NPASS Compound

Natural Product: NPC470881

Natural Product ID	NPC470881
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	2-(4-Hydroxy-3-Methoxyphenyl)Ethanol 1-O-[Beta-D-Apiofuranosyl-(1-6)-Beta-D-Glucopyranoside
IUPAC Name	(2R,3S,4S,5R,6R)-2-[[(2R,3R,4R)-3,4-dihydroxy-4-(hydroxymethyl)oxolan-2-yl]oxymethyl]-6-[2-(4-hydroxy-3-methoxyphenyl)ethoxy]oxane-3,4,5-triol
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL227742
PubChem CID	16681196
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 62 64 0 0 0 0 0 0 0 0999 V2000 8.0612 0.9931 -1.9137 C 0 0 0 0 0 0 0 0 0 0 0 0 8.1797 -0.3338 -1.3927 O 0 0 0 0 0 0 0 0 0 0 0 0 7.2370 -0.7567 -0.4641 C 0 0 0 0 0 0 0 0 0 0 0 0 7.3059 -2.0245 0.0683 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3678 -2.4393 0.9896 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3427 -1.5821 1.3908 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2584 -0.3138 0.8702 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2038 0.0825 -0.0483 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1613 0.5840 1.3086 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9420 0.4311 0.4228 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9272 1.2559 0.8216 O 0 0 0 0 0 0 0 0 0 0 0 0 0.7785 1.2307 0.1287 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2776 2.5037 -0.4359 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9745 2.2377 -1.2601 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9875 1.4306 -0.4229 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3085 0.2486 0.1603 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2301 0.6980 0.9642 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.1703 -0.5517 1.0711 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2535 -1.1760 0.5878 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.3571 -0.5581 0.1569 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5553 -1.1574 0.9008 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.5754 -1.2915 -0.1995 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9471 -0.5254 -1.3307 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6063 -0.8827 -1.1959 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.6902 -2.7598 -0.5528 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.5764 -2.9472 -1.6261 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.8099 -0.7787 0.1643 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.9556 -0.2529 1.8834 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.4931 2.3032 0.5377 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.6032 3.4422 -1.5637 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.1228 3.3250 0.6280 O 0 0 0 0 0 0 0 0 0 0 0 0 8.2995 -2.9116 -0.2946 O 0 0 0 0 0 0 0 0 0 0 0 0 8.0008 1.6553 -1.0090 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1267 1.1340 -2.4670 H 0 0 0 0 0 0 0 0 0 0 0 0 8.9616 1.2767 -2.4881 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4191 -3.4492 1.4164 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6163 -1.9286 2.1159 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1277 1.0739 -0.4472 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5202 1.6274 1.3486 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8359 0.3367 2.3596 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2613 0.5221 -0.6099 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5838 -0.6267 0.5582 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8676 0.4858 -0.7089 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9743 3.0176 -1.1151 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7518 1.6128 -2.1445 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7793 1.1729 -1.1294 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9084 -0.4016 -0.6670 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5241 0.1081 1.9506 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5449 -1.3204 1.6382 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3751 0.5154 0.3002 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3075 -2.1340 1.3307 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3465 -0.7957 -2.3236 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0450 0.5605 -1.1007 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7130 -3.1518 -0.8996 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0125 -3.3588 0.3077 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.3352 -2.3337 -1.4498 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.7050 0.1078 0.5816 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7860 0.6736 1.5360 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5820 3.1870 0.0818 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7988 3.4404 -2.5518 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3969 3.0818 1.4508 H 0 0 0 0 0 0 0 0 0 0 0 0 8.6968 -3.6119 0.3329 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 2 0 6 7 1 0 7 8 2 0 7 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 16 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 22 25 1 0 25 26 1 0 22 27 1 0 21 28 1 0 15 29 1 0 14 30 1 0 13 31 1 0 4 32 1 0 8 3 1 0 17 12 1 0 24 20 1 0 1 33 1 0 1 34 1 0 1 35 1 0 5 36 1 0 6 37 1 0 8 38 1 0 9 39 1 0 9 40 1 0 10 41 1 0 10 42 1 0 12 43 1 0 13 44 1 0 14 45 1 0 15 46 1 0 16 47 1 0 18 48 1 0 18 49 1 0 20 50 1 0 21 51 1 0 23 52 1 0 23 53 1 0 25 54 1 0 25 55 1 0 26 56 1 0 27 57 1 0 28 58 1 0 29 59 1 0 30 60 1 0 31 61 1 0 32 62 1 0 M END

Standard InCHIKey	MYOINCYRVGGFRT-LTRJMQNCSA-N
Standard InCHI	InChI=1S/C20H30O12/c1-28-12-6-10(2-3-11(12)22)4-5-29-18-16(25)15(24)14(23)13(32-18)7-30-19-17(26)20(27,8-21)9-31-19/h2-3,6,13-19,21-27H,4-5,7-9H2,1H3/t13-,14-,15+,16-,17+,18-,19-,20-/m1/s1
SMILES	COC1=C(C=CC(=C1)CCOC2C(C(C(C(O2)COC3C(C(CO3)(CO)O)O)O)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	462.17	Volume:	426.38 ? Van der Waals volume.
Dense:	1.084	LogP:	-1.246 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	-0.493 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-1.419 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	9.0	Rigid Bonds:	17.0
TPSA:	187.76 ? Topological Polar Surface Area.	H-Bond Acceptor:	12.0
H-Bond Donor:	7.0	Rings:	3.0
Heavy Atoms:	12.0

