NPASS Compound

Natural Product: NPC300262

Natural Product ID	NPC300262
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Lapathoside C
IUPAC Name	[(2R,3R,4S,5S)-3-hydroxy-5-(hydroxymethyl)-4-[(E)-3-(4-hydroxyphenyl)prop-2-enoyl]oxy-5-[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-[[(E)-3-(4-hydroxy-3-methoxyphenyl)prop-2-enoyl]oxymethyl]oxan-2-yl]oxyoxolan-2-yl]methyl (E)-3-(4-hydroxyphenyl)prop-2-enoate
Synonyms	Lapathoside C
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL510277
PubChem CID	11061786
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000476] Cinnamic acids and derivatives [CHEMONTID:0001391] Hydroxycinnamic acids and derivatives [CHEMONTID:0003002] Hydroxycinnamic acid esters [CHEMONTID:0000465] Coumaric acid esters

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 8.8523 -3.8157 -0.0720 C 0 0 0 0 0 0 0 0 0 0 0 0 9.8517 -3.0866 0.6046 O 0 0 0 0 0 0 0 0 0 0 0 0 9.5490 -1.7930 1.0280 C 0 0 0 0 0 0 0 0 0 0 0 0 8.2879 -1.2392 0.7840 C 0 0 0 0 0 0 0 0 0 0 0 0 7.9675 0.0274 1.1893 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6566 0.5971 0.9405 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6808 -0.0256 0.3253 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3704 0.6348 0.1156 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1725 1.7888 0.5100 O 0 0 0 0 0 0 0 0 0 0 0 0 3.3850 -0.0512 -0.5174 O 0 0 0 0 0 0 0 0 0 0 0 0 2.0861 0.3801 -0.8049 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3772 0.7038 0.4816 C 0 0 1 0 0 0 0 0 0 0 0 0 0.0815 1.0575 0.3492 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8808 0.1096 0.1590 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.0729 0.5630 0.6945 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.1209 0.7673 -0.1185 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.3197 0.9669 0.8750 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4639 1.1882 0.1022 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.5510 -0.3477 -0.8436 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.9388 0.0385 -2.0908 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.0905 1.2736 -2.3781 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.1625 1.9253 -1.0326 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.3172 2.9936 -0.7985 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.7657 4.2892 -0.5385 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0293 4.4055 -0.5222 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.9591 5.4485 -0.3008 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6544 5.5453 -0.2790 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1042 6.7791 -0.0265 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5111 7.9658 0.2560 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2645 9.1173 0.4653 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6298 9.0766 0.3920 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2180 7.8668 0.1065 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4762 6.7342 -0.1005 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4452 10.1838 0.5886 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.7209 2.0206 -3.3718 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.7873 -0.9554 -3.1869 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5782 -2.0752 -2.9766 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.5835 -2.9929 -1.9823 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7490 -2.8742 -1.0538 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.5389 -4.1126 -1.9691 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5581 -5.0047 -1.0109 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.4931 -6.1278 -0.9696 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.4104 -6.3153 -1.9565 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.2955 -7.3979 -1.8931 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.2297 -8.2607 -0.8342 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.3077 -8.0895 0.1786 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.4504 -7.0127 0.0850 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.0964 -9.3614 -0.7264 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.4599 -1.2069 0.7244 C 0 0 1 0 0 0 0 0 0 0 0 0 0.3342 -0.9632 1.9832 C 0 0 2 0 0 0 0 0 0 