NPASS Compound

Natural Product: NPC477015

Natural Product ID	NPC477015
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Plagioneurin C
IUPAC Name	[(1R)-1-hydroxy-1-[(2R,5R)-5-[(1R)-1-hydroxytridecyl]oxolan-2-yl]-15-[(2S)-2-methyl-5-oxo-2H-furan-4-yl]-8-oxopentadecan-3-yl] acetate
Synonyms	Plagioneurin C
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	16086528
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0003909] Fatty Acyls [CHEMONTID:0001334] Fatty alcohols [CHEMONTID:0002518] Annonaceous acetogenins

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 115116 0 0 0 0 0 0 0 0999 V2000 -13.9265 0.6099 1.4733 C 0 0 0 0 0 0 0 0 0 0 0 0 -13.1144 1.5023 0.5498 C 0 0 0 0 0 0 0 0 0 0 0 0 -13.0245 1.0253 -0.8412 C 0 0 0 0 0 0 0 0 0 0 0 0 -12.4963 -0.2922 -1.1676 C 0 0 0 0 0 0 0 0 0 0 0 0 -11.1157 -0.6012 -0.8060 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.7777 -0.6127 0.6513 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.2827 -1.0219 0.7056 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.7704 -1.1011 2.1049 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.8657 0.1962 2.7963 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.2301 1.3981 2.2642 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.7740 1.3789 2.0935 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1560 0.4403 1.1177 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6421 0.7231 1.1989 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.8977 -0.1745 0.2398 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.1710 0.1541 -1.1907 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8436 0.6678 -1.6965 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0460 0.8574 -0.4532 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.5492 -0.0329 0.4583 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.5387 0.5943 -0.6532 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.3609 -0.8389 -0.7885 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0389 -1.4151 -0.9766 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6514 -0.8843 -2.1932 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9638 -1.2673 -2.6870 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2311 -0.9654 -2.0641 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6390 -1.3938 -0.7220 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0956 -0.9512 -0.5319 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5749 -0.2680 -1.3833 O 0 0 0 0 0 0 0 0 0 0 0 0 6.8429 -1.3686 0.6599 C 0 0 0 0 0 0 0 0 0 0 0 0 8.2516 -0.8645 0.7354 C 0 0 0 0 0 0 0 0 0 0 0 0 9.0409 -1.3440 -0.4359 C 0 0 0 0 0 0 0 0 0 0 0 0 10.5053 -0.8250 -0.3365 C 0 0 0 0 0 0 0 0 0 0 0 0 11.1810 -1.3244 -1.5690 C 0 0 0 0 0 0 0 0 0 0 0 0 12.6056 -1.0275 -1.7600 C 0 0 0 0 0 0 0 0 0 0 0 0 13.0780 0.3687 -1.8446 C 0 0 0 0 0 0 0 0 0 0 0 0 12.8643 1.2257 -0.6568 C 0 0 0 0 0 0 0 0 0 0 0 0 12.2085 2.3577 -0.5628 C 0 0 0 0 0 0 0 0 0 0 0 0 12.2528 2.8630 0.8112 C 0 0 1 0 0 0 0 0 0 0 0 0 13.0080 1.9328 1.5271 O 0 0 0 0 0 0 0 0 0 0 0 0 13.3918 0.9260 0.6794 C 0 0 0 0 0 0 0 0 0 0 0 0 14.0853 -0.1161 0.9392 O 0 0 0 0 0 0 0 0 0 0 0 0 12.8991 4.2379 0.7938 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7569 -1.3679 0.1967 O 0 0 0 0 0 0 0 0 0 0 0 0 2.0194 -2.5165 0.9675 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5902 -3.6137 0.5851 O 0 0 0 0 0 0 0 0 0 0 0 0 2.8174 -2.2981 2.2135 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0396 1.4560 -1.5875 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.2918 0.3626 2.4965 O 0 0 0 0 0 0 0 0 0 0 0 0 -13.1769 0.0654 2.1184 H 0 0 0 0 0 0 0 0 0 0 0 0 -14.5286 1.1943 2.1846 H 0 0 0 0 0 0 0 0 0 0 0 0 -14.4768 -0.1669 0.9252 H 0 0 0 0 0 0 0 0 0 0 0 0 -13.8140 2.4413 0.4738 H 0 0 0 0 0 0 0 0 0 0 0 0 -12.2284 1.9325 1.0168 H 0 0 0 0 0 0 0 0 0 0 0 0 -14.0584 1.1309 -1.2996 H 0 0 0 0 0 0 0 0 0 0 0 0 -12.4029 1.7931 -1.3992 H 0 0 0 0 0 0 0 0 0 0 0 0 -13.1707 -1.1168 -0.7612 H 0 0 0 0 0 0 0 0 0 0 0 0 -12.5486 -0.3812 -2.3166 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.3609 0.0735 -1.3056 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.7888 -1.6290 -1.1886 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.3412 -1.3774 1.2220 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.8125 0.3303 1.1785 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.2028 -1.9823 0.1774 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.7816 -0.2450 0.0929 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.5441 -1.7810 2.6480 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8614 -1.6929 2.2287 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.3921 0.0267 3.8385 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.9686 0.3823 2.9908 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.7670 1.8214 1.3593 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.4398 2.2317 3.0322 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2351 1.1955 3.0799 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3778 2.4089 1.8007 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4949 0.7275 0.0840 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2476 -0.6180 1.2802 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4759 1.7865 1.0416 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1496 -1.2346 0.4259 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9752 0.9134 -1.3062 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4244 -0.7611 -1.7663 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3655 -0.0937 -2.3384 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9825 1.6311 -2.2627 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1895 1.9240 -0.1405 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0971 0.9205 0.3409 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0311 -1.2656 -1.5707 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7375 -1.3236 0.1722 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7907 -2.5453 -1.1675 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9050 -0.9759 -3.0732 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6464 0.2777 -2.0382 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9838 -0.9099 -3.8051 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8827 -2.4167 -2.8808 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5077 0.1533 -2.1721 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0448 -1.3938 -2.7843 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5042 -2.4473 -0.5430 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1376 -0.8051 0.1036 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3201 -1.0696 1.6136 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8124 -2.4977 0.6999 H 0 0 0 0 0 0 0 0 0 0 0 0 8.3023 0.2357 0.8770 H 0 0 0 0 0 0 0 0 0 0 0 0 8.6911 -1.2859 1.6848 H 0 0 0 0 0 0 0 0 0 0 0 0 8.6995 -0.9932 -1.3990 H 0 0 0 0 0 0 0 0 0 0 0 0 9.1435 -2.4499 -0.3650 H 0 0 0 0 0 0 0 0 0 0 0 0 10.8910 -1.2817 0.5893 H 0 0 0 0 0 0 0 0 0 0 0 0 10.4819 0.2645 -0.2648 H 0 0 0 0 0 0 0 0 0 0 0 0 10.5627 -1.0108 -2.4785 H 0 0 0 0 0 0 0 0 0 0 0 0 11.0776 -2.4590 -1.6237 H 0 0 0 0 0 0 0 0 0 0 0 0 12.9149 -1.5687 -2.7199 H 0 0 0 0 0 0 0 0 0 0 0 0 13.1709 -1.5283 -0.9088 H 0 0 0 0 0 0 0 0 0 0 0 0 14.1941 0.4053 -2.0506 H 0 0 0 0 0 0 0 0 0 0 0 0 12.6486 0.8547 -2.7572 H 0 0 0 0 0 0 0 0 0 0 0 0 11.7090 2.8424 -1.3885 H 0 0 0 0 0 0 0 0 0 0 0 0 11.2130 2.9500 1.2264 H 0 0 0 0 0 0 0 0 0 0 0 0 13.3360 4.4680 -0.1785 H 0 0 0 0 0 0 0 0 0 0 0 0 13.6079 4.2485 1.6454 H 0 0 0 0 0 0 0 0 0 0 0 0 12.1231 5.0290 1.0149 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4525 -2.9589 3.0392 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6680 -1.2728 2.5642 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9074 -2.4343 2.0148 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4675 1.3977 -2.4782 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0914 -0.5929 2.5957 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 0 7 8 1 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 17 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 26 27 2 0 26 28 1 0 28 29 1 0 29 30 1 0 30 31 1 0 31 32 1 0 32 33 1 0 33 34 1 0 34 35 1 0 35 36 2 0 36 37 1 0 37 38 1 0 38 39 1 0 39 40 2 0 37 41 1 0 21 42 1 0 42 43 1 0 43 44 2 0 43 45 1 0 19 46 1 0 13 47 1 0 18 14 1 0 39 35 1 0 1 48 1 0 1 49 1 0 1 50 1 0 2 51 1 0 2 52 1 0 3 53 1 0 3 54 1 0 4 55 1 0 4 56 1 0 5 57 1 0 5 58 1 0 6 59 1 0 6 60 1 0 7 61 1 0 7 62 1 0 8 63 1 0 8 64 1 0 9 65 1 0 9 66 1 0 10 67 1 0 10 68 1 0 11 69 1 0 11 70 1 0 12 71 1 0 12 72 1 0 13 73 1 6 14 74 1 1 15 75 1 0 15 76 1 0 16 77 1 0 16 78 1 0 17 79 1 1 19 80 1 1 20 81 1 0 20 82 1 0 21 83 1 0 22 84 1 0 22 85 1 0 23 86 1 0 23 87 1 0 24 88 1 0 24 89 1 0 25 90 1 0 25 91 1 0 28 92 1 0 28 93 1 0 29 94 1 0 29 95 1 0 30 96 1 0 30 97 1 0 31 98 1 0 31 99 1 0 32100 1 0 32101 1 0 33102 1 0 33103 1 0 34104 1 0 34105 1 0 36106 1 0 37107 1 1 41108 1 0 41109 1 0 41110 1 0 45111 1 0 45112 1 0 45113 1 0 46114 1 0 47115 1 0 M END

