NPASS Compound

Natural Product: NPC101399

Natural Product ID	NPC101399
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	3-O-Alpha-L-(2"",3""-Di-E-P-Coumaroyl)Rhamnoside
IUPAC Name	[(2S,3R,4R,5S,6S)-2-[5,7-dihydroxy-2-(4-hydroxyphenyl)-4-oxochromen-3-yl]oxy-5-hydroxy-3-[(E)-3-(4-hydroxyphenyl)prop-2-enoyl]oxy-6-methyloxan-4-yl] (E)-3-(4-hydroxyphenyl)prop-2-enoate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1075910
PubChem CID	6451113
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0001111] Flavonoid glycosides [CHEMONTID:0001583] Flavonoid O-glycosides [CHEMONTID:0003531] Flavonoid-3-O-glycosides

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 85 90 0 0 0 0 0 0 0 0999 V2000 10.6194 0.4953 0.9870 O 0 0 0 0 0 0 0 0 0 0 0 0 9.2763 0.2044 1.1555 C 0 0 0 0 0 0 0 0 0 0 0 0 8.6564 0.4177 2.3755 C 0 0 0 0 0 0 0 0 0 0 0 0 7.3316 0.1032 2.4525 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5890 -0.4115 1.3818 C 0 0 0 0 0 0 0 0 0 0 0 0 7.2202 -0.6137 0.1863 C 0 0 0 0 0 0 0 0 0 0 0 0 8.5549 -0.3095 0.0717 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1967 -0.7002 1.6487 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3115 -1.1526 0.7655 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9356 -1.4140 1.1294 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6748 -1.2303 2.3908 O 0 0 0 0 0 0 0 0 0 0 0 0 1.8790 -1.8031 0.3885 O 0 0 0 0 0 0 0 0 0 0 0 0 0.5917 -2.0097 0.8571 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.3627 -0.8190 0.5461 C 0 0 1 0 0 0 0 0 0 0 0 0 0.1825 -0.1446 -0.5501 O 0 0 0 0 0 0 0 0 0 0 0 0 1.0185 0.9697 -0.3816 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2597 1.2562 0.8384 O 0 0 0 0 0 0 0 0 0 0 0 0 1.5723 1.7676 -1.4169 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3437 2.8006 -1.0790 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9894 3.7188 -1.9797 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8564 3.6424 -3.3316 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5218 4.5858 -4.1528 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2994 5.5778 -3.6158 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4317 5.6506 -2.2262 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7779 4.7249 -1.4509 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9538 6.5022 -4.3971 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7155 -1.2846 0.3505 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.1512 -2.2211 1.2943 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.3500 -3.2928 1.4785 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.1244 -3.2641 0.5868 C 0 0 2 0 0 0 0 0 0 0 0 0 0.7078 -4.3810 0.8375 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.0846 -4.5647 1.1068 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6507 -0.2479 0.2469 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.9325 -0.3532 -0.2167 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0236 -0.3722 0.5677 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2522 -0.5024 -0.0078 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.4038 -0.6040 -1.2799 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3356 -0.5883 -2.1437 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0719 -0.4604 -1.6044 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0556 -0.4401 -2.3423 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.5536 -0.7032 -3.5128 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4566 -0.6850 -4.3600 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.8039 -0.8328 -4.0537 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.8976 -0.8494 -3.1902 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.6742 -0.7359 -1.8441 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.1865 -0.9800 -3.6966 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.9895 -0.2530 2.0147 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9062 0.0302 2.7801 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9442 0.1348 4.1821 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1247 -0.0517 4.8531 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2720 -0.3470 4.1021 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1850 -0.4386 2.7381 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2562 0.0353 6.2358 O 0 0 0 0 0 0 0 0 0 0 0 0 11.0930 1.1404 1.6003 H 0 0 0 0 0 0 0 0 0 0 0 0 9.2229 0.8117 3.2088 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8607 0.2814 3.4352 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6562 -0.9988 -0.6439 H 0 0 0 0 0 0 0 0 0 0 0 0 9.0973 -0.4570 -0.8807 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7979 -0.5397 2.6517 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6659 -1.3223 -0.2383 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6784 -1.9004 1.9962 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2497 -0.1155 1.4198 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4011 1.5827 -2.4501 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4997 2.9524 0.0054 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2719 2.9008 -3.8398 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3920 4.5131 -5.2078 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0416 6.4269 -1.8363 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9088 4.8066 -0.3631 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2900 7.3833 -4.0603 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8230 -1.8598 -0.6336 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9962 -3.4365 2.5212 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4218 -3.3406 -0.4731 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3312 -4.1786 1.5723 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0082 -4.6653 1.6934 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4097 -5.4624 1.2682 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2677 -4.5217 0.0044 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6054 -0.5728 -5.3488 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9665 -0.9279 -5.1364 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.4974 -0.7397 -1.1184 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.7779 -0.2259 -3.9762 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9468 0.2220 2.3092 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0515 0.3616 4.7511 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1731 -0.4936 4.6626 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0612 -0.6541 2.1559 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9398 -0.5256 6.7646 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 3 4 1 0 4 5 2 0 5 6 1 0 6 7 2 0 5 8 1 0 8 9 2 0 9 10 1 0 10 11 2 0 10 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 2 0 16 18 1 0 18 19 2 0 19 20 1 0 20 21 2 0 21 22 1 0 22 23 2 0 23 24 1 0 24 25 2 0 23 26 1 0 14 27 1 0 27 28 1 0 28 29 1 0 29 30 1 0 30 31 1 0 29 32 1 0 27 33 1 0 33 34 1 0 34 35 2 0 35 36 1 0 36 37 1 0 37 38 2 0 38 39 1 0 39 40 2 0 38 41 1 0 41 42 1 0 41 43 2 0 43 44 1 0 44 45 2 0 44 46 1 0 35 47 1 0 47 48 2 0 48 49 1 0 49 50 2 0 50 51 1 0 51 52 2 0 50 53 1 0 7 2 1 0 30 13 1 0 39 34 1 0 52 47 1 0 25 20 1 0 45 37 1 0 1 54 1 0 3 55 1 0 4 56 1 0 6 57 1 0 7 58 1 0 8 59 1 0 9 60 1 0 13 61 1 1 14 62 1 1 18 63 1 0 19 64 1 0 21 65 1 0 22 66 1 0 24 67 1 0 25 68 1 0 26 69 1 0 27 70 1 6 29 71 1 1 30 72 1 6 31 73 1 0 32 74 1 0 32 75 1 0 32 76 1 0 42 77 1 0 43 78 1 0 45 79 1 0 46 80 1 0 48 81 1 0 49 82 1 0 51 83 1 0 52 84 1 0 53 85 1 0 M END

