NPASS Compound

Natural Product: NPC563540

Natural Product ID	NPC563540
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Evonoside
IUPAC Name	3-[(3~{S},5~{R},8~{R},9~{S},10~{S},13~{R},17~{R})-14-hydroxy-3-[(2~{R},3~{R},4~{R},5~{S},6~{S})-5-hydroxy-6-methyl-3,4-bis[[(2~{R},3~{R},4~{S},5~{S},6~{R})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy]tetrahydropyran-2-yl]oxy-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]-2~{H}-furan-5-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds]

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 123130 0 0 0 0 0 0 0 0999 V2000 -3.7083 -1.2265 4.2214 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4967 -1.0415 3.3324 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.3038 0.3118 3.1389 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7695 0.6172 1.8948 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.6028 0.0005 1.6149 O 0 0 0 0 0 0 0 0 0 0 0 0 0.5046 0.7620 1.3295 C 0 0 1 0 0 0 0 0 0 0 0 0 1.5837 0.6617 2.3830 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8857 0.6294 1.6292 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0453 -0.6548 0.7983 C 0 0 1 0 0 0 0 0 0 0 0 0 2.7617 -1.7657 1.7991 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9587 -0.6237 -0.1975 C 0 0 2 0 0 0 0 0 0 0 0 0 2.3527 -0.6658 -1.6501 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6569 0.0760 -1.8640 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6637 -0.7923 -1.1333 C 0 0 2 0 0 0 0 0 0 0 0 0 4.4549 -0.6909 0.3305 C 0 0 2 0 0 0 0 0 0 0 0 0 5.2186 -1.9050 0.8972 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6721 -1.7740 0.6269 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0831 -0.8679 -0.4906 C 0 0 2 0 0 0 0 0 0 0 0 0 8.2247 -1.5812 -1.2117 C 0 0 0 0 0 0 0 0 0 0 0 0 7.6024 0.4336 0.0319 C 0 0 1 0 0 0 0 0 0 0 0 0 9.0493 0.7026 -0.1253 C 0 0 0 0 0 0 0 0 0 0 0 0 9.9172 0.8365 0.9057 C 0 0 0 0 0 0 0 0 0 0 0 0 11.2510 1.0921 0.4176 C 0 0 0 0 0 0 0 0 0 0 0 0 12.3136 1.2720 1.0638 O 0 0 0 0 0 0 0 0 0 0 0 0 11.1666 1.1083 -0.9570 O 0 0 0 0 0 0 0 0 0 0 0 0 9.8282 0.9616 -1.3390 C 0 0 0 0 0 0 0 0 0 0 0 0 6.8892 1.5560 -0.7033 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2869 0.8922 -1.8934 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0592 -0.5608 -1.5272 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3091 -1.2771 -2.7300 O 0 0 0 0 0 0 0 0 0 0 0 0 1.0180 0.5518 -0.0702 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7788 0.2717 0.7851 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.6911 1.2849 0.6399 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.5919 1.9844 -0.5609 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.7442 1.8804 -1.2982 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.1873 3.0302 -1.8975 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.1159 2.6938 -3.0736 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.2176 1.9760 -2.6522 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.0958 3.8871 -2.4605 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.6943 5.0460 -2.9761 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.1094 4.3072 -1.4226 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.8002 4.3113 -1.9214 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.2466 3.4165 -0.2195 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.2494 3.8773 0.6571 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4550 -1.0317 1.0601 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.7182 -0.8752 1.5750 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.7088 -1.5019 0.8251 C 0 0 1 0 0 0 0 0 0 0 0 0 -6.3540 -2.4950 1.5643 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.1709 -3.2772 0.7531 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.4115 -4.3199 -0.0334 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.3800 -5.0156 -0.7920 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.9562 -2.4417 -0.2277 C 0 0 1 0 0 0 0 0 0 0 0 0 -9.2422 -2.9571 -0.3291 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.1025 -1.0236 0.3283 C 0 0 2 0 0 0 0 0 0 0 0 0 -8.8309 -0.2941 -0.5936 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.7038 -0.4484 0.4100 C 0 0 1 0 0 0 0 0 0 0 0 0 -6.6613 0.6738 1.2316 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6836 -1.8395 2.0987 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.5512 -2.4390 1.6005 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.3001 -2.1312 3.8977 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3910 -1.3125 5.2657 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3863 -0.3271 4.1738 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6169 -1.4791 3.8849 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6808 1.7181 1.8527 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1619 1.8164 1.3775 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5157 -0.2574 2.9847 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6179 1.5520 3.0366 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7671 0.6517 2.3054 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9322 