NPASS Compound

Natural Product: NPC589445

Natural Product ID	NPC589445
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(2~{R},3~{S},4~{S},5~{R},6~{R})-2-(hydroxymethyl)-6-[(1~{R},2~{S},4~{S},5'~{R},6~{R},7~{S},8~{R},9~{S},12~{S},13~{R},16~{S},18~{S},19~{S})-5',7,9,13-tetramethyl-19-[(2~{R},3~{R},4~{S},5~{S},6~{R})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-spiro[5-oxapentacyclo[10.8.0.0^{2,9}.0^{4,8}.0^{13,18}]icosane-6,2'-tetrahydropyran]-16-yl]oxy-tetrahydropyran-3,4,5-triol
IUPAC Name	(2~{R},3~{S},4~{S},5~{R},6~{R})-2-(hydroxymethyl)-6-[(1~{R},2~{S},4~{S},5'~{R},6~{R},7~{S},8~{R},9~{S},12~{S},13~{R},16~{S},18~{S},19~{S})-5',7,9,13-tetramethyl-19-[(2~{R},3~{R},4~{S},5~{S},6~{R})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-spiro[5-oxapentacyclo[10.8.0.0^{2,9}.0^{4,8}.0^{13,18}]icosane-6,2'-tetrahydropyran]-16-yl]oxy-tetrahydropyran-3,4,5-triol
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 117124 0 0 0 0 0 0 0 0999 V2000 9.7407 0.7539 -2.1225 C 0 0 0 0 0 0 0 0 0 0 0 0 9.3379 1.0174 -0.6941 C 0 0 2 0 0 0 0 0 0 0 0 0 8.8068 -0.2192 0.0027 C 0 0 0 0 0 0 0 0 0 0 0 0 7.6879 0.2613 0.9311 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5656 0.7066 0.0256 C 0 0 1 0 0 0 0 0 0 0 0 0 6.9993 1.5764 -0.9425 O 0 0 0 0 0 0 0 0 0 0 0 0 8.2633 2.0881 -0.7101 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9184 -0.4250 -0.4845 O 0 0 0 0 0 0 0 0 0 0 0 0 4.7269 0.0085 -0.9772 C 0 0 1 0 0 0 0 0 0 0 0 0 3.5475 -0.9108 -0.6081 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4681 0.0757 -0.7453 C 0 0 1 0 0 0 0 0 0 0 0 0 1.1043 -0.2337 -0.3743 C 0 0 2 0 0 0 0 0 0 0 0 0 0.5251 -1.5303 -0.8161 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8719 -1.5688 -0.1547 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.4114 -2.8191 -0.2165 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.6284 -3.4021 1.0562 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.7566 -4.4605 1.2609 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.2428 -5.6842 0.9039 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.3839 -5.8216 -0.6141 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8790 -7.0690 -0.9557 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.5393 -6.0463 1.5939 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.3557 -7.0364 2.5580 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.1398 -4.8445 2.2957 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.4541 -5.0892 2.6891 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.0649 -3.6969 1.3065 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.6878 -2.6074 1.9269 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.6887 -0.5325 -0.8574 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.1510 -0.5605 -0.5422 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8909 0.3802 -1.4473 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.4029 1.4403 -0.6623 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.7795 1.5815 -0.8110 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.1086 2.7958 -1.3244 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.4424 3.7796 -0.4431 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.2439 4.3992 0.2491 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3582 4.9785 -0.6172 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.5018 3.3952 0.5502 C 0 0 1 0 0 0 0 0 0 0 0 0 -8.7191 4.0356 0.3301 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.7652 1.9065 0.5644 C 0 0 2 0 0 0 0 0 0 0 0 0 -8.3887 1.4983 1.7293 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.3997 1.2361 0.5076 C 0 0 1 0 0 0 0 0 0 0 0 0 -6.5160 -0.1514 0.5835 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.9471 1.0680 -2.4344 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8779 1.7672 -1.6678 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1497 0.8620 -0.6830 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.3015 1.4062 0.6946 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2876 0.8642 -1.0873 C 0 0 1 0 0 0 0 0 0 0 0 0 0.9841 2.1680 -1.0557 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0674 2.3598 -0.0737 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9502 1.1895 0.2053 C 0 0 1 0 0 0 0 0 0 0 0 0 2.7421 0.7933 1.6507 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3540 1.2911 -0.2122 C 0 0 1 0 0 0 0 0 0 0 0 0 5.4016 1.2897 0.8489 C 0 0 2 0 0 0 0 0 0 0 0 0 5.7845 2.6455 1.3541 C 0 0 0 0 0 0 0 0 0 0 0 0 8.8688 0.8922 -2.8243 H 0 0 0 0 0 0 0 0 0 0 0 0 10.1860 -0.2304 -2.2891 H 0 0 0 0 0 0 0 0 0 0 0 0 10.4555 1.5737 -2.4173 H 0 0 0 0 0 0 0 0 0 0 0 0 10.1970 1.4017 -0.1042 H 0 0 0 0 0 0 0 0 0 0 0 0 9.5666 -0.7897 0.5334 H 0 0 0 0 0 0 0 0 0 0 0 0 8.3005 -0.8294 -0.7895 H 0 0 0 0 0 0 0 0 0 0 0 0 8.0300 1.0777 1.5669 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3761 -0.6245 1.5334 H 0 0 0 0 0 0 0 0 0 0 0 0 8.3445 2.6361 0.2541 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4750 2.8222 -1.5216 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6938 0.2542 -2.0370 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6786 -1.3718 0.3639 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4743 -1.7313 -1.3630 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5770 0.5487 -1.7691 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9499 -0.1601 0.7240 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3738 -1.5928 -1.9165 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1232 -2.4012 -0.5208 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7083 -1.2255 0.8966 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3024 -2.6257 1.7887 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5052 -6.4527 1.2127 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0221 -4.9933 -1.0288 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3991 -5.7105 -1.1115 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1755 -7.0347 -1.8933 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3040 -6.4237 0.8839 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3751 -7.2311 2.5763 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4706 -4.6025 3.1464 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8561 -5.7377 2.0273 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6436 -3.9145 0.3845 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5896 -2.4771 1.5762 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5973 -0.7591 -1.9606 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5068 -1.6122 -0.6777 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3600 -0.2990 0.5161 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7196 -0.0831 -1.9949 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0961 0.7871 -1.5393 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8926 4.6211 -1.0531 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6839 3.6041 0.8161 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5473 5.1489 1.0054 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4104 4.9047 -0.3540 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1481 3.6721 1.5769 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.5730 4.9839 0.0459 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.3072 1.5678 -0.3482 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.8876 0.6569 1.5195 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7701 1.5400 1.3728 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8120 -0.4685 1.4681 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6292 0.4291 -3.2516 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5813 1.8770 -2.9042 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3746 2.6124 -1.1075 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1933 2.2653 -2.3804 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5693 1.0191 1.4275 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2949 1.3145 1.1401 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1092 2.5178 0.6293 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2941 0.5088 -2.1650 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2018 2.9629 -0.8632 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3842 2.4685 -2.0716 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6228 2.7884 0.8718 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7431 3.1920 -0.4330 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7471 1.1886 2.0173 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7210 -0.2854 1.8112 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4786 1.2693 2.3248 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5142 2.1801 -0.8496 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2475 0.5380 1.6502 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0317 3.2732 0.4755 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9323 3.1179 1.8546 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6111 2.5421 2.0642 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 6 6 7 1 0 5 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 0 16 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 18 21 1 0 21 22 1 0 21 23 1 0 23 24 1 0 23 25 1 0 25 26 1 0 14 27 1 0 27 28 1 0 28 29 1 0 29 30 1 0 30 31 1 0 31 32 1 0 32 33 1 0 33 34 1 0 34 35 1 0 33 36 1 0 36 37 1 0 36 38 1 0 38 39 1 0 38 40 1 0 40 41 1 0 29 42 1 0 42 43 1 0 43 44 1 0 44 45 1 1 44 46 1 0 46 47 1 0 47 48 1 0 48 49 1 0 49 50 1 1 49 51 1 0 51 52 1 0 52 53 1 0 7 2 1 0 51 9 1 0 52 5 1 0 49 11 1 0 46 12 1 0 25 16 1 0 44 27 1 0 40 31 1 0 1 54 1 0 1 55 1 0 1 56 1 0 2 57 1 1 3 58 1 0 3 59 1 0 4 60 1 0 4 61 1 0 7 62 1 0 7 63 1 0 9 64 1 6 10 65 1 0 10 66 1 0 11 67 1 6 12 68 1 1 13 69 1 0 13 70 1 0 14 71 1 1 16 72 1 1 18 73 1 1 19 74 1 0 19 75 1 0 20 76 1 0 21 77 1 6 22 78 1 0 23 79 1 1 24 80 1 0 25 81 1 6 26 82 1 0 27 83 1 6 28 84 1 0 28 85 1 0 29 86 1 6 31 87 1 6 33 88 1 6 34 89 1 0 34 90 1 0 35 91 1 0 36 92 1 1 37 93 1 0 38 94 1 6 39 95 1 0 40 96 1 1 41 97 1 0 42 98 1 0 42 99 1 0 43100 1 0 43101 1 0 45102 1 0 45103 1 0 45104 1 0 46105 1 6 47106 1 0 47107 1 0 48108 1 0 48109 1 0 50110 1 0 50111 1 0 50112 1 0 51113 1 6 52114 1 1 53115 1 0 53116 1 0 53117 1 0 M END