Standard InCHIKey	HKZIBACORRUGAC-FIFPDCARSA-N
Standard InCHI	InChI=1S/C39H32O14/c1-20-33(47)36(51-30(45)16-6-21-2-10-24(40)11-3-21)38(52-31(46)17-7-22-4-12-25(41)13-5-22)39(49-20)53-37-34(48)32-28(44)18-27(43)19-29(32)50-35(37)23-8-14-26(42)15-9-23/h2-20,33,36,38-44,47H,1H3/b16-6+,17-7+/t20-,33-,36+,38+,39-/m0/s1
SMILES	Oc1ccc(cc1)/C=C/C(=O)O[C@H]1[C@@H](OC(=O)/C=C/c2ccc(cc2)O)[C@@H](O[C@H]([C@@H]1O)C)Oc1c(oc2c(c1=O)c(O)cc(c2)O)c1ccc(cc1)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	724.18	Volume:	707.368 ? Van der Waals volume.
Dense:	1.024	LogP:	4.151 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.33 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-6.054 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	11.0	Rigid Bonds:	40.0
TPSA:	222.65 ? Topological Polar Surface Area.	H-Bond Acceptor:	14.0
H-Bond Donor:	6.0	Rings:	6.0
Heavy Atoms:	14.0

MedChem Properties

QED Drug-Likeness Score:	0.089	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.502	Fsp³:	0.154
MCE-18:	122.444 ? 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:	1.0	Fluc inhibitor:	1.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.897 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.704 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.441	Promiscuous compounds:	0.713

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.339	MDCK Permeability:	-5.028
Pgp-inhibitor:	0.109	Pgp-substrate:	0.011
PAMPA:	0.933 ? 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):	0.0
20% Bioavailability (F20%):	0.903	30% Bioavailability (F30%):	0.997
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.001
Plasma Protein Binding (PPB):	95.637%	Volume Distribution (VD):	-0.093
Fu:	6.944% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.449
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.005	CYP1A2-substrate:	0.311
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.543
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.128
CYP2D6-inhibitor:	0.545	CYP2D6-substrate:	0.998
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.92 ? 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):

3.826

Half-life (T1/2):

