NPASS Compound

Natural Product: NPC80732

Natural Product ID	NPC80732
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Quiquesetinerviuside A
IUPAC Name	[(2R,3R,4S,5S)-5-[(2R,3R,4R,5S,6R)-3,4-dihydroxy-5-[(E)-3-(4-hydroxy-3-methoxyphenyl)prop-2-enoyl]oxy-6-(hydroxymethyl)oxan-2-yl]oxy-3-hydroxy-4-[(E)-3-(4-hydroxy-3-methoxyphenyl)prop-2-enoyl]oxy-5-(hydroxymethyl)oxolan-2-yl]methyl (E)-3-(4-hydroxy-3-methoxyphenyl)prop-2-enoate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1224877
PubChem CID	49866356
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000476] Cinnamic acids and derivatives [CHEMONTID:0001391] Hydroxycinnamic acids and derivatives [CHEMONTID:0000059] Coumaric acids and derivatives

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

Chemical Representations

RDKit 2D 108112 0 0 0 0 0 0 0 0999 V2000 3.7981 -1.9284 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.6491 -0.9642 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5000 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7500 -1.2990 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.7500 -1.2990 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1595 -1.8121 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.4200 -3.2893 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9237 -3.3939 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5727 -3.4985 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.3677 -4.7884 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.7772 -5.3014 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7007 -4.1194 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8619 -2.8758 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3000 -1.4850 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.2235 -0.3030 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7089 -0.5118 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.6616 1.0877 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5851 2.2698 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0232 3.6605 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5378 3.8693 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9758 5.2601 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8993 6.4421 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3847 6.2333 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9467 4.8426 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3082 7.4153 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.7936 7.2066 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3374 7.8329 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.8498 -3.1552 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.0493 -6.0963 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3213 -6.8912 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.2690 -8.3902 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9446 -9.0944 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.5411 -9.1851 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.4887 -10.6842 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.7608 -11.4791 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.0852 -10.7749 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -11.3573 -11.5698 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -11.3049 -13.0688 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.9805 -13.7730 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.7084 -12.9782 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.9282 -15.2721 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.6037 -15.9763 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -12.5770 -13.8637 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.5000 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7500 1.2990 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7500 1.2990 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1595 1.8121 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.4200 3.2893 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2709 4.2535 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.8296 3.8023 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9786 2.8381 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3882 3.3512 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6486 4.8284 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 8.0582 5.3414 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 9.2072 4.3772 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 8.9468 2.9000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.5372 2.3870 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 10.0958 1.9358 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 9.8354 0.4586 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 10.6168 4.8902 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.4895 2.7762 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6491 0.9642 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 5.2077 -1.4153 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6132 0.1849 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6849 -2.1132 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6491 0.9642 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3897 -2.1082 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6773 -2.6358 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0283 -4.8903 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2302 -4.8467 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1196 -6.6496 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8987 -5.0221 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1863 -2.1716 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3497 1.8151 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0705 2.0610 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6143 2.6873 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4904 5.4688 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4321 4.6338 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0024 8.6920 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5849 5.7212 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.2790 6.9978 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2609 9.0149 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2593 -3.6682 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2544 -7.3683 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9933 -4.9306 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.8655 -8.4809 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1643 -11.3884 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.1376 -9.2758 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -12.6817 -10.8655 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3840 -13.6824 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.3080 -17.3008 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8995 -14.6519 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2793 -16.6806 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -12.5247 -15.3628 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8482 -0.6575 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0865 1.9801 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6715 2.7970 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0900 5.2795 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7181 1.3609 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4996 5.7926 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 8.3186 6.8186 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2768 0.9098 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 11.3126 0.1981 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 8.3581 0.7191 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 9.5749 -1.0186 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 11.7658 3.9261 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8470 3.4573 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1344 1.1731 0.0000 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 7 6 1 6 7 8 1 0 8 9 1 0 7 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 2 0 15 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 23 24 2 0 23 25 1 0 25 26 1 0 22 27 1 0 12 28 1 0 11 29 1 0 29 30 1 0 30 31 1 0 31 32 2 0 31 33 1 0 33 34 2 0 34 35 1 0 35 36 2 0 36 37 1 0 37 38 2 0 38 39 1 0 39 40 2 0 39 41 1 0 41 42 1 0 38 43 1 0 5 44 1 0 44 45 1 0 45 46 1 0 46 47 1 0 47 48 1 0 48 49 2 0 48 50 1 0 50 51 2 0 51 52 1 0 52 53 2 0 53 54 1 0 54 55 2 0 55 56 1 0 56 57 2 0 56 58 1 0 58 59 1 0 55 60 1 0 45 61 1 0 44 62 1 0 46 3 1 0 57 52 1 0 13 7 1 0 24 19 1 0 40 35 1 0 1 63 1 0 2 64 1 0 2 65 1 0 3 66 1 6 5 67 1 1 8 68 1 0 8 69 1 0 9 70 1 0 11 71 1 1 12 72 1 6 13 73 1 1 17 74 1 0 18 75 1 0 20 76 1 0 21 77 1 0 24 78 1 0 26 79 1 0 26 80 1 0 26 81 1 0 27 82 1 0 28 83 1 0 29 84 1 0 29 85 1 0 33 86 1 0 34 87 1 0 36 88 1 0 37 89 1 0 40 90 1 0 42 91 1 0 42 92 1 0 42 93 1 0 43 94 1 0 44 95 1 1 45 96 1 6 46 97 1 1 50 98 1 0 51 99 1 0 53100 1 0 54101 1 0 57102 1 0 59103 1 0 59104 1 0 59105 1 0 60106 1 0 61107 1 0 62108 1 0 M END