1.5004 0.9391 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6444 -1.9427 1.8453 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1785 -1.5582 2.7980 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1689 -2.7387 1.4722 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2771 -1.5238 -0.0732 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5075 -1.7152 -2.0085 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5392 -0.2564 -2.2817 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9331 0.1921 -2.9079 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6532 1.0642 -1.3607 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4136 -1.8524 -1.4632 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0436 0.1660 0.7129 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8424 -2.7723 0.2958 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9916 -1.9834 1.9632 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1405 -1.3516 1.5626 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1717 -2.7598 0.5199 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9694 -2.6937 -1.1146 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1902 -1.4113 -2.2924 H 0 0 0 0 0 0 0 0 0 0 0 0 9.1838 -1.4934 -0.7101 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3956 0.5286 1.1425 H 0 0 0 0 0 0 0 0 0 0 0 0 9.6809 0.7684 1.9573 H 0 0 0 0 0 0 0 0 0 0 0 0 9.7871 0.2290 -2.1365 H 0 0 0 0 0 0 0 0 0 0 0 0 9.5326 1.9532 -1.8042 H 0 0 0 0 0 0 0 0 0 0 0 0 7.6171 2.3585 -1.0298 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1931 2.0723 -0.0342 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0482 0.9740 -2.7217 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4166 1.4329 -2.2356 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7579 -0.9131 -3.4633 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1403 0.3358 -0.7097 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5082 1.4419 -0.5121 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1646 0.2567 -0.1440 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7660 1.5988 -1.2120 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7896 3.6356 -1.1948 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3794 3.6205 -3.6193 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5800 2.0519 -3.8144 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0656 1.0113 -2.7057 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5650 3.4037 -3.3073 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3014 5.8692 -2.5851 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2905 5.3596 -1.0770 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2650 4.8502 -1.2809 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3011 3.4416 0.3440 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1161 3.3624 1.5115 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5111 -1.6181 0.1176 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2818 -1.9912 -0.0532 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.9153 -3.8431 1.3773 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8635 -5.0348 0.6055 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7740 -3.8211 -0.7830 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.1973 -5.1635 -0.2700 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.5137 -2.4308 -1.2337 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.7715 -2.6691 0.4735 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.5791 -1.0262 1.3082 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.5261 0.2057 -0.1055 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4363 -0.1463 -0.6279 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0559 0.4206 2.0830 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3814 -2.6955 2.3491 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5779 -2.6487 0.6544 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 1 9 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 6 18 20 1 0 20 21 1 0 21 22 2 0 22 23 1 0 23 24 2 0 23 25 1 0 25 26 1 0 20 27 1 0 27 28 1 0 28 29 1 0 29 30 1 0 11 31 1 0 4 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 36 39 1 0 39 40 1 0 39 41 1 0 41 42 1 0 41 43 1 0 43 44 1 0 32 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 49 52 1 0 52 53 1 0 52 54 1 0 54 55 1 0 54 56 1 0 56 57 1 0 45 58 1 0 58 59 1 0 58 2 1 0 31 6 1 0 43 34 1 0 56 47 1 0 15 9 1 0 29 18 1 0 29 14 1 0 26 21 1 0 1 60 1 0 1 61 1 0 1 62 1 0 2 63 1 1 4 64 1 1 6 65 1 6 7 66 1 0 7 67 1 0 8 68 1 0 8 69 1 0 10 70 1 0 10 71 1 0 10 72 1 0 11 73 1 1 12 74 1 0 12 75 1 0 13 76 1 0 13 77 1 0 14 78 1 6 15 79 1 1 16 80 1 0 16 81 1 0 17 82 1 0 17 83 1 0 19 84 1 0 19 85 1 0 19 86 1 0 20 87 1 1 22 88 1 0 26 89 1 0 26 90 1 0 27 91 1 0 27 92 1 0 28 93 1 0 28 94 1 0 30 95 1 0 31 96 1 0 31 97 1 0 32 98 1 6 34 99 1 6 36100 1 1 37101 1 0 37102 1 0 38103 1 0 39104 1 6 40105 1 0 41106 1 1 42107 1 0 43108 1 1 44109 1 0 45110 1 6 47111 1 6 49112 1 1 50113 1 0 50114 1 0 51115 1 0 52116 1 6 53117 1 0 54118 1 1 55119 1 0 56120 1 6 57121 1 0 58122 1 1 59123 1 0 M END

