NPASS Compound

Natural Product: NPC520730

Natural Product ID	NPC520730
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	LupGG
IUPAC Name	(1~{R},3~{a}~{S},5~{a}~{R},5~{b}~{R},7~{a}~{R},9~{S},11~{a}~{R},11~{b}~{R},13~{a}~{R},13~{b}~{R})-9-[(2~{R},3~{R},4~{S},5~{S},6~{R})-4,5-dihydroxy-6-(hydroxymethyl)-3-[(2~{S},3~{R},4~{S},5~{S},6~{R})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-tetrahydropyran-2-yl]oxy-1-isopropenyl-5~{a},5~{b},8,8,11~{a}-pentamethyl-1,2,3,4,5,6,7,7~{a},9,10,11,11~{b},12,13,13~{a},13~{b}-hexadecahydrocyclopenta[a]chrysene-3~{a}-carboxylic acid
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 123129 0 0 0 0 0 0 0 0999 V2000 -6.7022 0.4950 -3.3755 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.5633 -0.0530 -2.5704 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.6802 -0.8624 -3.1290 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.4774 0.0779 -1.1079 C 0 0 2 0 0 0 0 0 0 0 0 0 -8.7307 0.8579 -0.6178 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.1205 2.1734 -0.0856 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9423 1.5000 0.6623 C 0 0 2 0 0 0 0 0 0 0 0 0 -7.5728 0.6186 1.6424 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.4785 -0.6212 1.7167 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.3909 1.1982 2.6361 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.0205 2.4958 1.2717 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7687 1.7755 1.6969 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1687 0.9174 0.6154 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.4771 1.8613 -0.3295 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1548 0.0216 -0.0870 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.4841 -0.7271 -1.1792 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2692 -1.5072 -0.7077 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3932 -0.6581 0.1468 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.0838 -1.2658 0.5429 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.2147 -2.5629 1.2847 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1930 -1.5255 -0.6470 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6233 -0.3411 -1.0436 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6881 -0.1456 0.0206 C 0 0 2 0 0 0 0 0 0 0 0 0 2.6590 -1.0951 -0.1919 O 0 0 0 0 0 0 0 0 0 0 0 0 3.8673 -0.5227 -0.6288 C 0 0 2 0 0 0 0 0 0 0 0 0 4.1414 -1.0871 -1.8524 O 0 0 0 0 0 0 0 0 0 0 0 0 5.4519 -1.4399 -2.0529 C 0 0 2 0 0 0 0 0 0 0 0 0 5.5198 -2.1257 -3.4197 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7105 -3.2576 -3.4556 O 0 0 0 0 0 0 0 0 0 0 0 0 6.0034 -2.4077 -1.0548 C 0 0 1 0 0 0 0 0 0 0 0 0 7.3520 -2.1046 -0.7909 O 0 0 0 0 0 0 0 0 0 0 0 0 5.2921 -2.2642 0.2913 C 0 0 2 0 0 0 0 0 0 0 0 0 4.1812 -3.0876 0.3315 O 0 0 0 0 0 0 0 0 0 0 0 0 4.9074 -0.8057 0.4175 C 0 0 1 0 0 0 0 0 0 0 0 0 6.0595 -0.0617 0.1541 O 0 0 0 0 0 0 0 0 0 0 0 0 6.4091 0.7820 1.1788 C 0 0 2 0 0 0 0 0 0 0 0 0 6.2798 2.0973 0.7441 O 0 0 0 0 0 0 0 0 0 0 0 0 7.1332 2.4485 -0.2709 C 0 0 2 0 0 0 0 0 0 0 0 0 6.4170 2.7462 -1.5778 C 0 0 0 0 0 0 0 0 0 0 0 0 7.3987 3.0855 -2.5060 O 0 0 0 0 0 0 0 0 0 0 0 0 8.2345 1.4729 -0.5293 C 0 0 1 0 0 0 0 0 0 0 0 0 9.2356 2.1683 -1.2446 O 0 0 0 0 0 0 0 0 0 0 0 0 8.8626 1.0702 0.7899 C 0 0 2 0 0 0 0 0 0 0 0 0 9.7734 0.0245 0.5302 O 0 0 0 0 0 0 0 0 0 0 0 0 7.7796 0.5785 1.7347 C 0 0 1 0 0 0 0 0 0 0 0 0 7.8786 1.3767 2.8951 O 0 0 0 0 0 0 0 0 0 0 0 0 1.1187 -0.3082 1.3962 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6161 -1.4725 2.1697 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5701 0.9472 2.1724 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3734 -0.1803 1.3396 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.0464 0.1064 2.6357 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3839 0.7387 2.2633 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1704 -0.0561 1.2775 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.9429 -1.0865 2.0562 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3377 0.8148 -0.5450 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.8625 1.0949 -3.1190 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8309 0.3373 -4.4649 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.4636 -1.0180 -2.3608 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.1098 -0.4008 -4.0429 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.2616 -1.8725 -3.3729 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.5407 -0.9214 -0.5959 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.1770 0.3600 0.2624 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.4487 1.0188 -1.4146 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.7888 2.6960 0.5910 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.7556 2.7247 -0.9572 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.5028 0.7192 3.5402 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5031 2.8865 2.1963 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8303 3.3680 0.6285 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9180 1.2952 2.6596 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0174 