NPASS Compound

Natural Product: NPC234684

Natural Product ID	NPC234684
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	ZUTULEYYCYQRIK-BFIMYRRTSA-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:0001013] Steroidal glycosides [CHEMONTID:0002364] Steroidal saponins

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 116123 0 0 0 0 0 0 0 0999 V2000 -6.6503 -3.5435 0.5295 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1114 -2.1336 0.7917 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.1573 -1.8167 -0.3228 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.8585 -0.7084 -1.0800 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.7697 0.3052 -1.4622 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5101 -0.4401 -1.1874 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.2796 0.3737 -1.0034 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.9032 0.9158 -2.3901 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5895 1.6506 -2.3385 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4829 0.7189 -1.8059 C 0 0 1 0 0 0 0 0 0 0 0 0 1.8547 1.3031 -1.9268 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7377 1.1012 -0.7485 C 0 0 1 0 0 0 0 0 0 0 0 0 2.5561 -0.2121 -0.0505 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1609 -0.7048 0.0536 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1139 0.2484 -0.4364 C 0 0 1 0 0 0 0 0 0 0 0 0 0.0009 1.3702 0.5661 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1765 -0.5288 -0.5727 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.4925 -1.3583 0.6398 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7751 -2.0864 0.4406 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8909 -1.1676 0.1124 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.0865 -0.1536 1.2132 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0608 1.1454 -1.1981 O 0 0 0 0 0 0 0 0 0 0 0 0 4.6859 2.2235 -0.5790 C 0 0 1 0 0 0 0 0 0 0 0 0 5.9544 1.7774 0.1419 C 0 0 1 0 0 0 0 0 0 0 0 0 6.3689 2.9489 1.0124 C 0 0 1 0 0 0 0 0 0 0 0 0 5.9566 4.2256 0.2738 C 0 0 2 0 0 0 0 0 0 0 0 0 6.0684 3.9745 -1.1962 C 0 0 2 0 0 0 0 0 0 0 0 0 5.7916 5.2950 -1.9237 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1178 3.0743 -1.6238 O 0 0 0 0 0 0 0 0 0 0 0 0 6.8270 5.2549 0.6322 O 0 0 0 0 0 0 0 0 0 0 0 0 5.5536 2.9020 2.1582 O 0 0 0 0 0 0 0 0 0 0 0 0 5.7504 0.6887 0.9614 O 0 0 0 0 0 0 0 0 0 0 0 0 6.5033 -0.4103 0.6351 C 0 0 1 0 0 0 0 0 0 0 0 0 7.4293 -0.8545 1.7762 C 0 0 1 0 0 0 0 0 0 0 0 0 8.4076 -1.8144 1.1125 C 0 0 2 0 0 0 0 0 0 0 0 0 7.7621 -2.8234 0.2417 C 0 0 1 0 0 0 0 0 0 0 0 0 6.3613 -2.5843 -0.1673 C 0 0 1 0 0 0 0 0 0 0 0 0 5.5486 -3.8231 0.2437 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5515 -3.8158 1.6576 O 0 0 0 0 0 0 0 0 0 0 0 0 5.7158 -1.5052 0.3560 O 0 0 0 0 0 0 0 0 0 0 0 0 8.5277 -2.9344 -0.9445 O 0 0 0 0 0 0 0 0 0 0 0 0 9.2326 -2.4152 2.0607 O 0 0 0 0 0 0 0 0 0 0 0 0 8.0973 0.1924 2.3494 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.8057 -0.1697 -0.2408 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.2610 -1.1832 0.5900 C 0 0 2 0 0 0 0 0 0 0 0 0 -7.6847 -0.6765 1.9501 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.2144 -0.5918 2.0419 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.6649 0.0822 0.7543 C 0 0 2 0 0 0 0 0 0 0 0 0 -11.1611 0.3019 0.8181 C 0 0 0 0 0 0 0 0 0 0 0 0 -11.5214 0.9223 -0.3877 O 0 0 0 0 0 0 0 0 0 0 0 0 -9.2816 -0.8379 -0.3802 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.3688 -1.8136 0.0235 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.8785 -4.3104 0.6935 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.5731 -3.7247 1.1235 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9140 -3.5687 -0.5504 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6763 -2.1190 1.7900 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9171 -2.6775 -0.9663 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3293 -1.1495 -1.9780 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8845 1.2552 -0.9424 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8742 0.4789 -2.5720 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3673 -1.1980 -1.9835 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4396 1.2564 -0.3776 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7017 1.5181 -2.8270 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7999 0.0020 -3.0410 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3190 1.9070 -3.3793 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6861 2.5734 -1.7720 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4522 -0.1832 -2.4745 