Standard InCHIKey	XGXBZAKHPZJFOQ-RRAKZCAWSA-N
Standard InCHI	InChI=1S/C41H64O18/c1-17-27(45)34(58-36-32(50)30(48)28(46)24(14-42)56-36)35(59-37-33(51)31(49)29(47)25(15-43)57-37)38(54-17)55-20-6-9-39(2)19(13-20)4-5-23-22(39)7-10-40(3)21(8-11-41(23,40)52)18-12-26(44)53-16-18/h12,17,19-25,27-38,42-43,45-52H,4-11,13-16H2,1-3H3/t17-,19+,20-,21+,22-,23+,24+,25+,27-,28+,29+,30-,31-,32+,33+,34+,35+,36+,37+,38-,39-,40+,41?/m0/s1
SMILES	C[C@@H]1O[C@@H](O[C@H]2CC[C@@]3(C)[C@H](CC[C@@H]4[C@@H]3CC[C@]3(C)[C@@H](C5=CC(=O)OC5)CCC43O)C2)[C@H](O[C@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O)[C@H](O[C@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O)[C@H]1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	844.41	Volume:	802.191 ? Van der Waals volume.
Dense:	1.053	LogP:	0.255 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.065 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.934 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	9.0	Rigid Bonds:	44.0
TPSA:	283.98 ? Topological Polar Surface Area.	H-Bond Acceptor:	18.0
H-Bond Donor:	10.0	Rings:	8.0
Heavy Atoms:	18.0

MedChem Properties

QED Drug-Likeness Score:	0.09	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	6.036	Fsp³:	0.927
MCE-18:	155.949 ? 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:	0.683	Fluc inhibitor:	0.001 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.009 ? 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:	0.181	Promiscuous compounds:	0.317

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.942	MDCK Permeability:	-5.049
Pgp-inhibitor:	0.0	Pgp-substrate:	0.974
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):	0.327
20% Bioavailability (F20%):	0.198	30% Bioavailability (F30%):	0.978
50% Bioavailability (F50%):	0.983

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.093
Plasma Protein Binding (PPB):	61.339%	Volume Distribution (VD):	-0.438
Fu:	32.253% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.003
BSEP inhibitor:	0.002

ADMET: Metabolism

CYP1A2-inhibitor:	0.008	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.003	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.998	CYP3A4-substrate:	0.005
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.024
HLM stability:	0.001 ? 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):

0.087

Half-life (T1/2):

4.722

ADMET: Toxicity

hERG Blockers:	0.019	hERG Blockers (10um):	0.17
Human Hepatotoxicity (H-HT):	0.773	Drug-induced Liver Injury (DILI):	0.952
AMES Toxicity:	0.889	Rat Oral Acute Toxicity:	0.284
Maximum Recommended Daily Dose:	0.988	Skin Sensitization:	1.0
Carcinogencity:	0.264	Eye Corrosion:	0.0
Eye Irritation:	0.0	Respiratory Toxicity:	0.612
Drug-induced Neurotoxicity:	0.0	Ototoxicity:	0.999
Hematotoxicity:	0.753	Drug-induced Nephrotoxicity:	0.997
Genotoxicity:	0.998	RPMI-8226 Immunitoxicity:	0.817
A549 Cytotoxicity:	0.289	Hek293 Cytotoxicity:	0.905
BCF:	0.64 ? 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:	3.22 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.493 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.641 ? 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
NPO54936	Euonymus europaeus L.	Genus	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO44651	Euonymus japonicus Thunb.	Genus	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO53451	Euonymus latifolius (L.) Mill.	Genus	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]

