Natural Product: NPC39708

Natural Product IDNPC39708
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 SPVPCROZEFMFBN-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 90976093
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002506] Isoflavonoids
        • [CHEMONTID:0002586] O-methylated isoflavonoids
          • [CHEMONTID:0002605] 3'-O-methylated isoflavonoids
            • [CHEMONTID:0002690] 3'-O-methylisoflavones

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 SPVPCROZEFMFBN-UHFFFAOYSA-N
Standard InCHI InChI=1S/C18H16O8/c1-23-12-6-11(21)17(24-2)18(25-3)14(12)9-7-26-13-5-8(19)4-10(20)15(13)16(9)22/h4-7,19-21H,1-3H3
SMILES COc1cc(c(c(c1c1coc2cc(cc(c2c1=O)O)O)OC)OC)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   360.08 Volume:   343.445
?
Van der Waals volume.
Dense:   1.048 LogP:   1.416
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.723
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.715
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   18.0
TPSA:   118.59
?
Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.65 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.747 Fsp3:   0.167
MCE-18:   20.0
?
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:   0.255 Fluc inhibitor:   0.14
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.56
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.453
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.353 Promiscuous compounds:   0.856

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.194 MDCK Permeability:   -4.816
Pgp-inhibitor:   0.03 Pgp-substrate:   0.239
PAMPA:   0.123
?
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%):   0.112 30% Bioavailability (F30%):   0.373
50% Bioavailability (F50%):   0.963

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.177 MRP1:   0.876
Plasma Protein Binding (PPB):   95.137% Volume Distribution (VD):   -0.358
Fu: 4.311%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.902
OATP1B3 inhibitor:   0.984 BCRP inhibitor:   0.926
BSEP inhibitor:   0.336

ADMET: Metabolism

CYP1A2-inhibitor:   0.986 CYP1A2-substrate:   0.321
CYP2C19-inhibitor:   0.243 CYP2C19-substrate:   0.169
CYP2C9-inhibitor:   0.997 CYP2C9-substrate:   0.706
CYP2D6-inhibitor:   0.999 CYP2D6-substrate:   0.983
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   0.075
CYP2B6-substrate:   0.001 CYP2C8-inhibitor:   0.97
HLM stability:   0.833
?
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):  4.074 Half-life (T1/2):  1.436

ADMET: Toxicity

hERG Blockers:  0.114 hERG Blockers (10um):  0.516
Human Hepatotoxicity (H-HT):  0.475 Drug-induced Liver Injury (DILI):  0.816
AMES Toxicity:  0.52 Rat Oral Acute Toxicity:  0.525
Maximum Recommended Daily Dose:  0.805 Skin Sensitization:  0.434
Carcinogencity:  0.779 Eye Corrosion:  0.025
Eye Irritation:  0.975 Respiratory Toxicity:  0.811
Drug-induced Neurotoxicity:  0.148 Ototoxicity:  0.184
Hematotoxicity:  0.153 Drug-induced Nephrotoxicity:  0.118
Genotoxicity:  0.847 RPMI-8226 Immunitoxicity:  0.128
A549 Cytotoxicity:  0.294 Hek293 Cytotoxicity:  0.641
BCF:   1.117
?
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:   3.599
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.619
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.872
?
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
NPO15828 Garcinia nervosa Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15828 Garcinia nervosa Species Clusiaceae 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 NPC39708 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
0.7193 Intermediate Similarity NPC19980
0.7119 Intermediate Similarity NPC483637
0.6833 Remote Similarity NPC45291
0.6667 Remote Similarity NPC279668
0.6667 Remote Similarity NPC481044
0.6552 Remote Similarity NPC78341
0.65 Remote Similarity NPC309154
0.6441 Remote Similarity NPC294409
0.6441 Remote Similarity NPC490701
0.6393 Remote Similarity NPC194653
0.6333 Remote Similarity NPC239363
0.629 Remote Similarity NPC254702
0.629 Remote Similarity NPC264550
0.623 Remote Similarity NPC200316
0.6129 Remote Similarity NPC278323
0.6032 Remote Similarity NPC142876
0.5846 Remote Similarity NPC167595
0.5789 Remote Similarity NPC193792
0.5763 Remote Similarity NPC87545
0.569 Remote Similarity NPC39426
0.569 Remote Similarity NPC608554
0.5652 Remote Similarity NPC128774
0.5507 Remote Similarity NPC233918
0.5507 Remote Similarity NPC268059
0.55 Remote Similarity NPC38065
0.5493 Remote Similarity NPC482075
0.5455 Remote Similarity NPC104728
0.5429 Remote Similarity NPC280937
0.5429 Remote Similarity NPC479305
0.5303 Remote Similarity NPC476055
0.5152 Remote Similarity NPC90665
0.5072 Remote Similarity NPC608523
0.5068 Remote Similarity NPC74178

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC39708 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
0.569 Remote Similarity NPD1510 Phase 2

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