NPASS Compound

Natural Product: NPC470927

Natural Product ID	NPC470927
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Velutinoside Iii
IUPAC Name	[(2R,3R,4R,5R,6R)-4-[(2S,3R,4R,5R,6S)-4,5-dihydroxy-6-methyl-3-[(2S,3S,4R,5R)-3,4,5-trihydroxyoxan-2-yl]oxyoxan-2-yl]oxy-5-hydroxy-6-[2-(3-hydroxy-4-methoxyphenyl)ethoxy]-2-[[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxymethyl]oxan-3-yl] (E)-3-(4-hydroxy-3-methoxyphenyl)prop-2-enoate
Synonyms	Velutinoside Iii
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL231869
PubChem CID	44429869
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0004603] Organic oxygen compounds [CHEMONTID:0000323] Organooxygen compounds [CHEMONTID:0000011] Carbohydrates and carbohydrate conjugates [CHEMONTID:0000198] Oligosaccharides

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

Chemical Representations

RDKit 2D 124129 0 0 0 0 0 0 0 0999 V2000 3.7981 -1.9284 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.6491 -0.9642 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5000 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7500 -1.2990 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.7500 -1.2990 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1595 -1.8121 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.4200 -3.2893 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6805 -4.7665 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0900 -4.2535 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.2391 -5.2176 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9891 -3.9186 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.4891 -3.9186 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.9891 -3.9186 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.4891 -3.9186 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -11.2391 -2.6196 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -12.7391 -2.6196 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -13.4891 -3.9186 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -12.7391 -5.2176 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -11.2391 -5.2176 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -13.4891 -6.5167 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -14.9891 -3.9186 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -15.7391 -5.2176 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9786 -6.6949 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5691 -7.2079 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4200 -6.2437 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6700 -7.5427 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.1700 -7.5427 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5800 -6.2437 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.5800 -8.8418 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0800 -8.8418 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8300 -10.1408 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0800 -11.4399 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8300 -12.7389 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3300 -12.7389 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0800 -11.4399 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3300 -10.1408 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5800 -11.4399 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 7.3300 -10.1408 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0800 -14.0379 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.3191 -8.5069 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.5691 -9.8060 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9786 -10.3190 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.2391 -11.7962 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6486 -11.2832 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0900 -12.7604 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6805 -12.2474 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4200 -10.7701 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0105 -11.2832 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.7500 -12.7604 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6595 -12.2474 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.8086 -13.2115 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5481 -14.6887 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1386 -15.2018 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0105 -14.2376 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7605 -15.5366 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8886 -16.5008 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.0481 -14.6887 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.4200 -13.7246 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.2391 -13.7246 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.4786 -6.6949 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.5000 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7500 1.2990 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7500 1.2990 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1595 1.8121 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.4895 2.7762 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6491 0.9642 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.5377 -3.4056 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7461 0.0588 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6849 -2.1132 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7580 0.8169 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3114 -2.7335 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8972 -3.0288 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9856 -3.7279 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1805 -4.7665 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3216 -5.7693 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4891 -2.4186 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.6719 -5.4074 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.9891 -2.4186 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.9891 -5.4186 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.4891 -1.3205 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -13.4891 -1.3205 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.4891 -6.5167 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -12.7391 -7.8157 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -17.0381 -4.4676 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -14.4401 -5.9676 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -16.4891 -6.5167 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2391 -8.1721 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5501 -7.8696 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0105 -5.7307 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1700 -10.1408 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8300 -7.5427 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6246 -11.0769 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0800 -14.0379 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0800 -8.8418 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 8.6290 -10.8908 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0310 -9.3908 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 8.0800 -8.8418 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5800 -14.0379 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5501 -9.1443 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9891 -13.0952 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1617 -12.6927 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1356 -9.8736 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.0582 -10.7701 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3400 -14.0594 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9070 -12.4402 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8125 -9.7179 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5235 -12.9533 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2181 -13.7246 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8507 -12.1326 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8086 -16.1660 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8844 -16.2988 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5023 -14.0809 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1744 -16.9174 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1386 -17.7999 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7981 -15.9878 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1765 -14.5634 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9786 -15.2018 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2286 -7.9939 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6491 -0.9642 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1595 1.8121 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6715 2.7970 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5078 1.1546 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8470 3.4573 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0586 0.4512 0.0000 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 2 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 2 0 18 20 1 0 17 21 1 0 21 22 1 0 10 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 26 27 1 0 27 28 2 0 27 29 1 0 29 30 2 0 30 31 1 0 31 32 2 0 32 33 1 0 33 34 2 0 34 35 1 0 35 36 2 0 35 37 1 0 37 38 1 0 34 39 1 0 24 40 1 0 40 41 1 0 41 42 1 0 42 43 1 0 43 44 1 0 43 45 1 0 45 46 1 0 46 47 1 0 47 48 1 0 48 49 1 0 49 50 1 0 50 51 1 0 51 52 1 0 52 53 1 0 53 54 1 0 54 55 1 0 53 56 1 0 52 57 1 0 46 58 1 0 45 59 1 0 23 60 1 0 5 61 1 0 61 62 1 0 62 63 1 0 63 64 1 0 62 65 1 0 61 66 1 0 63 3 1 0 25 8 1 0 36 31 1 0 47 41 1 0 54 49 1 0 19 14 1 0 1 67 1 0 2 68 1 0 2 69 1 0 3 70 1 6 5 71 1 6 7 72 1 0 7 73 1 0 8 74 1 1 10 75 1 1 12 76 1 0 12 77 1 0 13 78 1 0 13 79 1 0 15 80 1 0 16 81 1 0 19 82 1 0 20 83 1 0 22 84 1 0 22 85 1 0 22 86 1 0 23 87 1 6 24 88 1 1 25 89 1 6 29 90 1 0 30 91 1 0 32 92 1 0 33 93 1 0 36 94 1 0 38 95 1 0 38 96 1 0 38 97 1 0 39 98 1 0 41 99 1 6 43100 1 1 44101 1 0 44102 1 0 44103 1 0 45104 1 6 46105 1 1 47106 1 1 49107 1 1 51108 1 0 51109 1 0 52110 1 6 53111 1 6 54112 1 1 55113 1 0 56114 1 0 57115 1 0 58116 1 0 59117 1 0 60118 1 0 61119 1 1 62120 1 6 63121 1 1 64122 1 0 65123 1 0 66124 1 0 M END

