NPASS Compound

Natural Product: NPC47937

Natural Product ID	NPC47937
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Pyragonicin
IUPAC Name	(2S)-2-methyl-4-[(2R,8R,11R)-2,8,11-trihydroxy-11-[(2R,5R,6R)-5-hydroxy-6-tetradecyloxan-2-yl]undecyl]-2H-furan-5-one
Synonyms	Pyragonicin
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL448093
PubChem CID	10393745
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 106107 0 0 0 0 0 0 0 0999 V2000 11.3043 0.4962 -1.8425 C 0 0 0 0 0 0 0 0 0 0 0 0 11.3535 1.9942 -1.5654 C 0 0 0 0 0 0 0 0 0 0 0 0 11.2796 2.2332 -0.0750 C 0 0 0 0 0 0 0 0 0 0 0 0 9.9335 1.6308 0.4480 C 0 0 0 0 0 0 0 0 0 0 0 0 9.9076 1.8883 1.9006 C 0 0 0 0 0 0 0 0 0 0 0 0 8.7331 1.5225 2.6921 C 0 0 0 0 0 0 0 0 0 0 0 0 8.2905 0.1365 2.7762 C 0 0 0 0 0 0 0 0 0 0 0 0 7.8034 -0.5361 1.5615 C 0 0 0 0 0 0 0 0 0 0 0 0 7.3702 -1.9515 1.9860 C 0 0 0 0 0 0 0 0 0 0 0 0 6.8542 -2.7373 0.8345 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6556 -2.0205 0.2454 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1392 -2.8372 -0.8965 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9574 -2.1350 -1.5132 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8943 -1.9820 -0.4966 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6485 -1.2566 -1.0787 C 0 0 1 0 0 0 0 0 0 0 0 0 0.7988 -1.1932 -0.0538 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.2097 -0.2566 0.0103 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.0300 0.9622 -0.7794 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8272 0.8067 -2.0127 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0787 0.0631 -1.6503 C 0 0 1 0 0 0 0 0 0 0 0 0 2.9171 0.7633 -0.8022 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.7207 -0.0839 1.4181 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.2588 1.1528 1.8942 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3833 1.9148 1.4059 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7491 1.4046 1.3164 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.0152 0.2305 0.4233 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5194 -0.0856 0.5186 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8809 -1.2454 -0.3549 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.3443 -1.5225 -0.2358 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.1965 -0.3465 -0.6457 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.6679 -0.7542 -0.4894 C 0 0 2 0 0 0 0 0 0 0 0 0 -10.4709 0.4615 -0.9074 C 0 0 0 0 0 0 0 0 0 0 0 0 -11.9254 0.2548 -0.8250 C 0 0 0 0 0 0 0 0 0 0 0 0 -12.7452 0.3532 -1.8699 C 0 0 0 0 0 0 0 0 0 0 0 0 -14.1364 0.0917 -1.4673 C 0 0 1 0 0 0 0 0 0 0 0 0 -14.0357 -0.1692 -0.0822 O 0 0 0 0 0 0 0 0 0 0 0 0 -12.7313 -0.0794 0.3322 C 0 0 0 0 0 0 0 0 0 0 0 0 -12.2461 -0.2437 1.4879 O 0 0 0 0 0 0 0 0 0 0 0 0 -15.0218 1.3129 -1.7144 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.8360 -1.0740 0.8536 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.3744 1.2448 2.5705 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.2678 -1.2699 1.9470 O 0 0 0 0 0 0 0 0 0 0 0 0 10.2659 0.1059 -1.8373 H 0 0 0 0 0 0 0 0 0 0 0 0 11.8423 -0.0277 -1.0204 H 0 0 0 0 0 0 0 0 0 0 0 0 11.8480 0.3048 -2.7851 H 0 0 0 0 0 0 0 0 0 0 0 0 12.3306 2.3514 -1.9229 H 0 0 0 0 0 0 0 0 0 0 0 0 10.4903 2.5006 -2.0325 H 0 0 0 0 0 0 0 0 0 0 0 0 12.0759 1.6920 0.4496 H 0 0 0 0 0 0 0 0 0 0 0 0 11.2384 3.3145 0.1116 H 0 0 0 0 0 0 0 0 0 0 0 0 9.0864 1.9951 -0.1180 H 0 0 0 0 0 0 0 0 0 0 0 0 10.0888 0.5540 0.2056 H 0 0 0 0 0 0 0 0 0 0 0 0 10.1137 3.0011 2.0305 H 0 0 0 0 0 0 0 0 0 0 0 0 10.8171 1.3650 2.3551 H 0 0 0 0 0 0 0 0 0 0 0 0 8.8869 1.9645 3.7456 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8415 2.1613 2.3520 H 0 0 0 0 0 0 0 0 0 0 0 0 9.0922 -0.5134 3.2551 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4307 0.1061 3.5224 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4627 -0.6988 0.7266 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9248 0.0360 1.1851 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5970 -1.9082 2.7657 H 0 0 0 0 0 0 0 0 0 0 0 0 8.2700 -2.4564 2.3939 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5913 -2.8937 0.0265 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4868 -3.7055 1.2167 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9670 -1.8560 1.0726 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9164 -1.0213 -0.1816 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9561 -3.0169 -1.6151 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7826 -3.8105 -0.4580 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3294 -1.1738 -1.9247 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5458 -2.7728 -2.3450 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5214 -2.9887 -0.2205 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1410 -1.4626 0.4251 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3350 -1.8819 -1.9430 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0781 -0.8231 -0.4832 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2822 1.8030 -0.1418 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0282 1.2732 -1.1916 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9744 1.7449 -2.5584 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2725 0.1283 -2.7282 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6950 -0.1498 -2.5737 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3834 1.2031 -0.0834 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3077 -0.1567 1.9878 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4627 1.0058 3.0208 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3898 1.9007 1.9798 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4527 2.8221 2.1204 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1907 2.4983 0.4454 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3799 2.2374 0.8589 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4119 -0.6497 0.5576 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8954 0.5087 -0.6688 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0595 0.8312 0.3017 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6982 -0.3590 1.5797 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5767 -1.0522 -1.4038 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3419 -2.1646 -0.0481 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.5751 -2.4338 -0.8215 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.5690 -1.7910 0.8290 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.0476 0.4760 0.0830 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.9677 -0.0628 -1.6812 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.9063 -1.5918 -1.1755 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.1604 1.3335 -0.2890 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.1487 0.7079 -1.9382 H 0 0 0 0 0 0 0 0 0 0 0 0 -12.4322 0.5947 -2.8872 H 0 0 0 0 0 0 0 0 0 0 0 0 -14.5517 -0.8019 -1.9799 H 0 0 0 0 0 0 0 0 0 0 0 0 -16.0278 0.9887 -2.0074 H 0 0 0 0 0 0 0 0 0 0 0 0 -14.5209 1.9271 -2.4965 H 0 0 0 0 0 0 0 0 0 0 0 0 -15.0714 1.8711 -0.7550 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.2491 -0.4891 1.4056 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5705 2.1221 2.9828 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4069 -1.8549 1.1428 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 18 19 1 0 19 20 1 0 20 21 1 0 17 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 26 27 1 0 27 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 2 0 34 35 1 0 35 36 1 0 36 37 1 0 37 38 2 0 35 39 1 0 31 40 1 0 25 41 1 0 22 42 1 0 20 15 1 0 37 33 1 0 1 43 1 0 1 44 1 0 1 45 1 0 2 46 1 0 2 47 1 0 3 48 1 0 3 49 1 0 4 50 1 0 4 51 1 0 5 52 1 0 5 53 1 0 6 54 1 0 6 55 1 0 7 56 1 0 7 57 1 0 8 58 1 0 8 59 1 0 9 60 1 0 9 61 1 0 10 62 1 0 10 63 1 0 11 64 1 0 11 65 1 0 12 66 1 0 12 67 1 0 13 68 1 0 13 69 1 0 14 70 1 0 14 71 1 0 15 72 1 6 17 73 1 6 18 74 1 0 18 75 1 0 19 76 1 0 19 77 1 0 20 78 1 6 21 79 1 0 22 80 1 1 23 81 1 0 23 82 1 0 24 83 1 0 24 84 1 0 25 85 1 6 26 86 1 0 26 87 1 0 27 88 1 0 27 89 1 0 28 90 1 0 28 91 1 0 29 92 1 0 29 93 1 0 30 94 1 0 30 95 1 0 31 96 1 6 32 97 1 0 32 98 1 0 34 99 1 0 35100 1 6 39101 1 0 39102 1 0 39103 1 0 40104 1 0 41105 1 0 42106 1 0 M END