Standard InCHIKey	AAVRFXAMWONIOE-ZCFMUJEJSA-N
Standard InCHI	InChI=1S/C39H64O14/c1-17-5-10-39(48-16-17)18(2)28-25(53-39)13-22-20-12-24(50-36-34(47)32(45)30(43)27(15-41)52-36)23-11-19(6-8-37(23,3)21(20)7-9-38(22,28)4)49-35-33(46)31(44)29(42)26(14-40)51-35/h17-36,40-47H,5-16H2,1-4H3/t17-,18+,19+,20-,21+,22+,23-,24+,25+,26-,27-,28+,29-,30-,31+,32+,33-,34-,35-,36-,37-,38+,39-/m1/s1
SMILES	C[C@@H]1CC[C@@]2(OC1)O[C@H]1C[C@H]3[C@@H]4C[C@H](O[C@@H]5O[C@H](CO)[C@@H](O)[C@H](O)[C@H]5O)[C@H]5C[C@@H](O[C@@H]6O[C@H](CO)[C@@H](O)[C@H](O)[C@H]6O)CC[C@]5(C)[C@H]4CC[C@]3(C)[C@H]1[C@@H]2C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	756.43	Volume:	737.711 ? Van der Waals volume.
Dense:	1.025	LogP:	2.47 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.032 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.501 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	42.0
TPSA:	217.22 ? Topological Polar Surface Area.	H-Bond Acceptor:	14.0
H-Bond Donor:	8.0	Rings:	8.0
Heavy Atoms:	14.0

MedChem Properties

QED Drug-Likeness Score:	0.173	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	6.337	Fsp³:	1.0
MCE-18:	203.846 ? 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:	0.717	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.034 ? 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:	0.245	Promiscuous compounds:	0.015

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.031	MDCK Permeability:	-5.133
Pgp-inhibitor:	0.0	Pgp-substrate:	0.312
PAMPA:	0.983 ? 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%):	0.013	30% Bioavailability (F30%):	0.865
50% Bioavailability (F50%):	0.996

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.088	MRP1:	0.004
Plasma Protein Binding (PPB):	58.05%	Volume Distribution (VD):	-0.407
Fu:	34.867% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.651
BSEP inhibitor:	0.038

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:	0.011
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.998
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):

0.861

Half-life (T1/2):