Standard InCHIKey	KIPKMNJEYYODAH-GPLAAAJXSA-N
Standard InCHI	InChI=1S/C42H46O20/c1-54-28-16-22(4-10-25(28)45)7-13-33(48)57-20-32-36(51)40(60-35(50)15-9-24-6-12-27(47)30(18-24)56-3)42(21-44,61-32)62-41-38(53)37(52)39(31(19-43)58-41)59-34(49)14-8-23-5-11-26(46)29(17-23)55-2/h4-18,31-32,36-41,43-47,51-53H,19-21H2,1-3H3/b13-7+,14-8+,15-9+/t31-,32-,36-,37-,38-,39-,40+,41-,42+/m1/s1
SMILES	OC[C@H]1O[C@H](O[C@]2(CO)O[C@@H]([C@H]([C@@H]2OC(=O)/C=C/c2ccc(c(c2)OC)O)O)COC(=O)/C=C/c2ccc(c(c2)OC)O)[C@@H]([C@H]([C@@H]1OC(=O)/C=C/c1ccc(c(c1)OC)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	870.26	Volume:	828.463 ? Van der Waals volume.
Dense:	1.05	LogP:	1.65 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.98 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.254 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	20.0	Rigid Bonds:	35.0
TPSA:	296.12 ? Topological Polar Surface Area.	H-Bond Acceptor:	20.0
H-Bond Donor:	8.0	Rings:	5.0
Heavy Atoms:	20.0

MedChem Properties

QED Drug-Likeness Score:	0.052	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.269	Fsp³:	0.357
MCE-18:	126.0 ? 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:	0.934	Fluc inhibitor:	1.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.204 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.663 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.19	Promiscuous compounds:	0.294

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.236	MDCK Permeability:	-5.475
Pgp-inhibitor:	0.06	Pgp-substrate:	0.01
PAMPA:	0.849 ? 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):	0.775
20% Bioavailability (F20%):	0.997	30% Bioavailability (F30%):	1.0
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.001
Plasma Protein Binding (PPB):	72.066%	Volume Distribution (VD):	-0.42
Fu:	23.875% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.308
BSEP inhibitor:	0.988

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.003
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.001
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.999
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.252 ? 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):

1.462

Half-life (T1/2):