0 0 0 1.6549 -0.3357 1.5334 C 0 0 2 0 0 0 0 0 0 0 0 0 2.4129 0.1330 2.5921 O 0 0 0 0 0 0 0 0 0 0 0 0 0.4864 -2.1270 2.6815 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.5263 -2.0729 0.9415 O 0 0 0 0 0 0 0 0 0 0 0 0 8.9469 0.7552 1.8595 C 0 0 0 0 0 0 0 0 0 0 0 0 10.1756 0.2067 2.0940 C 0 0 0 0 0 0 0 0 0 0 0 0 10.4912 -1.0687 1.6832 C 0 0 0 0 0 0 0 0 0 0 0 0 11.7350 -1.6345 1.9163 O 0 0 0 0 0 0 0 0 0 0 0 0 7.9271 -3.9216 0.5260 H 0 0 0 0 0 0 0 0 0 0 0 0 8.6334 -3.2307 -1.0052 H 0 0 0 0 0 0 0 0 0 0 0 0 9.2366 -4.8310 -0.3349 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5666 -1.8507 0.2576 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4556 1.6047 1.2828 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8119 -1.0129 -0.0320 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6139 -0.4377 -1.3957 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1603 1.2863 -1.4647 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9096 1.6330 0.8616 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9590 -0.0338 -0.9532 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1281 1.8340 1.5245 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3956 0.0640 1.4742 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1659 0.6077 0.4917 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9961 0.4537 -2.0550 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1251 0.9530 -2.7300 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2221 2.3711 -1.0048 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4912 6.3932 -0.1154 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1003 4.6413 -0.4604 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5712 8.0622 0.3295 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2115 10.0689 0.6916 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3240 7.8452 0.0503 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0007 5.8168 -0.3243 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1638 10.9610 1.2075 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3498 1.5254 -3.9173 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1655 -0.4879 -4.1451 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7218 -1.2008 -3.4071 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2413 -4.1831 -2.7878 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8293 -4.8767 -0.2183 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.5293 -5.6929 -2.8142 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.0402 -7.5867 -2.6518 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2394 -8.7588 1.0251 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7318 -6.9025 0.9013 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.0631 -9.2228 -0.4282 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2296 -1.7190 0.0217 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1433 -0.2007 2.6261 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2236 -1.1516 1.0577 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4639 1.1304 2.5552 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3613 -2.5730 2.5932 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2851 -2.9573 0.5804 H 0 0 0 0 0 0 0 0 0 0 0 0 8.6773 1.7632 2.1762 H 0 0 0 0 0 0 0 0 0 0 0 0 10.9555 0.7709 2.6231 H 0 0 0 0 0 0 0 0 0 0 0 0 11.9208 -2.1484 2.7840 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 16 15 1 1 16 17 1 0 17 18 1 0 16 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 24 25 2 0 24 26 1 0 26 27 2 0 27 28 1 0 28 29 2 0 29 30 1 0 30 31 2 0 31 32 1 0 32 33 2 0 31 34 1 0 21 35 1 0 20 36 1 0 36 37 1 0 37 38 1 0 38 39 2 0 38 40 1 0 40 41 2 0 41 42 1 0 42 43 2 0 43 44 1 0 44 45 2 0 45 46 1 0 46 47 2 0 45 48 1 0 14 49 1 0 49 50 1 0 50 51 1 0 51 52 1 0 50 53 1 0 49 54 1 0 5 55 2 0 55 56 1 0 56 57 2 0 57 58 1 0 57 3 1 0 51 12 1 0 22 16 1 0 33 28 1 0 47 42 1 0 1 59 1 0 1 60 1 0 1 61 1 0 4 62 1 0 6 63 1 0 7 64 1 0 11 65 1 0 11 66 1 0 12 67 1 1 14 68 1 6 17 69 1 0 17 70 1 0 18 71 1 0 20 72 1 1 21 73 1 6 22 74 1 6 26 75 1 0 27 76 1 0 29 77 1 0 30 78 1 0 32 79 1 0 33 80 1 0 34 81 1 0 35 82 1 0 36 83 1 0 36 84 1 0 40 85 1 0 41 86 1 0 43 87 1 0 44 88 1 0 46 89 1 0 47 90 1 0 48 91 1 0 49 92 1 6 50 93 1 1 51 94 1 6 52 95 1 0 53 96 1 0 54 97 1 0 55 98 1 0 56 99 1 0 58100 1 0 M END

