NPASS Compound

Natural Product: NPC100558

Natural Product ID	NPC100558
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Ternstroside C
IUPAC Name	[(2R,3R,4S,5R,6R)-2-[2-(3,4-dihydroxyphenyl)ethoxy]-3,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl] 2-(3,4-dihydroxyphenyl)acetate
Synonyms	Ternstroside C
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL446760
PubChem CID	16091521
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0004603] Organic oxygen compounds [CHEMONTID:0000323] Organooxygen compounds [CHEMONTID:0000011] Carbohydrates and carbohydrate conjugates [CHEMONTID:0002105] Glycosyl compounds [CHEMONTID:0002207] O-glycosyl 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 59 61 0 0 0 0 0 0 0 0999 V2000 -2.3452 -4.1119 1.1764 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0589 -3.5987 1.2898 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5149 -3.1315 -0.0429 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.2555 -2.1506 -0.6249 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.2559 -0.9344 0.0137 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.2158 -0.8998 1.0055 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.2427 -0.0045 0.8226 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0285 -0.3473 -0.3918 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1554 0.5927 -0.6359 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3713 0.3032 -0.0730 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.4450 1.1630 -0.2828 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.2755 2.2955 -1.0532 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0512 2.5613 -1.6038 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9884 1.7207 -1.4028 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8800 3.7070 -2.3831 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.3651 3.1239 -1.2381 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0515 -0.5404 0.6181 C 0 0 1 0 0 0 0 0 0 0 0 0 1.2239 -1.3386 0.1151 C 0 0 2 0 0 0 0 0 0 0 0 0 0.9454 -2.8186 0.0842 C 0 0 2 0 0 0 0 0 0 0 0 0 1.6904 -3.4097 -0.9485 O 0 0 0 0 0 0 0 0 0 0 0 0 2.3283 -1.0136 0.9404 O 0 0 0 0 0 0 0 0 0 0 0 0 3.4369 -0.3774 0.3994 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3991 -0.1164 -0.8309 O 0 0 0 0 0 0 0 0 0 0 0 0 4.6013 -0.0337 1.2647 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6129 0.6243 0.4286 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5692 -0.1522 -0.1936 C 0 0 0 0 0 0 0 0 0 0 0 0 7.4998 0.4860 -0.9667 C 0 0 0 0 0 0 0 0 0 0 0 0 7.4700 1.8607 -1.1096 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5007 2.6257 -0.4762 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5647 2.0003 0.2993 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4542 4.0028 -0.6069 O 0 0 0 0 0 0 0 0 0 0 0 0 8.4130 2.5119 -1.8935 O 0 0 0 0 0 0 0 0 0 0 0 0 0.3275 0.8037 0.3704 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.3517 -5.0906 1.0616 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4317 -4.4062 1.7195 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0641 -2.7730 2.0309 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5821 -4.0333 -0.7226 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5105 -0.1736 -0.7456 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8631 0.0616 1.7477 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8416 1.0220 0.6761 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3806 -0.4570 -1.2598 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4662 -1.3743 -0.2105 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4738 -0.6033 0.5333 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.3754 0.9145 0.1650 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0223 1.9052 -1.8212 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0224 4.6202 -1.9298 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.5759 3.8514 -0.5605 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0231 -0.6574 1.7169 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4146 -1.0123 -0.9361 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3175 -3.2770 1.0227 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6441 -3.2814 -0.7802 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2904 0.6619 2.0606 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9806 -0.9692 1.7513 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5529 -1.2403 -0.0507 H 0 0 0 0 0 0 0 0 0 0 0 0 8.2592 -0.1189 -1.4623 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7767 2.5614 0.8215 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1583 4.6063 0.1514 H 0 0 0 0 0 0 0 0 0 0 0 0 9.3570 2.5664 -1.5030 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4526 1.2936 0.0148 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 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 2 0 10 11 1 0 11 12 2 0 12 13 1 0 13 14 2 0 13 15 1 0 12 16 1 0 5 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 18 21 1 0 21 22 1 0 22 23 2 0 22 24 1 0 24 25 1 0 25 26 2 0 26 27 1 0 27 28 2 0 28 29 1 0 29 30 2 0 29 31 1 0 28 32 1 0 17 33 1 0 19 3 1 0 30 25 1 0 14 9 1 0 1 34 1 0 2 35 1 0 2 36 1 0 3 37 1 6 5 38 1 6 7 39 1 0 7 40 1 0 8 41 1 0 8 42 1 0 10 43 1 0 11 44 1 0 14 45 1 0 15 46 1 0 16 47 1 0 17 48 1 1 18 49 1 6 19 50 1 1 20 51 1 0 24 52 1 0 24 53 1 0 26 54 1 0 27 55 1 0 30 56 1 0 31 57 1 0 32 58 1 0 33 59 1 0 M END

