NPASS Compound

Natural Product: NPC149873

Natural Product ID	NPC149873
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Pinoresinol-4'-O-[4',6'-O-(E)-Diferuloyl]-Beta-D-Glucopyranoside
IUPAC Name	[(2R,3S,4R,5R,6S)-6-[4-[(3R,3aS,6R,6aS)-3-(4-hydroxy-3-methoxyphenyl)-1,3,3a,4,6,6a-hexahydrofuro[3,4-c]furan-6-yl]-2-methoxyphenoxy]-4,5-dihydroxy-3-[(E)-3-(4-hydroxy-3-methoxyphenyl)prop-2-enoyl]oxyoxan-2-yl]methyl (E)-3-(4-hydroxy-3-methoxyphenyl)prop-2-enoate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL2251618
PubChem CID	17755702
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0001392] Lignans, neolignans and related compounds [CHEMONTID:0001511] Lignan glycosides

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 111117 0 0 0 0 0 0 0 0999 V2000 -3.9492 9.1840 1.3727 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3701 9.0805 1.5029 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.9575 7.8239 1.4243 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1913 6.6934 1.2266 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7490 5.4183 1.1421 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.1123 5.3598 1.2688 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.9105 6.4745 1.4681 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.3117 7.7216 1.5451 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.0803 8.8722 1.7452 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.9051 4.2483 0.9237 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3417 3.0167 0.8193 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4353 1.8777 0.5977 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2194 2.1462 0.5206 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.8777 0.5975 0.4778 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.0928 -0.5197 0.2512 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3359 -0.5229 -1.0619 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.7093 -1.8412 -1.3761 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.5101 -1.9307 -2.8785 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.1741 -0.5469 -3.3811 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.5775 0.2572 -2.2438 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.3271 -0.2869 -1.9555 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8864 0.3228 -1.8764 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1350 1.6654 -2.0403 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4218 2.1825 -1.9401 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5049 1.3751 -1.6724 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2692 0.0273 -1.5057 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9947 -0.4842 -1.6051 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8243 -1.8428 -1.4286 O 0 0 0 0 0 0 0 0 0 0 0 0 2.9107 -2.7105 -1.1533 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9022 1.9319 -1.5629 C 0 0 1 0 0 0 0 0 0 0 0 0 5.3495 1.9823 -0.1333 C 0 0 2 0 0 0 0 0 0 0 0 0 5.7057 3.3857 0.3267 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9453 3.2629 0.9611 O 0 0 0 0 0 0 0 0 0 0 0 0 7.6496 2.4437 0.0785 C 0 0 1 0 0 0 0 0 0 0 0 0 8.9408 1.9811 0.6251 C 0 0 0 0 0 0 0 0 0 0 0 0 9.7446 2.8762 1.2832 C 0 0 0 0 0 0 0 0 0 0 0 0 10.9502 2.4775 1.7999 C 0 0 0 0 0 0 0 0 0 0 0 0 11.3704 1.1696 1.6644 C 0 0 0 0 0 0 0 0 0 0 0 0 10.5753 0.2504 1.0039 C 0 0 0 0 0 0 0 0 0 0 0 0 9.3576 0.6831 0.4901 C 0 0 0 0 0 0 0 0 0 0 0 0 11.0162 -1.0415 0.8827 O 0 0 0 0 0 0 0 0 0 0 0 0 10.3114 -2.0718 0.2396 C 0 0 0 0 0 0 0 0 0 0 0 0 12.6111 0.7965 2.2068 O 0 0 0 0 0 0 0 0 0 0 0 0 6.6740 1.3007 -0.1026 C 0 0 2 0 0 0 0 0 0 0 0 0 6.7880 0.7024 -1.4606 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8033 1.1867 -2.2714 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.4154 0.4835 -1.1964 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.2617 0.1508 -3.8853 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.3655 -2.7246 -3.0647 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4813 -2.9293 -0.8966 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.9478 -3.7972 0.0420 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7804 -3.6214 0.4674 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.6993 -4.9314 0.5703 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9364 -5.1967 0.1786 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7316 -6.3086 0.6686 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.0148 -6.4721 0.1572 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.8263 -7.5097 0.5862 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.3937 -8.4177 1.5341 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1138 -8.2565 2.0455 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3252 -7.2154 1.6023 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6947 -9.1757 2.9960 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.3935 -9.0295 3.5318 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.2110 -9.4658 1.9680 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4053 8.7576 2.2140 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6088 8.6715 0.4247 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6852 10.2707 1.2158 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1125 6.7885 1.1322 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.6073 4.4049 1.2138 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.9848 6.4397 1.5687 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.0058 8.9588 1.3063 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8212 4.3895 0.8375 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3996 2.8248 0.8979 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3481 -0.6978 1.0789 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7792 -1.4119 0.2527 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1203 -0.3272 -1.8626 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7055 -1.8450 -0.9071 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3902 -2.3653 -3.3847 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4084 -0.6944 -4.1960 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3589 1.2866 -2.6738 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3139 2.3270 -2.2492 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6135 3.2454 -2.0709 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1183 -0.6092 -1.2960 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6138 -3.7730 -1.2015 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3602 -2.4254 -0.1780 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7129 -2.5686 -1.9308 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9049 2.9664 -1.9617 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6078 1.5127 0.5509 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8069 4.0212 -0.5848 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9278 3.8194 0.9912 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8335 2.9410 -0.8985 H 0 0 0 0 0 0 0 0 0 0 0 0 9.4281 3.9012 1.3965 H 0 0 0 0 0 0 0 0 0 0 0 0 11.6074 3.1839 2.3322 H 0 0 0 0 0 0 0 0 0 0 0 0 8.7679 -0.0504 -0.0126 H 0 0 0 0 0 0 0 0 0 0 0 0 9.3318 -2.3094 0.7210 H 0 0 0 0 0 0 0 0 0 0 0 0 10.1854 -1.8134 -0.8285 H 0 0 0 0 0 0 0 0 0 0 0 0 10.9267 -3.0156 0.3350 H 0 0 0 0 0 0 0 0 0 0 0 0 13.2940 0.2950 1.6538 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7620 0.5450 0.6980 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8624 -0.4040 -1.4457 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7727 1.0492 -1.8958 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9584 0.6600 -4.6947 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5570 -3.5975 -3.4356 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2386 -5.5740 1.2995 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3336 -4.5041 -0.5607 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3707 -5.7646 -0.5912 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.8342 -7.6594 0.2019 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3362 -7.1244 2.0231 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0850 -9.9235 4.1225 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6130 -8.8612 2.7871 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3429 -8.1746 4.2515 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.2530 -10.3250 1.3975 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 2 0 6 7 1 0 7 8 2 0 8 9 1 0 5 10 1 0 10 11 2 0 11 12 1 0 12 13 2 0 12 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 21 22 1 0 22 23 2 0 23 24 1 0 24 25 2 0 25 26 1 0 26 27 2 0 27 28 1 0 28 29 1 0 25 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 2 0 38 39 1 0 39 40 2 0 39 41 1 0 41 42 1 0 38 43 1 0 34 44 1 0 44 45 1 0 45 46 1 0 20 47 1 0 19 48 1 0 18 49 1 0 17 50 1 0 50 51 1 0 51 52 2 0 51 53 1 0 53 54 2 0 54 55 1 0 55 56 2 0 56 57 1 0 57 58 2 0 58 59 1 0 59 60 2 0 59 61 1 0 61 62 1 0 58 63 1 0 8 3 1 0 47 16 1 0 60 55 1 0 27 22 1 0 46 30 1 0 44 31 1 0 40 35 1 0 1 64 1 0 1 65 1 0 1 66 1 0 4 67 1 0 6 68 1 0 7 69 1 0 9 70 1 0 10 71 1 0 11 72 1 0 15 73 1 0 15 74 1 0 16 75 1 6 17 76 1 1 18 77 1 6 19 78 1 6 20 79 1 6 23 80 1 0 24 81 1 0 26 82 1 0 29 83 1 0 29 84 1 0 29 85 1 0 30 86 1 6 31 87 1 1 32 88 1 0 32 89 1 0 34 90 1 6 36 91 1 0 37 92 1 0 40 93 1 0 42 94 1 0 42 95 1 0 42 96 1 0 43 97 1 0 44 98 1 1 45 99 1 0 45100 1 0 48101 1 0 49102 1 0 53103 1 0 54104 1 0 56105 1 0 57106 1 0 60107 1 0 62108 1 0 62109 1 0 62110 1 0 63111 1 0 M END