3.035

ADMET: Toxicity

hERG Blockers:	0.025	hERG Blockers (10um):	0.051
Human Hepatotoxicity (H-HT):	0.647	Drug-induced Liver Injury (DILI):	0.987
AMES Toxicity:	0.957	Rat Oral Acute Toxicity:	0.011
Maximum Recommended Daily Dose:	0.014	Skin Sensitization:	1.0
Carcinogencity:	0.133	Eye Corrosion:	0.0
Eye Irritation:	0.001	Respiratory Toxicity:	0.001
Drug-induced Neurotoxicity:	0.001	Ototoxicity:	0.998
Hematotoxicity:	0.235	Drug-induced Nephrotoxicity:	0.838
Genotoxicity:	0.014	RPMI-8226 Immunitoxicity:	0.222
A549 Cytotoxicity:	0.866	Hek293 Cytotoxicity:	0.841
BCF:	1.849 ? 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:	3.41 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.607 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.027 ? 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
NPO8976	Agave americana	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8976	Agave americana	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO8976	Agave americana	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO8976	Agave americana	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO8976	Agave americana	Species	Asparagaceae	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 NPC589445 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	25739
0.1-0.2	20722
0.2-0.3	2798
0.3-0.4	389
0.4-0.5	96
0.5-0.6	74
0.6-0.7	29
0.7-0.8	1
0.8-0.85	1
0.85-0.9	0
0.9-0.95	1
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.9444	High Similarity	NPC485594
0.8	Intermediate Similarity	NPC277715
0.7317	Intermediate Similarity	NPC325828
0.7229	Intermediate Similarity	NPC234352
0.7195	Intermediate Similarity	NPC181845
0.7108	Intermediate Similarity	NPC297348
0.7108	Intermediate Similarity	NPC249204
0.7108	Intermediate Similarity	NPC48339
0.7108	Intermediate Similarity	NPC141769
0.7108	Intermediate Similarity	NPC477547
0.6962	Remote Similarity	NPC144790
0.6962	Remote Similarity	NPC149400
0.6897	Remote Similarity	NPC107188
0.6782	Remote Similarity	NPC206003
0.6782	Remote Similarity	NPC473610
0.6744	Remote Similarity	NPC477451
0.6742	Remote Similarity	NPC107962
0.6705	Remote Similarity	NPC211354
0.6484	Remote Similarity	NPC6295
0.6429	Remote Similarity	NPC24960
0.6344	Remote Similarity	NPC160426
0.6341	Remote Similarity	NPC88962
0.6322	Remote Similarity	NPC177834
0.6322	Remote Similarity	NPC485602
0.6292	Remote Similarity	NPC250393
0.6277	Remote Similarity	NPC475351
0.625	Remote Similarity	NPC294686
0.625	Remote Similarity	NPC131693
0.625	Remote Similarity	NPC475436
0.6154	Remote Similarity	NPC19400
0.6129	Remote Similarity	NPC485595
0.6082	Remote Similarity	NPC477809
0.6061	Remote Similarity	NPC97700
0.6061	Remote Similarity	NPC184617
0.6061	Remote Similarity	NPC30856
0.6	Remote Similarity	NPC113044
0.6	Remote Similarity	NPC283829
0.6	Remote Similarity	NPC14704
0.6	Remote Similarity	NPC161676
0.596	Remote Similarity	NPC128572
0.5957	Remote Similarity	NPC470432
0.5957	Remote Similarity	NPC230507
0.5934	Remote Similarity	NPC222731
0.5859	Remote Similarity	NPC300557
0.58	Remote Similarity	NPC480555
0.58	Remote Similarity	NPC150372
0.5789	Remote Similarity	NPC125324
0.5773	Remote Similarity	NPC485605
0.5729	Remote Similarity	NPC195297
0.5714	Remote Similarity	NPC485591
0.5699	Remote Similarity	NPC121453
0.566	Remote Similarity	NPC132080
0.5657	Remote Similarity	NPC475643
0.5657	Remote Similarity	NPC485603
0.5657	Remote Similarity	NPC602423
0.56	Remote Similarity	NPC92890
0.5591	Remote Similarity	NPC312678
0.5591	Remote Similarity	NPC253268
0.5577	Remote Similarity	NPC475625
0.5568	Remote Similarity	NPC481420
0.5568	Remote Similarity	NPC473774
0.5568	Remote Similarity	NPC481419
0.5568	Remote Similarity	NPC481417
0.5568	Remote Similarity	NPC481421
0.5567	Remote Similarity	NPC141433
0.5556	Remote Similarity	NPC473601
0.5545	Remote Similarity	NPC6806
0.5514	Remote Similarity	NPC477811
0.55	Remote Similarity	NPC470433
0.55	Remote Similarity	NPC46190
0.55	Remote Similarity	NPC171073
0.549	Remote Similarity	NPC485604
0.5429	Remote Similarity	NPC116756
0.5421	Remote Similarity	NPC476112
0.5421	Remote Similarity	NPC307534
0.5417	Remote Similarity	NPC485590
0.5392	Remote Similarity	NPC471464
0.5392	Remote Similarity	NPC51172
0.5392	Remote Similarity	NPC49032
0.5377	Remote Similarity	NPC232037
0.537	Remote Similarity	NPC480553
0.5333	Remote Similarity	NPC485600
0.5333	Remote Similarity	NPC475550
0.5327	Remote Similarity	NPC470864
0.5316	Remote Similarity	NPC296734
0.5312	Remote Similarity	NPC54619
0.5283	Remote Similarity	NPC473518
0.5258	Remote Similarity	NPC264101
0.5238	Remote Similarity	NPC115165
0.5238	Remote Similarity	NPC475319
0.5204	Remote Similarity	NPC215408
0.519	Remote Similarity	NPC248944
0.519	Remote Similarity	NPC7479
0.519	Remote Similarity	NPC257296
0.5189	Remote Similarity	NPC269297
0.5189	Remote Similarity	NPC222202
0.5185	Remote Similarity	NPC480554
0.5155	Remote Similarity	NPC306131
0.5155	Remote Similarity	NPC200802
0.514	Remote Similarity	NPC475333
0.514	Remote Similarity	NPC224098
0.514	Remote Similarity	NPC309278
0.514	Remote Similarity	NPC208383
0.5138	Remote Similarity	NPC83137
0.5125	Remote Similarity	NPC273290
0.5125	Remote Similarity	NPC232044
0.5093	Remote Similarity	NPC194207
0.5093	Remote Similarity	NPC22779
0.5091	Remote Similarity	NPC233433
0.5089	Remote Similarity	NPC470866
0.5055	Remote Similarity	NPC481418
0.5045	Remote Similarity	NPC31896
0.5043	Remote Similarity	NPC477808

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC589445 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7415
0.1-0.2	1649
0.2-0.3	76
0.3-0.4	6
0.4-0.5	1
0.5-0.6	1
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
0.7317	Intermediate Similarity	NPD8171	Phase 2
0.6304	Remote Similarity	NPD8170	Phase 2
0.519	Remote Similarity	NPD6928	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