Standard InCHIKey	FLSBWXVHDVCNEZ-OHLDOZIISA-N
Standard InCHI	InChI=1S/C22H26O11/c23-10-17-19(29)21(33-18(28)9-12-2-4-14(25)16(27)8-12)20(30)22(32-17)31-6-5-11-1-3-13(24)15(26)7-11/h1-4,7-8,17,19-27,29-30H,5-6,9-10H2/t17-,19-,20-,21+,22-/m1/s1
SMILES	OC[C@H]1O[C@@H](OCCc2ccc(c(c2)O)O)[C@@H]([C@H]([C@@H]1O)OC(=O)Cc1ccc(c(c1)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	466.15	Volume:	441.636 ? Van der Waals volume.
Dense:	1.056	LogP:	0.039 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	0.934 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.198 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	9.0	Rigid Bonds:	19.0
TPSA:	186.37 ? Topological Polar Surface Area.	H-Bond Acceptor:	11.0
H-Bond Donor:	7.0	Rings:	3.0
Heavy Atoms:	11.0

MedChem Properties

QED Drug-Likeness Score:	0.199	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.888	Fsp³:	0.409
MCE-18:	69.774 ? 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:	Rejected	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	1
Colloidal aggregators:	0.534	Fluc inhibitor:	0.251 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.036 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.359 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.157	Promiscuous compounds:	0.397

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.345	MDCK Permeability:	-5.151
Pgp-inhibitor:	0.0	Pgp-substrate:	0.021
PAMPA:	0.985 ? 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):	0.039
20% Bioavailability (F20%):	0.899	30% Bioavailability (F30%):	0.988
50% Bioavailability (F50%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.001	MRP1:	0.415
Plasma Protein Binding (PPB):	56.125%	Volume Distribution (VD):	-0.367
Fu:	38.47% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.951
OATP1B3 inhibitor:	0.998	BCRP inhibitor:	0.001
BSEP inhibitor:	0.001

ADMET: Metabolism

CYP1A2-inhibitor:	0.006	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.002	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.011	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.002	CYP2D6-substrate:	0.864
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.631
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.987
HLM stability:	0.956 ? 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):

11.62

Half-life (T1/2):

2.596

ADMET: Toxicity

hERG Blockers:	0.041	hERG Blockers (10um):	0.485
Human Hepatotoxicity (H-HT):	0.323	Drug-induced Liver Injury (DILI):	0.757
AMES Toxicity:	0.816	Rat Oral Acute Toxicity:	0.094
Maximum Recommended Daily Dose:	0.059	Skin Sensitization:	1.0
Carcinogencity:	0.067	Eye Corrosion:	0.0
Eye Irritation:	0.504	Respiratory Toxicity:	0.032
Drug-induced Neurotoxicity:	0.002	Ototoxicity:	0.973
Hematotoxicity:	0.092	Drug-induced Nephrotoxicity:	0.054
Genotoxicity:	0.892	RPMI-8226 Immunitoxicity:	0.008
A549 Cytotoxicity:	0.972	Hek293 Cytotoxicity:	0.329
BCF:	0.709 ? 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:	3.243 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.786 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.119 ? 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
NPO17348	Ternstroemia japonica	Species	Pentaphylacaceae	Eukaryota	n.a.	leaf	n.a.	PMID[17067150]
NPO17348	Ternstroemia japonica	Species	Pentaphylacaceae	Eukaryota	fresh leaves	n.a.	n.a.	PMID[17067150]
NPO17348	Ternstroemia japonica	Species	Pentaphylacaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO17348	Ternstroemia japonica	Species	Pentaphylacaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]

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	3

Activity Type	# Activity
Non-molecular	2
Tissue	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
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	3260.0	nM	PMID[17067150]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	1140.0	nM	PMID[17067150]
NPT1590	Tissue	Kidney	Rattus norvegicus	IC50	=	33290.0	nM	PMID[17067150]

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 NPC100558 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	12583
0.1-0.2	33877
0.2-0.3	3162
0.3-0.4	186
0.4-0.5	40
0.5-0.6	5
0.6-0.7	4
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
0.6613	Remote Similarity	NPC310252
0.6061	Remote Similarity	NPC123988
0.6061	Remote Similarity	NPC302583
0.6	Remote Similarity	NPC266045
0.5672	Remote Similarity	NPC84789
0.5455	Remote Similarity	NPC85565
0.5443	Remote Similarity	NPC483706
0.525	Remote Similarity	NPC205195
0.5067	Remote Similarity	NPC35731

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC100558 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3945
0.1-0.2	5059
0.2-0.3	141
0.3-0.4	4
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