Standard InCHIKey	HHUJWIFTKLKKSE-ORAGUUTESA-N
Standard InCHI	InChI=1S/C42H58O24/c1-17-28(48)32(52)38(66-40-33(53)29(49)22(46)15-59-40)42(61-17)65-37-35(55)41(58-11-10-19-5-8-23(56-2)21(45)12-19)63-26(16-60-39-34(54)31(51)30(50)25(14-43)62-39)36(37)64-27(47)9-6-18-4-7-20(44)24(13-18)57-3/h4-9,12-13,17,22,25-26,28-46,48-55H,10-11,14-16H2,1-3H3/b9-6+/t17-,22+,25+,26+,28-,29+,30+,31-,32+,33-,34+,35+,36+,37+,38+,39+,40-,41+,42-/m0/s1
SMILES	OC[C@H]1O[C@@H](OC[C@H]2O[C@@H](OCCc3ccc(c(c3)O)OC)[C@@H]([C@H]([C@@H]2OC(=O)/C=C/c2ccc(c(c2)OC)O)O[C@@H]2O[C@@H](C)[C@@H]([C@H]([C@H]2O[C@@H]2OC[C@H]([C@H]([C@@H]2O)O)O)O)O)O)[C@@H]([C@H]([C@@H]1O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	946.33	Volume:	873.523 ? Van der Waals volume.
Dense:	1.083	LogP:	-1.773 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	-0.512 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-1.586 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	18.0	Rigid Bonds:	38.0
TPSA:	361.36 ? Topological Polar Surface Area.	H-Bond Acceptor:	24.0
H-Bond Donor:	12.0	Rings:	6.0
Heavy Atoms:	24.0

MedChem Properties

QED Drug-Likeness Score:	0.053	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.888	Fsp³:	0.643
MCE-18:	157.507 ? 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:	1	PAINS Alert:	0
Colloidal aggregators:	0.691	Fluc inhibitor:	0.652 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.121 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.334 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.23	Promiscuous compounds:	0.287