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 NPC563540 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	16277
0.1-0.2	28277
0.2-0.3	3893
0.3-0.4	1119
0.4-0.5	119
0.5-0.6	82
0.6-0.7	68
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
0.8293	Intermediate Similarity	NPC5311
0.7955	Intermediate Similarity	NPC236973
0.7955	Intermediate Similarity	NPC292467
0.7912	Intermediate Similarity	NPC486146
0.764	Intermediate Similarity	NPC30483
0.764	Intermediate Similarity	NPC470897
0.7619	Intermediate Similarity	NPC99620
0.7586	Intermediate Similarity	NPC93883
0.75	Intermediate Similarity	NPC486143
0.75	Intermediate Similarity	NPC486142
0.75	Intermediate Similarity	NPC486149
0.7347	Intermediate Similarity	NPC486134
0.7347	Intermediate Similarity	NPC486141
0.7241	Intermediate Similarity	NPC77299
0.7241	Intermediate Similarity	NPC480906
0.7216	Intermediate Similarity	NPC475590
0.7159	Intermediate Similarity	NPC480914
0.7097	Intermediate Similarity	NPC240070
0.7071	Intermediate Similarity	NPC120390
0.7041	Intermediate Similarity	NPC486144
0.7041	Intermediate Similarity	NPC486145
0.7041	Intermediate Similarity	NPC486147
0.7041	Intermediate Similarity	NPC486148
0.6989	Remote Similarity	NPC32177
0.6989	Remote Similarity	NPC469756
0.6989	Remote Similarity	NPC275901
0.6966	Remote Similarity	NPC76572
0.6966	Remote Similarity	NPC193382
0.6915	Remote Similarity	NPC188234
0.6907	Remote Similarity	NPC486138
0.6907	Remote Similarity	NPC276838
0.69	Remote Similarity	NPC74259
0.6848	Remote Similarity	NPC480907
0.6771	Remote Similarity	NPC125077
0.6737	Remote Similarity	NPC480910
0.6737	Remote Similarity	NPC480909
0.6733	Remote Similarity	NPC475419
0.6667	Remote Similarity	NPC469750
0.6667	Remote Similarity	NPC474908
0.6635	Remote Similarity	NPC474423
0.6629	Remote Similarity	NPC471633
0.6598	Remote Similarity	NPC486135
0.6598	Remote Similarity	NPC208193
0.6598	Remote Similarity	NPC486137
0.6593	Remote Similarity	NPC199428
0.6593	Remote Similarity	NPC84949
0.6593	Remote Similarity	NPC109448
0.6593	Remote Similarity	NPC480562
0.6593	Remote Similarity	NPC74945
0.6593	Remote Similarity	NPC310341
0.6593	Remote Similarity	NPC31354
0.6593	Remote Similarity	NPC69576
0.6556	Remote Similarity	NPC84987
0.6531	Remote Similarity	NPC232785
0.6531	Remote Similarity	NPC486139
0.6489	Remote Similarity	NPC72260
0.6442	Remote Similarity	NPC486150
0.6436	Remote Similarity	NPC488938
0.6436	Remote Similarity	NPC488937
0.6392	Remote Similarity	NPC32793
0.6392	Remote Similarity	NPC116075
0.6364	Remote Similarity	NPC469749
0.6327	Remote Similarity	NPC231518
0.6327	Remote Similarity	NPC488944
0.63	Remote Similarity	NPC329986
0.63	Remote Similarity	NPC140092
0.63	Remote Similarity	NPC247190
0.6263	Remote Similarity	NPC55532
0.6224	Remote Similarity	NPC475556
0.6224	Remote Similarity	NPC311706
0.6214	Remote Similarity	NPC486136
0.6196	Remote Similarity	NPC196429
0.6176	Remote Similarity	NPC475219
0.6139	Remote Similarity	NPC488939
0.6129	Remote Similarity	NPC157376
0.6129	Remote Similarity	NPC17896
0.6129	Remote Similarity	NPC469755
0.6129	Remote Similarity	NPC284406
0.6129	Remote Similarity	NPC197707
0.6129	Remote Similarity	NPC251866
0.6129	Remote Similarity	NPC142066
0.6129	Remote Similarity	NPC603972
0.6122	Remote Similarity	NPC40749
0.6087	Remote Similarity	NPC99728
0.6087	Remote Similarity	NPC87250
0.6087	Remote Similarity	NPC244402
0.6087	Remote Similarity	NPC50305
0.6082	Remote Similarity	NPC488935
0.6082	Remote Similarity	NPC488936
0.6019	Remote Similarity	NPC488947
0.6	Remote Similarity	NPC475629
