NPASS Compound

Natural Product: NPC486138

Natural Product ID	NPC486138
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	PFTYEQWDSBMMNY-YSVUQGOESA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0001125] Steroid lactones [CHEMONTID:0001555] Cardenolides and derivatives [CHEMONTID:0001559] Cardenolide glycosides 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 3D 109115 0 0 0 0 0 0 0 0999 V2000 -3.6687 0.8895 2.3094 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0373 -0.2627 1.4088 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.9686 0.1571 0.3277 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.6152 -0.6525 -0.9253 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.2367 -0.0955 -1.3260 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.3516 0.0101 -0.1041 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.9249 -0.8700 0.8487 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0589 -0.3502 -0.3368 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0884 0.6303 -0.0694 C 0 0 2 0 0 0 0 0 0 0 0 0 0.6149 1.1211 -1.2712 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0366 0.8425 -1.4343 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6228 -0.2081 -0.5067 C 0 0 2 0 0 0 0 0 0 0 0 0 2.0382 -1.4998 -0.8884 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3910 -2.2463 -0.2098 O 0 0 0 0 0 0 0 0 0 0 0 0 2.2023 0.1165 0.9032 C 0 0 1 0 0 0 0 0 0 0 0 0 2.7700 1.4477 1.3591 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2561 1.5691 1.1923 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7867 0.2375 0.7017 C 0 0 1 0 0 0 0 0 0 0 0 0 4.1476 -0.2081 -0.5613 C 0 0 1 0 0 0 0 0 0 0 0 0 4.7099 -1.4767 -1.0779 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9592 -1.9828 -0.5405 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7661 -1.1456 0.4319 C 0 0 1 0 0 0 0 0 0 0 0 0 6.7575 -1.8873 1.7729 C 0 0 0 0 0 0 0 0 0 0 0 0 8.1497 -0.9830 -0.1150 C 0 0 1 0 0 0 0 0 0 0 0 0 7.9184 0.1694 -1.1049 C 0 0 0 0 0 0 0 0 0 0 0 0 6.8963 1.0489 -0.4334 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2814 0.2364 0.6071 C 0 0 1 0 0 0 0 0 0 0 0 0 6.7082 0.7172 1.8721 O 0 0 0 0 0 0 0 0 0 0 0 0 9.2643 -0.6244 0.7454 C 0 0 0 0 0 0 0 0 0 0 0 0 9.4035 -0.4953 2.0258 C 0 0 0 0 0 0 0 0 0 0 0 0 10.7735 -0.1067 2.3482 C 0 0 0 0 0 0 0 0 0 0 0 0 11.2120 0.0963 3.5361 O 0 0 0 0 0 0 0 0 0 0 0 0 11.4600 -0.0096 1.1672 O 0 0 0 0 0 0 0 0 0 0 0 0 10.6086 -0.3227 0.1128 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7162 0.1744 1.0859 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6568 -0.8986 -2.3326 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.4334 -0.3173 -3.5732 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7425 0.8973 -3.7817 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.8329 -1.0563 -4.7125 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4694 -0.4210 -1.9749 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.9998 -1.6620 -2.3780 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3049 0.0296 0.6484 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.9020 1.2757 0.4860 C 0 0 2 0 0 0 0 0 0 0 0 0 -7.4779 1.7773 1.7929 C 0 0 2 0 0 0 0 0 0 0 0 0 -8.4190 0.7746 2.3735 C 0 0 1 0 0 0 0 0 0 0 0 0 -9.0005 -0.0552 1.2628 C 0 0 2 0 0 0 0 0 0 0 0 0 -9.0870 0.6806 -0.0488 C 0 0 2 0 0 0 0 0 0 0 0 0 -9.5658 -0.3542 -1.0748 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.7847 -0.8892 -0.7273 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.8754 1.1414 -0.4961 O 0 0 0 0 0 0 0 0 0 0 0 0 -10.3043 -0.4127 1.6499 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.6886 -0.0142 3.2916 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.1599 2.9809 1.5659 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6989 0.6667 2.7995 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6369 1.8196 1.6883 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4688 1.0139 3.0478 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5834 -1.0131 2.0530 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7165 1.2166 0.0412 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5281 -1.7241 -0.6290 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4373 0.9319 -1.6877 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3926 1.0372 0.2392 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7332 1.4869 0.3105 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0860 