2.497

ADMET: Toxicity

hERG Blockers:	0.231	hERG Blockers (10um):	0.684
Human Hepatotoxicity (H-HT):	0.551	Drug-induced Liver Injury (DILI):	0.865
AMES Toxicity:	0.589	Rat Oral Acute Toxicity:	0.107
Maximum Recommended Daily Dose:	0.965	Skin Sensitization:	0.995
Carcinogencity:	0.202	Eye Corrosion:	0.0
Eye Irritation:	0.895	Respiratory Toxicity:	0.142
Drug-induced Neurotoxicity:	0.105	Ototoxicity:	0.26
Hematotoxicity:	0.006	Drug-induced Nephrotoxicity:	0.063
Genotoxicity:	0.993	RPMI-8226 Immunitoxicity:	0.06
A549 Cytotoxicity:	0.674	Hek293 Cytotoxicity:	0.992
BCF:	0.859 ? 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:	4.328 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.004 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.905 ? 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
NPO19205	Buxus sempervirens	Species	Buxaceae	Eukaryota	roots	n.a.	n.a.	PMID[10346940]
NPO28097	Platanus occidentalis	Species	Platanaceae	Eukaryota	whole?plant	USA	n.a.	PMID[16124770]
NPO28097	Platanus occidentalis	Species	Platanaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19904995]
NPO19205	Buxus sempervirens	Species	Buxaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[26722868]
NPO19205	Buxus sempervirens	Species	Buxaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO28097	Platanus occidentalis	Species	Platanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO19205	Buxus sempervirens	Species	Buxaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO19205	Buxus sempervirens	Species	Buxaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO19205	Buxus sempervirens	Species	Buxaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO19205	Buxus sempervirens	Species	Buxaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28097	Platanus occidentalis	Species	Platanaceae	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
IC50	5
MIC	2
Activity	4
Ratio IC50	1

Activity Type	# Activity
Cell line	1
Organism	10
Others	1

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
NPT165	Cell line	HeLa	Homo sapiens	IC50	=	20600.0	nM	PMID[18681480]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	600.0	nM	PMID[24448419]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	7000.0	nM	PMID[6631435]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	IC50	=	2.0	ug.mL-1	PMID[15104488]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	IC50	=	3.7	ug.mL-1	PMID[19604701]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	MIC	=	10.0	ug.mL-1	PMID[15104488]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	MIC	=	13.3	ug.mL-1	PMID[24928402]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	Activity	=	2.6	10'7/g	PMID[16499318]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	Activity	=	72.0	%	PMID[11575968]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	Activity	=	1.8	10'7/g	PMID[11575968]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	Activity	=	78.0	%	PMID[19105653]
NPT2	Others	Unspecified	n.a.	Ratio IC50	=	12.0	n.a.	PMID[21458279]

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 NPC101399 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	11684
0.1-0.2	33703
0.2-0.3	3665
0.3-0.4	500
0.4-0.5	172
0.5-0.6	83
0.6-0.7	24
0.7-0.8	0
0.8-0.85	4
0.85-0.9	0
0.9-0.95	0
0.95-1	3

