NPASS Compound

Natural Product: NPC469661

Natural Product ID	NPC469661
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(2S,3R,4S,5S,6R)-2-[5-[2-(3,5-Dihydroxyphenyl)Ethyl]-2-Hydroxyphenoxy]-6-(Hydroxymethyl)Oxane-3,4,5-Triol
IUPAC Name	(2S,3R,4S,5S,6R)-2-[5-[2-(3,5-dihydroxyphenyl)ethyl]-2-hydroxyphenoxy]-6-(hydroxymethyl)oxane-3,4,5-triol
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL109702
PubChem CID	44339715
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000253] Stilbenes [CHEMONTID:0000142] Stilbene 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 53 55 0 0 0 0 0 0 0 0999 V2000 -5.9036 -0.7527 1.4984 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.5891 -0.2612 1.6132 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4982 0.9395 0.7141 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.2408 1.5257 0.7340 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.3874 1.0545 -0.2474 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.2647 -0.3152 -0.1212 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.2033 -1.0960 0.1763 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0384 -0.5665 0.4209 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1095 -1.4137 0.7254 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9426 -2.7809 0.7855 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3145 -3.3179 0.5379 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3570 -2.4633 0.2394 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5927 -3.0432 -0.0002 O 0 0 0 0 0 0 0 0 0 0 0 0 2.4404 -0.8206 0.9858 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2139 -0.7188 -0.3283 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5468 -0.1266 -0.0779 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7050 1.2333 -0.1441 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9722 1.7770 0.0954 C 0 0 0 0 0 0 0 0 0 0 0 0 6.1510 3.1564 0.0324 O 0 0 0 0 0 0 0 0 0 0 0 0 7.0423 0.9717 0.3917 C 0 0 0 0 0 0 0 0 0 0 0 0 6.8728 -0.3867 0.4552 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6165 -0.9182 0.2172 C 0 0 0 0 0 0 0 0 0 0 0 0 7.9389 -1.2231 0.7529 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.8063 1.5065 -1.6300 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.3025 1.8367 -1.5191 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.8845 0.6765 -0.7028 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.2579 0.5801 -0.8925 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.8989 1.9657 -2.7442 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.1717 2.6711 -1.9758 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.5082 0.0439 1.4505 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8700 -1.0481 1.4030 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4828 0.0934 2.6588 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2275 1.7083 1.1010 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4052 1.5344 -0.0581 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2580 0.4909 0.3951 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7939 -3.4355 1.0262 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4303 -4.3871 0.5882 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7939 -3.3224 -0.9461 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3711 0.2192 1.3710 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0474 -1.3885 1.7025 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2966 -1.7060 -0.8208 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6840 -0.0569 -1.0453 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8670 1.8774 -0.3770 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0805 3.5226 -0.1921 H 0 0 0 0 0 0 0 0 0 0 0 0 8.0221 1.3737 0.5783 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5175 -1.9873 0.2748 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9386 -2.1486 0.3467 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7382 0.7042 -2.3852 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3490 2.7561 -0.8909 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3883 -0.2403 -1.0822 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3921 0.3505 -1.8496 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7487 2.9124 -3.0513 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4595 2.4439 -2.6516 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 2 0 8 9 1 0 9 10 2 0 10 11 1 0 11 12 2 0 12 13 1 0 9 14 1 0 14 15 1 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 1 0 18 20 2 0 20 21 1 0 21 22 2 0 21 23 1 0 5 24 1 0 24 25 1 0 25 26 1 0 26 27 1 0 25 28 1 0 24 29 1 0 26 3 1 0 12 7 1 0 22 16 1 0 1 30 1 0 2 31 1 0 2 32 1 0 3 33 1 1 5 34 1 1 8 35 1 0 10 36 1 0 11 37 1 0 13 38 1 0 14 39 1 0 14 40 1 0 15 41 1 0 15 42 1 0 17 43 1 0 19 44 1 0 20 45 1 0 22 46 1 0 23 47 1 0 24 48 1 6 25 49 1 1 26 50 1 6 27 51 1 0 28 52 1 0 29 53 1 0 M END

Standard InCHIKey	ALURDYSHZFKTJP-OUUBHVDSSA-N
Standard InCHI	InChI=1S/C20H24O9/c21-9-16-17(25)18(26)19(27)20(29-16)28-15-7-10(3-4-14(15)24)1-2-11-5-12(22)8-13(23)6-11/h3-8,16-27H,1-2,9H2/t16-,17-,18+,19-,20-/m1/s1
SMILES	OC[C@H]1O[C@@H](Oc2cc(ccc2O)CCc2cc(O)cc(c2)O)[C@@H]([C@H]([C@@H]1O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	408.14	Volume:	392.1 ? Van der Waals volume.
Dense:	1.041	LogP:	1.098 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.512 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.58 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	18.0
TPSA:	160.07 ? Topological Polar Surface Area.	H-Bond Acceptor:	9.0
H-Bond Donor:	7.0	Rings:	3.0
Heavy Atoms:	9.0

MedChem Properties

QED Drug-Likeness Score:	0.342	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.743	Fsp³:	0.4
MCE-18:	67.143 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.492	Fluc inhibitor:	0.341 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.06 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.312 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.269	Promiscuous compounds:	0.24