0.6531 -2.1600 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4447 2.2093 -1.4308 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6664 1.7594 -1.2423 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3657 0.5457 -2.4688 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2144 -1.8267 -1.9280 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5564 -0.7101 1.5548 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5387 1.5313 2.4410 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2169 2.2889 0.8871 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5636 2.4048 0.5300 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7899 1.7765 2.1584 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5431 -0.4923 1.4998 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3993 0.5972 -1.3179 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7187 -1.4252 -2.2111 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9107 -2.2657 -0.9030 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6583 -2.1962 -1.4098 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8674 -3.0007 -0.0872 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4639 -1.2795 2.6169 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9366 -2.6861 1.7097 H 0 0 0 0 0 0 0 0 0 0 0 0 7.6673 -2.4780 1.8248 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4071 -1.9148 -0.7321 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4806 -0.3123 -2.0294 H 0 0 0 0 0 0 0 0 0 0 0 0 8.8181 0.6835 -1.4087 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3768 1.9685 0.0138 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2426 1.4490 -1.2248 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7912 1.7020 1.7711 H 0 0 0 0 0 0 0 0 0 0 0 0 8.6523 -0.6498 2.8338 H 0 0 0 0 0 0 0 0 0 0 0 0 10.5833 0.5479 -0.5515 H 0 0 0 0 0 0 0 0 0 0 0 0 10.9439 -1.2376 -0.4438 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5516 0.8053 2.0172 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3449 -0.8333 1.4545 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9073 -0.5430 -5.0287 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5426 -0.9430 -5.5873 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7327 -2.1260 -4.5299 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5310 -2.0624 -1.4973 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6212 -1.5798 -3.2896 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1249 -2.3339 -2.5455 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1730 2.0519 0.1448 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6428 1.9698 2.4812 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.2209 1.3409 2.9021 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.3747 -0.9554 1.0925 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.8340 1.5015 -0.0480 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.7816 -1.1666 -1.0550 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.5311 0.0823 -2.0811 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.2654 -1.0848 -1.5909 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.9663 0.2261 1.3183 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.0539 -0.9286 3.2462 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.0980 3.2280 0.6192 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 6 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 6 13 14 2 0 12 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 21 22 1 0 22 23 1 1 22 24 1 0 24 25 1 0 25 26 1 0 26 27 1 0 27 28 1 1 24 29 1 0 29 30 2 0 30 31 1 0 31 32 2 0 31 33 1 0 33 34 1 0 15 35 1 0 5 36 1 0 36 37 1 0 37 38 2 0 37 39 1 0 4 40 1 0 40 41 1 0 3 42 1 0 42 43 1 0 43 44 1 0 44 45 1 0 45 46 1 0 46 47 1 0 47 48 1 0 48 49 1 0 47 50 1 0 46 51 1 0 45 52 1 0 44 53 1 0 7 2 1 0 35 9 1 0 50 43 1 0 19 12 1 0 27 22 1 0 34 29 1 0 27 18 1 0 1 54 1 0 1 55 1 0 1 56 1 0 2 57 1 1 3 58 1 6 4 59 1 1 5 60 1 6 6 61 1 1 9 62 1 1 10 63 1 0 10 64 1 0 11 65 1 0 11 66 1 0 13 67 1 0 15 68 1 1 16 69 1 0 16 70 1 0 17 71 1 0 17 72 1 0 18 73 1 1 19 74 1 6 20 75 1 0 20 76 1 0 21 77 1 0 21 78 1 0 23 79 1 0 23 80 1 0 23 81 1 0 24 82 1 6 25 83 1 0 25 84 1 0 26 85 1 0 26 86 1 0 28 87 1 0 30 88 1 0 34 89 1 0 34 90 1 0 35 91 1 0 35 92 1 0 39 93 1 0 39 94 1 0 39 95 1 0 41 96 1 0 41 97 1 0 41 98 1 0 43 99 1 6 44100 1 1 45101 1 1 46102 1 6 47103 1 1 48104 1 0 48105 1 0 49106 1 0 51107 1 0 52108 1 0 53109 1 0 M END

