NPASS Compound

Natural Product: NPC189589

Natural Product ID	NPC189589
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	4-Hydroxy-3,5-Dimethoxyphenyl Beta-D-Glucopyranosyl-(1->6)-Beta-D-Glucopyranoside
IUPAC Name	(2R,3S,4S,5R,6R)-2-(hydroxymethyl)-6-[[(2R,3S,4S,5R,6S)-3,4,5-trihydroxy-6-(4-hydroxy-3,5-dimethoxyphenoxy)oxan-2-yl]methoxy]oxane-3,4,5-triol
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL562563
PubChem CID	42638298
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:0004165] Phenolic 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 64 66 0 0 0 0 0 0 0 0999 V2000 3.7677 4.4473 0.2281 O 0 0 0 0 0 0 0 0 0 0 0 0 3.8042 3.2448 0.9104 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8855 2.0508 -0.0276 C 0 0 1 0 0 0 0 0 0 0 0 0 2.7802 2.0407 -0.8538 O 0 0 0 0 0 0 0 0 0 0 0 0 2.8170 0.8688 -1.6098 C 0 0 1 0 0 0 0 0 0 0 0 0 1.6304 0.5602 -2.2021 O 0 0 0 0 0 0 0 0 0 0 0 0 1.1407 -0.6922 -1.9047 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8352 -0.9170 -0.4551 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.1059 -0.0513 0.0414 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.9874 -0.5877 0.9708 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.1156 -1.1633 0.3931 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4420 -0.8170 0.5458 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8818 0.2046 1.3388 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2288 0.5574 1.4949 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5915 1.6008 2.3136 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.6727 2.3862 3.0426 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1425 -0.1970 0.7874 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7461 -1.2397 -0.0275 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4149 -1.5582 -0.1570 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6893 -1.9868 -0.7324 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.3588 -3.0514 -1.5717 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.4996 0.0778 0.8796 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.3069 -1.5318 1.9377 C 0 0 1 0 0 0 0 0 0 0 0 0 0.5610 -2.5560 1.3010 C 0 0 2 0 0 0 0 0 0 0 0 0 0.4589 -2.3853 -0.2044 C 0 0 2 0 0 0 0 0 0 0 0 0 1.4403 -3.1867 -0.7705 O 0 0 0 0 0 0 0 0 0 0 0 0 0.2830 -3.8554 1.7056 O 0 0 0 0 0 0 0 0 0 0 0 0 0.3386 -0.7989 2.9455 O 0 0 0 0 0 0 0 0 0 0 0 0 3.9308 1.0992 -2.6441 C 0 0 1 0 0 0 0 0 0 0 0 0 5.2252 1.0505 -1.8593 C 0 0 2 0 0 0 0 0 0 0 0 0 5.1899 2.0827 -0.7517 C 0 0 2 0 0 0 0 0 0 0 0 0 6.1814 1.6926 0.1745 O 0 0 0 0 0 0 0 0 0 0 0 0 6.3351 1.2087 -2.6714 O 0 0 0 0 0 0 0 0 0 0 0 0 3.9276 0.0869 -3.6000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.6730 4.8375 0.2626 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8414 3.1727 1.4861 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6122 3.1854 1.6516 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8492 1.1369 0.5947 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1709 0.0178 -1.0056 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7465 -1.5115 -2.3457 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1511 -0.7671 -2.4475 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7578 -0.7719 0.1366 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2965 0.2714 1.5974 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1635 0.7969 1.8943 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0622 1.7851 3.7578 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1370 3.2269 3.5583 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9509 2.8027 2.3086 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0482 -2.3698 -0.7849 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4800 -2.7339 -2.1944 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1979 -3.2545 -2.2817 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0503 -3.9775 -1.0291 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8662 0.8475 0.3218 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1389 -2.0850 2.4647 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6238 -2.3022 1.5683 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5360 -2.5584 -0.6055 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3306 -2.7807 -0.7837 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3971 -3.8896 2.4398 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2474 0.0027 3.1062 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8250 2.1027 -3.0874 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2388 0.0450 -1.3456 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4831 3.0910 -1.1187 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9390 2.3178 0.1899 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6975 0.2892 -2.8407 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2832 0.4527 -4.4359 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 1 0 10 11 1 0 11 12 1 0 12 13 2 0 13 14 1 0 14 15 1 0 15 16 1 0 14 17 2 0 17 18 1 0 18 19 2 0 18 20 1 0 20 21 1 0 17 22 1 0 10 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 24 27 1 0 23 28 1 0 5 29 1 0 29 30 1 0 30 31 1 0 31 32 1 0 30 33 1 0 29 34 1 0 31 3 1 0 25 8 1 0 19 12 1 0 1 35 1 0 2 36 1 0 2 37 1 0 3 38 1 1 5 39 1 1 7 40 1 0 7 41 1 0 8 42 1 1 10 43 1 1 13 44 1 0 16 45 1 0 16 46 1 0 16 47 1 0 19 48 1 0 21 49 1 0 21 50 1 0 21 51 1 0 22 52 1 0 23 53 1 1 24 54 1 1 25 55 1 6 26 56 1 0 27 57 1 0 28 58 1 0 29 59 1 6 30 60 1 1 31 61 1 6 32 62 1 0 33 63 1 0 34 64 1 0 M END