Standard InCHIKey	XLDSTCJDEYZOKR-CGWDHHCXSA-N
Standard InCHI	InChI=1S/C35H64O7/c1-3-4-5-6-7-8-9-10-11-12-13-17-20-33-32(39)23-24-34(42-33)31(38)22-21-29(36)18-15-14-16-19-30(37)26-28-25-27(2)41-35(28)40/h25,27,29-34,36-39H,3-24,26H2,1-2H3/t27-,29+,30+,31+,32+,33+,34+/m0/s1
SMILES	CCCCCCCCCCCCCC[C@H]1O[C@H](CC[C@H]1O)[C@@H](CC[C@@H](CCCCC[C@H](CC1=C[C@@H](OC1=O)C)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	596.47	Volume:	653.062 ? Van der Waals volume.
Dense:	0.913	LogP:	4.82 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.436 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.516 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	25.0	Rigid Bonds:	12.0
TPSA:	116.45 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	4.0	Rings:	2.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.066	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.611	Fsp³:	0.914
MCE-18:	32.687 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.822	Fluc inhibitor:	0.058 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.074 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.001 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.579	Promiscuous compounds:	0.276

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.205	MDCK Permeability:	-4.869
Pgp-inhibitor:	0.001	Pgp-substrate:	0.975
PAMPA:	0.05 ? 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):	0.007
20% Bioavailability (F20%):	0.948	30% Bioavailability (F30%):	1.0
50% Bioavailability (F50%):	0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.87
Plasma Protein Binding (PPB):	94.811%	Volume Distribution (VD):	0.323
Fu:	4.678% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.713
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.922
BSEP inhibitor:	0.988

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.004
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.002
CYP2C9-inhibitor:	0.001	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.809
CYP3A4-inhibitor:	0.002	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.902
HLM stability:	0.026 ? 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):

5.904

Half-life (T1/2):

1.244

ADMET: Toxicity

hERG Blockers:	0.565	hERG Blockers (10um):	0.847
Human Hepatotoxicity (H-HT):	0.681	Drug-induced Liver Injury (DILI):	0.301
AMES Toxicity:	0.232	Rat Oral Acute Toxicity:	0.097
Maximum Recommended Daily Dose:	0.932	Skin Sensitization:	1.0
Carcinogencity:	0.474	Eye Corrosion:	0.009
Eye Irritation:	0.651	Respiratory Toxicity:	0.987
Drug-induced Neurotoxicity:	0.047	Ototoxicity:	0.851
Hematotoxicity:	0.265	Drug-induced Nephrotoxicity:	0.963
Genotoxicity:	0.0	RPMI-8226 Immunitoxicity:	0.124
A549 Cytotoxicity:	0.997	Hek293 Cytotoxicity:	0.539
BCF:	1.134 ? 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:	4.932 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.161 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.659 ? 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
NPO7202	Goniothalamus giganteus	Species	Annonaceae	Eukaryota	n.a.	bark	n.a.	PMID[1479382]
NPO7202	Goniothalamus giganteus	Species	Annonaceae	Eukaryota	bark	n.a.	n.a.	PMID[1479382]
NPO7202	Goniothalamus giganteus	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[1791471]
NPO7202	Goniothalamus giganteus	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[2614426]
NPO7202	Goniothalamus giganteus	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[9322367]
NPO7202	Goniothalamus giganteus	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[9917277]
NPO7202	Goniothalamus giganteus	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7202	Goniothalamus giganteus	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO7202	Goniothalamus giganteus	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO7202	Goniothalamus giganteus	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO7202	Goniothalamus giganteus	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
ED50	6

