Natural Product: NPC112368

Natural Product IDNPC112368
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 QDFJNOVWEADTGJ-NHYWBVRUSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 23259931
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002506] Isoflavonoids
        • [CHEMONTID:0002617] Furanoisoflavonoids
          • [CHEMONTID:0001608] Pterocarpans

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 QDFJNOVWEADTGJ-NHYWBVRUSA-N
Standard InCHI InChI=1S/C16H14O5/c1-19-12-5-4-10-15-11(7-20-16(10)14(12)18)9-3-2-8(17)6-13(9)21-15/h2-6,11,15,17-18H,7H2,1H3/t11-,15-/m0/s1
SMILES COc1ccc2[C@H]3[C@@H](COc2c1O)c1ccc(cc1O3)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   286.08 Volume:   279.199
?
Van der Waals volume.
Dense:   1.025 LogP:   2.207
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.468
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.903
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   20.0
TPSA:   68.15
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   4.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.843 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.397 Fsp3:   0.25
MCE-18:   69.3
?
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:   0.672 Fluc inhibitor:   0.969
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.119
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.32
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.402 Promiscuous compounds:   0.399

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.014 MDCK Permeability:   -4.809
Pgp-inhibitor:   0.009 Pgp-substrate:   0.509
PAMPA:   0.022
?
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):   0.002
20% Bioavailability (F20%):   0.259 30% Bioavailability (F30%):   0.695
50% Bioavailability (F50%):   0.948

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.64 MRP1:   0.773
Plasma Protein Binding (PPB):   89.865% Volume Distribution (VD):   -0.49
Fu: 10.926%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.993
OATP1B3 inhibitor:   0.972 BCRP inhibitor:   0.588
BSEP inhibitor:   0.236

ADMET: Metabolism

CYP1A2-inhibitor:   0.414 CYP1A2-substrate:   0.908
CYP2C19-inhibitor:   0.941 CYP2C19-substrate:   0.795
CYP2C9-inhibitor:   0.939 CYP2C9-substrate:   0.006
CYP2D6-inhibitor:   0.175 CYP2D6-substrate:   0.414
CYP3A4-inhibitor:   0.975 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.001 CYP2C8-inhibitor:   0.996
HLM stability:   0.888
?
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):  5.126 Half-life (T1/2):  2.211

ADMET: Toxicity

hERG Blockers:  0.197 hERG Blockers (10um):  0.583
Human Hepatotoxicity (H-HT):  0.737 Drug-induced Liver Injury (DILI):  0.556
AMES Toxicity:  0.574 Rat Oral Acute Toxicity:  0.456
Maximum Recommended Daily Dose:  0.707 Skin Sensitization:  0.773
Carcinogencity:  0.56 Eye Corrosion:  0.016
Eye Irritation:  0.97 Respiratory Toxicity:  0.711
Drug-induced Neurotoxicity:  0.652 Ototoxicity:  0.568
Hematotoxicity:  0.256 Drug-induced Nephrotoxicity:  0.359
Genotoxicity:  0.606 RPMI-8226 Immunitoxicity:  0.093
A549 Cytotoxicity:  0.262 Hek293 Cytotoxicity:  0.679
BCF:   0.99
?
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:   3.53
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.96
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.242
?
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
NPO29027 Khaya grandifoliola Species Meliaceae Eukaryota n.a. seed n.a. PMID[10661881]
NPO15741 Embelia ribes Species Primulaceae Eukaryota n.a. leaf n.a. PMID[17124632]
NPO15741 Embelia ribes Species Primulaceae Eukaryota n.a. fruit n.a. PMID[17124632]
NPO15741 Embelia ribes Species Primulaceae Eukaryota n.a. n.a. n.a. PMID[17125236]
NPO15741 Embelia ribes Species Primulaceae Eukaryota roots n.a. n.a. PMID[17125236]
NPO10682 Cystoseira mediterranea Species Sargassaceae Eukaryota n.a. n.a. n.a. PMID[2045820]
NPO10682 Cystoseira mediterranea Species Sargassaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15741 Embelia ribes Species Primulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29027 Khaya grandifoliola Species Meliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15553 Barringtonia acutangula Species Lecythidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16182 Desmodium canadense Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1281 Schleichera trijuga Species Sapindaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16096 Astragalus adsurgens Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15741 Embelia ribes Species Primulaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO5457 Dalbergia congestiflora Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15741 Embelia ribes Species Primulaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO29027 Khaya grandifoliola Species Meliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12581 Corydalis densiflora Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15206 Mabea fistulifera Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15553 Barringtonia acutangula Species Lecythidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13520 Craibiodendron yunnanense Species Ericaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13641 Napoleonaea vogelii Species Lecythidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5457 Dalbergia congestiflora Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7887 Schultesia guianensis Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10447 Triclisia subcordata Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10947 Aspilia parvifolia Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1281 Schleichera trijuga Species Sapindaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15741 Embelia ribes Species Primulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16096 Astragalus adsurgens Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10682 Cystoseira mediterranea Species Sargassaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16182 Desmodium canadense Species Fabaceae 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 NPC112368 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
0.7273 Intermediate Similarity NPC309124
0.7143 Intermediate Similarity NPC236306
0.6964 Remote Similarity NPC32633
0.6731 Remote Similarity NPC471215
0.6731 Remote Similarity NPC262573
0.629 Remote Similarity NPC71288
0.629 Remote Similarity NPC301961
0.6102 Remote Similarity NPC39064
0.6102 Remote Similarity NPC47283
0.5873 Remote Similarity NPC236014
0.5833 Remote Similarity NPC232164
0.5833 Remote Similarity NPC473739
0.5672 Remote Similarity NPC121925
0.5667 Remote Similarity NPC27495
0.5574 Remote Similarity NPC198358
0.5574 Remote Similarity NPC295697
0.5455 Remote Similarity NPC475836
0.5323 Remote Similarity NPC73320
0.5303 Remote Similarity NPC474687
0.5303 Remote Similarity NPC605244
0.5246 Remote Similarity NPC129684
0.5246 Remote Similarity NPC299520
0.5238 Remote Similarity NPC107161
0.5224 Remote Similarity NPC118114
0.5161 Remote Similarity NPC265433
0.5161 Remote Similarity NPC270456
0.5161 Remote Similarity NPC162659
0.5072 Remote Similarity NPC296915

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC112368 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