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3811 0.9214 -2.8473 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7465 2.3989 -2.1009 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5360 1.9365 -0.0209 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1535 -1.0062 -0.5841 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0584 -0.1163 0.9521 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9455 -0.8749 1.1493 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0144 -1.6975 -0.4183 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9962 1.4223 1.0524 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1814 2.3705 0.1274 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7311 1.2604 1.4068 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0012 -1.2581 -1.4146 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6748 -2.1202 0.7279 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4526 -0.7751 1.5853 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0343 -2.6006 1.4112 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6415 -2.8195 -0.3811 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2805 -0.6785 2.1581 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8887 0.5735 0.9788 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1566 0.4172 1.3354 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9940 2.7559 0.0950 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7012 1.5858 -0.6581 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4243 2.9511 1.2767 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9293 4.5203 0.5121 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1155 3.6201 -1.4155 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4687 5.0581 -2.9539 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9243 5.7610 -1.4106 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6738 5.9383 -1.9705 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7731 5.3999 1.5978 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0962 2.7361 2.9705 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1630 -0.2465 -0.2426 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8374 -1.4598 2.4915 H 0 0 0 0 0 0 0 0 0 0 0 0 9.0764 -1.1680 0.4966 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9128 -3.8338 0.7290 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2242 -2.5373 -1.2876 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0216 -4.7522 -0.0822 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4863 -3.7202 -0.0449 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3786 -4.2890 1.9911 H 0 0 0 0 0 0 0 0 0 0 0 0 8.9168 -2.0465 -1.1966 H 0 0 0 0 0 0 0 0 0 0 0 0 10.1641 -2.4816 1.7170 H 0 0 0 0 0 0 0 0 0 0 0 0 9.0632 -0.0225 2.3727 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2683 0.3284 2.1681 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3794 -1.3577 2.7729 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.4625 0.0158 2.9352 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.5865 -1.6395 2.1146 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.1152 1.0467 0.7099 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.7001 -0.6227 1.0133 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.3753 1.0442 1.6134 H 0 0 0 0 0 0 0 0 0 0 0 0 -12.2494 1.5806 -0.2410 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.7332 -0.1980 -1.1308 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.1523 -1.2691 -0.8899 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 1 15 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 1 1 12 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 27 29 1 0 26 30 1 0 25 31 1 0 24 32 1 0 32 33 1 0 33 34 1 0 34 35 1 0 35 36 1 0 36 37 1 0 37 38 1 0 38 39 1 0 37 40 1 0 36 41 1 0 35 42 1 0 34 43 1 0 4 44 1 0 45 44 1 6 45 46 1 0 46 47 1 0 47 48 1 0 48 49 1 0 49 50 1 0 48 51 1 0 51 52 1 0 45 2 1 0 20 3 1 0 29 23 1 0 40 33 1 0 52 45 1 0 20 6 1 0 17 7 1 0 15 10 1 0 1 53 1 0 1 54 1 0 1 55 1 0 2 56 1 1 3 57 1 6 4 58 1 6 5 59 1 0 5 60 1 0 6 61 1 6 7 62 1 1 8 63 1 0 8 64 1 0 9 65 1 0 9 66 1 0 10 67 1 6 11 68 1 0 11 69 1 0 12 70 1 1 13 71 1 0 13 72 1 0 14 73 1 0 14 74 1 0 16 75 1 0 16 76 1 0 16 77 1 0 17 78 1 6 18 79 1 0 18 80 1 0 19 81 1 0 19 82 1 0 21 83 1 0 21 84 1 0 21 85 1 0 23 86 1 1 24 87 1 6 25 88 1 1 26 89 1 6 27 90 1 1 28 91 1 0 28 92 1 0 28 93 1 0 30 94 1 0 31 95 1 0 33 96 1 6 34 97 1 1 35 98 1 6 36 99 1 1 37100 1 6 38101 1 0 38102 1 0 39103 1 0 41104 1 0 42105 1 0 43106 1 0 46107 1 0 46108 1 0 47109 1 0 47110 1 0 48111 1 6 49112 1 0 49113 1 0 50114 1 0 51115 1 0 51116 1 0 M END