Activity Type	# Activity
Cell line	6

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
NPT306	Cell line	PC-3	Homo sapiens	ED50	=	1.2	10'-1 ug/ml	PMID[10096871]
NPT783	Cell line	MIA PaCa-2	Homo sapiens	ED50	=	5.8	10'-2 ug/ml	PMID[10096871]
NPT81	Cell line	A549	Homo sapiens	ED50	=	2.0	ug ml-1	PMID[10096871]
NPT83	Cell line	MCF7	Homo sapiens	ED50	=	1.6	ug ml-1	PMID[10096871]
NPT139	Cell line	HT-29	Homo sapiens	ED50	=	2.8	ug ml-1	PMID[10096871]
NPT376	Cell line	A498	Homo sapiens	ED50	=	1.3	10'-1 ug/ml	PMID[10096871]

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
-	Artemia	LC50	=	0.9	ug.mL-1	PMID[10096871]

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 NPC47937 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	16957
0.1-0.2	29530
0.2-0.3	3020
0.3-0.4	115
0.4-0.5	31
0.5-0.6	40
0.6-0.7	77
0.7-0.8	0
0.8-0.85	16
0.85-0.9	10
0.9-0.95	1
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.9318	High Similarity	NPC182383
0.8889	High Similarity	NPC232555
0.8889	High Similarity	NPC171174
0.8889	High Similarity	NPC114694
0.8889	High Similarity	NPC485248
0.8889	High Similarity	NPC142117
0.8889	High Similarity	NPC480249
0.8889	High Similarity	NPC485249
0.8889	High Similarity	NPC240695
0.8696	High Similarity	NPC488632
0.8667	High Similarity	NPC473669
0.8444	Intermediate Similarity	NPC107986
0.8444	Intermediate Similarity	NPC223871
0.8444	Intermediate Similarity	NPC231009
0.8444	Intermediate Similarity	NPC103284
0.8444	Intermediate Similarity	NPC110710
0.8444	Intermediate Similarity	NPC1083
0.8444	Intermediate Similarity	NPC82795
0.8444	Intermediate Similarity	NPC286338
0.8444	Intermediate Similarity	NPC603931
0.8444	Intermediate Similarity	NPC604237
0.8261	Intermediate Similarity	NPC488253
0.8261	Intermediate Similarity	NPC488251
0.8222	Intermediate Similarity	NPC606043
0.8125	Intermediate Similarity	NPC280621
0.8125	Intermediate Similarity	NPC48338
0.8125	Intermediate Similarity	NPC488628
0.7959	Intermediate Similarity	NPC42598
0.78	Intermediate Similarity	NPC20621
0.78	Intermediate Similarity	NPC318963
0.78	Intermediate Similarity	NPC602738
0.78	Intermediate Similarity	NPC605101
0.7674	Intermediate Similarity	NPC608138
0.76	Intermediate Similarity	NPC178215
0.7551	Intermediate Similarity	NPC93794
0.7551	Intermediate Similarity	NPC134865
0.7551	Intermediate Similarity	NPC473504
0.7551	Intermediate Similarity	NPC103523
0.7551	Intermediate Similarity	NPC81778
0.7551	Intermediate Similarity	NPC40066
0.7551	Intermediate Similarity	NPC488627
0.7551	Intermediate Similarity	NPC488631
0.7451	Intermediate Similarity	NPC488250
0.7347	Intermediate Similarity	NPC81045
0.7347	Intermediate Similarity	NPC39754
0.7347	Intermediate Similarity	NPC171135
0.7347	Intermediate Similarity	NPC61257
0.7347	Intermediate Similarity	NPC320569
0.7347	Intermediate Similarity	NPC133730
