NPASS Compound

Natural Product: NPC476398

Natural Product ID	NPC476398
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	1-(3,4-Dihydroxyphenylethyl)-O-Alpha-L-Lyxopyranosil-(1->2)-A-L-Rhamnopyranosil-(1->3)-6-O-Transferuloyl-Beta-D-Glucopyranoside
IUPAC Name	[(2R,3R,4S,5R,6R)-4-[(2S,3R,4R,5R,6S)-4,5-dihydroxy-6-methyl-3-[(2S,3R,4R,5S)-3,4,5-trihydroxyoxan-2-yl]oxyoxan-2-yl]oxy-6-[2-(3,4-dihydroxyphenyl)ethoxy]-3,5-dihydroxyoxan-2-yl]methyl (E)-3-(4-hydroxy-3-methoxyphenyl)prop-2-enoate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL595383
PubChem CID	45101504
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 3D 100104 0 0 0 0 0 0 0 0999 V2000 7.9927 -3.5734 5.6842 C 0 0 0 0 0 0 0 0 0 0 0 0 8.8274 -3.7101 4.5758 O 0 0 0 0 0 0 0 0 0 0 0 0 8.3385 -3.3755 3.3067 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0563 -2.9135 3.1083 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6111 -2.5910 1.8226 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2417 -2.1209 1.6757 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7052 -1.7321 0.5383 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3140 -1.2634 0.4245 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8984 -0.8975 -0.7025 O 0 0 0 0 0 0 0 0 0 0 0 0 2.4543 -1.2088 1.4822 O 0 0 0 0 0 0 0 0 0 0 0 0 1.1239 -0.7787 1.4983 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8907 0.6652 1.1920 C 0 0 1 0 0 0 0 0 0 0 0 0 1.3525 1.0296 -0.0348 O 0 0 0 0 0 0 0 0 0 0 0 0 0.3698 1.5322 -0.8777 C 0 0 1 0 0 0 0 0 0 0 0 0 0.8200 1.8911 -2.1313 O 0 0 0 0 0 0 0 0 0 0 0 0 0.6858 3.2494 -2.3994 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4530 4.1458 -1.4869 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2403 5.5777 -1.8597 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0780 6.1763 -2.7619 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8866 7.4997 -3.1055 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8604 8.2220 -2.5481 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0071 7.6432 -1.6408 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2123 6.3267 -1.3113 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0283 8.3978 -1.0880 O 0 0 0 0 0 0 0 0 0 0 0 0 0.6870 9.5455 -2.9057 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8390 0.5985 -0.9127 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.5221 0.7751 0.4108 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.5369 1.0838 1.4597 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.6173 2.4336 1.8351 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.4037 -0.2457 0.7215 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.7131 0.1189 0.7431 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.3727 -0.1235 1.9576 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.6629 0.3260 1.9508 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.6459 1.8548 1.8983 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.5589 -0.1664 0.8637 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.8654 -0.2047 -0.4635 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.4779 -0.7647 -0.2538 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.7785 -1.0565 -1.3845 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.5343 -2.4220 -1.4834 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.1646 -2.7324 -1.3870 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.0480 -4.0441 -0.9232 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1754 -4.9273 -1.3658 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.8071 -4.5120 -2.6716 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.0338 -3.0180 -2.7536 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.3555 -2.6791 -3.0252 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.0692 -5.1093 -2.7367 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6387 -6.2104 -1.5635 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.8637 1.0632 -1.0384 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.8810 -1.5105 1.1933 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.6472 1.0905 -1.9446 O 0 0 0 0 0 0 0 0 0 0 0 0 7.5058 -2.7586 0.7999 C 0 0 0 0 0 0 0 0 0 0 0 0 8.7974 -3.2229 0.9914 C 0 0 0 0 0 0 0 0 0 0 0 0 9.2357 -3.5399 2.2521 C 0 0 0 0 0 0 0 0 0 0 0 0 10.5246 -4.0102 2.4935 O 0 0 0 0 0 