081 -2.2965 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6083 -0.2868 -2.0795 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9014 -0.9251 -0.7438 C 0 0 2 0 0 0 0 0 0 0 0 0 2.4418 0.0330 0.2803 C 0 0 1 0 0 0 0 0 0 0 0 0 3.1853 1.3267 0.3486 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6260 -0.6336 1.6445 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5552 -1.7759 1.6378 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7521 -1.6755 0.7662 C 0 0 1 0 0 0 0 0 0 0 0 0 4.2740 -1.4471 -0.6584 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3129 -0.6484 -1.4238 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2791 -2.8399 -1.3146 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6615 -0.6823 1.0812 O 0 0 0 0 0 0 0 0 0 0 0 0 6.9740 -0.8356 1.4424 C 0 0 0 0 0 0 0 0 0 0 0 0 7.4190 -2.0058 1.4989 O 0 0 0 0 0 0 0 0 0 0 0 0 7.7981 0.3524 1.7451 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6597 -2.5645 0.5295 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8042 -1.2609 2.3912 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2893 3.3077 3.1979 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8991 4.1096 2.4430 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6028 4.3309 1.7728 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0016 1.4342 -1.0057 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3340 -0.0512 -1.7153 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0523 0.6255 1.2053 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8520 -0.4894 0.1074 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9668 -1.8551 0.8105 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8664 -1.6479 -0.7859 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4559 0.4603 1.3334 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5247 0.7548 2.1717 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8643 0.8717 2.1602 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4700 2.1343 0.9884 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5709 -0.8518 0.2464 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4547 2.5864 -1.6424 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5313 1.5496 -3.0586 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6614 2.5715 -2.1792 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6725 0.8919 -2.6662 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9125 -0.7018 -3.0814 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4859 -0.7234 -2.4231 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1079 -1.7119 -1.6395 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3604 2.1842 -2.6429 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8902 2.1418 -1.7788 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5003 2.8289 -0.9230 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7792 -1.2653 -2.2365 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0263 0.2581 -3.2937 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1338 0.6375 -2.2830 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9503 -1.0285 -2.8537 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1933 -1.8081 -0.6847 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8761 1.3941 1.2439 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8315 1.5387 -0.5176 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4504 2.1347 0.5475 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6448 -1.0093 2.0579 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9735 0.1007 2.4164 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8232 -1.9919 2.7119 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9885 -2.6929 1.3161 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3007 -2.6603 0.8636 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9212 -0.3338 -2.3879 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7643 0.1595 -0.8125 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1542 -1.3679 -1.6523 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0993 -3.4534 -0.9105 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2333 -2.7769 -2.4009 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3291 -3.3243 -0.9530 H 0 0 0 0 0 0 0 0 0 0 0 0 7.6419 1.1675 1.0086 H 0 0 0 0 0 0 0 0 0 0 0 0 8.8836 0.1279 1.7640 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5622 0.7856 2.7440 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2900 -2.9420 1.3451 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9133 -3.3426 0.2658 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3500 -2.4112 -0.3512 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7267 -0.2552 2.8326 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7091 -1.7337 2.8341 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9425 -1.9182 2.6148 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 5 3 1 1 5 6 1 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 2 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 16 19 1 6 15 20 1 6 15 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 24 25 1 1 24 26 1 0 26 27 1 0 27 28 1 0 28 29 1 0 29 30 1 0 29 31 1 0 28 32 1 0 32 33 1 0 33 34 2 0 33 35 1 0 8 36 1 0 8 37 1 0 18 5 1 0 29 23 1 0 10 5 1 0 16 11 1 0 24 14 1 0 1 38 1 0 1 39 1 0 1 40 1 0 6 41 1 0 6 42 1 0 7 43 1 0 7 44 1 0 9 45 1 0 9 46 1 0 10 47 1 1 12 48 1 0 13 49 1 0 13 50 1 0 14 51 1 1 17 52 1 0 17 53 1 0 18 54 1 0 18 55 1 0 19 56 1 0 19 57 1 0 19 58 1 0 20 59 1 0 20 60 1 0 20 61 1 0 21 62 1 0 21 63 1 0 22 64 1 0 22 65 1 0 23 66 1 6 25 67 1 0 25 68 1 0 25 69 1 0 26 70 1 0 26 71 1 0 27 72 1 0 27 73 1 0 28 74 1 6 30 75 1 0 30 76 1 0 30 77 1 0 31 78 1 0 31 79 1 0 31 80 1 0 35 81 1 0 35 82 1 0 35 83 1 0 36 84 1 0 36 85 1 0 36 86 1 0 37 87 1 0 37 88 1 0 37 89 1 0 M END