3.408

ADMET: Toxicity

hERG Blockers:	0.048	hERG Blockers (10um):	0.522
Human Hepatotoxicity (H-HT):	0.445	Drug-induced Liver Injury (DILI):	0.837
AMES Toxicity:	0.918	Rat Oral Acute Toxicity:	0.068
Maximum Recommended Daily Dose:	0.43	Skin Sensitization:	1.0
Carcinogencity:	0.041	Eye Corrosion:	0.0
Eye Irritation:	0.049	Respiratory Toxicity:	0.052
Drug-induced Neurotoxicity:	0.121	Ototoxicity:	0.848
Hematotoxicity:	0.102	Drug-induced Nephrotoxicity:	0.887
Genotoxicity:	0.237	RPMI-8226 Immunitoxicity:	0.464
A549 Cytotoxicity:	0.849	Hek293 Cytotoxicity:	0.796
BCF:	0.613 ? 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:	3.361 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.153 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.368 ? 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
NPO32697	calamus quiquesetinervius	Species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[20056545]
NPO32697	calamus quiquesetinervius	Species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[20825224]
NPO32697	calamus quiquesetinervius	Species	n.a.	n.a.	n.a.	n.a.	n.a.	Database[COCONUT]

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	4
Activity	2

Activity Type	# Activity
Cell line	3
Others	1
Non-molecular	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
NPT113	Cell line	RAW264.7	Mus musculus	IC50	=	78100.0	nM	DOI[10.6019/CHEMBL1201861]
NPT113	Cell line	RAW264.7	Mus musculus	Activity	>	90.0	%	PMID[23398362]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	6800.0	nM	PMID[20825224]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	>	200000.0	nM	PMID[20825224]
NPT1	Others	Radical scavenging activity	n.a.	IC50	=	62500.0	nM	PMID[19506058]

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 NPC80732 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	12963
0.1-0.2	32312
0.2-0.3	3809
0.3-0.4	627
0.4-0.5	108
0.5-0.6	18
0.6-0.7	12
0.7-0.8	0
0.8-0.85	4
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8415	Intermediate Similarity	NPC199311
0.825	Intermediate Similarity	NPC262182
0.8193	Intermediate Similarity	NPC287615
0.8023	Intermediate Similarity	NPC261122
0.7738	Intermediate Similarity	NPC192763
0.7738	Intermediate Similarity	NPC300262
0.75	Intermediate Similarity	NPC83743
0.7412	Intermediate Similarity	NPC216819
0.7386	Intermediate Similarity	NPC210611
0.6905	Remote Similarity	NPC472612
0.6548	Remote Similarity	NPC225307
0.6522	Remote Similarity	NPC3460
0.6452	Remote Similarity	NPC472611
0.6413	Remote Similarity	NPC125823
0.6413	Remote Similarity	NPC7145
0.6413	Remote Similarity	NPC143480
0.6364	Remote Similarity	NPC90896
0.625	Remote Similarity	NPC226005
0.6211	Remote Similarity	NPC201148
0.6022	Remote Similarity	NPC283839
0.6	Remote Similarity	NPC85192
0.5938	Remote Similarity	NPC215095
0.5729	Remote Similarity	NPC173343
0.5699	Remote Similarity	NPC289967
0.5632	Remote Similarity	NPC297342
0.5368	Remote Similarity	NPC476865
0.5354	Remote Similarity	NPC149873
0.5326	Remote Similarity	NPC28637
0.5294	Remote Similarity	NPC28651
0.5248	Remote Similarity	NPC59516
0.5181	Remote Similarity	NPC157554
0.5169	Remote Similarity	NPC601579
0.5161	Remote Similarity	NPC471405
0.5158	Remote Similarity	NPC44730
0.5158	Remote Similarity	NPC476868
0.5054	Remote Similarity	NPC291296
0.5053	Remote Similarity	NPC476869
0.5051	Remote Similarity	NPC11411
0.505	Remote Similarity	NPC7191

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC80732 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4031
0.1-0.2	5024
0.2-0.3	89
0.3-0.4	5
0.4-0.5	1
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