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC217822
1.0	High Similarity	NPC11847
1.0	High Similarity	NPC198938
0.8	Intermediate Similarity	NPC221288
0.8	Intermediate Similarity	NPC194836
0.8	Intermediate Similarity	NPC91493
0.8	Intermediate Similarity	NPC605081
0.7952	Intermediate Similarity	NPC48093
0.75	Intermediate Similarity	NPC104883
0.75	Intermediate Similarity	NPC488679
0.7368	Intermediate Similarity	NPC483767
0.7368	Intermediate Similarity	NPC483769
0.7368	Intermediate Similarity	NPC483768
0.7368	Intermediate Similarity	NPC483766
0.7292	Intermediate Similarity	NPC478277
0.7292	Intermediate Similarity	NPC478276
0.7292	Intermediate Similarity	NPC478275
0.7292	Intermediate Similarity	NPC92815
0.7234	Intermediate Similarity	NPC205824
0.7113	Intermediate Similarity	NPC483765
0.701	Intermediate Similarity	NPC218161
0.6804	Remote Similarity	NPC188815
0.6768	Remote Similarity	NPC96605
0.6768	Remote Similarity	NPC280642
0.6727	Remote Similarity	NPC275977
0.6607	Remote Similarity	NPC72554
0.6577	Remote Similarity	NPC231787
0.6465	Remote Similarity	NPC85751
0.6465	Remote Similarity	NPC19240
0.6444	Remote Similarity	NPC216496
0.6379	Remote Similarity	NPC97817
0.6346	Remote Similarity	NPC470712
0.6304	Remote Similarity	NPC259957
0.6296	Remote Similarity	NPC156785
0.6296	Remote Similarity	NPC162394
0.6296	Remote Similarity	NPC474522
0.6292	Remote Similarity	NPC104677
0.6262	Remote Similarity	NPC474093
0.6262	Remote Similarity	NPC104910
0.6198	Remote Similarity	NPC33083
0.6196	Remote Similarity	NPC129217
0.6174	Remote Similarity	NPC30011
0.6075	Remote Similarity	NPC470718
0.6036	Remote Similarity	NPC241781
0.6019	Remote Similarity	NPC223426
0.5962	Remote Similarity	NPC214621
0.5962	Remote Similarity	NPC34267
0.5957	Remote Similarity	NPC224530
0.5932	Remote Similarity	NPC249560
0.5851	Remote Similarity	NPC159579
0.5842	Remote Similarity	NPC297503
0.5789	Remote Similarity	NPC85707
0.5743	Remote Similarity	NPC470125
0.5741	Remote Similarity	NPC217520
0.567	Remote Similarity	NPC476215
0.5652	Remote Similarity	NPC111929
0.5652	Remote Similarity	NPC320283
0.5652	Remote Similarity	NPC41121
0.5648	Remote Similarity	NPC477895
0.5625	Remote Similarity	NPC470713
0.5596	Remote Similarity	NPC164704
0.5583	Remote Similarity	NPC487502
0.5534	Remote Similarity	NPC477628
0.5514	Remote Similarity	NPC81042
0.547	Remote Similarity	NPC25946
0.5435	Remote Similarity	NPC288084
0.536	Remote Similarity	NPC475179
0.534	Remote Similarity	NPC129264
0.534	Remote Similarity	NPC35167
0.5333	Remote Similarity	NPC473554
0.5333	Remote Similarity	NPC139060
0.5327	Remote Similarity	NPC260504
0.5327	Remote Similarity	NPC36138
0.5327	Remote Similarity	NPC89809
0.5326	Remote Similarity	NPC54802
0.5326	Remote Similarity	NPC197304
0.5315	Remote Similarity	NPC470715
0.5312	Remote Similarity	NPC52550
0.5306	Remote Similarity	NPC484158
0.5294	Remote Similarity	NPC470405
0.5294	Remote Similarity	NPC163242
0.5294	Remote Similarity	NPC272068
0.5288	Remote Similarity	NPC61904
0.5263	Remote Similarity	NPC488734
0.5263	Remote Similarity	NPC77672
0.5263	Remote Similarity	NPC133671
0.5263	Remote Similarity	NPC135391
0.5263	Remote Similarity	NPC78263
0.5263	Remote Similarity	NPC250069
0.5263	Remote Similarity	NPC488735
0.5263	Remote Similarity	NPC488739
0.5263	Remote Similarity	NPC488732
0.5263	Remote Similarity	NPC488738
0.5243	Remote Similarity	NPC473862
0.5238	Remote Similarity	NPC12013
0.5238	Remote Similarity	NPC11432
0.5238	Remote Similarity	NPC477613
0.5221	Remote Similarity	NPC139571
0.5221	Remote Similarity	NPC470716
0.52	Remote Similarity	NPC170052
0.52	Remote Similarity	NPC135846
0.5149	Remote Similarity	NPC95866
0.5146	Remote Similarity	NPC173582
0.5146	Remote Similarity	NPC265885
0.5146	Remote Similarity	NPC181465
0.5146	Remote Similarity	NPC215710
0.5146	Remote Similarity	NPC473438
0.5146	Remote Similarity	NPC253788
0.5143	Remote Similarity	NPC472992
0.514	Remote Similarity	NPC603079
0.5104	Remote Similarity	NPC127546
0.5104	Remote Similarity	NPC57625
0.5104	Remote Similarity	NPC173637
0.5104	Remote Similarity	NPC317489
0.5104	Remote Similarity	NPC223424
0.5104	Remote Similarity	NPC600591
0.5096	Remote Similarity	NPC304741
0.5085	Remote Similarity	NPC488737
0.5051	Remote Similarity	NPC175107
0.5049	Remote Similarity	NPC258044
0.5049	Remote Similarity	NPC217387
0.5049	Remote Similarity	NPC139320
0.5048	Remote Similarity	NPC144097
0.5046	Remote Similarity	NPC221342
0.5046	Remote Similarity	NPC476470
0.5043	Remote Similarity	NPC470717
0.5041	Remote Similarity	NPC21359
0.5041	Remote Similarity	NPC460984

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC101399 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3775
0.1-0.2	5315
0.2-0.3	53
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