2.5980 1.9001 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4471 2.1579 0.0266 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0277 2.8512 -0.3276 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4494 1.5645 -1.3730 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5192 -0.7365 0.6374 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2077 -1.5032 -1.5482 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2153 -0.1393 -2.0790 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7113 -1.7395 -1.6645 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5723 -2.4724 -0.3216 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1069 0.2234 -0.5103 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2059 -2.5009 2.3697 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1444 -3.1231 1.0054 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3869 -3.2847 1.0147 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7013 -1.9060 -1.5380 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5437 -2.3414 -0.3795 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1354 -0.6006 -2.0038 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0416 0.5668 -1.2423 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1229 0.8558 -0.1896 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7774 0.5818 -0.7107 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1197 -0.5438 -2.1519 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5590 -2.4575 -3.6426 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1830 -1.4526 -4.2233 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1681 -3.3635 -2.6392 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9354 -3.4681 -1.3765 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8649 -2.0964 -1.6194 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9709 -2.5011 1.1303 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0497 -3.4706 1.2363 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5238 -0.5470 1.4129 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6707 0.6711 2.0097 H 0 0 0 0 0 0 0 0 0 0 0 0 7.6257 3.4217 0.0201 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6859 3.5899 -1.4322 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8850 1.8339 -1.9129 H 0 0 0 0 0 0 0 0 0 0 0 0 7.6594 2.3553 -3.0975 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9645 0.6157 -1.1531 H 0 0 0 0 0 0 0 0 0 0 0 0 10.1189 1.7511 -1.1353 H 0 0 0 0 0 0 0 0 0 0 0 0 9.3957 1.9437 1.1738 H 0 0 0 0 0 0 0 0 0 0 0 0 10.0662 -0.3651 1.4058 H 0 0 0 0 0 0 0 0 0 0 0 0 8.0009 -0.4485 2.0319 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7111 0.8179 3.6912 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9278 -1.6369 3.0238 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8561 -2.3766 1.6136 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5860 -1.1675 2.6636 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6018 1.1927 1.8707 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9184 1.7930 1.9138 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5896 0.7168 3.2457 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5328 0.7574 0.7131 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4456 0.8994 3.1498 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1451 -0.7119 3.3338 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1610 1.7743 1.9869 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9567 0.7673 3.2335 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8486 -0.7184 2.5510 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2684 -1.4085 2.9068 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2003 -1.9975 1.5298 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0173 1.6729 -1.2128 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 2 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 1 8 9 2 0 8 10 1 0 7 11 1 0 11 12 1 0 12 13 1 0 13 14 1 6 13 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 1 0 19 20 1 1 19 21 1 0 21 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 28 29 1 0 27 30 1 0 30 31 1 0 30 32 1 0 32 33 1 0 32 34 1 0 34 35 1 0 35 36 1 0 36 37 1 0 37 38 1 0 38 39 1 0 39 40 1 0 38 41 1 0 41 42 1 0 41 43 1 0 43 44 1 0 43 45 1 0 45 46 1 0 23 47 1 0 47 48 1 0 47 49 1 0 47 50 1 0 50 51 1 0 51 52 1 0 52 53 1 0 53 54 1 1 15 55 1 0 55 4 1 0 55 7 1 0 53 13 1 0 53 18 1 0 50 19 1 0 34 25 1 0 45 36 1 0 1 56 1 0 1 57 1 0 3 58 1 0 3 59 1 0 3 60 1 0 4 61 1 1 5 62 1 0 5 63 1 0 6 64 1 0 6 65 1 0 10 66 1 0 11 67 1 0 11 68 1 0 12 69 1 0 12 70 1 0 14 71 1 0 14 72 1 0 14 73 1 0 15 74 1 1 16 75 1 0 16 76 1 0 17 77 1 0 17 78 1 0 18 79 1 6 20 80 1 0 20 81 1 0 20 82 1 0 21 83 1 0 21 84 1 0 22 85 1 0 22 86 1 0 23 87 1 1 25 88 1 6 27 89 1 6 28 90 1 0 28 91 1 0 29 92 1 0 30 93 1 6 31 94 1 0 32 95 1 1 33 96 1 0 34 97 1 1 36 98 1 1 38 99 1 1 39100 1 0 39101 1 0 40102 1 0 41103 1 6 42104 1 0 43105 1 1 44106 1 0 45107 1 1 46108 1 0 48109 1 0 48110 1 0 48111 1 0 49112 1 0 49113 1 0 49114 1 0 50115 1 6 51116 1 0 51117 1 0 52118 1 0 52119 1 0 54120 1 0 54121 1 0 54122 1 0 55123 1 6 M END

