NPASS Compound

Natural Product: NPC582377

Natural Product ID	NPC582377
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	[(2~{R},3~{R},4~{S},5~{R},6~{S})-3,4,5-trihydroxy-6-[4-[(2~{S})-7-hydroxy-4-oxo-chroman-2-yl]phenoxy]tetrahydropyran-2-yl]methyl acetate
IUPAC Name	[(2~{R},3~{R},4~{S},5~{R},6~{S})-3,4,5-trihydroxy-6-[4-[(2~{S})-7-hydroxy-4-oxo-chroman-2-yl]phenoxy]tetrahydropyran-2-yl]methyl acetate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic 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 57 60 0 0 0 0 0 0 0 0999 V2000 -4.4318 -3.6390 -0.9485 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9126 -2.2227 -0.7676 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0991 -2.0386 -0.4023 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.0992 -1.1459 -0.9886 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.4325 0.2122 -0.8505 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8108 0.4904 0.5851 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.7605 0.1860 1.3778 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.7793 1.1049 1.5668 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.9018 1.0461 0.5017 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.5718 0.7290 0.6005 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1217 0.4202 1.7444 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4756 0.1067 1.7732 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1942 0.0949 0.6106 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6315 -0.2349 0.6158 C 0 0 2 0 0 0 0 0 0 0 0 0 4.5399 0.9463 0.5999 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7897 0.7668 -0.1457 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5695 1.7261 -0.2666 O 0 0 0 0 0 0 0 0 0 0 0 0 6.1200 -0.5047 -0.7363 C 0 0 0 0 0 0 0 0 0 0 0 0 7.3882 -0.8363 -1.1765 C 0 0 0 0 0 0 0 0 0 0 0 0 7.6685 -2.0648 -1.7377 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6799 -3.0171 -1.8808 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9046 -4.2666 -2.4369 O 0 0 0 0 0 0 0 0 0 0 0 0 5.4155 -2.6847 -1.4411 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1505 -1.4539 -0.8827 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8729 -1.1366 -0.4459 O 0 0 0 0 0 0 0 0 0 0 0 0 1.5410 0.3981 -0.5596 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2093 0.7050 -0.5766 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2440 2.5291 1.6997 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.9033 2.6394 2.9331 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.2231 2.9284 0.6351 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.6653 3.0585 -0.6203 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.3284 1.8948 0.6800 C 0 0 1 0 0 0 0 0 0 0 0 0 -6.3033 2.1129 -0.2681 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.2353 -4.3584 -0.8012 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9741 -3.6966 -1.9686 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6042 -3.7829 -0.2242 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5341 0.7902 -1.1615 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3153 0.4874 -1.4880 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6646 -0.1669 0.8351 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2697 0.8573 2.5091 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4306 0.4209 2.7015 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9494 -0.1251 2.7143 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8380 -0.8217 1.5559 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8295 1.2022 1.6589 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0129 1.8264 0.1540 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1500 -0.0676 -1.0521 H 0 0 0 0 0 0 0 0 0 0 0 0 8.6668 -2.2780 -2.0650 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8730 -4.5488 -2.6184 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6198 -3.4105 -1.5400 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1287 0.3853 -1.4854 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3074 0.9444 -1.5008 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3544 3.1818 1.7530 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6311 1.8931 3.5472 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6749 3.9055 0.9101 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0534 3.8359 -0.5881 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7861 1.9920 1.7086 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0385 2.6843 0.1012 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 2 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 2 0 11 12 1 0 12 13 2 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 2 0 16 18 1 0 18 19 2 0 19 20 1 0 20 21 2 0 21 22 1 0 21 23 1 0 23 24 2 0 24 25 1 0 13 26 1 0 26 27 2 0 8 28 1 0 28 29 1 0 28 30 1 0 30 31 1 0 30 32 1 0 32 33 1 0 32 6 1 0 27 10 1 0 25 14 1 0 24 18 1 0 1 34 1 0 1 35 1 0 1 36 1 0 5 37 1 0 5 38 1 0 6 39 1 1 8 40 1 1 11 41 1 0 12 42 1 0 14 43 1 1 15 44 1 0 15 45 1 0 19 46 1 0 20 47 1 0 22 48 1 0 23 49 1 0 26 50 1 0 27 51 1 0 28 52 1 1 29 53 1 0 30 54 1 1 31 55 1 0 32 56 1 1 33 57 1 0 M END

Standard InCHIKey	HKUBLIRXXFRGKE-QYVMVQNOSA-N
Standard InCHI	InChI=1S/C23H24O10/c1-11(24)30-10-19-20(27)21(28)22(29)23(33-19)31-14-5-2-12(3-6-14)17-9-16(26)15-7-4-13(25)8-18(15)32-17/h2-8,17,19-23,25,27-29H,9-10H2,1H3/t17-,19+,20-,21-,22+,23+/m0/s1
SMILES	CC(=O)OC[C@H]1O[C@@H](OC2=CC=C([C@@H]3CC(=O)C4=CC=C(O)C=C4O3)C=C2)[C@H](O)[C@@H](O)[C@H]1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	460.14	Volume:	438.949 ? Van der Waals volume.
Dense:	1.048	LogP:	0.943 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.356 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.918 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	25.0
TPSA:	151.98 ? Topological Polar Surface Area.	H-Bond Acceptor:	10.0
H-Bond Donor:	4.0	Rings:	4.0
Heavy Atoms:	10.0

