NPASS Compound

Natural Product: NPC94179

Natural Product ID	NPC94179
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(3R)-1,7-Bis-(3,4-Dihydroxyphenyl)-3-Heptanol-3-O-Beta-D-Xylopyranoside
IUPAC Name	(2S,3R,4S,5R)-2-[(3R)-1,7-bis(3,4-dihydroxyphenyl)heptan-3-yl]oxyoxane-3,4,5-triol
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1774775
PubChem CID	24011643
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0002650] Diarylheptanoids [CHEMONTID:0002651] Linear diarylheptanoids

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 65 67 0 0 0 0 0 0 0 0999 V2000 -5.1232 -3.5992 -1.9711 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.4065 -2.9812 -0.9795 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.6413 -1.4872 -0.9244 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0239 -0.9102 0.1800 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6169 -1.0605 0.0997 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.3126 -2.5604 0.1764 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.9087 -3.1649 -1.1032 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.5639 -4.5190 -1.1668 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.9938 -2.8744 0.2016 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.9769 -0.4245 1.0927 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0538 0.5552 0.8542 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.3582 1.8697 1.4601 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5961 2.5087 0.9556 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5666 2.9148 -0.4679 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0848 2.1506 -1.4664 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9989 2.5963 -2.7931 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4062 3.7882 -3.1301 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8816 4.5660 -2.1310 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9697 4.1227 -0.8391 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2693 5.7886 -2.4343 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.3102 4.2473 -4.4308 O 0 0 0 0 0 0 0 0 0 0 0 0 0.3625 0.0816 1.1833 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4179 1.1036 0.9597 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7671 0.5241 1.3110 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1300 -0.6653 0.4910 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4954 -1.0960 0.9501 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6383 -2.0088 1.9763 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9077 -2.3837 2.3745 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0512 -1.8726 1.7763 C 0 0 0 0 0 0 0 0 0 0 0 0 6.8927 -0.9612 0.7520 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6212 -0.5929 0.3613 C 0 0 0 0 0 0 0 0 0 0 0 0 8.0152 -0.4196 0.1197 O 0 0 0 0 0 0 0 0 0 0 0 0 8.3030 -2.2883 2.2207 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.5555 -4.3318 -2.3420 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6895 -3.3936 0.0146 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1596 -1.0579 -1.8268 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7124 -1.2240 -0.9858 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3439 -0.7567 -0.9280 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9190 -2.9654 1.0063 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4823 -2.6177 -1.9700 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2242 -5.0901 -0.6906 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8236 -3.5499 0.8970 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0210 0.6886 -0.2692 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2927 1.8699 2.5763 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4976 2.5592 1.1689 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4856 1.8262 1.0603 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8022 3.4389 1.5370 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5819 1.2150 -1.3191 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4079 1.9928 -3.5858 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5574 4.7301 -0.0350 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2767 5.9373 -2.3587 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9073 4.9979 -4.7480 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4379 -0.3017 2.2166 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6261 -0.7863 0.5098 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4890 1.4512 -0.0932 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3255 2.0149 1.5976 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7771 0.1906 2.3831 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5658 1.3156 1.2728 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2056 -0.4532 -0.5941 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4386 -1.5284 0.6153 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7409 -2.4169 2.4538 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0218 -3.0987 3.1783 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4983 0.1270 -0.4479 H 0 0 0 0 0 0 0 0 0 0 0 0 8.0280 0.5805 -0.0188 H 0 0 0 0 0 0 0 0 0 0 0 0 9.0468 -2.3110 1.5091 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 6 9 1 0 5 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 2 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 2 0 18 20 1 0 17 21 1 0 11 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 26 27 2 0 27 28 1 0 28 29 2 0 29 30 1 0 30 31 2 0 30 32 1 0 29 33 1 0 7 2 1 0 19 14 1 0 31 26 1 0 1 34 1 0 2 35 1 1 3 36 1 0 3 37 1 0 5 38 1 6 6 39 1 1 7 40 1 6 8 41 1 0 9 42 1 0 11 43 1 6 12 44 1 0 12 45 1 0 13 46 1 0 13 47 1 0 15 48 1 0 16 49 1 0 19 50 1 0 20 51 1 0 21 52 1 0 22 53 1 0 22 54 1 0 23 55 1 0 23 56 1 0 24 57 1 0 24 58 1 0 25 59 1 0 25 60 1 0 27 61 1 0 28 62 1 0 31 63 1 0 32 64 1 0 33 65 1 0 M END

Standard InCHIKey	PVCSOVFCVIEUFH-IGCYBFCNSA-N
Standard InCHI	InChI=1S/C24H32O9/c25-17-9-6-14(11-19(17)27)3-1-2-4-16(8-5-15-7-10-18(26)20(28)12-15)33-24-23(31)22(30)21(29)13-32-24/h6-7,9-12,16,21-31H,1-5,8,13H2/t16-,21-,22+,23-,24+/m1/s1
SMILES	O[C@@H]1CO[C@H]([C@@H]([C@H]1O)O)O[C@@H](CCc1ccc(c(c1)O)O)CCCCc1ccc(c(c1)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	464.2	Volume:	461.284 ? Van der Waals volume.
Dense:	1.006	LogP:	1.683 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.901 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.93 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	10.0	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:	0.205	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.961	Fsp³:	0.5
MCE-18:	65.556 ? 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:	1
Colloidal aggregators:	0.536	Fluc inhibitor:	0.404 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.044 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.219 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.177	Promiscuous compounds:	0.133

