Natural Product: NPC246638

Natural Product IDNPC246638
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Tetracenomycin D
IUPAC Name 1,3,8,11-tetrahydroxy-10-methyltetracene-5,12-dione
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2289227
PubChem CID 443788
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0000022] Naphthacenes
        • [CHEMONTID:0000155] Tetracenequinones

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 RZKZJERAFMFNMF-UHFFFAOYSA-N
Standard InCHI InChI=1S/C19H12O6/c1-7-2-9(20)3-8-4-11-16(18(24)14(7)8)19(25)15-12(17(11)23)5-10(21)6-13(15)22/h2-6,20-22,24H,1H3
SMILES Oc1cc(O)c2c(c1)C(=O)c1c(C2=O)c(O)c2c(c1)cc(cc2C)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   336.06 Volume:   329.331
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Van der Waals volume.
Dense:   1.02 LogP:   3.789
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.031
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -6.518
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The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   23.0
TPSA:   115.06
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Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   4.0 Rings:   4.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.392 GASA:   1.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.705 Fsp3:   0.053
MCE-18:   50.0
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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:   0 PAINS Alert:   1
Colloidal aggregators:   0.786 Fluc inhibitor:   0.615
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.18
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.385
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.521 Promiscuous compounds:   0.297

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.421 MDCK Permeability:   -4.842
Pgp-inhibitor:   0.035 Pgp-substrate:   0.047
PAMPA:   0.846
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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):   0.005
20% Bioavailability (F20%):   0.118 30% Bioavailability (F30%):   0.698
50% Bioavailability (F50%):   0.985

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.76
Plasma Protein Binding (PPB):   94.102% Volume Distribution (VD):   0.187
Fu: 8.691%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.963
OATP1B3 inhibitor:   0.996 BCRP inhibitor:   0.155
BSEP inhibitor:   0.188

ADMET: Metabolism

CYP1A2-inhibitor:   0.992 CYP1A2-substrate:   0.999
CYP2C19-inhibitor:   0.285 CYP2C19-substrate:   0.975
CYP2C9-inhibitor:   0.414 CYP2C9-substrate:   0.008
CYP2D6-inhibitor:   0.799 CYP2D6-substrate:   0.846
CYP3A4-inhibitor:   0.004 CYP3A4-substrate:   0.39
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.967
?
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):  1.778 Half-life (T1/2):  1.757

ADMET: Toxicity

hERG Blockers:  0.065 hERG Blockers (10um):  0.539
Human Hepatotoxicity (H-HT):  0.77 Drug-induced Liver Injury (DILI):  0.951
AMES Toxicity:  0.956 Rat Oral Acute Toxicity:  0.606
Maximum Recommended Daily Dose:  0.828 Skin Sensitization:  0.94
Carcinogencity:  0.839 Eye Corrosion:  0.0
Eye Irritation:  0.986 Respiratory Toxicity:  0.942
Drug-induced Neurotoxicity:  0.274 Ototoxicity:  0.512
Hematotoxicity:  0.672 Drug-induced Nephrotoxicity:  0.666
Genotoxicity:  0.997 RPMI-8226 Immunitoxicity:  0.433
A549 Cytotoxicity:  0.981 Hek293 Cytotoxicity:  0.883
BCF:   1.419
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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:   4.194
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.884
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.417
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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
NPO25734 Tinospora sagittata Species Menispermaceae Eukaryota n.a. n.a. n.a. PMID[28836430]
NPO3876 Andrographis elongata Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5724 Bacillus anthracis Species Bacillaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO3876 Andrographis elongata Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO25734 Tinospora sagittata Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO25734 Tinospora sagittata Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO5724 Bacillus anthracis Species Bacillaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO3876 Andrographis elongata Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25734 Tinospora sagittata Species Menispermaceae 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
NPT1198 Organism Magnaporthe grisea Magnaporthe grisea IC50 > 25.0 ug.mL-1 PMID[23360202]
NPT5492 Organism Proteus sp. Proteus sp. MIC = 16.0 ug.mL-1 PMID[34933562]
NPT29703 Organism Mycolicibacterium phlei Mycolicibacterium phlei MIC = 7.7 ug.mL-1 PMID[34933562]
NPT79 Organism Bacillus subtilis Bacillus subtilis MIC = 16.0 ug.mL-1 PMID[34933562]
NPT1199 Organism Valsa mali Valsa mali IC50 > 25.0 ug.mL-1 PMID[23360202]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 16.0 ug.mL-1 PMID[34933562]
NPT1238 Organism Staphylococcus Staphylococcus MIC = 7.7 ug.mL-1 PMID[34933562]

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 NPC246638 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
0.6538 Remote Similarity NPC601142
0.6538 Remote Similarity NPC601530
0.6538 Remote Similarity NPC606267
0.6538 Remote Similarity NPC610829
0.5714 Remote Similarity NPC93232
0.5538 Remote Similarity NPC489445
0.5102 Remote Similarity NPC254847

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC246638 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
0.5102 Remote Similarity NPD1509 Clinical (unspecified phase)

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