MedChem Properties

QED Drug-Likeness Score:	0.473	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.937	Fsp³:	0.391
MCE-18:	85.938 ? 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:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.613	Fluc inhibitor:	0.601 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.134 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.299 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.113	Promiscuous compounds:	0.262

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.077	MDCK Permeability:	-5.013
Pgp-inhibitor:	0.075	Pgp-substrate:	0.468
PAMPA:	0.933 ? 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):	0.005
20% Bioavailability (F20%):	0.018	30% Bioavailability (F30%):	0.54
50% Bioavailability (F50%):	0.913

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.262
Plasma Protein Binding (PPB):	89.345%	Volume Distribution (VD):	-0.255
Fu:	10.308% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.838
OATP1B3 inhibitor:	0.992	BCRP inhibitor:	0.578
BSEP inhibitor:	0.972

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.14
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.49
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.007
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.104
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.992
HLM stability:	0.947 ? 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):

2.566

Half-life (T1/2):

2.927

ADMET: Toxicity

hERG Blockers:	0.089	hERG Blockers (10um):	0.327
Human Hepatotoxicity (H-HT):	0.687	Drug-induced Liver Injury (DILI):	0.92
AMES Toxicity:	0.878	Rat Oral Acute Toxicity:	0.192
Maximum Recommended Daily Dose:	0.172	Skin Sensitization:	0.86
Carcinogencity:	0.205	Eye Corrosion:	0.0
Eye Irritation:	0.51	Respiratory Toxicity:	0.068
Drug-induced Neurotoxicity:	0.191	Ototoxicity:	0.858
Hematotoxicity:	0.153	Drug-induced Nephrotoxicity:	0.869
Genotoxicity:	0.897	RPMI-8226 Immunitoxicity:	0.114
A549 Cytotoxicity:	0.329	Hek293 Cytotoxicity:	0.26
BCF:	0.632 ? 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:	3.321 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.887 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.236 ? 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
NPO7154	Glycyrrhiza uralensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1007/s11164-015-2099-x]
NPO7154	Glycyrrhiza uralensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1134/S1021443711030101]
NPO7154	Glycyrrhiza uralensis	Species	Fabaceae	Eukaryota	n.a.	root	n.a.	PMID[16441081]
NPO7154	Glycyrrhiza uralensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[16675659]
NPO7154	Glycyrrhiza uralensis	Species	Fabaceae	Eukaryota	n.a.	root	n.a.	PMID[22074222]
NPO7154	Glycyrrhiza uralensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[22074222]
NPO7154	Glycyrrhiza uralensis	Species	Fabaceae	Eukaryota	n.a.	rhizome	n.a.	PMID[23867078]
NPO7154	Glycyrrhiza uralensis	Species	Fabaceae	Eukaryota	n.a.	root	n.a.	PMID[23867078]
NPO7154	Glycyrrhiza uralensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[24479468]
NPO7154	Glycyrrhiza uralensis	Species	Fabaceae	Eukaryota	roots	n.a.	n.a.	PMID[24957203]
NPO7154	Glycyrrhiza uralensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[25445757]
NPO7154	Glycyrrhiza uralensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[25744461]
NPO7154	Glycyrrhiza uralensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[26841168]
NPO7154	Glycyrrhiza uralensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[32196343]
NPO7154	Glycyrrhiza uralensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7154	Glycyrrhiza uralensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO7154	Glycyrrhiza uralensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO7154	Glycyrrhiza uralensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO7154	Glycyrrhiza uralensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO7154	Glycyrrhiza uralensis	Species	Fabaceae	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

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

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 NPC582377 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	11711
0.1-0.2	33022
0.2-0.3	4201
0.3-0.4	813
0.4-0.5	84
0.5-0.6	24
0.6-0.7	2
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
0.75	Intermediate Similarity	NPC170475
0.6163	Remote Similarity	NPC472876
0.6047	Remote Similarity	NPC271270
0.5797	Remote Similarity	NPC192229
0.5682	Remote Similarity	NPC200708
0.5682	Remote Similarity	NPC604887
0.5679	Remote Similarity	NPC26195
0.5542	Remote Similarity	NPC43638
0.5506	Remote Similarity	NPC472386
0.5432	Remote Similarity	NPC169248
0.5432	Remote Similarity	NPC72649
0.5385	Remote Similarity	NPC43587
0.5326	Remote Similarity	NPC44328
0.5326	Remote Similarity	NPC79056
0.5301	Remote Similarity	NPC39351
0.5294	Remote Similarity	NPC329225
0.5294	Remote Similarity	NPC147686
0.527	Remote Similarity	NPC479769
0.5269	Remote Similarity	NPC293629
0.5263	Remote Similarity	NPC67134
0.5181	Remote Similarity	NPC291153
0.5161	Remote Similarity	NPC190450
0.5143	Remote Similarity	NPC476480
0.5143	Remote Similarity	NPC84585
0.5119	Remote Similarity	NPC219163
0.5119	Remote Similarity	NPC471457
0.5059	Remote Similarity	NPC206378

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC582377 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3130
0.1-0.2	5846
0.2-0.3	160
0.3-0.4	12
0.4-0.5	0
0.5-0.6	2
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
0.5326	Remote Similarity	NPD7074	Phase 3
0.5294	Remote Similarity	NPD1549	Phase 2

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