0.7347	Intermediate Similarity	NPC191929
0.7347	Intermediate Similarity	NPC100454
0.7347	Intermediate Similarity	NPC242364
0.7347	Intermediate Similarity	NPC172821
0.7347	Intermediate Similarity	NPC156804
0.7347	Intermediate Similarity	NPC274446
0.7347	Intermediate Similarity	NPC485251
0.7347	Intermediate Similarity	NPC151403
0.7347	Intermediate Similarity	NPC261952
0.7347	Intermediate Similarity	NPC605171
0.7308	Intermediate Similarity	NPC69082
0.7308	Intermediate Similarity	NPC488249
0.7308	Intermediate Similarity	NPC20339
0.7255	Intermediate Similarity	NPC473687
0.7255	Intermediate Similarity	NPC204686
0.7255	Intermediate Similarity	NPC219498
0.7255	Intermediate Similarity	NPC308412
0.7255	Intermediate Similarity	NPC134885
0.7255	Intermediate Similarity	NPC488247
0.7255	Intermediate Similarity	NPC210218
0.7255	Intermediate Similarity	NPC488248
0.72	Intermediate Similarity	NPC477011
0.717	Intermediate Similarity	NPC231096
0.717	Intermediate Similarity	NPC475581
0.717	Intermediate Similarity	NPC62118
0.717	Intermediate Similarity	NPC107717
0.717	Intermediate Similarity	NPC488252
0.7091	Intermediate Similarity	NPC488630
0.7091	Intermediate Similarity	NPC488625
0.7091	Intermediate Similarity	NPC488626
0.7037	Intermediate Similarity	NPC488623
0.7037	Intermediate Similarity	NPC488624
0.7037	Intermediate Similarity	NPC488629
0.6981	Remote Similarity	NPC473478
0.6981	Remote Similarity	NPC473651
0.6981	Remote Similarity	NPC66346
0.6939	Remote Similarity	NPC100921
0.6939	Remote Similarity	NPC475159
0.6939	Remote Similarity	NPC131002
0.6939	Remote Similarity	NPC473780
0.6939	Remote Similarity	NPC477018
0.6939	Remote Similarity	NPC604521
0.6875	Remote Similarity	NPC112685
0.6852	Remote Similarity	NPC283085
0.6852	Remote Similarity	NPC169511
0.6852	Remote Similarity	NPC287164
0.6852	Remote Similarity	NPC234077
0.6852	Remote Similarity	NPC132496
0.6852	Remote Similarity	NPC130359
0.6852	Remote Similarity	NPC14901
0.6852	Remote Similarity	NPC606740
0.6852	Remote Similarity	NPC608614
0.6792	Remote Similarity	NPC134807
0.6727	Remote Similarity	NPC233551
0.6727	Remote Similarity	NPC40376
0.6727	Remote Similarity	NPC21208
0.6604	Remote Similarity	NPC132940
0.6552	Remote Similarity	NPC473663
0.6552	Remote Similarity	NPC473723
0.6552	Remote Similarity	NPC475173
0.6545	Remote Similarity	NPC258068
0.6545	Remote Similarity	NPC476583
0.6491	Remote Similarity	NPC91067
0.6491	Remote Similarity	NPC480081
0.6481	Remote Similarity	NPC329838
0.6481	Remote Similarity	NPC20533
0.6415	Remote Similarity	NPC480079
0.6364	Remote Similarity	NPC473707
0.6333	Remote Similarity	NPC482766
0.6327	Remote Similarity	NPC73310
0.6327	Remote Similarity	NPC473529
0.6327	Remote Similarity	NPC180363
0.6327	Remote Similarity	NPC94875
0.6327	Remote Similarity	NPC11332
0.6327	Remote Similarity	NPC145914