Standard InCHIKey	BMQJMZFDNFDQNP-JFRFVCMESA-N
Standard InCHI	InChI=1S/C20H30O14/c1-29-8-3-7(4-9(30-2)12(8)22)32-20-18(28)16(26)14(24)11(34-20)6-31-19-17(27)15(25)13(23)10(5-21)33-19/h3-4,10-11,13-28H,5-6H2,1-2H3/t10-,11-,13-,14-,15+,16+,17-,18-,19-,20-/m1/s1
SMILES	OC[C@H]1O[C@@H](OC[C@H]2O[C@@H](Oc3cc(OC)c(c(c3)OC)O)[C@@H]([C@H]([C@@H]2O)O)O)[C@@H]([C@H]([C@@H]1O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	494.16	Volume:	443.961 ? Van der Waals volume.
Dense:	1.113	LogP:	-1.072 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	-0.337 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-1.014 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	8.0	Rigid Bonds:	18.0
TPSA:	217.22 ? Topological Polar Surface Area.	H-Bond Acceptor:	14.0
H-Bond Donor:	8.0	Rings:	3.0
Heavy Atoms:	14.0

MedChem Properties

QED Drug-Likeness Score:	0.175	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.343	Fsp³:	0.7
MCE-18:	82.529 ? 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:	1
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.435	Fluc inhibitor:	0.122 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.104 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.032 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.162	Promiscuous compounds:	0.232

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.355	MDCK Permeability:	-5.313
Pgp-inhibitor:	0.0	Pgp-substrate:	0.63
PAMPA:	0.802 ? 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):	0.98
20% Bioavailability (F20%):	0.034	30% Bioavailability (F30%):	0.967
50% Bioavailability (F50%):	0.948

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.006	MRP1:	0.228
Plasma Protein Binding (PPB):	68.77%	Volume Distribution (VD):	-0.411
Fu:	32.906% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.201
BSEP inhibitor:	0.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.008	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.004	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.167
HLM stability:	0.012 ? 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):

1.194

Half-life (T1/2):

4.68

ADMET: Toxicity

hERG Blockers:	0.011	hERG Blockers (10um):	0.046
Human Hepatotoxicity (H-HT):	0.508	Drug-induced Liver Injury (DILI):	0.819
AMES Toxicity:	0.927	Rat Oral Acute Toxicity:	0.003
Maximum Recommended Daily Dose:	0.002	Skin Sensitization:	0.996
Carcinogencity:	0.093	Eye Corrosion:	0.0
Eye Irritation:	0.062	Respiratory Toxicity:	0.002
Drug-induced Neurotoxicity:	0.004	Ototoxicity:	0.985
Hematotoxicity:	0.335	Drug-induced Nephrotoxicity:	0.803
Genotoxicity:	0.051	RPMI-8226 Immunitoxicity:	0.176
A549 Cytotoxicity:	0.251	Hek293 Cytotoxicity:	0.16
BCF:	0.113 ? 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:	2.316 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	3.91 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.1 ? 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
NPO33268	wheat	n.a.	n.a.	n.a.	wheat germ	n.a.	n.a.	PMID[19284743]
NPO33268	wheat	n.a.	n.a.	n.a.	wheat bran	n.a.	n.a.	PMID[21658963]
NPO33268	wheat	n.a.	n.a.	n.a.	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
Activity	1

Activity Type	# Activity
Non-molecular	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.	Activity	=	0.85	n.a.	PMID[19284743]

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 NPC189589 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	21890
0.1-0.2	23479
0.2-0.3	3022
0.3-0.4	1087
0.4-0.5	333
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	1

Similarity Score	Similarity Level	Natural Product ID
0.9804	High Similarity	NPC208769
0.7931	Intermediate Similarity	NPC37074
0.7797	Intermediate Similarity	NPC287780
0.7797	Intermediate Similarity	NPC60982
0.7451	Intermediate Similarity	NPC192810
0.7069	Intermediate Similarity	NPC57751
0.6667	Remote Similarity	NPC60756
0.6154	Remote Similarity	NPC87696
0.6094	Remote Similarity	NPC469622
0.5781	Remote Similarity	NPC171533
0.5763	Remote Similarity	NPC221090
0.5714	Remote Similarity	NPC46958
0.5536	Remote Similarity	NPC276195
0.5467	Remote Similarity	NPC602634
0.5439	Remote Similarity	NPC217854
0.5405	Remote Similarity	NPC168358
0.5373	Remote Similarity	NPC298845
0.5366	Remote Similarity	NPC164047
0.5366	Remote Similarity	NPC470452
0.5366	Remote Similarity	NPC102028
0.5366	Remote Similarity	NPC470453
0.5366	Remote Similarity	NPC63105
0.5362	Remote Similarity	NPC469621
0.5342	Remote Similarity	NPC3293
0.5316	Remote Similarity	NPC61791
0.5312	Remote Similarity	NPC132895
0.5301	Remote Similarity	NPC213052
0.5273	Remote Similarity	NPC145112
0.5246	Remote Similarity	NPC470270
0.5246	Remote Similarity	NPC145900
0.5211	Remote Similarity	NPC119125
0.5172	Remote Similarity	NPC484157
0.5085	Remote Similarity	NPC153149
0.507	Remote Similarity	NPC213723
0.5065	Remote Similarity	NPC229687
0.506	Remote Similarity	NPC470448

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC189589 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6159
0.1-0.2	2890
0.2-0.3	69
0.3-0.4	27
0.4-0.5	5
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