NPASS Compound

Natural Product: NPC25821

Natural Product ID	NPC25821
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	4-Hydroxymethyl-2-Methoxyphenyl-1-O-Beta-D-Apiofuranosyl-(1-6)-O-Beta-D-Glucopyranoside
IUPAC Name	(2R,3S,4S,5R,6S)-2-[[(2R,3R,4R)-3,4-dihydroxy-4-(hydroxymethyl)oxolan-2-yl]oxymethyl]-6-[4-(hydroxymethyl)-2-methoxyphenoxy]oxane-3,4,5-triol
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1923076
PubChem CID	21580495
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0004603] Organic oxygen compounds [CHEMONTID:0000323] Organooxygen compounds [CHEMONTID:0000011] Carbohydrates and carbohydrate conjugates [CHEMONTID:0002105] Glycosyl compounds [CHEMONTID:0004165] Phenolic glycosides

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 59 61 0 0 0 0 0 0 0 0999 V2000 3.6094 -0.9000 -3.3796 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1620 -0.6512 -2.0786 O 0 0 0 0 0 0 0 0 0 0 0 0 3.9063 -0.0519 -1.0804 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2214 0.3548 -1.3520 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0209 0.9536 -0.4202 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4881 1.1574 0.8404 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2116 0.7619 1.1019 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3639 0.1396 0.1529 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1252 -0.1956 0.5582 O 0 0 0 0 0 0 0 0 0 0 0 0 1.0578 -0.7916 -0.0481 C 0 0 1 0 0 0 0 0 0 0 0 0 0.6785 -2.1290 0.5969 C 0 0 1 0 0 0 0 0 0 0 0 0 0.3430 -1.8393 2.0252 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.1166 -0.3900 2.1953 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.9038 -0.0408 0.9654 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.6549 1.2460 1.0811 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4415 1.5506 -0.0195 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4178 0.6379 -0.2913 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.8135 1.2780 -0.3070 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.5937 0.1387 -0.9632 C 0 0 1 0 0 0 0 0 0 0 0 0 -6.7915 0.6746 -1.7135 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.6175 1.3336 -0.8262 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.5612 -0.4492 -1.8684 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3473 0.1567 -1.5941 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.9262 -0.7458 0.0370 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.2655 1.5689 0.9551 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0771 0.0309 -0.1238 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8891 -0.3735 3.3491 O 0 0 0 0 0 0 0 0 0 0 0 0 1.3270 -2.1847 2.9211 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.4064 -2.6215 -0.1260 O 0 0 0 0 0 0 0 0 0 0 0 0 7.4109 1.3745 -0.7362 C 0 0 0 0 0 0 0 0 0 0 0 0 8.2681 0.3304 -0.4566 O 0 0 0 0 0 0 0 0 0 0 0 0 4.3688 -1.7059 -3.3350 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0100 0.0390 -3.8362 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7260 -1.2028 -3.9890 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5815 0.1675 -2.3588 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1159 1.6371 1.6016 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8289 0.9402 2.1068 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2777 -1.0512 -1.0948 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5197 -2.8099 0.4536 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5611 -2.4589 2.2812 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7341 0.2954 2.3691 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6288 -0.8623 0.8063 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3051 1.3039 1.9744 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9343 2.1081 1.1915 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4916 -0.2233 0.3714 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8020 2.1592 -0.9903 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4162 1.2967 -2.5362 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3461 -0.2043 -2.1011 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3965 1.0616 0.1006 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8314 -0.1468 -2.9175 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5556 -1.5370 -1.7920 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8977 -0.9161 0.1279 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0236 2.5150 1.1550 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2623 0.5129 3.5601 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5025 -1.5308 3.6203 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1431 -3.3900 -0.6901 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4557 1.5834 -1.8321 H 0 0 0 0 0 0 0 0 0 0 0 0 7.6189 2.2719 -0.1285 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4853 -0.1769 -1.2892 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 9 10 1 0 10 11 1 0 11 12 1 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 18 19 1 0 19 20 1 0 20 21 1 0 19 22 1 0 22 23 1 0 19 24 1 1 18 25 1 0 14 26 1 0 13 27 1 0 12 28 1 0 11 29 1 0 5 30 1 0 30 31 1 0 8 3 1 0 26 10 1 0 23 17 1 0 1 32 1 0 1 33 1 0 1 34 1 0 4 35 1 0 6 36 1 0 7 37 1 0 10 38 1 6 11 39 1 1 12 40 1 1 13 41 1 1 14 42 1 6 15 43 1 0 15 44 1 0 17 45 1 1 18 46 1 6 20 47 1 0 20 48 1 0 21 49 1 0 22 50 1 0 22 51 1 0 24 52 1 0 25 53 1 0 27 54 1 0 28 55 1 0 29 56 1 0 30 57 1 0 30 58 1 0 31 59 1 0 M END

