Natural Product: NPC239445

Natural Product IDNPC239445
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 VQBWFYNSXWMURP-FQEVSTJZSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0000337] Flavans
          • [CHEMONTID:0003642] 8-prenylated flavans
            • [CHEMONTID:0003508] 8-prenylated flavanones

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 VQBWFYNSXWMURP-FQEVSTJZSA-N
Standard InCHI InChI=1S/C21H22O3/c1-14(2)9-10-17-19(23-3)12-11-16-18(22)13-20(24-21(16)17)15-7-5-4-6-8-15/h4-9,11-12,20H,10,13H2,1-3H3/t20-/m0/s1
SMILES CC(=CCc1c(ccc2C(=O)C[C@@H](c3ccccc3)Oc12)OC)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   322.16 Volume:   351.382
?
Van der Waals volume.
Dense:   0.917 LogP:   5.005
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   4.144
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.596
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   19.0
TPSA:   35.53
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.75 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.89 Fsp3:   0.286
MCE-18:   53.519
?
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:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.972 Fluc inhibitor:   0.908
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.448
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.624
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.362 Promiscuous compounds:   0.038

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.693 MDCK Permeability:   -4.65
Pgp-inhibitor:   0.999 Pgp-substrate:   0.006
PAMPA:   0.021
?
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%):   0.032 30% Bioavailability (F30%):   0.533
50% Bioavailability (F50%):   0.978

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.029 MRP1:   0.769
Plasma Protein Binding (PPB):   96.919% Volume Distribution (VD):   0.36
Fu: 2.798%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.945
OATP1B3 inhibitor:   0.98 BCRP inhibitor:   0.958
BSEP inhibitor:   0.998

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.068 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.003
CYP3A4-inhibitor:   0.032 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   1.0
?
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):  7.693 Half-life (T1/2):  0.956

ADMET: Toxicity

hERG Blockers:  0.28 hERG Blockers (10um):  0.552
Human Hepatotoxicity (H-HT):  0.883 Drug-induced Liver Injury (DILI):  0.75
AMES Toxicity:  0.737 Rat Oral Acute Toxicity:  0.886
Maximum Recommended Daily Dose:  0.743 Skin Sensitization:  0.918
Carcinogencity:  0.337 Eye Corrosion:  0.003
Eye Irritation:  0.831 Respiratory Toxicity:  0.9
Drug-induced Neurotoxicity:  0.982 Ototoxicity:  0.614
Hematotoxicity:  0.436 Drug-induced Nephrotoxicity:  0.954
Genotoxicity:  0.936 RPMI-8226 Immunitoxicity:  0.088
A549 Cytotoxicity:  0.574 Hek293 Cytotoxicity:  0.383
BCF:   2.196
?
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:   4.668
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.669
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   6.162
?
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
NPO12514 Fasciospongia cavernosa Species Thorectidae Eukaryota n.a. n.a. n.a. PMID[10514323]
NPO12514 Fasciospongia cavernosa Species Thorectidae Eukaryota n.a. n.a. n.a. PMID[8594155]
NPO12514 Fasciospongia cavernosa Species Thorectidae Eukaryota n.a. n.a. n.a. PMID[9677277]
NPO21131 Lepista nuda Species Tricholomataceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21535 Bursera leptophloeos Species Burseraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1322 Solidago arguta Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13666 Salvia phlomoides Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7018 Quamoclit pennata n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO10256 Liquidambar orientalis Species Altingiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12514 Fasciospongia cavernosa Species Thorectidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11494 Echinogorgia complexa Species Paramuriceidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26405 Duguetia staudtii Species Annonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4006 Crotalaria dura Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10256 Liquidambar orientalis Species Altingiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO21131 Lepista nuda Species Tricholomataceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO10256 Liquidambar orientalis Species Altingiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO26405 Duguetia staudtii Species Annonaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21131 Lepista nuda Species Tricholomataceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO10256 Liquidambar orientalis Species Altingiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO10256 Liquidambar orientalis Species Altingiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO10256 Liquidambar orientalis Species Altingiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7018 Quamoclit pennata n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO11494 Echinogorgia complexa Species Paramuriceidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26405 Duguetia staudtii Species Annonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13666 Salvia phlomoides Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12514 Fasciospongia cavernosa Species Thorectidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21131 Lepista nuda Species Tricholomataceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4006 Crotalaria dura Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21535 Bursera leptophloeos Species Burseraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1322 Solidago arguta Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19409 Vespa crabro Species Vespidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23181 Ursinia eckloniana Species Asteraceae 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 NPC239445 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
0.7407 Intermediate Similarity NPC259685
0.6102 Remote Similarity NPC147145
0.6 Remote Similarity NPC11566
0.5806 Remote Similarity NPC250214
0.5714 Remote Similarity NPC220998
0.5667 Remote Similarity NPC472409
0.5667 Remote Similarity NPC14439
0.5667 Remote Similarity NPC30457
0.5645 Remote Similarity NPC476342
0.5556 Remote Similarity NPC149026
0.5484 Remote Similarity NPC76372
0.5484 Remote Similarity NPC37496
0.5469 Remote Similarity NPC471285
0.5455 Remote Similarity NPC485642
0.5455 Remote Similarity NPC611561
0.5312 Remote Similarity NPC95936
0.5238 Remote Similarity NPC164980
0.5238 Remote Similarity NPC169591
0.5238 Remote Similarity NPC298223
0.5238 Remote Similarity NPC604412
0.5231 Remote Similarity NPC310130
0.5224 Remote Similarity NPC155063
0.5156 Remote Similarity NPC1089
0.5156 Remote Similarity NPC87486
0.5156 Remote Similarity NPC124780
0.5094 Remote Similarity NPC314329
0.5094 Remote Similarity NPC603208

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC239445 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
0.5094 Remote Similarity NPD1547 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