NPASS Compound

Natural Product: NPC101731

Natural Product ID	NPC101731
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Palstatin
IUPAC Name	5,7-dihydroxy-2-[(2R,3R)-2-(4-hydroxy-3,5-dimethoxyphenyl)-3-(hydroxymethyl)-5-methoxy-2,3-dihydro-1,4-benzodioxin-7-yl]chromen-4-one
Synonyms	Palstatin
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL523569
PubChem CID	5323578
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0001392] Lignans, neolignans and related compounds [CHEMONTID:0001844] Flavonolignans

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 62 66 0 0 0 0 0 0 0 0999 V2000 4.3272 -4.2112 -1.5263 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1495 -3.1358 -1.8385 O 0 0 0 0 0 0 0 0 0 0 0 0 4.9545 -1.8095 -1.4771 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8581 -1.4146 -0.7309 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6659 -0.0922 -0.3699 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6013 0.8405 -0.7738 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7127 0.4764 -1.5234 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8865 -0.8455 -1.8728 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9805 -1.2527 -2.6189 O 0 0 0 0 0 0 0 0 0 0 0 0 6.6707 1.3854 -1.9446 O 0 0 0 0 0 0 0 0 0 0 0 0 6.4831 2.7404 -1.5759 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4704 0.2872 0.4465 C 0 0 2 0 0 0 0 0 0 0 0 0 2.6004 -0.1426 1.8690 C 0 0 1 0 0 0 0 0 0 0 0 0 3.7762 0.5142 2.5681 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9260 0.2178 1.8805 O 0 0 0 0 0 0 0 0 0 0 0 0 1.3920 0.1285 2.5424 O 0 0 0 0 0 0 0 0 0 0 0 0 0.1970 0.1159 1.8530 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0137 0.3589 2.5099 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1992 0.3446 1.8129 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2739 0.0943 0.4477 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0870 -0.1441 -0.1955 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1124 -0.1304 0.5028 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3413 -0.3702 -0.1299 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.5702 0.0993 -0.2360 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7274 -0.1693 -1.5757 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9802 -0.1542 -2.1869 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1333 -0.3970 -3.4042 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.0949 0.1371 -1.4330 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.3649 0.1702 -1.9714 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.4777 0.4634 -1.2111 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.2592 0.7259 0.1343 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9909 0.6930 0.6734 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8743 0.3982 -0.0938 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6730 0.3700 0.4268 O 0 0 0 0 0 0 0 0 0 0 0 0 -9.3700 1.0268 0.9342 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.5562 -0.1013 -3.3390 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.9363 0.6068 3.8669 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.1289 0.8621 4.5779 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9588 -5.1314 -1.3556 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7284 -4.1092 -0.6016 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6009 -4.4559 -2.3503 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1327 -2.1869 -0.4295 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4709 1.8779 -0.5030 H 0 0 0 0 0 0 0 0 0 0 0 0 7.6512 -0.6184 -2.9882 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4541 3.0518 -1.8485 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1588 3.4241 -2.1282 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6491 2.7899 -0.4801 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2942 1.3745 0.3804 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8019 -1.2415 1.9245 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6388 1.6083 2.6079 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8456 0.0789 3.5772 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5976 -0.2525 2.4325 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1413 0.5322 2.3048 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0826 -0.3451 -1.2606 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8649 -0.4003 -2.1819 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.4877 0.5003 -1.5872 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8218 0.9014 1.7413 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.6392 2.0170 0.9235 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.1680 -0.9108 -3.5419 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4110 1.9193 4.3617 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8782 0.7559 5.6587 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8827 0.1343 4.2676 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 7 10 1 0 10 11 1 0 5 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 13 16 1 0 16 17 1 0 17 18 2 0 18 19 1 0 19 20 2 0 20 21 1 0 21 22 2 0 22 23 1 0 20 24 1 0 24 25 2 0 25 26 1 0 26 27 2 0 26 28 1 0 28 29 2 0 29 30 1 0 30 31 2 0 31 32 1 0 32 33 2 0 33 34 1 0 31 35 1 0 29 36 1 0 18 37 1 0 37 38 1 0 8 3 1 0 23 12 1 0 34 24 1 0 22 17 1 0 33 28 1 0 1 39 1 0 1 40 1 0 1 41 1 0 4 42 1 0 6 43 1 0 9 44 1 0 11 45 1 0 11 46 1 0 11 47 1 0 12 48 1 1 13 49 1 6 14 50 1 0 14 51 1 0 15 52 1 0 19 53 1 0 21 54 1 0 25 55 1 0 30 56 1 0 32 57 1 0 35 58 1 0 36 59 1 0 38 60 1 0 38 61 1 0 38 62 1 0 M END

