Natural Product: NPC179970

Natural Product IDNPC179970
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Munetone
IUPAC Name 7-(5-methoxy-2,2-dimethylchromen-6-yl)-2,2-dimethylpyrano[3,2-g]chromen-6-one
Synonyms Munetone
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL463492
PubChem CID 12312999
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002506] Isoflavonoids
        • [CHEMONTID:0001612] Isoflavans
          • [CHEMONTID:0001827] Isoflavanones
            • [CHEMONTID:0003526] 6-prenylated isoflavanones

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 JANOATQYNVFIDV-UHFFFAOYSA-N
Standard InCHI InChI=1S/C26H24O5/c1-25(2)10-8-15-12-18-22(13-21(15)31-25)29-14-19(23(18)27)16-6-7-20-17(24(16)28-5)9-11-26(3,4)30-20/h6-14H,1-5H3
SMILES COc1c2C=CC(Oc2ccc1c1coc2c(c1=O)cc1c(c2)OC(C=C1)(C)C)(C)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   416.16 Volume:   433.056
?
Van der Waals volume.
Dense:   0.961 LogP:   4.909
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.945
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.733
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   28.0
TPSA:   57.9
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   0.0 Rings:   5.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.525 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.265 Fsp3:   0.269
MCE-18:   65.758
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.971 Fluc inhibitor:   0.769
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.831
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.75
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.393 Promiscuous compounds:   0.533

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.757 MDCK Permeability:   -4.737
Pgp-inhibitor:   0.92 Pgp-substrate:   0.003
PAMPA:   0.234
?
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):   0.008
20% Bioavailability (F20%):   0.642 30% Bioavailability (F30%):   0.845
50% Bioavailability (F50%):   0.991

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.354 MRP1:   0.888
Plasma Protein Binding (PPB):   98.162% Volume Distribution (VD):   0.255
Fu: 1.469%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.996
OATP1B3 inhibitor:   0.994 BCRP inhibitor:   0.99
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.004 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.098 CYP2C19-substrate:   0.976
CYP2C9-inhibitor:   0.352 CYP2C9-substrate:   0.015
CYP2D6-inhibitor:   0.002 CYP2D6-substrate:   0.877
CYP3A4-inhibitor:   0.04 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.002 CYP2C8-inhibitor:   1.0
HLM stability:   0.939
?
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):  5.57 Half-life (T1/2):  0.624

ADMET: Toxicity

hERG Blockers:  0.324 hERG Blockers (10um):  0.575
Human Hepatotoxicity (H-HT):  0.568 Drug-induced Liver Injury (DILI):  0.732
AMES Toxicity:  0.743 Rat Oral Acute Toxicity:  0.771
Maximum Recommended Daily Dose:  0.793 Skin Sensitization:  0.202
Carcinogencity:  0.922 Eye Corrosion:  0.001
Eye Irritation:  0.623 Respiratory Toxicity:  0.904
Drug-induced Neurotoxicity:  0.586 Ototoxicity:  0.431
Hematotoxicity:  0.288 Drug-induced Nephrotoxicity:  0.383
Genotoxicity:  0.49 RPMI-8226 Immunitoxicity:  0.123
A549 Cytotoxicity:  0.086 Hek293 Cytotoxicity:  0.416
BCF:   2.108
?
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:   4.865
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   7.038
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   6.573
?
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
NPO10386 Mundulea chapelieri Species Fabaceae Eukaryota bark an elevation of 850 m (171725? S; 484030? E), Toamasina, Madagascar 2002-JAN PMID[15043430]
NPO10386 Mundulea chapelieri Species Fabaceae Eukaryota n.a. leaf n.a. PMID[15043430]
NPO10386 Mundulea chapelieri Species Fabaceae Eukaryota n.a. flower n.a. PMID[15043430]
NPO10386 Mundulea chapelieri Species Fabaceae Eukaryota n.a. bark n.a. PMID[15043430]
NPO14197 Patrinia scabra Species Caprifoliaceae Eukaryota Roots n.a. n.a. PMID[23002924]
NPO14197 Patrinia scabra Species Caprifoliaceae Eukaryota Roots n.a. n.a. PMID[29799195]
NPO10386 Mundulea chapelieri Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14197 Patrinia scabra Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO14197 Patrinia scabra Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14502 Pogonolepis muelleriana Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10386 Mundulea chapelieri Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9663 Artemisia igniaria Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14197 Patrinia scabra Species Caprifoliaceae 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
NPT179 Cell line A2780 Homo sapiens IC50 = 20.0 ug.mL-1 PMID[15043430]

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 NPC179970 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
0.7538 Intermediate Similarity NPC488135
0.7397 Intermediate Similarity NPC477530
0.6667 Remote Similarity NPC5840
0.6364 Remote Similarity NPC78071
0.5185 Remote Similarity NPC229847
0.5135 Remote Similarity NPC607923
0.5065 Remote Similarity NPC128961
0.506 Remote Similarity NPC189270

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC179970 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
NPD

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