Standard InCHIKey	CROSCHPQOAEYSN-OTCFHACESA-N
Standard InCHI	InChI=1S/C19H28O12/c1-27-11-4-9(5-20)2-3-10(11)30-17-15(24)14(23)13(22)12(31-17)6-28-18-16(25)19(26,7-21)8-29-18/h2-4,12-18,20-26H,5-8H2,1H3/t12-,13-,14+,15-,16+,17-,18-,19-/m1/s1
SMILES	COc1cc(ccc1O[C@H]1[C@@H]([C@H]([C@@H]([C@@H](CO[C@H]2[C@@H]([C@@](CO)(CO2)O)O)O1)O)O)O)CO

Calculated Properties

Physi-Chem Properties

Molecular Weight:	448.16	Volume:	409.084 ? Van der Waals volume.
Dense:	1.096	LogP:	-0.822 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	-0.023 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-1.17 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	8.0	Rigid Bonds:	17.0
TPSA:	187.76 ? Topological Polar Surface Area.	H-Bond Acceptor:	12.0
H-Bond Donor:	7.0	Rings:	3.0
Heavy Atoms:	12.0

MedChem Properties

QED Drug-Likeness Score:	0.212	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.345	Fsp³:	0.684
MCE-18:	78.375 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.351	Fluc inhibitor:	0.01 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.022 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.021 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.107	Promiscuous compounds:	0.029

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.061	MDCK Permeability:	-5.121
Pgp-inhibitor:	0.0	Pgp-substrate:	0.25
PAMPA:	0.94 ? 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):	0.909
20% Bioavailability (F20%):	0.172	30% Bioavailability (F30%):	0.99
50% Bioavailability (F50%):	0.871

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.097	MRP1:	0.062
Plasma Protein Binding (PPB):	51.898%	Volume Distribution (VD):	-0.426
Fu:	52.035% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.025
BSEP inhibitor:	0.001

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.002	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.002	CYP3A4-substrate:	0.013
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.615
HLM stability:	0.0 ? 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):

1.751

Half-life (T1/2):