Standard InCHIKey	IBZMIWHQUSQKBP-WFDUAHCHSA-N
Standard InCHI	InChI=1S/C39H68O8/c1-4-5-6-7-8-9-10-11-15-18-25-35(42)37-26-27-38(47-37)36(43)29-34(46-31(3)40)24-20-19-23-33(41)22-17-14-12-13-16-21-32-28-30(2)45-39(32)44/h28,30,34-38,42-43H,4-27,29H2,1-3H3/t30-,34?,35+,36+,37+,38+/m0/s1
SMILES	CCCCCCCCCCCC[C@H]([C@H]1CC[C@@H](O1)[C@@H](CC(CCCCC(=O)CCCCCCCC2=C[C@@H](OC2=O)C)OC(=O)C)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	664.49	Volume:	725.763 ? Van der Waals volume.
Dense:	0.916	LogP:	6.46 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.252 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.898 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	30.0	Rigid Bonds:	13.0
TPSA:	119.36 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	2.0	Rings:	2.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.06	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.66	Fsp³:	0.872
MCE-18:	34.192 ? 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:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.826	Fluc inhibitor:	0.027 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.048 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.003 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.483	Promiscuous compounds:	0.394

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.225	MDCK Permeability:	-4.802
Pgp-inhibitor:	0.019	Pgp-substrate:	0.643
PAMPA:	0.008 ? 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):	0.058
20% Bioavailability (F20%):	0.929	30% Bioavailability (F30%):	0.982
50% Bioavailability (F50%):	0.991

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.996
Plasma Protein Binding (PPB):	97.594%	Volume Distribution (VD):	0.618
Fu:	2.518% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.461
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.169
BSEP inhibitor:	0.991

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	1.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.912
CYP2C9-inhibitor:	0.034	CYP2C9-substrate:	0.29
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.998
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.997
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.5 ? 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):

4.565

Half-life (T1/2):

1.694

ADMET: Toxicity

hERG Blockers:	0.586	hERG Blockers (10um):	0.868
Human Hepatotoxicity (H-HT):	0.569	Drug-induced Liver Injury (DILI):	0.464
AMES Toxicity:	0.525	Rat Oral Acute Toxicity:	0.111
Maximum Recommended Daily Dose:	0.897	Skin Sensitization:	1.0
Carcinogencity:	0.399	Eye Corrosion:	0.015
Eye Irritation:	0.541	Respiratory Toxicity:	0.815
Drug-induced Neurotoxicity:	0.167	Ototoxicity:	0.452
Hematotoxicity:	0.153	Drug-induced Nephrotoxicity:	0.943
Genotoxicity:	0.0	RPMI-8226 Immunitoxicity:	0.145
A549 Cytotoxicity:	0.949	Hek293 Cytotoxicity:	0.452
BCF:	0.605 ? 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:	4.864 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.462 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.15 ? 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
NPO22123	Disepalum plagioneurum	Species	Annonaceae	Eukaryota	leaves	Tam Kim, Cao Bang Province, in North Vietnam	2000-JUN	PMID[16989521]
NPO22123	Disepalum plagioneurum	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO22123	Disepalum plagioneurum	Species	Annonaceae	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	1

Activity Type	# Activity
Cell line	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
NPT91	Cell line	KB	Homo sapiens	IC50	=	26	nM	PMID[16989521]

