Natural Product: NPC564549

Natural Product IDNPC564549
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 3-(1,3-benzodioxol-5-yl)-6-methoxy-7-[(2~{S},3~{S},4~{S},5~{S},6~{R})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-chromen-4-one
IUPAC Name 3-(1,3-benzodioxol-5-yl)-6-methoxy-7-[(2~{S},3~{S},4~{S},5~{S},6~{R})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-chromen-4-one
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

Standard InCHIKey CJHLOIVYCZZNBR-LFDQFFAPSA-N
Standard InCHI InChI=1S/C23H22O11/c1-29-15-5-11-14(6-17(15)33-23-22(28)21(27)20(26)18(7-24)34-23)30-8-12(19(11)25)10-2-3-13-16(4-10)32-9-31-13/h2-6,8,18,20-24,26-28H,7,9H2,1H3/t18-,20-,21+,22+,23-/m1/s1
SMILES COC1=CC2=C(C=C1O[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@@H]1O)OC=C(C1=CC=C3OCOC3=C1)C2=O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   474.12 Volume:   439.183
?
Van der Waals volume.
Dense:   1.08 LogP:   0.805
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.436
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.119
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The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   28.0
TPSA:   157.28
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Topological Polar Surface Area.
 H-Bond Acceptor:   11.0
H-Bond Donor:   4.0 Rings:   5.0
Heavy Atoms:   11.0

MedChem Properties

QED Drug-Likeness Score:   0.405 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.844 Fsp3:   0.348
MCE-18:   98.226
?
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:   0 PAINS Alert:   0
Colloidal aggregators:   0.638 Fluc inhibitor:   0.41
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.93
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.638
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.038 Promiscuous compounds:   0.387

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.925 MDCK Permeability:   -5.22
Pgp-inhibitor:   0.0 Pgp-substrate:   0.135
PAMPA:   0.991
?
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):   0.814
20% Bioavailability (F20%):   0.497 30% Bioavailability (F30%):   0.439
50% Bioavailability (F50%):   0.979

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.007 MRP1:   0.399
Plasma Protein Binding (PPB):   85.789% Volume Distribution (VD):   -0.076
Fu: 13.836%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.995
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.075
BSEP inhibitor:   0.051

ADMET: Metabolism

CYP1A2-inhibitor:   0.614 CYP1A2-substrate:   0.001
CYP2C19-inhibitor:   0.001 CYP2C19-substrate:   0.005
CYP2C9-inhibitor:   0.511 CYP2C9-substrate:   0.068
CYP2D6-inhibitor:   0.002 CYP2D6-substrate:   0.104
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.987
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.166
HLM stability:   0.027
?
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):  2.243 Half-life (T1/2):  3.021

ADMET: Toxicity

hERG Blockers:  0.044 hERG Blockers (10um):  0.096
Human Hepatotoxicity (H-HT):  0.739 Drug-induced Liver Injury (DILI):  0.986
AMES Toxicity:  0.964 Rat Oral Acute Toxicity:  0.126
Maximum Recommended Daily Dose:  0.182 Skin Sensitization:  0.989
Carcinogencity:  0.794 Eye Corrosion:  0.0
Eye Irritation:  0.145 Respiratory Toxicity:  0.109
Drug-induced Neurotoxicity:  0.164 Ototoxicity:  0.885
Hematotoxicity:  0.803 Drug-induced Nephrotoxicity:  0.876
Genotoxicity:  0.879 RPMI-8226 Immunitoxicity:  0.278
A549 Cytotoxicity:  0.775 Hek293 Cytotoxicity:  0.55
BCF:   0.484
?
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:   3.211
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.805
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.918
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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
NPO10942 Retama sphaerocarpa Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[38847466]
NPO23436 Cladrastis sikokiana Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10942 Retama sphaerocarpa Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23436 Cladrastis sikokiana Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10942 Retama sphaerocarpa 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
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 NPC564549 and all remaining natural products in the NPASS database.
●  The right table: Most similar natural products (Tc>=0.5 or Top200).

Similarity Score Similarity Level Natural Product ID
0.8158 Intermediate Similarity NPC601607
0.8082 Intermediate Similarity NPC135345
0.7403 Intermediate Similarity NPC105511
0.6714 Remote Similarity NPC148497
0.6709 Remote Similarity NPC45165
0.6235 Remote Similarity NPC229729
0.622 Remote Similarity NPC259070
0.5977 Remote Similarity NPC307518
0.5952 Remote Similarity NPC161749
0.5952 Remote Similarity NPC603782
0.5909 Remote Similarity NPC48773
0.5882 Remote Similarity NPC73511
0.5814 Remote Similarity NPC205076
0.5765 Remote Similarity NPC258035
0.5747 Remote Similarity NPC224462
0.5658 Remote Similarity NPC602183
0.557 Remote Similarity NPC260640
0.5568 Remote Similarity NPC481043
0.5556 Remote Similarity NPC195919
0.5556 Remote Similarity NPC479407
0.5455 Remote Similarity NPC100720
0.5402 Remote Similarity NPC156457
0.5393 Remote Similarity NPC474442
0.5357 Remote Similarity NPC25547
0.5301 Remote Similarity NPC38438
0.5275 Remote Similarity NPC607201
0.525 Remote Similarity NPC96294
0.5227 Remote Similarity NPC197896
0.5227 Remote Similarity NPC313163
0.5222 Remote Similarity NPC479402
0.5161 Remote Similarity NPC129930
0.5056 Remote Similarity NPC234739
0.5055 Remote Similarity NPC479401
0.5055 Remote Similarity NPC609451

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC564549 and all drugs/candidates.
●  The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

Similarity Score Similarity Level Drug ID Developmental Stage
0.5952 Remote Similarity NPD4381 Clinical (unspecified phase)

Bioactivity similarity

  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