Standard InCHIKey	VTZCFEUQVQTSSV-LVNUYWAMSA-N
Standard InCHI	InChI=1S/C33H52O4/c1-21(34)37-26-13-14-30(6)24(29(26,4)5)12-15-32(8)25(30)11-10-22-23-20-28(2,3)16-18-33(23,27(35)36-9)19-17-31(22,32)7/h10,23-26H,11-20H2,1-9H3/t23-,24-,25+,26-,30-,31+,32+,33-/m0/s1
SMILES	COC(=O)[C@@]12CCC(C[C@H]2C2=CC[C@H]3[C@@]([C@@]2(CC1)C)(C)CC[C@@H]1[C@]3(C)CC[C@@H](C1(C)C)OC(=O)C)(C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	512.39	Volume:	563.793 ? Van der Waals volume.
Dense:	0.909	LogP:	5.685 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.551 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-7.196 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	28.0
TPSA:	52.6 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	0.0	Rings:	5.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.279	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.646	Fsp³:	0.879
MCE-18:	105.806 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.931	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.014 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.0 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.562	Promiscuous compounds:	0.184

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.175	MDCK Permeability:	-4.941
Pgp-inhibitor:	0.997	Pgp-substrate:	0.002
PAMPA:	0.634 ? 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%):	0.407	30% Bioavailability (F30%):	0.515
50% Bioavailability (F50%):	0.986

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.248	MRP1:	0.803
Plasma Protein Binding (PPB):	96.753%	Volume Distribution (VD):	0.069
Fu:	3.972% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.964	BCRP inhibitor:	0.506
BSEP inhibitor:	0.998

ADMET: Metabolism

CYP1A2-inhibitor:	0.002	CYP1A2-substrate:	0.621
CYP2C19-inhibitor:	0.928	CYP2C19-substrate:	0.977
CYP2C9-inhibitor:	0.311	CYP2C9-substrate:	0.053
CYP2D6-inhibitor:	0.023	CYP2D6-substrate:	0.086
CYP3A4-inhibitor:	0.302	CYP3A4-substrate:	0.911
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	1.0 ? 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):

6.287

Half-life (T1/2):

0.397

ADMET: Toxicity

hERG Blockers:	0.083	hERG Blockers (10um):	0.235
Human Hepatotoxicity (H-HT):	0.588	Drug-induced Liver Injury (DILI):	0.518
AMES Toxicity:	0.33	Rat Oral Acute Toxicity:	0.498
Maximum Recommended Daily Dose:	0.605	Skin Sensitization:	0.814
Carcinogencity:	0.846	Eye Corrosion:	0.091
Eye Irritation:	0.278	Respiratory Toxicity:	0.783
Drug-induced Neurotoxicity:	0.115	Ototoxicity:	0.333
Hematotoxicity:	0.473	Drug-induced Nephrotoxicity:	0.71
Genotoxicity:	0.719	RPMI-8226 Immunitoxicity:	0.036
A549 Cytotoxicity:	0.354	Hek293 Cytotoxicity:	0.306
BCF:	2.44 ? 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:	4.878 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.126 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.831 ? 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
NPO2117	Plakortis nigra	Species	Plakinidae	Eukaryota	n.a.	Palauan	n.a.	PMID[12350142]
NPO2117	Plakortis nigra	Species	Plakinidae	Eukaryota	n.a.	Indo-Pacific	n.a.	PMID[15387674]
NPO33322	caesalpinia volkensii	Species	Fabaceae	Eukaryota	stem bark	n.a.	n.a.	PMID[23562058]
NPO2543	Anthopleura pacifica	Species	Actiniidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO2117	Plakortis nigra	Species	Plakinidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO24317	Primula integrifolia	Species	Primulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO28655	Perovskia angustifolia	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13905	Galaxaura filamentosa	Species	Galaxauraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO28722	Radermachera xylocarpa	Species	Bignoniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO2117	Plakortis nigra	Species	Plakinidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO24317	Primula integrifolia	Species	Primulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO22067	Pogostemon stellatus	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO2543	Anthopleura pacifica	Species	Actiniidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13905	Galaxaura filamentosa	Species	Galaxauraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28655	Perovskia angustifolia	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
IC50	9
Activity	7