0.5962	Remote Similarity	NPC479360
0.5962	Remote Similarity	NPC479359
0.5962	Remote Similarity	NPC488943
0.5962	Remote Similarity	NPC488942
0.5957	Remote Similarity	NPC6108
0.5957	Remote Similarity	NPC89514
0.5957	Remote Similarity	NPC480915
0.5938	Remote Similarity	NPC483822
0.5938	Remote Similarity	NPC471353
0.5938	Remote Similarity	NPC305574
0.5888	Remote Similarity	NPC117445
0.5888	Remote Similarity	NPC308262
0.5825	Remote Similarity	NPC146857
0.5773	Remote Similarity	NPC484202
0.5743	Remote Similarity	NPC479353
0.5743	Remote Similarity	NPC479354
0.5743	Remote Similarity	NPC486130
0.5686	Remote Similarity	NPC264336
0.5686	Remote Similarity	NPC488941
0.5686	Remote Similarity	NPC488940
0.5686	Remote Similarity	NPC486127
0.567	Remote Similarity	NPC146456
0.567	Remote Similarity	NPC250556
0.5636	Remote Similarity	NPC488945
0.5636	Remote Similarity	NPC488946
0.5631	Remote Similarity	NPC59288
0.5625	Remote Similarity	NPC286809
0.5612	Remote Similarity	NPC179412
0.5612	Remote Similarity	NPC471356
0.5607	Remote Similarity	NPC479358
0.5596	Remote Similarity	NPC329675
0.5567	Remote Similarity	NPC243196
0.5464	Remote Similarity	NPC479356
0.5464	Remote Similarity	NPC479355
0.5464	Remote Similarity	NPC99080
0.5455	Remote Similarity	NPC194716
0.5446	Remote Similarity	NPC173555
0.5421	Remote Similarity	NPC476221
0.5421	Remote Similarity	NPC477709
0.5421	Remote Similarity	NPC479357
0.5421	Remote Similarity	NPC486132
0.5421	Remote Similarity	NPC486131
0.5408	Remote Similarity	NPC10823
0.54	Remote Similarity	NPC193893
0.5385	Remote Similarity	NPC610296
0.537	Remote Similarity	NPC486128
0.5361	Remote Similarity	NPC219085
0.5312	Remote Similarity	NPC158344
0.5258	Remote Similarity	NPC473852
0.5234	Remote Similarity	NPC125324
0.5227	Remote Similarity	NPC268829
0.5227	Remote Similarity	NPC295110
0.5204	Remote Similarity	NPC309034
0.52	Remote Similarity	NPC77319
0.52	Remote Similarity	NPC471351
0.52	Remote Similarity	NPC180079
0.52	Remote Similarity	NPC471355
0.5192	Remote Similarity	NPC27363
0.5179	Remote Similarity	NPC486140
0.5155	Remote Similarity	NPC474418
0.5152	Remote Similarity	NPC34390
0.5149	Remote Similarity	NPC9499
0.5149	Remote Similarity	NPC471360
0.5149	Remote Similarity	NPC469751
0.5149	Remote Similarity	NPC471361
0.5149	Remote Similarity	NPC86159
0.5149	Remote Similarity	NPC469752
0.5149	Remote Similarity	NPC469754
0.5149	Remote Similarity	NPC70542
0.5146	Remote Similarity	NPC103534
0.5146	Remote Similarity	NPC44899
0.5146	Remote Similarity	NPC5883
0.5146	Remote Similarity	NPC304260
0.5146	Remote Similarity	NPC29639
0.5143	Remote Similarity	NPC206003
0.5143	Remote Similarity	NPC473610
0.5143	Remote Similarity	NPC608063
0.5133	Remote Similarity	NPC486133
0.5098	Remote Similarity	NPC471354
0.5098	Remote Similarity	NPC27507
0.5044	Remote Similarity	NPC51172
0.5044	Remote Similarity	NPC49032

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC563540 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6329
0.1-0.2	2695
0.2-0.3	105
0.3-0.4	4
0.4-0.5	7
0.5-0.6	6
0.6-0.7	4
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
0.6489	Remote Similarity	NPD8294	Phase 4
0.6327	Remote Similarity	NPD8033	Approved
0.6263	Remote Similarity	NPD8377	Phase 4
0.6129	Remote Similarity	NPD7319	Approved
0.567	Remote Similarity	NPD7507	Pre-clinical
0.5446	Remote Similarity	NPD8296	Phase 4
0.5283	Remote Similarity	NPD8378	Pre-clinical
0.5283	Remote Similarity	NPD8379	Approved
0.52	Remote Similarity	NPD8335	Phase 4
0.5149	Remote Similarity	NPD8380	Approved

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