Standard InCHIKey	WYNKDHNSWBVRAM-QVHYGTEESA-N
Standard InCHI	InChI=1S/C40H42O18/c1-52-28-18-24(6-14-27(28)44)9-16-32(46)53-19-29-34(48)36(50)37(51)39(55-29)58-40(21-41)38(56-33(47)17-8-23-4-12-26(43)13-5-23)35(49)30(57-40)20-54-31(45)15-7-22-2-10-25(42)11-3-22/h2-18,29-30,34-39,41-44,48-51H,19-21H2,1H3/b15-7+,16-9+,17-8+/t29-,30-,34-,35-,36+,37-,38+,39-,40+/m1/s1
SMILES	COc1cc(/C=C/C(=O)OC[C@H]2O[C@H](O[C@]3(CO)O[C@@H]([C@H]([C@@H]3OC(=O)/C=C/c3ccc(cc3)O)O)COC(=O)/C=C/c3ccc(cc3)O)[C@@H]([C@H]([C@@H]2O)O)O)ccc1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	810.24	Volume:	776.291 ? Van der Waals volume.
Dense:	1.044	LogP:	1.911 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.025 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.613 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	18.0	Rigid Bonds:	35.0
TPSA:	277.66 ? Topological Polar Surface Area.	H-Bond Acceptor:	18.0
H-Bond Donor:	8.0	Rings:	5.0
Heavy Atoms:	18.0

MedChem Properties

QED Drug-Likeness Score:	0.059	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.108	Fsp³:	0.325
MCE-18:	120.226 ? 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:	0
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.893	Fluc inhibitor:	0.999 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.175 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.665 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.246	Promiscuous compounds:	0.285

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.323	MDCK Permeability:	-5.387
Pgp-inhibitor:	0.005	Pgp-substrate:	0.008
PAMPA:	0.996 ? 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):	0.582
20% Bioavailability (F20%):	1.0	30% Bioavailability (F30%):	1.0
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.0
Plasma Protein Binding (PPB):	86.831%	Volume Distribution (VD):	-0.212
Fu:	10.99% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.001
BSEP inhibitor:	0.941

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.236
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.874
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.08
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.778
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.082 ? 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):

1.985

Half-life (T1/2):

2.757

ADMET: Toxicity

hERG Blockers:	0.062	hERG Blockers (10um):	0.307
Human Hepatotoxicity (H-HT):	0.529	Drug-induced Liver Injury (DILI):	0.871
AMES Toxicity:	0.971	Rat Oral Acute Toxicity:	0.014
Maximum Recommended Daily Dose:	0.635	Skin Sensitization:	1.0
Carcinogencity:	0.165	Eye Corrosion:	0.0
Eye Irritation:	0.069	Respiratory Toxicity:	0.005
Drug-induced Neurotoxicity:	0.186	Ototoxicity:	0.792
Hematotoxicity:	0.051	Drug-induced Nephrotoxicity:	0.943
Genotoxicity:	0.861	RPMI-8226 Immunitoxicity:	0.359
A549 Cytotoxicity:	0.862	Hek293 Cytotoxicity:	0.974
BCF:	0.512 ? 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:	3.439 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.844 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.384 ? 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
NPO7193	Persicaria lapathifolia	Species	Polygonaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[11678656]
NPO7193	Persicaria lapathifolia	Species	Polygonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7193	Persicaria lapathifolia	Species	Polygonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO7193	Persicaria lapathifolia	Species	Polygonaceae	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
Activity	8
IC50	1

Activity Type	# Activity
Cell line	5
Others	4

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
NPT80	Cell line	Raji	Homo sapiens	Activity	=	70.0	%	PMID[11678656]
NPT80	Cell line	Raji	Homo sapiens	Activity	>	80.0	%	PMID[11678656]
NPT165	Cell line	HeLa	Homo sapiens	IC50	=	12610.0	nM	PMID[23153813]
NPT2	Others	Unspecified	n.a.	Activity	=	33.6	%	PMID[11678656]
NPT2	Others	Unspecified	n.a.	Activity	=	59.0	%	PMID[11678656]
NPT2	Others	Unspecified	n.a.	Activity	=	83.5	%	PMID[11678656]
NPT2	Others	Unspecified	n.a.	Activity	=	100.0	%	PMID[11678656]

