Natural Product: NPC55662

Natural Product IDNPC55662
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 BELWAPDLROYTBA-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3327039
PubChem CID n.a.
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 BELWAPDLROYTBA-UHFFFAOYSA-N
Standard InCHI InChI=1S/C23H20O5/c1-22(2)9-7-12-15(27-22)5-6-16-18(12)20(25)19-14(24)11-17-13(21(19)26-16)8-10-23(3,4)28-17/h5-11,24H,1-4H3
SMILES Oc1cc2OC(C)(C)C=Cc2c2c1c(=O)c1c(o2)ccc2c1C=CC(O2)(C)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   376.13 Volume:   383.805
?
Van der Waals volume.
Dense:   0.98 LogP:   4.71
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.605
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.079
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   27.0
TPSA:   68.9
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   1.0 Rings:   5.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.558 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.347 Fsp3:   0.261
MCE-18:   66.276
?
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:   0.726 Fluc inhibitor:   0.699
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.761
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.735
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.372 Promiscuous compounds:   0.201

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.906 MDCK Permeability:   -4.711
Pgp-inhibitor:   0.944 Pgp-substrate:   0.102
PAMPA:   0.15
?
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):   0.003
20% Bioavailability (F20%):   0.733 30% Bioavailability (F30%):   0.992
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.704 MRP1:   0.836
Plasma Protein Binding (PPB):   98.143% Volume Distribution (VD):   0.308
Fu: 1.408%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.993
OATP1B3 inhibitor:   0.802 BCRP inhibitor:   0.957
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.125 CYP1A2-substrate:   0.977
CYP2C19-inhibitor:   0.775 CYP2C19-substrate:   0.05
CYP2C9-inhibitor:   0.649 CYP2C9-substrate:   0.734
CYP2D6-inhibitor:   0.005 CYP2D6-substrate:   0.746
CYP3A4-inhibitor:   0.038 CYP3A4-substrate:   0.997
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.997
HLM stability:   0.959
?
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):  4.143 Half-life (T1/2):  0.772

ADMET: Toxicity

hERG Blockers:  0.107 hERG Blockers (10um):  0.487
Human Hepatotoxicity (H-HT):  0.467 Drug-induced Liver Injury (DILI):  0.937
AMES Toxicity:  0.717 Rat Oral Acute Toxicity:  0.677
Maximum Recommended Daily Dose:  0.578 Skin Sensitization:  0.678
Carcinogencity:  0.902 Eye Corrosion:  0.028
Eye Irritation:  0.94 Respiratory Toxicity:  0.875
Drug-induced Neurotoxicity:  0.061 Ototoxicity:  0.158
Hematotoxicity:  0.168 Drug-induced Nephrotoxicity:  0.104
Genotoxicity:  0.405 RPMI-8226 Immunitoxicity:  0.076
A549 Cytotoxicity:  0.076 Hek293 Cytotoxicity:  0.366
BCF:   1.928
?
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:   4.656
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.735
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.945
?
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]
NPO8797 Cudrania tricuspidata Species Moraceae Eukaryota Root barks n.a. n.a. PMID[25051453]
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]
NPO8797 Cudrania tricuspidata Species Moraceae Eukaryota n.a. n.a. n.a. PMID[27420919]
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]
NPO8797 Cudrania tricuspidata Species Moraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO30804 Cudrania tricuspidata Species Moraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO8797 Cudrania tricuspidata Species Moraceae 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
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. EC50 = 4500.0 nM PMID[25051453]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 > 30000.0 nM PMID[25322455]

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 NPC55662 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
0.7536 Intermediate Similarity NPC472402
0.6761 Remote Similarity NPC95842
0.6716 Remote Similarity NPC120105
0.6567 Remote Similarity NPC166054
0.6 Remote Similarity NPC275122
0.6 Remote Similarity NPC5322
0.5867 Remote Similarity NPC482612
0.5811 Remote Similarity NPC38219
0.5714 Remote Similarity NPC482611
0.561 Remote Similarity NPC479156
0.5584 Remote Similarity NPC481615
0.5429 Remote Similarity NPC242100
0.5417 Remote Similarity NPC211811
0.5417 Remote Similarity NPC24673
0.5375 Remote Similarity NPC481613
0.5342 Remote Similarity NPC293852
0.527 Remote Similarity NPC166757
0.527 Remote Similarity NPC170492
0.5132 Remote Similarity NPC471984
0.5132 Remote Similarity NPC236488
0.5065 Remote Similarity NPC15435
0.506 Remote Similarity NPC479157

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC55662 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