Standard InCHIKey	KIEFQALNZCXSHH-ZEQKJWHPSA-N
Standard InCHI	InChI=1S/C27H24O11/c1-33-19-6-13(7-20(34-2)25(19)32)26-23(11-28)38-27-21(35-3)4-12(5-22(27)37-26)17-10-16(31)24-15(30)8-14(29)9-18(24)36-17/h4-10,23,26,28-30,32H,11H2,1-3H3/t23-,26-/m1/s1
SMILES	COc1cc(cc(c1O)OC)[C@@H]1[C@@H](CO)Oc2c(cc(cc2O1)c1cc(=O)c2c(cc(cc2o1)O)O)OC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	524.13	Volume:	500.457 ? Van der Waals volume.
Dense:	1.047	LogP:	2.721 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.45 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.779 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	29.0
TPSA:	157.28 ? Topological Polar Surface Area.	H-Bond Acceptor:	11.0
H-Bond Donor:	4.0	Rings:	5.0
Heavy Atoms:	11.0

MedChem Properties

QED Drug-Likeness Score:	0.293	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.714	Fsp³:	0.222
MCE-18:	96.758 ? 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:	Accepted	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.595	Fluc inhibitor:	0.553 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.873 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.787 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.136	Promiscuous compounds:	0.699

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.488	MDCK Permeability:	-5.027
Pgp-inhibitor:	0.62	Pgp-substrate:	0.483
PAMPA:	0.006 ? 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):	0.002
20% Bioavailability (F20%):	0.031	30% Bioavailability (F30%):	0.322
50% Bioavailability (F50%):	0.995

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.001	MRP1:	0.954
Plasma Protein Binding (PPB):	96.547%	Volume Distribution (VD):	-0.017
Fu:	2.772% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.997
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.999
BSEP inhibitor:	0.994

ADMET: Metabolism

CYP1A2-inhibitor:	0.893	CYP1A2-substrate:	0.611
CYP2C19-inhibitor:	0.631	CYP2C19-substrate:	0.169
CYP2C9-inhibitor:	0.986	CYP2C9-substrate:	0.706
CYP2D6-inhibitor:	0.994	CYP2D6-substrate:	0.998
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.572
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.943
HLM stability:	0.166 ? 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):

3.677

Half-life (T1/2):