2.839

ADMET: Toxicity

hERG Blockers:	0.017	hERG Blockers (10um):	0.06
Human Hepatotoxicity (H-HT):	0.673	Drug-induced Liver Injury (DILI):	0.502
AMES Toxicity:	0.937	Rat Oral Acute Toxicity:	0.008
Maximum Recommended Daily Dose:	0.02	Skin Sensitization:	0.989
Carcinogencity:	0.332	Eye Corrosion:	0.0
Eye Irritation:	0.385	Respiratory Toxicity:	0.011
Drug-induced Neurotoxicity:	0.059	Ototoxicity:	0.937
Hematotoxicity:	0.159	Drug-induced Nephrotoxicity:	0.665
Genotoxicity:	0.671	RPMI-8226 Immunitoxicity:	0.128
A549 Cytotoxicity:	0.195	Hek293 Cytotoxicity:	0.229
BCF:	0.093 ? 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:	2.125 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	3.835 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	2.821 ? 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
NPO14559	Acer saccharum	Species	Sapindaceae	Eukaryota	bark	n.a.	n.a.	PMID[22032697]
NPO14559	Acer saccharum	Species	Sapindaceae	Eukaryota	n.a.	bark	n.a.	PMID[22032697]
NPO15954	Pyrenula japonica	Species	Pyrenulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO16693	Byrsonima crassifolia	Species	Malpighiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO26304	Hymenocallis littoralis	Species	Amaryllidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO14559	Acer saccharum	Species	Sapindaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO17757	Plectranthus saccatus	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO5016	Glossogyne tenuifolia	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO9141	Epimedium wushanense	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO16210	Androcymbium palaestinum	Species	Colchicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO18071	Euryops pedunculatus	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12630	Senecio oxyodontus	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO15594	Aplidiopsis confluata	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[COCONUT]
NPO16693	Byrsonima crassifolia	Species	Malpighiaceae	Eukaryota		n.a.	n.a.	Database[FooDB]
NPO16693	Byrsonima crassifolia	Species	Malpighiaceae	Eukaryota	Leaf	n.a.	n.a.	Database[FooDB]
NPO16693	Byrsonima crassifolia	Species	Malpighiaceae	Eukaryota	Fruit	n.a.	n.a.	Database[FooDB]
NPO14559	Acer saccharum	Species	Sapindaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO26304	Hymenocallis littoralis	Species	Amaryllidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO9141	Epimedium wushanense	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO14559	Acer saccharum	Species	Sapindaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO26304	Hymenocallis littoralis	Species	Amaryllidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO15954	Pyrenula japonica	Species	Pyrenulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO9141	Epimedium wushanense	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO9141	Epimedium wushanense	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO16326	Scopolia parviflora	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO11755	Banisteriopsis caapi	Species	Malpighiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO14001	Ceroplastes pseudoceriferus	Species	Coccidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO5016	Glossogyne tenuifolia	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO26304	Hymenocallis littoralis	Species	Amaryllidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO15740	Garcinia purpurea	Species	Clusiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO14507.1	Quercus ithaburensis subsp. macrolepis	Subspecies	Fagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO16049	Cryptocarya pleurosperma	Species	Lauraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO16210	Androcymbium palaestinum	Species	Colchicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO16693	Byrsonima crassifolia	Species	Malpighiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO9141	Epimedium wushanense	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO18071	Euryops pedunculatus	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO17917	Thamnophis sirtalis	Species	Colubridae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO11280	Aphanoascus terreus	Species	Onygenaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO10751	Bothriocline laxa	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO17600	Gnathotrichus sulcatus	Species	Curculionidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO15594	Aplidiopsis confluata	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[UNPD]
NPO16326	Scopolia parviflora	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO17444	Gleichenia japonica	Species	Gleicheniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO15954	Pyrenula japonica	Species	Pyrenulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12630	Senecio oxyodontus	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO17757	Plectranthus saccatus	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO14559	Acer saccharum	Species	Sapindaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO17141	Lonchocarpus longistylus	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO619	Ankistrodesmus braunii	Species	Selenastraceae	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	2

Activity Type	# Activity
Cell line	2

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
NPT393	Cell line	HCT-116	Homo sapiens	IC50	<	5.0	ug.mL-1	PMID[22032697]
NPT492	Cell line	Caco-2	Homo sapiens	IC50	<	5.0	ug.mL-1	PMID[22032697]

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 NPC25821 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	14769
0.1-0.2	31456
0.2-0.3	2963
0.3-0.4	541
0.4-0.5	103
0.5-0.6	15
0.6-0.7	9
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8254	Intermediate Similarity	NPC227980
0.6769	Remote Similarity	NPC171533
0.6522	Remote Similarity	NPC111785
0.6479	Remote Similarity	NPC242756
0.6389	Remote Similarity	NPC23253
0.6377	Remote Similarity	NPC287429
0.6197	Remote Similarity	NPC289438
0.619	Remote Similarity	NPC166040
0.6081	Remote Similarity	NPC34965
0.6081	Remote Similarity	NPC327032
0.5867	Remote Similarity	NPC470510
0.5789	Remote Similarity	NPC602810
0.575	Remote Similarity	NPC212748
0.5733	Remote Similarity	NPC160780
0.5526	Remote Similarity	NPC6836
0.5385	Remote Similarity	NPC470881
0.5286	Remote Similarity	NPC264784
0.525	Remote Similarity	NPC476442
0.525	Remote Similarity	NPC215512
0.525	Remote Similarity	NPC252833
0.5205	Remote Similarity	NPC298845
0.5128	Remote Similarity	NPC195196
0.5122	Remote Similarity	NPC602634
0.5067	Remote Similarity	NPC60756
0.5063	Remote Similarity	NPC197708

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC25821 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4444
0.1-0.2	4584
0.2-0.3	113
0.3-0.4	9
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