0 0 0 0 0 0 0 8.3794 -4.1050 6.5861 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9750 -2.4931 5.9552 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0136 -4.0000 5.4603 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3930 -2.7975 3.9390 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5643 -2.0682 2.5444 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3288 -1.7645 -0.3471 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7045 -1.0312 2.5095 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5472 -1.4491 0.7877 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5064 1.2411 1.9488 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0103 2.4595 -0.4030 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4033 3.5213 -2.2913 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9375 3.4920 -3.4503 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5521 3.9689 -1.5431 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1461 4.0780 -0.4264 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8914 5.6148 -3.2092 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5775 7.9327 -3.8259 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4635 5.8697 -0.5942 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7167 7.9782 -0.4731 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4933 10.1540 -2.8715 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5423 -0.4386 -1.1360 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1899 1.6843 0.2687 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8248 0.5248 2.3991 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1789 2.5988 2.4112 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9377 1.1608 0.4889 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1083 0.1048 2.9700 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6184 2.2595 0.8867 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7088 2.2120 2.4031 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4832 2.2854 2.4600 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.5178 0.4082 0.8176 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3966 -0.9386 -1.1212 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6608 -1.7488 0.2853 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9905 -2.9748 -0.6081 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0646 -4.4531 -1.2738 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9930 -4.0380 0.1996 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9855 -5.0105 -0.6003 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1543 -4.8508 -3.4993 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4255 -2.5732 -3.5858 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9870 -3.4061 -2.8906 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0390 -6.0692 -2.5767 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7915 -6.7830 -0.7708 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0745 1.1232 -1.6633 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2664 -1.8729 1.8606 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1391 1.2269 -2.7788 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1814 -2.5166 -0.2110 H 0 0 0 0 0 0 0 0 0 0 0 0 9.4920 -3.3513 0.1781 H 0 0 0 0 0 0 0 0 0 0 0 0 10.7014 -4.9881 2.6723 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 1 0 6 7 2 0 7 8 1 0 8 9 2 0 8 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 2 0 19 20 1 0 20 21 2 0 21 22 1 0 22 23 2 0 22 24 1 0 21 25 1 0 14 26 1 0 26 27 1 0 27 28 1 0 28 29 1 0 27 30 1 0 30 31 1 0 31 32 1 0 32 33 1 0 33 34 1 0 33 35 1 0 35 36 1 0 36 37 1 0 37 38 1 0 38 39 1 0 39 40 1 0 40 41 1 0 41 42 1 0 42 43 1 0 43 44 1 0 44 45 1 0 43 46 1 0 42 47 1 0 36 48 1 0 35 49 1 0 26 50 1 0 5 51 2 0 51 52 1 0 52 53 2 0 53 54 1 0 53 3 1 0 28 12 1 0 37 31 1 0 44 39 1 0 23 18 1 0 1 55 1 0 1 56 1 0 1 57 1 0 4 58 1 0 6 59 1 0 7 60 1 0 11 61 1 0 11 62 1 0 12 63 1 1 14 64 1 1 16 65 1 0 16 66 1 0 17 67 1 0 17 68 1 0 19 69 1 0 20 70 1 0 23 71 1 0 24 72 1 0 25 73 1 0 26 74 1 6 27 75 1 6 28 76 1 1 29 77 1 0 31 78 1 6 33 79 1 1 34 80 1 0 34 81 1 0 34 82 1 0 35 83 1 6 36 84 1 6 37 85 1 1 39 86 1 1 41 87 1 0 41 88 1 0 42 89 1 1 43 90 1 6 44 91 1 6 45 92 1 0 46 93 1 0 47 94 1 0 48 95 1 0 49 96 1 0 50 97 1 0 51 98 1 0 52 99 1 0 54100 1 0 M END