Standard InCHIKey	PFTYEQWDSBMMNY-YSVUQGOESA-N
Standard InCHI	InChI=1S/C38H56O15/c1-18-31(53-34-30(45)29(44)28(43)26(15-39)52-34)32(47-4)33(50-19(2)41)35(49-18)51-22-7-11-37(17-40)21(14-22)5-6-25-24(37)8-10-36(3)23(9-12-38(25,36)46)20-13-27(42)48-16-20/h13,17-18,21-26,28-35,39,43-46H,5-12,14-16H2,1-4H3/t18-,21-,22+,23-,24+,25-,26-,28-,29+,30-,31-,32+,33-,34+,35-,36-,37-,38+/m0/s1
SMILES	C[C@H]1[C@@H]([C@H]([C@@H]([C@@H](O1)O[C@@H]1CC[C@]2(C=O)[C@@H](CC[C@H]3[C@H]2CC[C@@]2(C)[C@@H](CC[C@@]32O)C2=CC(=O)OC2)C1)OC(=O)C)OC)O[C@@H]1[C@H]([C@@H]([C@H]([C@H](CO)O1)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	752.36	Volume:	727.216 ? Van der Waals volume.
Dense:	1.035	LogP:	0.641 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.221 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.937 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	10.0	Rigid Bonds:	40.0
TPSA:	216.97 ? Topological Polar Surface Area.	H-Bond Acceptor:	15.0
H-Bond Donor:	5.0	Rings:	7.0
Heavy Atoms:	15.0

MedChem Properties

QED Drug-Likeness Score:	0.124	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.818	Fsp³:	0.868
MCE-18:	133.859 ? 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:	0.909	Fluc inhibitor:	0.001 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.005 ? 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:	0.159	Promiscuous compounds:	0.402

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.186	MDCK Permeability:	-5.226
Pgp-inhibitor:	0.0	Pgp-substrate:	0.891
PAMPA:	1.0 ? 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):	0.298
20% Bioavailability (F20%):	0.181	30% Bioavailability (F30%):	0.91
50% Bioavailability (F50%):	0.985

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.003	MRP1:	0.168
Plasma Protein Binding (PPB):	41.552%	Volume Distribution (VD):	-0.426
Fu:	59.686% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.01
BSEP inhibitor:	0.058

ADMET: Metabolism

CYP1A2-inhibitor:	0.001	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.702	CYP3A4-substrate:	0.556
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.88
HLM stability:	0.002 ? 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):

0.962

Half-life (T1/2):

2.708

ADMET: Toxicity

hERG Blockers:	0.009	hERG Blockers (10um):	0.068
Human Hepatotoxicity (H-HT):	0.905	Drug-induced Liver Injury (DILI):	0.893
AMES Toxicity:	0.961	Rat Oral Acute Toxicity:	0.212
Maximum Recommended Daily Dose:	0.721	Skin Sensitization:	1.0
Carcinogencity:	0.91	Eye Corrosion:	0.0
Eye Irritation:	0.001	Respiratory Toxicity:	0.101
Drug-induced Neurotoxicity:	0.006	Ototoxicity:	0.968
Hematotoxicity:	0.782	Drug-induced Nephrotoxicity:	0.997
Genotoxicity:	0.977	RPMI-8226 Immunitoxicity:	0.513
A549 Cytotoxicity:	0.912	Hek293 Cytotoxicity:	0.786
BCF:	0.505 ? 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:	3.436 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.27 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.392 ? 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
NPO8402	Thevetia peruviana	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[26714048]
NPO8402	Thevetia peruviana	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[39027575]
NPO8402	Thevetia peruviana	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8402	Thevetia peruviana	Species	Apocynaceae	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	4