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.021	MDCK Permeability:	-5.089
Pgp-inhibitor:	0.0	Pgp-substrate:	0.088
PAMPA:	0.958 ? 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):	0.07
20% Bioavailability (F20%):	0.906	30% Bioavailability (F30%):	0.994
50% Bioavailability (F50%):	0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.05	MRP1:	0.027
Plasma Protein Binding (PPB):	78.538%	Volume Distribution (VD):	-0.022
Fu:	22.507% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.069
BSEP inhibitor:	0.016

ADMET: Metabolism

CYP1A2-inhibitor:	0.141	CYP1A2-substrate:	0.076
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.664
CYP2C9-inhibitor:	0.953	CYP2C9-substrate:	0.112
CYP2D6-inhibitor:	0.001	CYP2D6-substrate:	0.079
CYP3A4-inhibitor:	0.018	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.225 ? 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):

3.71

Half-life (T1/2):

3.465

ADMET: Toxicity

hERG Blockers:	0.115	hERG Blockers (10um):	0.56
Human Hepatotoxicity (H-HT):	0.617	Drug-induced Liver Injury (DILI):	0.137
AMES Toxicity:	0.728	Rat Oral Acute Toxicity:	0.024
Maximum Recommended Daily Dose:	0.114	Skin Sensitization:	0.995
Carcinogencity:	0.028	Eye Corrosion:	0.0
Eye Irritation:	0.724	Respiratory Toxicity:	0.022
Drug-induced Neurotoxicity:	0.012	Ototoxicity:	0.862
Hematotoxicity:	0.051	Drug-induced Nephrotoxicity:	0.577
Genotoxicity:	0.477	RPMI-8226 Immunitoxicity:	0.149
A549 Cytotoxicity:	0.723	Hek293 Cytotoxicity:	0.685
BCF:	0.829 ? 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:	3.482 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.019 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.215 ? 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
NPO88	Rheum undulatum	Species	Polygonaceae	Eukaryota	rhizome	n.a.	n.a.	PMID[10714491]
NPO88	Rheum undulatum	Species	Polygonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO88	Rheum undulatum	Species	Polygonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO88	Rheum undulatum	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
IC50	1
Inhibition	1

Activity Type	# Activity
Organism	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

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT32	Organism	Mus musculus	Mus musculus	IC50	>	100000.0	nM	PMID[20696583]
NPT32	Organism	Mus musculus	Mus musculus	Inhibition	=	6.0	%	PMID[19359068]

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 NPC469661 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	21986
0.1-0.2	22837
0.2-0.3	3782
0.3-0.4	920
0.4-0.5	275
0.5-0.6	42
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
0.7719	Intermediate Similarity	NPC210015
0.7097	Intermediate Similarity	NPC65530
0.6393	Remote Similarity	NPC205054
0.6197	Remote Similarity	NPC147596
0.6029	Remote Similarity	NPC189115
0.6	Remote Similarity	NPC59324
0.5873	Remote Similarity	NPC19470
0.5818	Remote Similarity	NPC197757
0.5571	Remote Similarity	NPC212770
0.5538	Remote Similarity	NPC26080
0.5538	Remote Similarity	NPC165686
0.55	Remote Similarity	NPC9248
0.5484	Remote Similarity	NPC221090
0.5441	Remote Similarity	NPC478871
0.5441	Remote Similarity	NPC478870
0.5441	Remote Similarity	NPC478872
0.5441	Remote Similarity	NPC478873
0.5424	Remote Similarity	NPC484157
0.5362	Remote Similarity	NPC278961
0.5362	Remote Similarity	NPC134260
0.5362	Remote Similarity	NPC113680
0.5362	Remote Similarity	NPC252169
0.5323	Remote Similarity	NPC12308
0.5303	Remote Similarity	NPC214910
0.5303	Remote Similarity	NPC481303
0.5286	Remote Similarity	NPC604095
0.5278	Remote Similarity	NPC177742
0.527	Remote Similarity	NPC191046
0.5254	Remote Similarity	NPC142319
0.5205	Remote Similarity	NPC52277
0.5161	Remote Similarity	NPC60589
0.5161	Remote Similarity	NPC469708
0.5156	Remote Similarity	NPC166168
0.5139	Remote Similarity	NPC210192
0.5139	Remote Similarity	NPC475096
0.5139	Remote Similarity	NPC106944
0.5132	Remote Similarity	NPC199459
0.5132	Remote Similarity	NPC602810
0.5125	Remote Similarity	NPC299706
0.5125	Remote Similarity	NPC115466
0.5125	Remote Similarity	NPC61604
0.5082	Remote Similarity	NPC192810
0.5077	Remote Similarity	NPC40377
0.5077	Remote Similarity	NPC9912
0.5075	Remote Similarity	NPC65942
0.5075	Remote Similarity	NPC248307
0.5072	Remote Similarity	NPC85799
0.5072	Remote Similarity	NPC303422

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC469661 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5215
0.1-0.2	3788
0.2-0.3	134
0.3-0.4	11
0.4-0.5	2
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