Standard InCHIKey	UUTFGEZECHAQKE-OUUVDBOPSA-N
Standard InCHI	InChI=1S/C35H46O19/c1-15-25(41)28(44)32(54-33-29(45)26(42)21(39)13-50-33)35(51-15)53-31-27(43)23(14-49-24(40)8-5-16-4-7-19(37)22(12-16)47-2)52-34(30(31)46)48-10-9-17-3-6-18(36)20(38)11-17/h3-8,11-12,15,21,23,25-39,41-46H,9-10,13-14H2,1-2H3/b8-5+/t15-,21-,23+,25-,26+,27+,28+,29+,30+,31-,32+,33-,34+,35-/m0/s1
SMILES	COc1cc(/C=C/C(=O)OC[C@H]2O[C@@H](OCCc3ccc(c(c3)O)O)[C@@H]([C@H]([C@@H]2O)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)ccc1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	770.26	Volume:	717.056 ? Van der Waals volume.
Dense:	1.074	LogP:	-0.433 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	0.563 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-1.744 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	14.0	Rigid Bonds:	32.0
TPSA:	293.21 ? Topological Polar Surface Area.	H-Bond Acceptor:	19.0
H-Bond Donor:	10.0	Rings:	5.0
Heavy Atoms:	19.0

MedChem Properties

QED Drug-Likeness Score:	0.058	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.281	Fsp³:	0.571
MCE-18:	127.636 ? 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:	1
Colloidal aggregators:	0.694	Fluc inhibitor:	0.664 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.14 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.424 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.14	Promiscuous compounds:	0.294

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.472	MDCK Permeability:	-5.286
Pgp-inhibitor:	0.0	Pgp-substrate:	0.574
PAMPA:	0.999 ? 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):	0.845
20% Bioavailability (F20%):	0.99	30% Bioavailability (F30%):	0.997
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.012
Plasma Protein Binding (PPB):	67.719%	Volume Distribution (VD):	-0.361
Fu:	30.142% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.099
BSEP inhibitor:	0.045

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:	0.002
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.04 ? 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):

0.938

Half-life (T1/2):

3.729

ADMET: Toxicity

hERG Blockers:	0.027	hERG Blockers (10um):	0.588
Human Hepatotoxicity (H-HT):	0.292	Drug-induced Liver Injury (DILI):	0.857
AMES Toxicity:	0.916	Rat Oral Acute Toxicity:	0.008
Maximum Recommended Daily Dose:	0.028	Skin Sensitization:	1.0
Carcinogencity:	0.008	Eye Corrosion:	0.0
Eye Irritation:	0.063	Respiratory Toxicity:	0.002
Drug-induced Neurotoxicity:	0.0	Ototoxicity:	0.992
Hematotoxicity:	0.066	Drug-induced Nephrotoxicity:	0.734
Genotoxicity:	0.145	RPMI-8226 Immunitoxicity:	0.177
A549 Cytotoxicity:	0.888	Hek293 Cytotoxicity:	0.44
BCF:	0.616 ? 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:	3.259 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.042 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.242 ? 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
NPO33377	teucrium chamaedris	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19674906]

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
Activity	4
IC50	4

Activity Type	# Activity
Others	2
Non-molecular	6

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
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Activity	=	0.5	n.a.	PMID[19674906]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Activity	=	0.7	n.a.	PMID[19674906]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Activity	=	3.8	n.a.	PMID[19674906]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	18100.0	nM	PMID[19674906]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	37300.0	nM	PMID[19674906]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	46700.0	nM	PMID[19674906]
NPT1	Others	Radical scavenging activity	n.a.	Activity	=	1.9	n.a.	PMID[23398362]
NPT1	Others	Radical scavenging activity	n.a.	IC50	=	11000.0	nM	PMID[15217281]

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 NPC476398 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	15919
0.1-0.2	29181
0.2-0.3	4100
0.3-0.4	508
0.4-0.5	114
0.5-0.6	21
0.6-0.7	9
0.7-0.8	0
0.8-0.85	0
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8556	High Similarity	NPC476397
0.7451	Intermediate Similarity	NPC94871
0.729	Intermediate Similarity	NPC257970
0.7216	Intermediate Similarity	NPC600370
0.6827	Remote Similarity	NPC471062
0.6792	Remote Similarity	NPC473427
0.6667	Remote Similarity	NPC470927
0.6632	Remote Similarity	NPC64141
0.625	Remote Similarity	NPC96795
0.625	Remote Similarity	NPC264632
0.6216	Remote Similarity	NPC188393
0.6147	Remote Similarity	NPC64195
0.6122	Remote Similarity	NPC205195
0.5982	Remote Similarity	NPC229505
0.5946	Remote Similarity	NPC306890
0.5918	Remote Similarity	NPC235294
0.5849	Remote Similarity	NPC100998
0.5806	Remote Similarity	NPC287597
0.5684	Remote Similarity	NPC34293
0.5603	Remote Similarity	NPC476386
0.5596	Remote Similarity	NPC259347
0.5429	Remote Similarity	NPC476383
0.537	Remote Similarity	NPC205864
0.537	Remote Similarity	NPC247032
0.5351	Remote Similarity	NPC470933
0.5294	Remote Similarity	NPC260425
0.5278	Remote Similarity	NPC34587
0.5273	Remote Similarity	NPC34927
0.5238	Remote Similarity	NPC131532
0.5192	Remote Similarity	NPC321638
0.5172	Remote Similarity	NPC470934
0.5133	Remote Similarity	NPC141455
0.5104	Remote Similarity	NPC288416
0.5047	Remote Similarity	NPC76406

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC476398 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4762
0.1-0.2	4314
0.2-0.3	71
0.3-0.4	2
0.4-0.5	1
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