Activity Type	# Activity
Cell line	1
Non-molecular	2
Others	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
NPT1312	Cell line	SW1990	Homo sapiens	IC50	=	970.0	nM	PMID[26714048]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	590.0	nM	PMID[26714048]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	1230.0	nM	PMID[26714048]
NPT27	Others	Unspecified	n.a.	IC50	>	10000.0	nM	PMID[26714048]

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 NPC486138 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	14722
0.1-0.2	29697
0.2-0.3	4518
0.3-0.4	710
0.4-0.5	71
0.5-0.6	68
0.6-0.7	48
0.7-0.8	0
0.8-0.85	7
0.85-0.9	1
0.9-0.95	1
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC276838
0.9222	High Similarity	NPC486150
0.875	High Similarity	NPC486146
0.8222	Intermediate Similarity	NPC232785
0.8222	Intermediate Similarity	NPC486139
0.8214	Intermediate Similarity	NPC480914
0.8132	Intermediate Similarity	NPC329986
0.8132	Intermediate Similarity	NPC140092
0.8105	Intermediate Similarity	NPC486134
0.8105	Intermediate Similarity	NPC486141
0.7692	Intermediate Similarity	NPC188234
0.7527	Intermediate Similarity	NPC125077
0.7273	Intermediate Similarity	NPC469750
0.7158	Intermediate Similarity	NPC486143
0.7158	Intermediate Similarity	NPC486135
0.7158	Intermediate Similarity	NPC486142
0.7158	Intermediate Similarity	NPC486137
0.7158	Intermediate Similarity	NPC486149
0.7143	Intermediate Similarity	NPC488938
0.7143	Intermediate Similarity	NPC488937
0.7079	Intermediate Similarity	NPC5311
0.7079	Intermediate Similarity	NPC77299
0.7079	Intermediate Similarity	NPC480906
0.6842	Remote Similarity	NPC292467
0.6733	Remote Similarity	NPC486144
0.6733	Remote Similarity	NPC486145
0.6733	Remote Similarity	NPC486147
0.6733	Remote Similarity	NPC486136
0.6733	Remote Similarity	NPC486148
0.6702	Remote Similarity	NPC480907
0.6667	Remote Similarity	NPC146857
0.6667	Remote Similarity	NPC236973
0.6667	Remote Similarity	NPC488939
0.6667	Remote Similarity	NPC32177
0.6667	Remote Similarity	NPC247190
0.6667	Remote Similarity	NPC469756
0.6667	Remote Similarity	NPC275901
0.6667	Remote Similarity	NPC488947
0.6602	Remote Similarity	NPC120390
0.6602	Remote Similarity	NPC74259
0.6602	Remote Similarity	NPC475419
0.6598	Remote Similarity	NPC240070
0.6562	Remote Similarity	NPC30483
0.6562	Remote Similarity	NPC470897
0.6538	Remote Similarity	NPC474908
0.6452	Remote Similarity	NPC76572
0.6452	Remote Similarity	NPC193382
0.6429	Remote Similarity	NPC480910
0.6429	Remote Similarity	NPC480909
0.6383	Remote Similarity	NPC250556
0.6364	Remote Similarity	NPC475629
0.6364	Remote Similarity	NPC486127
0.6355	Remote Similarity	NPC474423
0.6304	Remote Similarity	NPC99620
0.6263	Remote Similarity	NPC32793
0.6263	Remote Similarity	NPC116075
0.6263	Remote Similarity	NPC486130
0.625	Remote Similarity	NPC479358
0.6237	Remote Similarity	NPC84987
0.6226	Remote Similarity	NPC329675
0.6226	Remote Similarity	NPC194716
0.617	Remote Similarity	NPC480915
0.6146	Remote Similarity	NPC93883
0.6095	Remote Similarity	NPC475590
0.6058	Remote Similarity	NPC476221