Activity Type	# Activity
Cell line	13
Organism	2
Non-molecular	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
NPT179	Cell line	A2780	Homo sapiens	Activity	=	15.68	%	PMID[24361521]
NPT179	Cell line	A2780	Homo sapiens	Activity	=	72.47	%	PMID[24361521]
NPT179	Cell line	A2780	Homo sapiens	Activity	=	9.43	%	PMID[24361521]
NPT179	Cell line	A2780	Homo sapiens	Activity	=	2.41	%	PMID[24361521]
NPT179	Cell line	A2780	Homo sapiens	Activity	=	28.8	%	PMID[24361521]
NPT179	Cell line	A2780	Homo sapiens	Activity	=	15.9	%	PMID[24361521]
NPT179	Cell line	A2780	Homo sapiens	Activity	=	55.29	%	PMID[24361521]
NPT886	Cell line	NIH3T3	Mus musculus	IC50	=	34300.0	nM	PMID[24361521]
NPT83	Cell line	MCF7	Homo sapiens	IC50	=	16700.0	nM	PMID[24361521]
NPT139	Cell line	HT-29	Homo sapiens	IC50	=	26700.0	nM	PMID[24361521]
NPT81	Cell line	A549	Homo sapiens	IC50	=	26100.0	nM	PMID[24361521]
NPT179	Cell line	A2780	Homo sapiens	IC50	=	8600.0	nM	PMID[24361521]
NPT1215	Cell line	8505C	Homo sapiens	IC50	=	20500.0	nM	PMID[24361521]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	24440.0	nM	PMID[23562058]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	18690.0	nM	PMID[23562058]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	34100.0	nM	PMID[24361521]

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 NPC46912 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	22927
0.1-0.2	22871
0.2-0.3	3008
0.3-0.4	811
0.4-0.5	170
0.5-0.6	45
0.6-0.7	12
0.7-0.8	0
0.8-0.85	2
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	NPC162107
0.8246	Intermediate Similarity	NPC195334
0.8103	Intermediate Similarity	NPC224145
0.7581	Intermediate Similarity	NPC191965
0.746	Intermediate Similarity	NPC286786
0.7164	Intermediate Similarity	NPC488520
0.7143	Intermediate Similarity	NPC127855
0.7031	Intermediate Similarity	NPC10005
0.7031	Intermediate Similarity	NPC91525
0.697	Remote Similarity	NPC488523
0.6825	Remote Similarity	NPC267517
0.6765	Remote Similarity	NPC488525
0.6719	Remote Similarity	NPC246708
0.6508	Remote Similarity	NPC290495
0.6479	Remote Similarity	NPC488522
0.6301	Remote Similarity	NPC488524
0.6286	Remote Similarity	NPC481363
0.6269	Remote Similarity	NPC136313
0.6176	Remote Similarity	NPC481361
0.6098	Remote Similarity	NPC214484
0.6	Remote Similarity	NPC120840
0.597	Remote Similarity	NPC475049
0.5882	Remote Similarity	NPC137306
0.5821	Remote Similarity	NPC480944
0.5811	Remote Similarity	NPC86368
0.5797	Remote Similarity	NPC9892
0.5747	Remote Similarity	NPC249848
0.5747	Remote Similarity	NPC107966
0.5634	Remote Similarity	NPC23621
0.5581	Remote Similarity	NPC48499
0.5571	Remote Similarity	NPC329943
0.5556	Remote Similarity	NPC223301
0.5556	Remote Similarity	NPC171544
0.5541	Remote Similarity	NPC488521
0.5495	Remote Similarity	NPC30735
0.5455	Remote Similarity	NPC235405
0.5455	Remote Similarity	NPC475516
0.5435	Remote Similarity	NPC10607
0.5333	Remote Similarity	NPC39211
0.5333	Remote Similarity	NPC157868
0.5319	Remote Similarity	NPC297263
0.5303	Remote Similarity	NPC142754
0.5294	Remote Similarity	NPC235341
0.5275	Remote Similarity	NPC469946
0.527	Remote Similarity	NPC113989
0.525	Remote Similarity	NPC167383
0.5217	Remote Similarity	NPC192791
0.5217	Remote Similarity	NPC470588
0.5217	Remote Similarity	NPC112352
0.52	Remote Similarity	NPC477875
0.5195	Remote Similarity	NPC477876
0.5152	Remote Similarity	NPC290598
0.5152	Remote Similarity	NPC30590
0.5122	Remote Similarity	NPC237503
0.5106	Remote Similarity	NPC40775
0.5106	Remote Similarity	NPC251768
0.5106	Remote Similarity	NPC159309
0.5106	Remote Similarity	NPC46665
0.5106	Remote Similarity	NPC86222
0.5068	Remote Similarity	NPC488519
0.5067	Remote Similarity	NPC485589
0.5053	Remote Similarity	NPC475591
0.5053	Remote Similarity	NPC63159
0.5053	Remote Similarity	NPC236870
0.5053	Remote Similarity	NPC235438
0.505	Remote Similarity	NPC475287

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC46912 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7337
0.1-0.2	1769
0.2-0.3	37
0.3-0.4	5
0.4-0.5	2
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