Natural Product: NPC214714

Natural Product IDNPC214714
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Ht-2 Toxin
IUPAC Name n.a.
Synonyms HT-2 toxin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL440357
PubChem CID 10093830
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 PNKLMTPXERFKEN-MLXHEQMXSA-N
Standard InCHI InChI=1S/C22H32O8/c1-11(2)6-16(24)29-14-8-21(9-27-13(4)23)15(7-12(14)3)30-19-17(25)18(26)20(21,5)22(19)10-28-22/h7,11,14-15,17-19,25-26H,6,8-10H2,1-5H3/t14-,15+,17+,18+,19+,20+,21+,22-/m0/s1
SMILES CC(C)CC(=O)O[C@H]1C[C@@]2(COC(=O)C)[C@@H](C=C1C)O[C@@H]1[C@@H]([C@H]([C@@]2(C)[C@@]21CO2)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   424.21 Volume:   417.255
?
Van der Waals volume.
Dense:   1.017 LogP:   2.394
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.418
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.848
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   19.0
TPSA:   114.82
?
Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   2.0 Rings:   4.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.383 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   6.11 Fsp3:   0.818
MCE-18:   105.0
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.702 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.012
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.001
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.144 Promiscuous compounds:   0.691

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.08 MDCK Permeability:   -4.731
Pgp-inhibitor:   0.001 Pgp-substrate:   0.992
PAMPA:   0.972
?
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):   0.029
20% Bioavailability (F20%):   0.753 30% Bioavailability (F30%):   0.505
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.925 MRP1:   0.944
Plasma Protein Binding (PPB):   75.348% Volume Distribution (VD):   0.0
Fu: 26.562%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.363
OATP1B3 inhibitor:   0.096 BCRP inhibitor:   0.002
BSEP inhibitor:   0.513

ADMET: Metabolism

CYP1A2-inhibitor:   0.001 CYP1A2-substrate:   0.09
CYP2C19-inhibitor:   0.008 CYP2C19-substrate:   0.004
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.498
CYP3A4-inhibitor:   0.534 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.68
HLM stability:   0.541
?
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):  2.618 Half-life (T1/2):  2.371

ADMET: Toxicity

hERG Blockers:  0.012 hERG Blockers (10um):  0.12
Human Hepatotoxicity (H-HT):  0.345 Drug-induced Liver Injury (DILI):  0.824
AMES Toxicity:  0.997 Rat Oral Acute Toxicity:  0.846
Maximum Recommended Daily Dose:  0.865 Skin Sensitization:  1.0
Carcinogencity:  0.647 Eye Corrosion:  0.003
Eye Irritation:  0.683 Respiratory Toxicity:  0.778
Drug-induced Neurotoxicity:  0.755 Ototoxicity:  0.802
Hematotoxicity:  0.815 Drug-induced Nephrotoxicity:  0.992
Genotoxicity:  0.969 RPMI-8226 Immunitoxicity:  0.741
A549 Cytotoxicity:  0.76 Hek293 Cytotoxicity:  0.315
BCF:   0.592
?
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:   3.317
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.134
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.48
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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
NPO15511 Fusarium heterosporum Species Nectriaceae Eukaryota n.a. n.a. n.a. PMID[7264681]
NPO15511 Fusarium heterosporum Species Nectriaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15511 Fusarium heterosporum Species Nectriaceae 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
NPT111 Cell line K562 Homo sapiens EC50 = 47.1 nM PMID[26287401]
NPT312 Organism Saccharomyces cerevisiae Saccharomyces cerevisiae Ratio = 66.7 n.a. PMID[20430633]
NPT312 Organism Saccharomyces cerevisiae Saccharomyces cerevisiae Activity = 66.7 n.a. PMID[22647719]
NPT419 Organism Oryctolagus cuniculus Oryctolagus cuniculus ED50 = 0.16 ug PMID[8410974]

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 = 9.0 n.a. PMID[15454228]





 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
- Arabidopsis thaliana LD50 = 1.0 uM PubChem BioAssay data set
- Mus musculus LD50 = 3.8 mg/kg ToxVal
- Mus musculus LD50 = 9.0 mg.kg-1 PMID[24582477]
- Gallus gallus LD50 = 6.25 mg.kg-1 DrugMatrix in vivo data: Biochemistry
- Cavia porcellus LD50 = 0.5 mg/kg ToxVal
- Sus scrofa domesticus PMTDI = 2.5e-05 mg/kg ToxVal

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 NPC214714 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
1.0 High Similarity NPC607785
0.8393 Intermediate Similarity NPC232515
0.7049 Intermediate Similarity NPC200672
0.6724 Remote Similarity NPC182811
0.6333 Remote Similarity NPC601146
0.619 Remote Similarity NPC475986
0.6032 Remote Similarity NPC79449
0.6032 Remote Similarity NPC474957
0.5968 Remote Similarity NPC347923
0.5968 Remote Similarity NPC608318
0.5846 Remote Similarity NPC26557
0.5672 Remote Similarity NPC252242
0.5672 Remote Similarity NPC475956
0.5588 Remote Similarity NPC260809
0.5588 Remote Similarity NPC474783

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC214714 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