0.6058	Remote Similarity	NPC477709
0.604	Remote Similarity	NPC231518
0.604	Remote Similarity	NPC488944
0.6	Remote Similarity	NPC486128
0.6	Remote Similarity	NPC488943
0.6	Remote Similarity	NPC488942
0.5979	Remote Similarity	NPC179412
0.5979	Remote Similarity	NPC471356
0.5922	Remote Similarity	NPC469749
0.5905	Remote Similarity	NPC486132
0.5905	Remote Similarity	NPC486131
0.5833	Remote Similarity	NPC17896
0.5833	Remote Similarity	NPC469755
0.5833	Remote Similarity	NPC284406
0.5833	Remote Similarity	NPC197707
0.5833	Remote Similarity	NPC251866
0.5816	Remote Similarity	NPC483822
0.5784	Remote Similarity	NPC475556
0.5784	Remote Similarity	NPC311706
0.578	Remote Similarity	NPC117445
0.578	Remote Similarity	NPC308262
0.5729	Remote Similarity	NPC196429
0.5701	Remote Similarity	NPC479360
0.5701	Remote Similarity	NPC479359
0.5676	Remote Similarity	NPC488945
0.5676	Remote Similarity	NPC488946
0.5673	Remote Similarity	NPC208193
0.5657	Remote Similarity	NPC305574
0.5636	Remote Similarity	NPC486140
0.5625	Remote Similarity	NPC471633
0.5612	Remote Similarity	NPC84949
0.5612	Remote Similarity	NPC480562
0.5612	Remote Similarity	NPC74945
0.5612	Remote Similarity	NPC31354
0.5612	Remote Similarity	NPC69576
0.5586	Remote Similarity	NPC329784
0.5586	Remote Similarity	NPC486133
0.5577	Remote Similarity	NPC610296
0.5545	Remote Similarity	NPC72260
0.5524	Remote Similarity	NPC59288
0.551	Remote Similarity	NPC6108
0.551	Remote Similarity	NPC157376
0.551	Remote Similarity	NPC89514
0.551	Remote Similarity	NPC142066
0.551	Remote Similarity	NPC603972
0.55	Remote Similarity	NPC471353
0.5481	Remote Similarity	NPC479353
0.5481	Remote Similarity	NPC479354
0.5464	Remote Similarity	NPC99728
0.5464	Remote Similarity	NPC87250
0.5464	Remote Similarity	NPC244402
0.5464	Remote Similarity	NPC50305
0.5463	Remote Similarity	NPC475219
0.5455	Remote Similarity	NPC199428
0.5455	Remote Similarity	NPC109448
0.5455	Remote Similarity	NPC10823
0.5455	Remote Similarity	NPC310341
0.5429	Remote Similarity	NPC488941
0.5429	Remote Similarity	NPC488940
0.5408	Remote Similarity	NPC219085
0.5347	Remote Similarity	NPC484202
0.5345	Remote Similarity	NPC486152
0.53	Remote Similarity	NPC243196
0.5283	Remote Similarity	NPC264336
0.5248	Remote Similarity	NPC146456
0.5248	Remote Similarity	NPC88668
0.5248	Remote Similarity	NPC180079
0.5182	Remote Similarity	NPC479357
0.5152	Remote Similarity	NPC473852
0.5094	Remote Similarity	NPC40749
0.5093	Remote Similarity	NPC55532
0.5055	Remote Similarity	NPC196931
0.5051	Remote Similarity	NPC158344
0.5047	Remote Similarity	NPC608063

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC486138 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6117
0.1-0.2	2932
0.2-0.3	82
0.3-0.4	5
0.4-0.5	9
0.5-0.6	3
0.6-0.7	2
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
0.6383	Remote Similarity	NPD7507	Pre-clinical
0.604	Remote Similarity	NPD8033	Approved
0.5833	Remote Similarity	NPD7319	Approved
0.5545	Remote Similarity	NPD8294	Phase 4
0.5377	Remote Similarity	NPD8377	Phase 4

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