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.88	MDCK Permeability:	-5.08
Pgp-inhibitor:	0.001	Pgp-substrate:	0.126
PAMPA:	0.533 ? 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):	0.041
20% Bioavailability (F20%):	0.989	30% Bioavailability (F30%):	1.0
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.129
Plasma Protein Binding (PPB):	86.109%	Volume Distribution (VD):	-0.357
Fu:	11.849% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.996
OATP1B3 inhibitor:	0.991	BCRP inhibitor:	0.546
BSEP inhibitor:	0.209

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.003
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.111	CYP2D6-substrate:	0.994
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.987
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.999
HLM stability:	0.921 ? 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):

6.081

Half-life (T1/2):

2.003

ADMET: Toxicity

hERG Blockers:	0.205	hERG Blockers (10um):	0.825
Human Hepatotoxicity (H-HT):	0.34	Drug-induced Liver Injury (DILI):	0.451
AMES Toxicity:	0.614	Rat Oral Acute Toxicity:	0.079
Maximum Recommended Daily Dose:	0.419	Skin Sensitization:	1.0
Carcinogencity:	0.059	Eye Corrosion:	0.011
Eye Irritation:	0.597	Respiratory Toxicity:	0.124
Drug-induced Neurotoxicity:	0.001	Ototoxicity:	0.976
Hematotoxicity:	0.06	Drug-induced Nephrotoxicity:	0.108
Genotoxicity:	0.014	RPMI-8226 Immunitoxicity:	0.013
A549 Cytotoxicity:	0.996	Hek293 Cytotoxicity:	0.67
BCF:	1.72 ? 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:	4.771 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.981 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.368 ? 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
NPO4971	Alnus firma	Species	Betulaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21504848]
NPO32876	alnus hirsuta f. sibirica	Species	Betulaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[23465614]
NPO4971	Alnus firma	Species	Betulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO32876	alnus hirsuta f. sibirica	Species	Betulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO4971	Alnus firma	Species	Betulaceae	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
Inhibition	6
IC50	4
Activity	3

Activity Type	# Activity
Cell line	9
No target	2
Non-molecular	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
NPT520	Cell line	3T3-L1	Mus musculus	Activity	=	97.0	%	PubChem BioAssay data set
NPT520	Cell line	3T3-L1	Mus musculus	Activity	=	110.8	%	PMID[21044847]
NPT520	Cell line	3T3-L1	Mus musculus	Activity	=	93.2	%	PMID[12398540]
NPT113	Cell line	RAW264.7	Mus musculus	IC50	=	38900.0	nM	PMID[33422907]
NPT113	Cell line	RAW264.7	Mus musculus	Inhibition	=	20.8	%	PMID[33422907]
NPT113	Cell line	RAW264.7	Mus musculus	Inhibition	=	7.7	%	PMID[33422907]
NPT113	Cell line	RAW264.7	Mus musculus	Inhibition	=	28.0	%	PMID[33422907]
NPT113	Cell line	RAW264.7	Mus musculus	Inhibition	=	12.5	%	PMID[33422907]
NPT113	Cell line	RAW264.7	Mus musculus	Inhibition	=	4.2	%	PMID[33422907]
NPT28833	No target	No relevant target	n.a.	IC50	=	38900.0	nM	PMID[33422907]
NPT28833	No target	No relevant target	n.a.	IC50	=	8700.0	nM	PMID[33422907]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Inhibition	=	22.7	%	PMID[21504848]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	>	100000.0	nM	PMID[21504848]

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 NPC94179 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	12861
0.1-0.2	33160
0.2-0.3	3535
0.3-0.4	239
0.4-0.5	40
0.5-0.6	12
0.6-0.7	5
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
0.7458	Intermediate Similarity	NPC103398
0.7458	Intermediate Similarity	NPC608691
0.7333	Intermediate Similarity	NPC264900
0.6984	Remote Similarity	NPC158325
0.6984	Remote Similarity	NPC193018
0.6812	Remote Similarity	NPC184092
0.6769	Remote Similarity	NPC180171
0.6032	Remote Similarity	NPC158673
0.5938	Remote Similarity	NPC201402
0.5882	Remote Similarity	NPC476407
0.5857	Remote Similarity	NPC471067
0.5645	Remote Similarity	NPC200988
0.5645	Remote Similarity	NPC145023
0.5541	Remote Similarity	NPC232454
0.5541	Remote Similarity	NPC470907
0.5541	Remote Similarity	NPC178449
0.5522	Remote Similarity	NPC293686
0.5294	Remote Similarity	NPC231607
0.5156	Remote Similarity	NPC602133
0.5072	Remote Similarity	NPC469686

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC94179 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4075
0.1-0.2	4967
0.2-0.3	102
0.3-0.4	6
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