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 NPC477015 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	17767
0.1-0.2	29098
0.2-0.3	2681
0.3-0.4	88
0.4-0.5	33
0.5-0.6	107
0.6-0.7	55
0.7-0.8	0
0.8-0.85	4
0.85-0.9	2
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8772	High Similarity	NPC477017
0.8772	High Similarity	NPC477016
0.8364	Intermediate Similarity	NPC477014
0.8364	Intermediate Similarity	NPC477013
0.8269	Intermediate Similarity	NPC144415
0.8269	Intermediate Similarity	NPC608157
0.75	Intermediate Similarity	NPC605396
0.7193	Intermediate Similarity	NPC477010
0.7143	Intermediate Similarity	NPC241360
0.7143	Intermediate Similarity	NPC293136
0.7115	Intermediate Similarity	NPC73310
0.7115	Intermediate Similarity	NPC473529
0.7115	Intermediate Similarity	NPC180363
0.7115	Intermediate Similarity	NPC94875
0.7115	Intermediate Similarity	NPC11332
0.7115	Intermediate Similarity	NPC145914
0.7115	Intermediate Similarity	NPC601174
0.7115	Intermediate Similarity	NPC601403
0.7115	Intermediate Similarity	NPC603568
0.7115	Intermediate Similarity	NPC604330
0.7115	Intermediate Similarity	NPC608300
0.7115	Intermediate Similarity	NPC611200
0.7115	Intermediate Similarity	NPC611571
0.7069	Intermediate Similarity	NPC477012
0.6885	Remote Similarity	NPC280612
0.6727	Remote Similarity	NPC329829
0.6727	Remote Similarity	NPC475159
0.6727	Remote Similarity	NPC131002
0.6727	Remote Similarity	NPC473780
0.6727	Remote Similarity	NPC604521
0.6724	Remote Similarity	NPC473687
0.6724	Remote Similarity	NPC204686
0.6724	Remote Similarity	NPC219498
0.6724	Remote Similarity	NPC65930
0.6724	Remote Similarity	NPC308412
0.6724	Remote Similarity	NPC134885
0.6724	Remote Similarity	NPC488247
0.6724	Remote Similarity	NPC210218
0.6724	Remote Similarity	NPC488248
0.6667	Remote Similarity	NPC163093
0.6667	Remote Similarity	NPC258068
0.6667	Remote Similarity	NPC476583
0.661	Remote Similarity	NPC134807
0.6491	Remote Similarity	NPC156804
0.6462	Remote Similarity	NPC482766
0.6429	Remote Similarity	NPC25764
0.6429	Remote Similarity	NPC235809
0.6429	Remote Similarity	NPC39279
0.6429	Remote Similarity	NPC39167
0.6429	Remote Similarity	NPC292809
0.6429	Remote Similarity	NPC202055
0.6429	Remote Similarity	NPC606804
0.6429	Remote Similarity	NPC607425
0.6429	Remote Similarity	NPC608574
0.6393	Remote Similarity	NPC473995
0.6379	Remote Similarity	NPC607439
0.6333	Remote Similarity	NPC329615
0.6167	Remote Similarity	NPC478998
0.614	Remote Similarity	NPC100921
0.614	Remote Similarity	NPC477018
0.6129	Remote Similarity	NPC120398
0.6129	Remote Similarity	NPC471567
0.6102	Remote Similarity	NPC473156
0.6102	Remote Similarity	NPC282815
0.6102	Remote Similarity	NPC600956
0.6094	Remote Similarity	NPC473520
0.6066	Remote Similarity	NPC329838
0.6032	Remote Similarity	NPC320458
0.6032	Remote Similarity	NPC480082
0.6	Remote Similarity	NPC473671
0.6	Remote Similarity	NPC219652
0.6	Remote Similarity	NPC475268
0.6	Remote Similarity	NPC473840
0.6	Remote Similarity	NPC470400
0.6	Remote Similarity	NPC77871
0.6	Remote Similarity	NPC9678
0.6	Remote Similarity	NPC253801
0.6	Remote Similarity	NPC319036
0.6	Remote Similarity	NPC605867
0.5902	Remote Similarity	NPC132940
0.5833	Remote Similarity	NPC610454
0.5806	Remote Similarity	NPC20621
0.5806	Remote Similarity	NPC318963
0.5806	Remote Similarity	NPC20533
0.5806	Remote Similarity	NPC485250
0.5806	Remote Similarity	NPC600188
0.5806	Remote Similarity	NPC605101
0.5738	Remote Similarity	NPC25703
0.569	Remote Similarity	NPC606043
0.5645	Remote Similarity	NPC473699