0.6327	Remote Similarity	NPC601174
0.6327	Remote Similarity	NPC601403
0.6327	Remote Similarity	NPC603568
0.6327	Remote Similarity	NPC604330
0.6327	Remote Similarity	NPC608300
0.6327	Remote Similarity	NPC611200
0.6327	Remote Similarity	NPC611571
0.6316	Remote Similarity	NPC239517
0.6226	Remote Similarity	NPC473649
0.6226	Remote Similarity	NPC473156
0.6226	Remote Similarity	NPC154097
0.6226	Remote Similarity	NPC488246
0.6226	Remote Similarity	NPC163093
0.6226	Remote Similarity	NPC159750
0.6226	Remote Similarity	NPC73248
0.6226	Remote Similarity	NPC282815
0.6226	Remote Similarity	NPC480080
0.6226	Remote Similarity	NPC470401
0.6226	Remote Similarity	NPC600956
0.6226	Remote Similarity	NPC610454
0.6182	Remote Similarity	NPC309211
0.6182	Remote Similarity	NPC477010
0.614	Remote Similarity	NPC477014
0.614	Remote Similarity	NPC477013
0.6111	Remote Similarity	NPC473671
0.6111	Remote Similarity	NPC475268
0.6111	Remote Similarity	NPC470400
0.6111	Remote Similarity	NPC77871
0.6111	Remote Similarity	NPC9678
0.6111	Remote Similarity	NPC241360
0.6111	Remote Similarity	NPC293136
0.6111	Remote Similarity	NPC319036
0.6111	Remote Similarity	NPC604764
0.6111	Remote Similarity	NPC605867
0.6066	Remote Similarity	NPC279267
0.5962	Remote Similarity	NPC329829
0.5714	Remote Similarity	NPC473904
0.5667	Remote Similarity	NPC280612
0.566	Remote Similarity	NPC25764
0.566	Remote Similarity	NPC235809
0.566	Remote Similarity	NPC39279
0.566	Remote Similarity	NPC39167
0.566	Remote Similarity	NPC292809
0.566	Remote Similarity	NPC202055
0.566	Remote Similarity	NPC606804
0.566	Remote Similarity	NPC607425
0.566	Remote Similarity	NPC608574
0.5636	Remote Similarity	NPC144415
0.5636	Remote Similarity	NPC607439
0.5636	Remote Similarity	NPC608157
0.5614	Remote Similarity	NPC329615
0.5593	Remote Similarity	NPC89001
0.5556	Remote Similarity	NPC477017
0.5556	Remote Similarity	NPC477016
0.5439	Remote Similarity	NPC480251
0.5439	Remote Similarity	NPC480250
0.5439	Remote Similarity	NPC65930
0.5424	Remote Similarity	NPC120398
0.5424	Remote Similarity	NPC471567
0.5424	Remote Similarity	NPC488244
0.5357	Remote Similarity	NPC600524
0.5357	Remote Similarity	NPC608355
0.5333	Remote Similarity	NPC320458
0.5263	Remote Similarity	NPC219652
0.5263	Remote Similarity	NPC473840
0.5254	Remote Similarity	NPC11456
0.5254	Remote Similarity	NPC139418
0.5254	Remote Similarity	NPC477012
0.52	Remote Similarity	NPC609415
0.5167	Remote Similarity	NPC473995
0.5156	Remote Similarity	NPC488245
0.5088	Remote Similarity	NPC482767
0.5088	Remote Similarity	NPC475260
0.5088	Remote Similarity	NPC488621
0.5088	Remote Similarity	NPC473775

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC47937 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6451
0.1-0.2	2642
0.2-0.3	57
0.3-0.4	0
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