Standard InCHIKey	ZUTULEYYCYQRIK-BFIMYRRTSA-N
Standard InCHI	InChI=1S/C39H64O13/c1-18-28-26(52-39(18)12-7-20(15-40)17-47-39)14-25-23-6-5-21-13-22(8-10-37(21,3)24(23)9-11-38(25,28)4)49-36-34(32(45)29(42)19(2)48-36)51-35-33(46)31(44)30(43)27(16-41)50-35/h18-36,40-46H,5-17H2,1-4H3/t18-,19-,20+,21-,22+,23+,24-,25-,26-,27+,28-,29-,30+,31-,32+,33+,34+,35-,36-,37-,38-,39+/m0/s1
SMILES	C[C@H]1[C@H]2[C@H](C[C@H]3[C@@H]4CC[C@H]5C[C@@H](CC[C@]5(C)[C@H]4CC[C@]23C)O[C@H]2[C@@H]([C@@H]([C@H]([C@H](C)O2)O)O)O[C@H]2[C@@H]([C@H]([C@@H]([C@@H](CO)O2)O)O)O)O[C@@]21CC[C@H](CO)CO2

Calculated Properties

Physi-Chem Properties

Molecular Weight:	740.43	Volume:	728.921 ? Van der Waals volume.
Dense:	1.016	LogP:	2.087 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.705 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.795 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	42.0
TPSA:	196.99 ? Topological Polar Surface Area.	H-Bond Acceptor:	13.0
H-Bond Donor:	7.0	Rings:	8.0
Heavy Atoms:	13.0

MedChem Properties

QED Drug-Likeness Score:	0.194	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	6.259	Fsp³:	1.0
MCE-18:	200.0 ? 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:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.706	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.023 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.0 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.236	Promiscuous compounds:	0.047

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.06	MDCK Permeability:	-5.179
Pgp-inhibitor:	0.002	Pgp-substrate:	0.818
PAMPA:	0.936 ? 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):	0.006
20% Bioavailability (F20%):	0.475	30% Bioavailability (F30%):	0.923
50% Bioavailability (F50%):	0.941

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.028	MRP1:	0.709
Plasma Protein Binding (PPB):	78.885%	Volume Distribution (VD):	-0.447
Fu:	17.233% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.993
OATP1B3 inhibitor:	0.751	BCRP inhibitor:	0.022
BSEP inhibitor:	0.011

ADMET: Metabolism

CYP1A2-inhibitor:	0.174	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.01	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.006
CYP3A4-inhibitor:	0.027	CYP3A4-substrate:	0.053
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.388
HLM stability:	0.138 ? 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):

1.069

Half-life (T1/2):

2.478

ADMET: Toxicity

hERG Blockers:	0.017	hERG Blockers (10um):	0.035
Human Hepatotoxicity (H-HT):	0.628	Drug-induced Liver Injury (DILI):	0.892
AMES Toxicity:	0.97	Rat Oral Acute Toxicity:	0.051
Maximum Recommended Daily Dose:	0.041	Skin Sensitization:	1.0
Carcinogencity:	0.502	Eye Corrosion:	0.0
Eye Irritation:	0.004	Respiratory Toxicity:	0.026
Drug-induced Neurotoxicity:	0.007	Ototoxicity:	0.998
Hematotoxicity:	0.414	Drug-induced Nephrotoxicity:	0.994
Genotoxicity:	0.236	RPMI-8226 Immunitoxicity:	0.309
A549 Cytotoxicity:	0.993	Hek293 Cytotoxicity:	0.93
BCF:	1.685 ? 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:	3.319 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.264 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.802 ? 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
NPO11520	Homalanthus acuminatus	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO11520	Homalanthus acuminatus	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO2470	Abies spectabilis	Species	Pinaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO11520	Homalanthus acuminatus	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO10817	Perilla ocymoides	Species	Araneidae	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