Standard InCHIKey	IKOMYZTZWSQHKE-PEUCKEPFSA-N
Standard InCHI	InChI=1S/C46H48O17/c1-54-34-17-24(5-11-30(34)47)7-15-39(50)58-23-38-45(63-40(51)16-8-25-6-12-31(48)35(18-25)55-2)41(52)42(53)46(62-38)61-33-14-10-27(20-37(33)57-4)44-29-22-59-43(28(29)21-60-44)26-9-13-32(49)36(19-26)56-3/h5-20,28-29,38,41-49,52-53H,21-23H2,1-4H3/b15-7+,16-8+/t28-,29-,38-,41-,42-,43+,44+,45-,46-/m1/s1
SMILES	COc1cc(ccc1O)/C=C/C(=O)OC[C@@H]1[C@H]([C@@H]([C@H]([C@H](Oc2ccc(cc2OC)[C@H]2[C@@H]3CO[C@@H](c4ccc(c(c4)OC)O)[C@@H]3CO2)O1)O)O)OC(=O)/C=C/c1ccc(c(c1)OC)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	872.29	Volume:	851.527 ? Van der Waals volume.
Dense:	1.024	LogP:	2.155 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.257 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.787 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	17.0	Rigid Bonds:	43.0
TPSA:	227.59 ? Topological Polar Surface Area.	H-Bond Acceptor:	17.0
H-Bond Donor:	5.0	Rings:	7.0
Heavy Atoms:	17.0

MedChem Properties

QED Drug-Likeness Score:	0.081	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.204	Fsp³:	0.348
MCE-18:	147.613 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.986	Fluc inhibitor:	1.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.284 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.658 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.136	Promiscuous compounds:	0.234

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.006	MDCK Permeability:	-5.415
Pgp-inhibitor:	0.455	Pgp-substrate:	0.008
PAMPA:	0.001 ? 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):	0.003
20% Bioavailability (F20%):	0.91	30% Bioavailability (F30%):	0.994
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.029
Plasma Protein Binding (PPB):	89.619%	Volume Distribution (VD):	-0.235
Fu:	11.305% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.884
BSEP inhibitor:	0.997

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.711
CYP2C19-inhibitor:	0.113	CYP2C19-substrate:	0.001
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.009
CYP3A4-inhibitor:	0.981	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.675 ? 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):

3.274

Half-life (T1/2):

3.923

ADMET: Toxicity

hERG Blockers:	0.086	hERG Blockers (10um):	0.447
Human Hepatotoxicity (H-HT):	0.732	Drug-induced Liver Injury (DILI):	0.986
AMES Toxicity:	0.897	Rat Oral Acute Toxicity:	0.044
Maximum Recommended Daily Dose:	0.37	Skin Sensitization:	0.999
Carcinogencity:	0.13	Eye Corrosion:	0.0
Eye Irritation:	0.19	Respiratory Toxicity:	0.049
Drug-induced Neurotoxicity:	0.113	Ototoxicity:	0.636
Hematotoxicity:	0.071	Drug-induced Nephrotoxicity:	0.96
Genotoxicity:	0.66	RPMI-8226 Immunitoxicity:	0.51
A549 Cytotoxicity:	0.777	Hek293 Cytotoxicity:	0.808
BCF:	1.004 ? 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:	3.99 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.279 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.92 ? 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
NPO33277.1	rhus javanica	Under-species	n.a.	n.a.	root	n.a.	n.a.	PMID[17616139]

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
EC50	1
Inhibition	1

Activity Type	# Activity
Organism	2

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT786	Organism	Tobacco mosaic virus	Tobacco mosaic virus	EC50	=	190.0	ug.mL-1	PMID[25615796]
NPT786	Organism	Tobacco mosaic virus	Tobacco mosaic virus	Inhibition	=	50.3	%	PMID[25615796]

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 NPC149873 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	13222
0.1-0.2	32574
0.2-0.3	3265
0.3-0.4	643
0.4-0.5	129
0.5-0.6	19
0.6-0.7	2
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8372	Intermediate Similarity	NPC59516
0.7791	Intermediate Similarity	NPC11411
0.7333	Intermediate Similarity	NPC7191
0.6092	Remote Similarity	NPC38041
0.6092	Remote Similarity	NPC22150
0.5816	Remote Similarity	NPC199311
0.5657	Remote Similarity	NPC287615
0.5591	Remote Similarity	NPC471405
0.5588	Remote Similarity	NPC261122
0.5513	Remote Similarity	NPC27843
0.5513	Remote Similarity	NPC7171
0.5417	Remote Similarity	NPC478055
0.5354	Remote Similarity	NPC80732
0.5275	Remote Similarity	NPC286235
0.5217	Remote Similarity	NPC279298
0.5172	Remote Similarity	NPC246947
0.5109	Remote Similarity	NPC51328
0.5109	Remote Similarity	NPC252402
0.5109	Remote Similarity	NPC102934
0.5109	Remote Similarity	NPC55158
0.5102	Remote Similarity	NPC44730
0.5057	Remote Similarity	NPC276753
0.5057	Remote Similarity	NPC205796
0.5052	Remote Similarity	NPC157816

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC149873 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4796
0.1-0.2	4276
0.2-0.3	71
0.3-0.4	7
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