MedChem Properties

QED Drug-Likeness Score:	0.2	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.391	Fsp³:	0.7
MCE-18:	77.647 ? 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:	0
Colloidal aggregators:	0.006	Fluc inhibitor:	0.028 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.032 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.264 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.084	Promiscuous compounds:	0.235

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.524	MDCK Permeability:	-5.211
Pgp-inhibitor:	0.0	Pgp-substrate:	0.985
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):	0.998
20% Bioavailability (F20%):	0.978	30% Bioavailability (F30%):	0.996
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.001	MRP1:	0.791
Plasma Protein Binding (PPB):	46.796%	Volume Distribution (VD):	-0.587
Fu:	56.473% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.02
OATP1B3 inhibitor:	0.677	BCRP inhibitor:	0.305
BSEP inhibitor:	0.003

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.074	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.963	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.001
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.615
HLM stability:	0.025 ? 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):

2.002

Half-life (T1/2):

2.118

ADMET: Toxicity

hERG Blockers:	0.05	hERG Blockers (10um):	0.331
Human Hepatotoxicity (H-HT):	0.428	Drug-induced Liver Injury (DILI):	0.174
AMES Toxicity:	0.886	Rat Oral Acute Toxicity:	0.14
Maximum Recommended Daily Dose:	0.113	Skin Sensitization:	0.567
Carcinogencity:	0.283	Eye Corrosion:	0.0
Eye Irritation:	0.037	Respiratory Toxicity:	0.026
Drug-induced Neurotoxicity:	0.335	Ototoxicity:	0.939
Hematotoxicity:	0.097	Drug-induced Nephrotoxicity:	0.182
Genotoxicity:	0.226	RPMI-8226 Immunitoxicity:	0.116
A549 Cytotoxicity:	0.061	Hek293 Cytotoxicity:	0.598
BCF:	0.24 ? 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:	2.164 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	3.954 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	2.791 ? 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
NPO30984	Fraxinus sieboldiana	Species	Oleaceae	Eukaryota	stem bark	n.a.	n.a.	PMID[17461599]
NPO30984	Fraxinus sieboldiana	Species	Oleaceae	Eukaryota	n.a.	stem	n.a.	PMID[20961093]
NPO30984	Fraxinus sieboldiana	Species	Oleaceae	Eukaryota	Stem bark	Lu Mountain, Jiangxi Province, China	2004-AUG	PMID[20961093]
NPO30984	Fraxinus sieboldiana	Species	Oleaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[26697686]
NPO30984	Fraxinus sieboldiana	Species	Oleaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]

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
Inhibition	1
IC50	5

Activity Type	# Activity
Cell line	3
Subcellular	1
Others	2

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
NPT179	Cell line	A2780	Homo sapiens	IC50	>	5000.0	nM	PMID[17722904]
NPT180	Cell line	HCT-8	Homo sapiens	IC50	>	5000.0	nM	PMID[9917310]
NPT81	Cell line	A549	Homo sapiens	IC50	>	5000.0	nM	DOI[10.6019/CHEMBL1201861]
NPT1084	Subcellular	Liver microsomes	Rattus norvegicus	IC50	>	10000.0	nM	DOI[10.6019/CHEMBL1201861]
NPT2	Others	Unspecified	n.a.	Inhibition	=	44.3	%	PMID[15568791]
NPT2	Others	Unspecified	n.a.	IC50	=	1600.0	nM	DOI[10.6019/CHEMBL1201861]

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 NPC470881 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	17149
0.1-0.2	27890
0.2-0.3	3889
0.3-0.4	757
0.4-0.5	137
0.5-0.6	27
0.6-0.7	3
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
0.7353	Intermediate Similarity	NPC90318
0.7183	Intermediate Similarity	NPC6836
0.7027	Intermediate Similarity	NPC252833
0.6986	Remote Similarity	NPC602810
0.618	Remote Similarity	NPC98624
0.6053	Remote Similarity	NPC195196
0.5957	Remote Similarity	NPC470934
0.5867	Remote Similarity	NPC476448
0.5867	Remote Similarity	NPC469548
0.5867	Remote Similarity	NPC476445
0.5658	Remote Similarity	NPC289438
0.557	Remote Similarity	NPC164172
0.5455	Remote Similarity	NPC227980
0.5432	Remote Similarity	NPC232454
0.5432	Remote Similarity	NPC470907
0.5432	Remote Similarity	NPC178449
0.5395	Remote Similarity	NPC473867
0.5395	Remote Similarity	NPC287429
0.5385	Remote Similarity	NPC25821
0.5375	Remote Similarity	NPC34965
0.5333	Remote Similarity	NPC278961
0.5333	Remote Similarity	NPC113680
0.5316	Remote Similarity	NPC473924
0.5301	Remote Similarity	NPC472860
0.5301	Remote Similarity	NPC484816
0.5294	Remote Similarity	NPC212748
0.527	Remote Similarity	NPC171533
0.525	Remote Similarity	NPC23253
0.5205	Remote Similarity	NPC264784
0.5152	Remote Similarity	NPC219040
0.5125	Remote Similarity	NPC242756
0.5098	Remote Similarity	NPC188393
0.507	Remote Similarity	NPC472026

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC470881 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4700
0.1-0.2	4310
0.2-0.3	131
0.3-0.4	9
0.4-0.5	0
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