2.186

ADMET: Toxicity

hERG Blockers:	0.064	hERG Blockers (10um):	0.298
Human Hepatotoxicity (H-HT):	0.689	Drug-induced Liver Injury (DILI):	0.909
AMES Toxicity:	0.77	Rat Oral Acute Toxicity:	0.328
Maximum Recommended Daily Dose:	0.623	Skin Sensitization:	0.967
Carcinogencity:	0.839	Eye Corrosion:	0.004
Eye Irritation:	0.954	Respiratory Toxicity:	0.538
Drug-induced Neurotoxicity:	0.152	Ototoxicity:	0.291
Hematotoxicity:	0.173	Drug-induced Nephrotoxicity:	0.116
Genotoxicity:	0.929	RPMI-8226 Immunitoxicity:	0.141
A549 Cytotoxicity:	0.579	Hek293 Cytotoxicity:	0.838
BCF:	0.902 ? 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:	3.635 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.82 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.076 ? 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
NPO19975	Pycnandra acuminata	Species	Sapotaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1016/j.phytochem.2007.07.001]
NPO40862	Hymeneae palustris	Species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[12608861]
NPO5140	Dipteryx odorata	Species	Fabaceae	Eukaryota	seeds	n.a.	n.a.	PMID[12762787]
NPO5140	Dipteryx odorata	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[12762809]
NPO6412	Echinacea pallida	Species	Asteraceae	Eukaryota	root	n.a.	n.a.	PMID[15921428]
NPO8129	Inocybe geophylla	Species	Inocybaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO5140	Dipteryx odorata	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO6412	Echinacea pallida	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO6856.1	Artemisia ludoviciana subsp. mexicana	Subspecies	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO10010	Evernia vulpina	Species	Parmeliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO11339	Litsea salicifolia	Species	Lauraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8609	Hopea utilis	Species	Dipterocarpaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO5534	Alternaria kikuchiana	Species	Pleosporaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7874	Helichrysum lepidissimum	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO1695	Monascus pilosus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12828	Dysidea tupha	Species	Dysideidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO5140	Dipteryx odorata	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO20569	Psychotria serpens	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO633	Mesembryanthemum expansum	Species	Aizoaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO5140	Dipteryx odorata	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO6856.1	Artemisia ludoviciana subsp. mexicana	Subspecies	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO20569	Psychotria serpens	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO633	Mesembryanthemum expansum	Species	Aizoaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO20569	Psychotria serpens	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO10010	Evernia vulpina	Species	Parmeliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12602	Leuzea centauroides	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO218	Acer carpinifolium	Species	Sapindaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO11506	Stipa vaseyi	Species	Poaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO26095	Hypericum revolutum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO20569	Psychotria serpens	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO5534	Alternaria kikuchiana	Species	Pleosporaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO19975	Pycnandra acuminata	Species	Sapotaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1695	Monascus pilosus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO5140	Dipteryx odorata	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO6412	Echinacea pallida	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12118	Cleistopholis staudtii	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO11339	Litsea salicifolia	Species	Lauraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO6861	Galium dasypodum	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO940	Vernonia anisochaetoides	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12828	Dysidea tupha	Species	Dysideidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO4759	Helleborus multifidus	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO10970	Osmorhiza aristata	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8129	Inocybe geophylla	Species	Inocybaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO7874	Helichrysum lepidissimum	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO4322	Scabiosa succisa	Species	Caprifoliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO633	Mesembryanthemum expansum	Species	Aizoaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO6856.1	Artemisia ludoviciana subsp. mexicana	Subspecies	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8609	Hopea utilis	Species	Dipterocarpaceae	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	1
GI50	7

Activity Type	# Activity
Cell line	7
Organism	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
NPT90	Cell line	DU-145	Homo sapiens	GI50	>	10.0	ug.mL-1	PMID[12608861]
NPT575	Cell line	KM-20L2	Homo sapiens	GI50	>	10.0	ug.mL-1	PMID[12608861]
NPT397	Cell line	NCI-H460	Homo sapiens	GI50	=	5.9	ug.mL-1	PMID[12608861]
NPT395	Cell line	SF-268	Homo sapiens	GI50	>	10.0	ug.mL-1	PMID[12608861]
NPT83	Cell line	MCF7	Homo sapiens	GI50	=	3.6	ug.mL-1	PMID[12608861]
NPT1081	Cell line	BXPC-3	Homo sapiens	GI50	=	3.2	ug.mL-1	PMID[12608861]
NPT168	Cell line	P388	Mus musculus	GI50	=	8.5	ug.mL-1	PMID[12608861]
NPT1522	Organism	Neisseria gonorrhoeae	Neisseria gonorrhoeae	MIC	=	1.0	ug.mL-1	PMID[12608861]

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 NPC101731 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	27328
0.1-0.2	19189
0.2-0.3	2648
0.3-0.4	598
0.4-0.5	70
0.5-0.6	11
0.6-0.7	8
0.7-0.8	0
0.8-0.85	3
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8442	Intermediate Similarity	NPC84324
0.8289	Intermediate Similarity	NPC165970
0.8182	Intermediate Similarity	NPC288131
0.7059	Intermediate Similarity	NPC476410
0.7024	Intermediate Similarity	NPC113163
0.6941	Remote Similarity	NPC66618
0.6941	Remote Similarity	NPC305987
0.65	Remote Similarity	NPC63454
0.65	Remote Similarity	NPC183851
0.6429	Remote Similarity	NPC62536
0.6353	Remote Similarity	NPC172202
0.6353	Remote Similarity	NPC284127
0.6197	Remote Similarity	NPC120464
0.5842	Remote Similarity	NPC475212
0.5733	Remote Similarity	NPC606638
0.5676	Remote Similarity	NPC600900
0.5541	Remote Similarity	NPC483773
0.5526	Remote Similarity	NPC12200
0.5256	Remote Similarity	NPC183950
0.5181	Remote Similarity	NPC183
0.5132	Remote Similarity	NPC231772
0.5132	Remote Similarity	NPC601901
0.5128	Remote Similarity	NPC52005
0.5109	Remote Similarity	NPC309025

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC101731 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5115
0.1-0.2	3971
0.2-0.3	57
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