0.5645	Remote Similarity	NPC51249
0.5625	Remote Similarity	NPC130359
0.5625	Remote Similarity	NPC14901
0.5606	Remote Similarity	NPC322529
0.5593	Remote Similarity	NPC107986
0.5593	Remote Similarity	NPC223871
0.5593	Remote Similarity	NPC231009
0.5593	Remote Similarity	NPC103284
0.5593	Remote Similarity	NPC110710
0.5593	Remote Similarity	NPC1083
0.5593	Remote Similarity	NPC82795
0.5593	Remote Similarity	NPC286338
0.5593	Remote Similarity	NPC603931
0.5593	Remote Similarity	NPC604237
0.5574	Remote Similarity	NPC473649
0.5574	Remote Similarity	NPC154097
0.5574	Remote Similarity	NPC159750
0.5574	Remote Similarity	NPC73248
0.5574	Remote Similarity	NPC470401
0.5574	Remote Similarity	NPC600524
0.5574	Remote Similarity	NPC608355
0.5556	Remote Similarity	NPC309211
0.5538	Remote Similarity	NPC89001
0.5522	Remote Similarity	NPC473905
0.55	Remote Similarity	NPC488253
0.55	Remote Similarity	NPC473669
0.55	Remote Similarity	NPC488251
0.5484	Remote Similarity	NPC604764
0.5469	Remote Similarity	NPC473478
0.5469	Remote Similarity	NPC473651
0.5469	Remote Similarity	NPC66346
0.5455	Remote Similarity	NPC609415
0.541	Remote Similarity	NPC232555
0.541	Remote Similarity	NPC171174
0.541	Remote Similarity	NPC182383
0.541	Remote Similarity	NPC114694
0.541	Remote Similarity	NPC485248
0.541	Remote Similarity	NPC142117
0.541	Remote Similarity	NPC480249
0.541	Remote Similarity	NPC485249
0.541	Remote Similarity	NPC240695
0.5397	Remote Similarity	NPC178215
0.5385	Remote Similarity	NPC283085
0.5385	Remote Similarity	NPC169511
0.5385	Remote Similarity	NPC287164
0.5385	Remote Similarity	NPC234077
0.5385	Remote Similarity	NPC132496
0.5373	Remote Similarity	NPC488630
0.5373	Remote Similarity	NPC488625
0.5373	Remote Similarity	NPC488626
0.5323	Remote Similarity	NPC488632
0.5323	Remote Similarity	NPC134865
0.5323	Remote Similarity	NPC103523
0.5323	Remote Similarity	NPC488627
0.5323	Remote Similarity	NPC488631
0.5323	Remote Similarity	NPC477011
0.5294	Remote Similarity	NPC475206
0.5238	Remote Similarity	NPC280621
0.5238	Remote Similarity	NPC48338
0.5238	Remote Similarity	NPC488628
0.5231	Remote Similarity	NPC11456
0.5231	Remote Similarity	NPC139418
0.5161	Remote Similarity	NPC81045
0.5161	Remote Similarity	NPC39754
0.5161	Remote Similarity	NPC171135
0.5161	Remote Similarity	NPC61257
0.5161	Remote Similarity	NPC320569
0.5161	Remote Similarity	NPC133730
0.5161	Remote Similarity	NPC191929
0.5161	Remote Similarity	NPC100454
0.5161	Remote Similarity	NPC242364
0.5161	Remote Similarity	NPC172821
0.5161	Remote Similarity	NPC274446
0.5161	Remote Similarity	NPC485251
0.5161	Remote Similarity	NPC151403
0.5161	Remote Similarity	NPC261952
0.5161	Remote Similarity	NPC605171
0.5152	Remote Similarity	NPC231096
0.5152	Remote Similarity	NPC475581
0.5152	Remote Similarity	NPC62118
0.5152	Remote Similarity	NPC107717
0.5152	Remote Similarity	NPC488252
0.5147	Remote Similarity	NPC91067
0.5079	Remote Similarity	NPC93794
0.5079	Remote Similarity	NPC473504
0.5079	Remote Similarity	NPC81778
0.5079	Remote Similarity	NPC40066
0.5079	Remote Similarity	NPC47937
0.5077	Remote Similarity	NPC488250
0.5077	Remote Similarity	NPC602738
0.5075	Remote Similarity	NPC488623
0.5075	Remote Similarity	NPC488624
0.5075	Remote Similarity	NPC233551
0.5075	Remote Similarity	NPC40376
0.5075	Remote Similarity	NPC21208
0.5075	Remote Similarity	NPC488629

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC477015 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6572
0.1-0.2	2529
0.2-0.3	48
0.3-0.4	1
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