Natural Product: NPC83922

Natural Product IDNPC83922
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Manglexanthone
IUPAC Name 5,8-dihydroxy-9-methoxy-2,2-dimethyl-10-(3-methylbut-2-enyl)pyrano[3,2-b]xanthen-6-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2437088
PubChem CID 10001484
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000123] Benzopyrans
        • [CHEMONTID:0003410] 1-benzopyrans
          • [CHEMONTID:0002817] Dibenzopyrans
            • [CHEMONTID:0000200] Xanthenes
              • [CHEMONTID:0000204] Xanthones
                • [CHEMONTID:0003518] 4-prenylated xanthones

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 IGOVDGFRUNTYAS-UHFFFAOYSA-N
Standard InCHI InChI=1S/C24H24O6/c1-12(2)6-7-14-22-15(10-16(25)23(14)28-5)21(27)19-18(29-22)11-17-13(20(19)26)8-9-24(3,4)30-17/h6,8-11,25-26H,7H2,1-5H3
SMILES COc1c(O)cc2c(c1CC=C(C)C)oc1c(c2=O)c(O)c2c(c1)OC(C=C2)(C)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   408.16 Volume:   418.447
?
Van der Waals volume.
Dense:   0.975 LogP:   4.854
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.798
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.43
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   23.0
TPSA:   89.13
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   2.0 Rings:   4.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.465 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.279 Fsp3:   0.292
MCE-18:   55.742
?
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:   0.862 Fluc inhibitor:   0.631
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.864
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.812
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.218 Promiscuous compounds:   0.222

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.015 MDCK Permeability:   -4.678
Pgp-inhibitor:   0.802 Pgp-substrate:   0.01
PAMPA:   0.738
?
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):   0.055
20% Bioavailability (F20%):   0.968 30% Bioavailability (F30%):   0.996
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.004 MRP1:   0.982
Plasma Protein Binding (PPB):   96.414% Volume Distribution (VD):   0.09
Fu: 3.175%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   0.997 BCRP inhibitor:   0.982
BSEP inhibitor:   0.998

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.994 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.043 CYP2C9-substrate:   0.307
CYP2D6-inhibitor:   0.012 CYP2D6-substrate:   0.111
CYP3A4-inhibitor:   0.361 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   1.0
?
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):  3.968 Half-life (T1/2):  1.154

ADMET: Toxicity

hERG Blockers:  0.045 hERG Blockers (10um):  0.528
Human Hepatotoxicity (H-HT):  0.481 Drug-induced Liver Injury (DILI):  0.684
AMES Toxicity:  0.64 Rat Oral Acute Toxicity:  0.826
Maximum Recommended Daily Dose:  0.719 Skin Sensitization:  0.902
Carcinogencity:  0.658 Eye Corrosion:  0.001
Eye Irritation:  0.669 Respiratory Toxicity:  0.972
Drug-induced Neurotoxicity:  0.158 Ototoxicity:  0.2
Hematotoxicity:  0.183 Drug-induced Nephrotoxicity:  0.221
Genotoxicity:  0.87 RPMI-8226 Immunitoxicity:  0.074
A549 Cytotoxicity:  0.219 Hek293 Cytotoxicity:  0.624
BCF:   1.932
?
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:   4.79
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.692
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   6.032
?
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
NPO22497 Picrasma javanica Species Simaroubaceae Eukaryota n.a. n.a. n.a. PMID[26606140]
NPO21218 Salvia aegyptiaca Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22435 Abies lasiocarpa Species Pinaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21218 Salvia aegyptiaca Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO22370 Baccharis calvescens Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20085 Solenopsis xyloni Species Formicidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5221 Thamnolia subuliformis Species Icmadophilaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3555 Cavernularia obesa Species Veretillidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22435 Abies lasiocarpa Species Pinaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22497 Picrasma javanica Species Simaroubaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21652 Decarya madagascariensis Species Didiereaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20963 Sarcopyramis bodinieri Species Melastomataceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21218 Salvia aegyptiaca Species Lamiaceae 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
NPT91 Cell line KB Homo sapiens IC50 = 1900.0 nM PMID[24113365]

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 NPC83922 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
0.6892 Remote Similarity NPC275780
0.6575 Remote Similarity NPC70272
0.6533 Remote Similarity NPC229632
0.6447 Remote Similarity NPC207690
0.6447 Remote Similarity NPC472450
0.6164 Remote Similarity NPC101957
0.6133 Remote Similarity NPC16492
0.6104 Remote Similarity NPC178964
0.6081 Remote Similarity NPC200246
0.6026 Remote Similarity NPC471973
0.5952 Remote Similarity NPC39091
0.5946 Remote Similarity NPC479166
0.5867 Remote Similarity NPC6633
0.5789 Remote Similarity NPC479165
0.575 Remote Similarity NPC472276
0.575 Remote Similarity NPC204879
0.5733 Remote Similarity NPC36852
0.5679 Remote Similarity NPC239752
0.5542 Remote Similarity NPC481612
0.5526 Remote Similarity NPC166054
0.5465 Remote Similarity NPC472449
0.5422 Remote Similarity NPC472448
0.5375 Remote Similarity NPC29876
0.5309 Remote Similarity NPC103238
0.5185 Remote Similarity NPC306321
0.5176 Remote Similarity NPC78803
0.5135 Remote Similarity NPC473076
0.5132 Remote Similarity NPC255133

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC83922 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