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

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 NPC234684 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	27690
0.1-0.2	18856
0.2-0.3	2549
0.3-0.4	508
0.4-0.5	139
0.5-0.6	59
0.6-0.7	38
0.7-0.8	1
0.8-0.85	1
0.85-0.9	6
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8659	High Similarity	NPC477451
0.8642	High Similarity	NPC297348
0.8642	High Similarity	NPC249204
0.8642	High Similarity	NPC48339
0.8642	High Similarity	NPC141769
0.8642	High Similarity	NPC477547
0.814	Intermediate Similarity	NPC211354
0.7865	Intermediate Similarity	NPC6295
0.7753	Intermediate Similarity	NPC107962
0.7528	Intermediate Similarity	NPC19400
0.7312	Intermediate Similarity	NPC160426
0.7273	Intermediate Similarity	NPC234352
0.7222	Intermediate Similarity	NPC206003
0.7222	Intermediate Similarity	NPC473610
0.7159	Intermediate Similarity	NPC325828
0.7111	Intermediate Similarity	NPC222731
0.7079	Intermediate Similarity	NPC294686
0.6947	Remote Similarity	NPC113044
0.6947	Remote Similarity	NPC283829
0.6947	Remote Similarity	NPC161676
0.6869	Remote Similarity	NPC128572
0.6774	Remote Similarity	NPC107188
0.6742	Remote Similarity	NPC485594
0.6701	Remote Similarity	NPC475351
0.66	Remote Similarity	NPC471464
0.6566	Remote Similarity	NPC475643
0.6562	Remote Similarity	NPC125324
0.6562	Remote Similarity	NPC485595
0.65	Remote Similarity	NPC248746
0.65	Remote Similarity	NPC92890
0.6495	Remote Similarity	NPC141433
0.6495	Remote Similarity	NPC195297
0.6442	Remote Similarity	NPC475625
0.6421	Remote Similarity	NPC54619
0.6413	Remote Similarity	NPC177834
0.6373	Remote Similarity	NPC480555
0.6373	Remote Similarity	NPC150372
0.6311	Remote Similarity	NPC184617
0.6211	Remote Similarity	NPC250393
0.6211	Remote Similarity	NPC474399
0.6176	Remote Similarity	NPC477809
0.617	Remote Similarity	NPC291203
0.617	Remote Similarity	NPC217205
0.6154	Remote Similarity	NPC97700
0.6154	Remote Similarity	NPC30856
0.6129	Remote Similarity	NPC181845
0.6117	Remote Similarity	NPC51172
0.6117	Remote Similarity	NPC49032
0.6082	Remote Similarity	NPC306131
0.6082	Remote Similarity	NPC200802
0.6078	Remote Similarity	NPC470433
0.6078	Remote Similarity	NPC46190
0.6078	Remote Similarity	NPC171073
0.6055	Remote Similarity	NPC480553
0.6038	Remote Similarity	NPC475550
0.5978	Remote Similarity	NPC24960
0.5962	Remote Similarity	NPC300557
0.5909	Remote Similarity	NPC132080
0.5872	Remote Similarity	NPC480554
0.5816	Remote Similarity	NPC128123
0.5816	Remote Similarity	NPC121453
0.5784	Remote Similarity	NPC305423
0.5784	Remote Similarity	NPC14704
0.5769	Remote Similarity	NPC602423
0.5741	Remote Similarity	NPC269297
0.5741	Remote Similarity	NPC222202
0.5699	Remote Similarity	NPC473774
0.5699	Remote Similarity	NPC481419
0.5699	Remote Similarity	NPC481417
0.5688	Remote Similarity	NPC475333
0.5688	Remote Similarity	NPC224098
0.5688	Remote Similarity	NPC208383
0.5652	Remote Similarity	NPC277715
0.5648	Remote Similarity	NPC475319
0.5636	Remote Similarity	NPC194207
0.5636	Remote Similarity	NPC232037
0.5636	Remote Similarity	NPC22779
0.5588	Remote Similarity	NPC470432
0.5588	Remote Similarity	NPC230507
0.5586	Remote Similarity	NPC470864
0.5545	Remote Similarity	NPC116756
0.5536	Remote Similarity	NPC83137
0.5524	Remote Similarity	NPC473601
0.5517	Remote Similarity	NPC480556
0.5514	Remote Similarity	NPC42171
0.5514	Remote Similarity	NPC6806
0.549	Remote Similarity	NPC485601
0.5455	Remote Similarity	NPC210157
0.5405	Remote Similarity	NPC13193
0.5392	Remote Similarity	NPC264101
0.5391	Remote Similarity	NPC232054
0.5385	Remote Similarity	NPC70204
0.5376	Remote Similarity	NPC144790
0.5376	Remote Similarity	NPC149400
0.5368	Remote Similarity	NPC481420
0.5368	Remote Similarity	NPC481421
0.5345	Remote Similarity	NPC470866
0.534	Remote Similarity	NPC215408
0.5268	Remote Similarity	NPC309278
0.5225	Remote Similarity	NPC115165
0.5217	Remote Similarity	NPC233433
0.521	Remote Similarity	NPC224314
0.5175	Remote Similarity	NPC108072
0.5152	Remote Similarity	NPC481424
0.5152	Remote Similarity	NPC481422
0.5133	Remote Similarity	NPC32361
0.5093	Remote Similarity	NPC98696
0.5091	Remote Similarity	NPC274200
0.505	Remote Similarity	NPC131693
0.505	Remote Similarity	NPC475436
0.5045	Remote Similarity	NPC151134
0.5041	Remote Similarity	NPC220836
0.5041	Remote Similarity	NPC477808
0.5038	Remote Similarity	NPC481189

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC234684 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7773
0.1-0.2	1300
0.2-0.3	63
0.3-0.4	6
0.4-0.5	5
0.5-0.6	0
0.6-0.7	1
0.7-0.8	1
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
0.7159	Intermediate Similarity	NPD8171	Phase 2
0.6061	Remote Similarity	NPD8170	Phase 2

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