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 NPC300262 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	11983
0.1-0.2	32125
0.2-0.3	4662
0.3-0.4	833
0.4-0.5	184
0.5-0.6	41
0.6-0.7	11
0.7-0.8	0
0.8-0.85	5
0.85-0.9	2
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8608	High Similarity	NPC262182
0.85	High Similarity	NPC83743
0.8313	Intermediate Similarity	NPC125823
0.8313	Intermediate Similarity	NPC7145
0.8313	Intermediate Similarity	NPC143480
0.8101	Intermediate Similarity	NPC472612
0.8023	Intermediate Similarity	NPC201148
0.7931	Intermediate Similarity	NPC261122
0.7738	Intermediate Similarity	NPC80732
0.7722	Intermediate Similarity	NPC225307
0.7586	Intermediate Similarity	NPC3460
0.7471	Intermediate Similarity	NPC287615
0.7471	Intermediate Similarity	NPC199311
0.7262	Intermediate Similarity	NPC90896
0.7143	Intermediate Similarity	NPC226005
0.7111	Intermediate Similarity	NPC472611
0.7111	Intermediate Similarity	NPC210611
0.6932	Remote Similarity	NPC216819
0.6854	Remote Similarity	NPC283839
0.6667	Remote Similarity	NPC192763
0.663	Remote Similarity	NPC85192
0.6559	Remote Similarity	NPC215095
0.6364	Remote Similarity	NPC476869
0.6333	Remote Similarity	NPC289967
0.6322	Remote Similarity	NPC28637
0.6186	Remote Similarity	NPC28651
0.617	Remote Similarity	NPC173343
0.6071	Remote Similarity	NPC601579
0.5978	Remote Similarity	NPC476865
0.593	Remote Similarity	NPC297342
0.5778	Remote Similarity	NPC471405
0.5761	Remote Similarity	NPC476868
0.5682	Remote Similarity	NPC219677
0.5667	Remote Similarity	NPC291296
0.5667	Remote Similarity	NPC10205
0.5652	Remote Similarity	NPC476866
0.5625	Remote Similarity	NPC11411
0.5607	Remote Similarity	NPC484988
0.5591	Remote Similarity	NPC471881
0.5529	Remote Similarity	NPC479473
0.5529	Remote Similarity	NPC275721
0.5529	Remote Similarity	NPC288416
0.5529	Remote Similarity	NPC479468
0.5529	Remote Similarity	NPC479474
0.5517	Remote Similarity	NPC291153
0.5488	Remote Similarity	NPC157554
0.5455	Remote Similarity	NPC34293
0.54	Remote Similarity	NPC600370
0.5333	Remote Similarity	NPC479771
0.5333	Remote Similarity	NPC252114
0.5263	Remote Similarity	NPC488082
0.5258	Remote Similarity	NPC479767
0.5253	Remote Similarity	NPC133984
0.5233	Remote Similarity	NPC470572
0.5213	Remote Similarity	NPC157816
0.5204	Remote Similarity	NPC488081
0.5161	Remote Similarity	NPC156692
0.5161	Remote Similarity	NPC281798
0.514	Remote Similarity	NPC470416
0.5114	Remote Similarity	NPC229784
0.5109	Remote Similarity	NPC252833
0.5106	Remote Similarity	NPC476867
0.5104	Remote Similarity	NPC21516
0.5093	Remote Similarity	NPC480796
0.5093	Remote Similarity	NPC472993
0.5086	Remote Similarity	NPC25946
0.5053	Remote Similarity	NPC204937
0.5053	Remote Similarity	NPC476864
0.5052	Remote Similarity	NPC186073

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC300262 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4127
0.1-0.2	4907
0.2-0.3	109
0.3-0.4	6
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