Natural Product: NPC88645

Natural Product IDNPC88645
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 5-Hydroxy-1,3-Dimethoxyxanthone
IUPAC Name 4-hydroxy-2,3-dimethoxyxanthen-9-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3814641
PubChem CID 378690
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

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 HWDHDJJDOUMUHF-UHFFFAOYSA-N
Standard InCHI InChI=1S/C15H12O5/c1-18-11-7-9-12(16)8-5-3-4-6-10(8)20-14(9)13(17)15(11)19-2/h3-7,17H,1-2H3
SMILES COc1cc2c(c(c1OC)O)oc1c(c2=O)cccc1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   272.07 Volume:   267.823
?
Van der Waals volume.
Dense:   1.016 LogP:   2.023
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.157
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.683
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   17.0
TPSA:   68.9
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.726 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.165 Fsp3:   0.133
MCE-18:   17.0
?
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:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.193 Fluc inhibitor:   0.792
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.855
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.419
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.419 Promiscuous compounds:   0.485

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.912 MDCK Permeability:   -4.679
Pgp-inhibitor:   0.844 Pgp-substrate:   0.192
PAMPA:   0.067
?
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):   0.092
20% Bioavailability (F20%):   0.152 30% Bioavailability (F30%):   0.313
50% Bioavailability (F50%):   0.748

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.203 MRP1:   0.787
Plasma Protein Binding (PPB):   96.982% Volume Distribution (VD):   -0.483
Fu: 3.685%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.918
OATP1B3 inhibitor:   0.985 BCRP inhibitor:   0.823
BSEP inhibitor:   0.942

ADMET: Metabolism

CYP1A2-inhibitor:   0.995 CYP1A2-substrate:   0.17
CYP2C19-inhibitor:   0.822 CYP2C19-substrate:   0.274
CYP2C9-inhibitor:   0.27 CYP2C9-substrate:   0.009
CYP2D6-inhibitor:   0.588 CYP2D6-substrate:   0.668
CYP3A4-inhibitor:   0.397 CYP3A4-substrate:   0.169
CYP2B6-substrate:   0.019 CYP2C8-inhibitor:   0.785
HLM stability:   0.93
?
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):  4.242 Half-life (T1/2):  1.457

ADMET: Toxicity

hERG Blockers:  0.101 hERG Blockers (10um):  0.466
Human Hepatotoxicity (H-HT):  0.507 Drug-induced Liver Injury (DILI):  0.862
AMES Toxicity:  0.566 Rat Oral Acute Toxicity:  0.499
Maximum Recommended Daily Dose:  0.417 Skin Sensitization:  0.568
Carcinogencity:  0.755 Eye Corrosion:  0.307
Eye Irritation:  0.964 Respiratory Toxicity:  0.59
Drug-induced Neurotoxicity:  0.29 Ototoxicity:  0.18
Hematotoxicity:  0.386 Drug-induced Nephrotoxicity:  0.171
Genotoxicity:  0.436 RPMI-8226 Immunitoxicity:  0.072
A549 Cytotoxicity:  0.135 Hek293 Cytotoxicity:  0.246
BCF:   1.041
?
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:   3.759
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.81
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.321
?
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
NPO26234 Annona muricata Species Annonaceae Eukaryota n.a. n.a. n.a. PMID[11473425]
NPO26234 Annona muricata Species Annonaceae Eukaryota n.a. n.a. n.a. PMID[11975482]
NPO22748 Neophaeosphaeria quadriseptata Species Leptosphaeriaceae Eukaryota n.a. n.a. n.a. PMID[16499313]
NPO24232 Boehmeria pannosa Species Urticaceae Eukaryota roots n.a. n.a. PMID[16872154]
NPO26529 Hypericum oblongifolium Species Hypericaceae Eukaryota n.a. whole plant n.a. PMID[16880649]
NPO26234 Annona muricata Species Annonaceae Eukaryota n.a. stem n.a. PMID[17401878]
NPO26234 Annona muricata Species Annonaceae Eukaryota n.a. leaf n.a. PMID[17401878]
NPO26234 Annona muricata Species Annonaceae Eukaryota n.a. root n.a. PMID[17401878]
NPO40174 Kielmeyera variabilis Species Calophyllaceae Eukaryota n.a. n.a. n.a. PMID[26900954]
NPO26234 Annona muricata Species Annonaceae Eukaryota Leaves n.a. n.a. PMID[7494150]
NPO26234 Annona muricata Species Annonaceae Eukaryota Leaves n.a. n.a. PMID[7673926]
NPO26234 Annona muricata Species Annonaceae Eukaryota Leaves n.a. n.a. PMID[7673935]
NPO26234 Annona muricata Species Annonaceae Eukaryota Leaves n.a. n.a. PMID[7673936]
NPO26234 Annona muricata Species Annonaceae Eukaryota leaves n.a. n.a. PMID[8946744]
NPO26234 Annona muricata Species Annonaceae Eukaryota seeds n.a. n.a. PMID[8991944]
NPO26234 Annona muricata Species Annonaceae Eukaryota Leaves n.a. n.a. PMID[9584396]
NPO26315 Trikentrion flabelliforme Species Raspailiidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26529 Hypericum oblongifolium Species Hypericaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4308 Pericome caudata Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26234 Annona muricata Species Annonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26234 Annona muricata Species Annonaceae Eukaryota n.a. n.a. Database[FooDB]
NPO26234 Annona muricata Species Annonaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO26234 Annona muricata Species Annonaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO26234 Annona muricata Species Annonaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO26234 Annona muricata Species Annonaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO26315 Trikentrion flabelliforme Species Raspailiidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26234 Annona muricata Species Annonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25943 Cirsium carolinianum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26529 Hypericum oblongifolium Species Hypericaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25812 Dipentodon sinicus Species Dipentodontaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24232 Boehmeria pannosa Species Urticaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3170 Piper lanceifolium Species Piperaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22748 Neophaeosphaeria quadriseptata Species Leptosphaeriaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4308 Pericome caudata Species Asteraceae 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
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 64.0 ug.mL-1 PMID[26900954]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 128.0 ug.mL-1 PMID[26900954]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC > 512.0 ug.mL-1 PMID[26900954]
NPT1101 Organism Staphylococcus aureus subsp. aureus RN4220 Staphylococcus aureus subsp. aureus RN4220 MIC > 512.0 ug.mL-1 PMID[26900954]

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 NPC88645 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
0.7143 Intermediate Similarity NPC17055
0.6923 Remote Similarity NPC271232
0.6226 Remote Similarity NPC294502
0.62 Remote Similarity NPC231013
0.6154 Remote Similarity NPC292214
0.5926 Remote Similarity NPC271779
0.5741 Remote Similarity NPC608745
0.5686 Remote Similarity NPC600210
0.5686 Remote Similarity NPC605893
0.56 Remote Similarity NPC606736
0.5556 Remote Similarity NPC200221
0.5556 Remote Similarity NPC610896
0.5472 Remote Similarity NPC608827
0.5345 Remote Similarity NPC244371
0.5294 Remote Similarity NPC278787
0.5227 Remote Similarity NPC475269
0.5227 Remote Similarity NPC35744
0.5088 Remote Similarity NPC11158

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC88645 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