Standard InCHIKey	ANDZVSZQVVZFCT-QQIJCRMXSA-N
Standard InCHI	InChI=1S/C42H68O13/c1-20(2)21-10-15-42(37(50)51)17-16-40(6)22(28(21)42)8-9-26-39(5)13-12-27(38(3,4)25(39)11-14-41(26,40)7)54-36-34(32(48)30(46)24(19-44)53-36)55-35-33(49)31(47)29(45)23(18-43)52-35/h21-36,43-49H,1,8-19H2,2-7H3,(H,50,51)/t21-,22+,23+,24+,25-,26+,27-,28+,29+,30+,31-,32-,33+,34+,35-,36-,39-,40+,41+,42-/m0/s1
SMILES	C=C(C)[C@@H]1CC[C@]2(C(=O)O)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC[C@H](O[C@@H]6O[C@H](CO)[C@@H](O)[C@H](O)[C@H]6O[C@@H]6O[C@H](CO)[C@@H](O)[C@H](O)[C@H]6O)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12

Calculated Properties

Physi-Chem Properties

Molecular Weight:	780.47	Volume:	784.093 ? Van der Waals volume.
Dense:	0.995	LogP:	1.778 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.456 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.05 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	8.0	Rigid Bonds:	39.0
TPSA:	215.83 ? Topological Polar Surface Area.	H-Bond Acceptor:	13.0
H-Bond Donor:	8.0	Rings:	7.0
Heavy Atoms:	13.0

MedChem Properties

QED Drug-Likeness Score:	0.132	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.759	Fsp³:	0.929
MCE-18:	149.333 ? 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:	0.952	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.004 ? 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:	0.222	Promiscuous compounds:	0.185

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.956	MDCK Permeability:	-5.131
Pgp-inhibitor:	0.0	Pgp-substrate:	0.005
PAMPA:	0.992 ? 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):	0.018
20% Bioavailability (F20%):	0.033	30% Bioavailability (F30%):	0.977
50% Bioavailability (F50%):	0.959

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.022	MRP1:	0.648
Plasma Protein Binding (PPB):	84.812%	Volume Distribution (VD):	-0.523
Fu:	11.024% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.004
BSEP inhibitor:	0.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.6	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.002	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.001
HLM stability:	0.0 ? 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):

0.43

Half-life (T1/2):

