Natural Product: NPC303460

Natural Product IDNPC303460
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 1,3,7-Trihydroxy-4-(1,1-Dimethyl-2-Propenyl)-5,6-(2,2-Dimethylchromeno) Xanthone
IUPAC Name 5,8,10-trihydroxy-3,3-dimethyl-11-(2-methylbut-3-en-2-yl)pyrano[2,3-c]xanthen-7-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL440392
PubChem CID 44405880
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:0003521] Pyranoxanthones

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 VDIZUJPZYMJMRS-UHFFFAOYSA-N
Standard InCHI InChI=1S/C23H22O6/c1-6-22(2,3)17-14(25)10-13(24)16-18(27)12-9-15(26)20-11(19(12)28-21(16)17)7-8-23(4,5)29-20/h6-10,24-26H,1H2,2-5H3
SMILES C=CC(c1c(O)cc(c2c1oc1c3C=CC(Oc3c(cc1c2=O)O)(C)C)O)(C)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   394.14 Volume:   401.152
?
Van der Waals volume.
Dense:   0.983 LogP:   3.953
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.18
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.816
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   23.0
TPSA:   100.13
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   3.0 Rings:   4.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.43 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.538 Fsp3:   0.261
MCE-18:   60.0
?
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:   0.855 Fluc inhibitor:   0.272
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.73
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.84
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.348 Promiscuous compounds:   0.253

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.104 MDCK Permeability:   -4.752
Pgp-inhibitor:   0.492 Pgp-substrate:   0.154
PAMPA:   0.615
?
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):   0.01
20% Bioavailability (F20%):   0.939 30% Bioavailability (F30%):   0.998
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.008 MRP1:   0.971
Plasma Protein Binding (PPB):   97.807% Volume Distribution (VD):   0.036
Fu: 2.087%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.997
OATP1B3 inhibitor:   0.939 BCRP inhibitor:   0.994
BSEP inhibitor:   0.996

ADMET: Metabolism

CYP1A2-inhibitor:   0.002 CYP1A2-substrate:   0.996
CYP2C19-inhibitor:   0.709 CYP2C19-substrate:   0.548
CYP2C9-inhibitor:   0.94 CYP2C9-substrate:   0.027
CYP2D6-inhibitor:   0.006 CYP2D6-substrate:   0.991
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.979
CYP2B6-substrate:   0.002 CYP2C8-inhibitor:   1.0
HLM stability:   0.991
?
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):  2.162 Half-life (T1/2):  1.564

ADMET: Toxicity

hERG Blockers:  0.036 hERG Blockers (10um):  0.501
Human Hepatotoxicity (H-HT):  0.393 Drug-induced Liver Injury (DILI):  0.804
AMES Toxicity:  0.521 Rat Oral Acute Toxicity:  0.795
Maximum Recommended Daily Dose:  0.796 Skin Sensitization:  0.851
Carcinogencity:  0.76 Eye Corrosion:  0.033
Eye Irritation:  0.977 Respiratory Toxicity:  0.955
Drug-induced Neurotoxicity:  0.068 Ototoxicity:  0.229
Hematotoxicity:  0.115 Drug-induced Nephrotoxicity:  0.102
Genotoxicity:  0.793 RPMI-8226 Immunitoxicity:  0.117
A549 Cytotoxicity:  0.294 Hek293 Cytotoxicity:  0.607
BCF:   1.75
?
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:   4.435
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.449
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.593
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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
NPO30804 Cudrania tricuspidata Species Moraceae Eukaryota n.a. n.a. n.a. PMID[15787460]
NPO30804 Cudrania tricuspidata Species Moraceae Eukaryota n.a. root n.a. PMID[15787460]
NPO30804 Cudrania tricuspidata Species Moraceae Eukaryota n.a. n.a. n.a. PMID[16203143]
NPO30804 Cudrania tricuspidata Species Moraceae Eukaryota n.a. n.a. n.a. PMID[16919944]
NPO30804 Cudrania tricuspidata Species Moraceae Eukaryota root bark n.a. n.a. PMID[17608532]
NPO30804 Cudrania tricuspidata Species Moraceae Eukaryota n.a. n.a. n.a. PMID[17950599]
NPO30804 Cudrania tricuspidata Species Moraceae Eukaryota fruits n.a. n.a. PMID[19113968]
NPO30804 Cudrania tricuspidata Species Moraceae Eukaryota Roots n.a. n.a. PMID[19191562]
NPO30804 Cudrania tricuspidata Species Moraceae Eukaryota n.a. root n.a. PMID[19280148]
NPO30804 Cudrania tricuspidata Species Moraceae Eukaryota n.a. n.a. n.a. PMID[19285413]
NPO30804 Cudrania tricuspidata Species Moraceae Eukaryota n.a. n.a. n.a. PMID[19660948]
NPO30804 Cudrania tricuspidata Species Moraceae Eukaryota n.a. root n.a. PMID[21319773]
NPO30804 Cudrania tricuspidata Species Moraceae Eukaryota Roots n.a. n.a. PMID[25322455]
NPO30804 Cudrania tricuspidata Species Moraceae Eukaryota root barks purchased from the local herbal market, Chungbuk, Korea 2012-JUL PMID[26227773]
NPO30804 Cudrania tricuspidata Species Moraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO30804 Cudrania tricuspidata Species Moraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO30804 Cudrania tricuspidata Species Moraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]

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
NPT1214 Individual protein Acyl coenzyme A:cholesterol acyltransferase 1 Homo sapiens IC50 = 40000.0 nM PMID[17665951]
NPT2584 Individual protein Acyl coenzyme A:cholesterol acyltransferase 2 Homo sapiens IC50 = 28800.0 nM PMID[11325244]
NPT344 Individual protein Sialidase Clostridium perfringens Inhibition = 30.0 % PMID[21134751]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT1 Others Radical scavenging activity n.a. IC50 < 200000.0 nM PMID[21736388]
NPT1 Others Radical scavenging activity n.a. IC50 = 64500.0 nM Open TG-GATES in vivo data: Hematology
NPT1 Others Radical scavenging activity n.a. IC50 = 55500.0 nM DOI[10.6019/CHEMBL1201861]
NPT614 Tissue Plasma Rattus norvegicus IC50 = 12600.0 nM PMID[17417907]
NPT2 Others Unspecified n.a. IC50 = 24900.0 nM PMID[8021914]

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 NPC303460 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
0.7059 Intermediate Similarity NPC306321
0.6667 Remote Similarity NPC236488
0.5867 Remote Similarity NPC472276
0.5844 Remote Similarity NPC481612
0.5735 Remote Similarity NPC180011
0.5584 Remote Similarity NPC78332
0.5455 Remote Similarity NPC79053
0.5278 Remote Similarity NPC259456
0.5205 Remote Similarity NPC36852
0.5195 Remote Similarity NPC603436

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC303460 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