Natural Product: NPC298729

Natural Product IDNPC298729
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 KNXAGUANLPVZSV-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 74015882
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0002279] Benzene and substituted derivatives
        • [CHEMONTID:0000120] Benzophenones

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 KNXAGUANLPVZSV-UHFFFAOYSA-N
Standard InCHI InChI=1S/C15H12O6/c1-7-5-10(17)13(11(18)6-7)14(19)12-8(15(20)21)3-2-4-9(12)16/h2-6,16-18H,1H3,(H,20,21)
SMILES Cc1cc(c(c(c1)O)C(=O)c1c(cccc1O)C(=O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   288.06 Volume:   282.533
?
Van der Waals volume.
Dense:   1.02 LogP:   3.174
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.221
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.935
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   14.0
TPSA:   115.06
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   4.0 Rings:   2.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.642 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.316 Fsp3:   0.067
MCE-18:   15.0
?
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:   0 PAINS Alert:   0
Colloidal aggregators:   0.186 Fluc inhibitor:   0.038
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.248
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.253
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.725 Promiscuous compounds:   0.587

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.116 MDCK Permeability:   -4.756
Pgp-inhibitor:   0.0 Pgp-substrate:   0.119
PAMPA:   0.996
?
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):   0.007
20% Bioavailability (F20%):   0.007 30% Bioavailability (F30%):   0.043
50% Bioavailability (F50%):   0.554

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.006 MRP1:   0.989
Plasma Protein Binding (PPB):   94.649% Volume Distribution (VD):   -0.625
Fu: 5.849%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.967
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.002
BSEP inhibitor:   0.046

ADMET: Metabolism

CYP1A2-inhibitor:   0.961 CYP1A2-substrate:   0.614
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.766
CYP2C9-inhibitor:   0.002 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.003 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.96 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.876
HLM stability:   0.982
?
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):  1.861 Half-life (T1/2):  1.63

ADMET: Toxicity

hERG Blockers:  0.011 hERG Blockers (10um):  0.094
Human Hepatotoxicity (H-HT):  0.427 Drug-induced Liver Injury (DILI):  0.705
AMES Toxicity:  0.453 Rat Oral Acute Toxicity:  0.189
Maximum Recommended Daily Dose:  0.244 Skin Sensitization:  0.649
Carcinogencity:  0.108 Eye Corrosion:  0.004
Eye Irritation:  0.992 Respiratory Toxicity:  0.917
Drug-induced Neurotoxicity:  0.03 Ototoxicity:  0.369
Hematotoxicity:  0.262 Drug-induced Nephrotoxicity:  0.775
Genotoxicity:  0.702 RPMI-8226 Immunitoxicity:  0.103
A549 Cytotoxicity:  0.207 Hek293 Cytotoxicity:  0.1
BCF:   0.447
?
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:   3.018
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.187
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.642
?
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
NPO15822 Stypopodium zonale Species Dictyotaceae Eukaryota n.a. n.a. n.a. PMID[10395524]
NPO15822 Stypopodium zonale Species Dictyotaceae Eukaryota n.a. n.a. n.a. PMID[12444716]
NPO18853 Alstonia scholaris Species Apocynaceae Eukaryota n.a. n.a. n.a. PMID[21043460]
NPO24324 Halobacterium salinarum Species Halobacteriaceae Archaea n.a. n.a. n.a. PMID[24823651]
NPO7118 Manglietiastrum sinicum Species Magnoliaceae Eukaryota Mature Carpels n.a. n.a. PMID[25116183]
NPO14170 Streptomyces neyagawaensis Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO7118 Manglietiastrum sinicum Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27088 Oscillatoria nigro-viridis Species Oscillatoriaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO18050 Stilbe ericoides Species Stilbaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15822 Stypopodium zonale Species Dictyotaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18853 Alstonia scholaris Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18853 Alstonia scholaris Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO18853 Alstonia scholaris Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18853 Alstonia scholaris Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO18853 Alstonia scholaris Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14170 Streptomyces neyagawaensis Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO17903 Nepeta ruderalis Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15822 Stypopodium zonale Species Dictyotaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7118 Manglietiastrum sinicum Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17356 Peltigera malacea Species Peltigeraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18050 Stilbe ericoides Species Stilbaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2290 Clarkia exilis Species Onagraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27088 Oscillatoria nigro-viridis Species Oscillatoriaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO24324 Halobacterium salinarum Species Halobacteriaceae Archaea n.a. n.a. n.a. Database[UNPD]
NPO11976 Elaeocarpus sikkimensis Species Elaeocarpaceae 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

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 NPC298729 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
0.6957 Remote Similarity NPC161632
0.566 Remote Similarity NPC609641

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC298729 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