2.471

ADMET: Toxicity

hERG Blockers:	0.007	hERG Blockers (10um):	0.005
Human Hepatotoxicity (H-HT):	0.847	Drug-induced Liver Injury (DILI):	0.956
AMES Toxicity:	0.806	Rat Oral Acute Toxicity:	0.004
Maximum Recommended Daily Dose:	0.006	Skin Sensitization:	1.0
Carcinogencity:	0.613	Eye Corrosion:	0.0
Eye Irritation:	0.023	Respiratory Toxicity:	0.028
Drug-induced Neurotoxicity:	0.001	Ototoxicity:	0.995
Hematotoxicity:	0.656	Drug-induced Nephrotoxicity:	0.972
Genotoxicity:	0.372	RPMI-8226 Immunitoxicity:	0.035
A549 Cytotoxicity:	0.229	Hek293 Cytotoxicity:	0.125
BCF:	0.921 ? 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:	3.412 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.809 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.079 ? 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
NPO7158	Schefflera venulosa	Species	Araliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7158	Schefflera venulosa	Species	Araliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO7158	Schefflera venulosa	Species	Araliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO7158	Schefflera venulosa	Species	Araliaceae	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 NPC520730 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	22617
0.1-0.2	22135
0.2-0.3	3780
0.3-0.4	941
0.4-0.5	322
0.5-0.6	47
0.6-0.7	5
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	Natural Product ID
0.7912	Intermediate Similarity	NPC204392
0.766	Intermediate Similarity	NPC275668
0.7614	Intermediate Similarity	NPC488208
0.7363	Intermediate Similarity	NPC488205
0.7294	Intermediate Similarity	NPC88744
0.7234	Intermediate Similarity	NPC240734
0.7111	Intermediate Similarity	NPC51947
0.701	Intermediate Similarity	NPC91838
0.6667	Remote Similarity	NPC488207
0.6559	Remote Similarity	NPC236753
0.6316	Remote Similarity	NPC164194
0.6304	Remote Similarity	NPC224414
0.6058	Remote Similarity	NPC488206
0.598	Remote Similarity	NPC114304
0.5978	Remote Similarity	NPC252253
0.5976	Remote Similarity	NPC4309
0.596	Remote Similarity	NPC25605
0.5914	Remote Similarity	NPC45959
0.5854	Remote Similarity	NPC271974
0.5854	Remote Similarity	NPC247312
0.5833	Remote Similarity	NPC160506
0.5729	Remote Similarity	NPC139271
0.5714	Remote Similarity	NPC304011
0.561	Remote Similarity	NPC264317
0.561	Remote Similarity	NPC294438
0.5579	Remote Similarity	NPC312553
0.5543	Remote Similarity	NPC473844
0.5542	Remote Similarity	NPC488164
0.5542	Remote Similarity	NPC264005
0.5534	Remote Similarity	NPC488561
0.5532	Remote Similarity	NPC159036
0.5521	Remote Similarity	NPC472987
0.5506	Remote Similarity	NPC76486
0.5437	Remote Similarity	NPC127056
0.5392	Remote Similarity	NPC12288
0.5385	Remote Similarity	NPC472949
0.537	Remote Similarity	NPC470478
0.5312	Remote Similarity	NPC606107
0.5294	Remote Similarity	NPC201655
0.5275	Remote Similarity	NPC91497
0.5258	Remote Similarity	NPC8039
0.5258	Remote Similarity	NPC120123
0.5233	Remote Similarity	NPC16377
0.5227	Remote Similarity	NPC478841
0.5227	Remote Similarity	NPC488166
0.5155	Remote Similarity	NPC472897
0.5155	Remote Similarity	NPC472896
0.5152	Remote Similarity	NPC208477
0.5143	Remote Similarity	NPC109079
0.5098	Remote Similarity	NPC473481
0.5091	Remote Similarity	NPC257468
0.5088	Remote Similarity	NPC480939
0.5086	Remote Similarity	NPC151543
0.5057	Remote Similarity	NPC151191
0.5053	Remote Similarity	NPC470312
0.5052	Remote Similarity	NPC274507
0.5052	Remote Similarity	NPC203974
0.5052	Remote Similarity	NPC611039
0.5047	Remote Similarity	NPC80843
0.5045	Remote Similarity	NPC302887

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC520730 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6351
0.1-0.2	2698
0.2-0.3	89
0.3-0.4	8
0.4-0.5	1
0.5-0.6	3
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
0.5833	Remote Similarity	NPD8035	Phase 2
0.567	Remote Similarity	NPD8034	Phase 2
0.561	Remote Similarity	NPD7520	Phase 1

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