Natural Product: NPC169923

Natural Product IDNPC169923
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 ZSRVBNXAPSQDFY-OJVARPOJSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 10038552
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001550] Sesquiterpenoids
          • [CHEMONTID:0001789] Trichothecenes

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 ZSRVBNXAPSQDFY-OJVARPOJSA-N
Standard InCHI InChI=1S/C15H22O4/c1-9-3-4-14(7-16)11(5-9)19-12-6-10(17)13(14,2)15(12)8-18-15/h5,10-12,16-17H,3-4,6-8H2,1-2H3/t10-,11-,12-,13-,14-,15+/m1/s1
SMILES CC1=C[C@@H]2[C@@](CC1)(CO)[C@@]1(C)[C@@H](C[C@H]([C@]31CO3)O2)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   266.15 Volume:   266.295
?
Van der Waals volume.
Dense:   0.999 LogP:   0.782
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.093
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.429
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   17.0
TPSA:   62.22
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   2.0 Rings:   4.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.549 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   5.98 Fsp3:   0.867
MCE-18:   92.857
?
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:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.14 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.02
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.014
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.317 Promiscuous compounds:   0.749

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.54 MDCK Permeability:   -4.679
Pgp-inhibitor:   0.027 Pgp-substrate:   0.835
PAMPA:   0.997
?
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):   0.03
20% Bioavailability (F20%):   0.589 30% Bioavailability (F30%):   0.264
50% Bioavailability (F50%):   0.982

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.787 MRP1:   0.103
Plasma Protein Binding (PPB):   57.38% Volume Distribution (VD):   0.205
Fu: 40.881%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.962
OATP1B3 inhibitor:   0.036 BCRP inhibitor:   0.979
BSEP inhibitor:   0.889

ADMET: Metabolism

CYP1A2-inhibitor:   0.192 CYP1A2-substrate:   0.008
CYP2C19-inhibitor:   0.457 CYP2C19-substrate:   0.002
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.18
CYP2D6-inhibitor:   0.011 CYP2D6-substrate:   0.005
CYP3A4-inhibitor:   0.917 CYP3A4-substrate:   0.005
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.048
HLM stability:   0.044
?
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):  13.189 Half-life (T1/2):  2.968

ADMET: Toxicity

hERG Blockers:  0.071 hERG Blockers (10um):  0.515
Human Hepatotoxicity (H-HT):  0.487 Drug-induced Liver Injury (DILI):  0.602
AMES Toxicity:  0.895 Rat Oral Acute Toxicity:  0.944
Maximum Recommended Daily Dose:  0.971 Skin Sensitization:  0.992
Carcinogencity:  0.505 Eye Corrosion:  0.022
Eye Irritation:  0.94 Respiratory Toxicity:  0.983
Drug-induced Neurotoxicity:  0.554 Ototoxicity:  0.629
Hematotoxicity:  0.256 Drug-induced Nephrotoxicity:  0.324
Genotoxicity:  0.955 RPMI-8226 Immunitoxicity:  0.453
A549 Cytotoxicity:  0.041 Hek293 Cytotoxicity:  0.186
BCF:   0.76
?
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:   3.217
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.755
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.95
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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
NPO10849.2 Eucalyptus camaldulensis Under-species n.a. n.a. n.a. n.a. n.a. PMID[12502346]
NPO59923 Myriactis nepalensis Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[35889501]
NPO10849.2 Eucalyptus camaldulensis Under-species n.a. n.a. n.a. n.a. n.a. PMID[37049738]
NPO10849.2 Eucalyptus camaldulensis Under-species n.a. n.a. n.a. n.a. n.a. PMID[37880275]
NPO47329 Merremia vitifolia Species Convolvulaceae Eukaryota n.a. n.a. n.a. PMID[39398064]
NPO40950 Verrucarol diacetoxyscirpenol Species n.a. n.a. n.a. n.a. n.a. PMID[6481362]
NPO10849.2 Eucalyptus camaldulensis Under-species n.a. n.a. n.a. n.a. n.a. Database[COCONUT]

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
NPO10849.2 Eucalyptus camaldulensis Oil Leaves 0.56 n.a. n.a. % PMID[37880275]
NPO47329 Merremia vitifolia n.a. n.a. 0.873 n.a. n.a. % PMID[39398064]
NPO59923 Myriactis nepalensis Oil n.a. 0.1 n.a. n.a. % PMID[35889501]

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
NPT32 Organism Mus musculus Mus musculus Activity = 15.8 ug ml-1 PMID[6481362]





 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
- Mus musculus LD50 >= 42.2 mg.kg-1 PMID[6481362]

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 NPC169923 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
0.7391 Intermediate Similarity NPC218381
0.6667 Remote Similarity NPC486496
0.5472 Remote Similarity NPC123505

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC169923 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