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.503	MDCK Permeability:	-5.372
Pgp-inhibitor:	0.0	Pgp-substrate:	0.997
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):	0.99
20% Bioavailability (F20%):	0.921	30% Bioavailability (F30%):	0.999
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.015
Plasma Protein Binding (PPB):	66.751%	Volume Distribution (VD):	-0.334
Fu:	29.97% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.005
BSEP inhibitor:	0.001

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	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:	0.02	CYP3A4-substrate:	0.006
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.236 ? 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):

0.527

Half-life (T1/2):

4.263

ADMET: Toxicity

hERG Blockers:	0.008	hERG Blockers (10um):	0.045
Human Hepatotoxicity (H-HT):	0.412	Drug-induced Liver Injury (DILI):	0.773
AMES Toxicity:	0.987	Rat Oral Acute Toxicity:	0.001
Maximum Recommended Daily Dose:	0.006	Skin Sensitization:	1.0
Carcinogencity:	0.004	Eye Corrosion:	0.0
Eye Irritation:	0.001	Respiratory Toxicity:	0.001
Drug-induced Neurotoxicity:	0.001	Ototoxicity:	0.999
Hematotoxicity:	0.422	Drug-induced Nephrotoxicity:	0.965
Genotoxicity:	0.018	RPMI-8226 Immunitoxicity:	0.48
A549 Cytotoxicity:	0.941	Hek293 Cytotoxicity:	0.783
BCF:	0.438 ? 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:	3.119 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.834 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.909 ? 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
NPO6536	Marrubium velutinum	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17287127]
NPO6536	Marrubium velutinum	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO6536	Marrubium velutinum	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO6536	Marrubium velutinum	Species	Lamiaceae	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
Inhibition	1

Activity Type	# Activity
Individual protein	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT43	Individual protein	Tyrosinase	Agaricus bisporus	Inhibition	=	13.21	%	PubChem BioAssay data set

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 NPC470927 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	14972
0.1-0.2	29232
0.2-0.3	4949
0.3-0.4	599
0.4-0.5	64
0.5-0.6	18
0.6-0.7	14
0.7-0.8	0
0.8-0.85	2
0.85-0.9	1
0.9-0.95	1
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.9208	High Similarity	NPC257970
0.8515	High Similarity	NPC473427
0.8235	Intermediate Similarity	NPC306890
0.8218	Intermediate Similarity	NPC470933
0.7961	Intermediate Similarity	NPC64195
0.781	Intermediate Similarity	NPC94871
0.7723	Intermediate Similarity	NPC259347
0.7692	Intermediate Similarity	NPC471062
0.6964	Remote Similarity	NPC476386
0.6937	Remote Similarity	NPC229505
0.6857	Remote Similarity	NPC34927
0.6667	Remote Similarity	NPC476398
0.6636	Remote Similarity	NPC96795
0.6636	Remote Similarity	NPC264632
0.6518	Remote Similarity	NPC470934
0.6355	Remote Similarity	NPC298257
0.6355	Remote Similarity	NPC175214
0.6239	Remote Similarity	NPC100998
0.6204	Remote Similarity	NPC205864
0.6204	Remote Similarity	NPC247032
0.6111	Remote Similarity	NPC34587
0.6055	Remote Similarity	NPC252292
0.5888	Remote Similarity	NPC76406
0.5877	Remote Similarity	NPC476384
0.5856	Remote Similarity	NPC600370
0.5776	Remote Similarity	NPC476380
0.5641	Remote Similarity	NPC476381
0.5575	Remote Similarity	NPC476397
0.5565	Remote Similarity	NPC300894
0.5565	Remote Similarity	NPC23845
0.5439	Remote Similarity	NPC119537
0.5405	Remote Similarity	NPC611289
0.5385	Remote Similarity	NPC476382
0.5138	Remote Similarity	NPC260425
0.5135	Remote Similarity	NPC472350
0.5135	Remote Similarity	NPC197316
0.5135	Remote Similarity	NPC89105
0.5083	Remote Similarity	NPC476375
0.5083	Remote Similarity	NPC106818
0.5041	Remote Similarity	NPC87403

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC470927 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4999
0.1-0.2	4081
0.2-0.3	67
0.3-0.4	2
0.4-0.5	0
0.5-0.6	1
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
0.5135	Remote Similarity	NPD7266	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