Natural Product: NPC470412

Natural Product IDNPC470412
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Phomallenic Acid C
IUPAC Name octadeca-9,10-dien-12,14-diynoic acid
Synonyms Phomallenic Acid C
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2028081
PubChem CID 11608761
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0003909] Fatty Acyls
        • [CHEMONTID:0000262] Fatty acids and conjugates
          • [CHEMONTID:0002949] Long-chain fatty acids

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 KSAZGINEUAUMNR-UHFFFAOYSA-N
Standard InCHI InChI=1S/C18H24O2/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18(19)20/h8,10H,2-3,11-17H2,1H3,(H,19,20)
SMILES CCCC#CC#CC=C=CCCCCCCCC(=O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   272.18 Volume:   319.009
?
Van der Waals volume.
Dense:   0.853 LogP:   5.257
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.187
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.605
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The logarithm of aqueous solubility value.
Rotatable Bonds:   9.0 Rigid Bonds:   5.0
TPSA:   37.3
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   1.0 Rings:   0.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.385 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.389 Fsp3:   0.556
MCE-18:   0.0
?
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:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.014 Fluc inhibitor:   0.008
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.015
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.044
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.855 Promiscuous compounds:   0.049

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.973 MDCK Permeability:   -4.66
Pgp-inhibitor:   0.0 Pgp-substrate:   0.0
PAMPA:   0.999
?
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):   0.006
20% Bioavailability (F20%):   0.002 30% Bioavailability (F30%):   0.001
50% Bioavailability (F50%):   0.751

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.006
Plasma Protein Binding (PPB):   99.363% Volume Distribution (VD):   0.123
Fu: 0.267%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.001
OATP1B3 inhibitor:   0.024 BCRP inhibitor:   0.934
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.196
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   0.02
CYP2D6-inhibitor:   0.023 CYP2D6-substrate:   0.056
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.008
CYP2B6-substrate:   0.984 CYP2C8-inhibitor:   1.0
HLM stability:   0.0
?
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):  3.173 Half-life (T1/2):  1.082

ADMET: Toxicity

hERG Blockers:  0.043 hERG Blockers (10um):  0.26
Human Hepatotoxicity (H-HT):  0.416 Drug-induced Liver Injury (DILI):  0.776
AMES Toxicity:  0.187 Rat Oral Acute Toxicity:  0.301
Maximum Recommended Daily Dose:  0.633 Skin Sensitization:  0.674
Carcinogencity:  0.31 Eye Corrosion:  0.994
Eye Irritation:  0.997 Respiratory Toxicity:  0.997
Drug-induced Neurotoxicity:  0.084 Ototoxicity:  0.465
Hematotoxicity:  0.062 Drug-induced Nephrotoxicity:  0.105
Genotoxicity:  0.001 RPMI-8226 Immunitoxicity:  0.045
A549 Cytotoxicity:  0.006 Hek293 Cytotoxicity:  0.183
BCF:   1.239
?
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:   4.123
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.478
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.583
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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
NPO32661 Phoma sp. Species Didymellaceae Eukaryota n.a. n.a. n.a. PMID[16562839]
NPO32661 Phoma sp. Species Didymellaceae Eukaryota n.a. n.a. n.a. PMID[16643061]
NPO32661 Phoma sp. Species Didymellaceae Eukaryota giant jellyfish Nemopilema nomurai n.a. n.a. PMID[22483395]
NPO32661 Phoma sp. Species Didymellaceae Eukaryota n.a. n.a. n.a. PMID[26651221]
NPO32661 Phoma sp. Species Didymellaceae Eukaryota n.a. n.a. n.a. PMID[30785282]
NPO32661 Phoma sp. Species Didymellaceae Eukaryota n.a. n.a. n.a. PMID[31120749]
NPO32661 Phoma sp. Species Didymellaceae Eukaryota n.a. n.a. n.a. PMID[7561907]
NPO32661 Phoma sp. Species Didymellaceae Eukaryota 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

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
NPT16 Organism Staphylococcus aureus Staphylococcus aureus Activity = 0.15 ug ml-1 PMID[26900657]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 3.9 ug.mL-1 Open TG-GATES in vivo data: Hematology
NPT175 Organism Enterococcus faecalis Enterococcus faecalis MIC > 100.0 ug.mL-1 PMID[8496706]
NPT19 Organism Escherichia coli Escherichia coli MIC > 100.0 ug.mL-1 PMID[19008110]
NPT19 Organism Escherichia coli Escherichia coli MIC = 12.5 ug.mL-1 PMID[20055477]
NPT2 Others Unspecified n.a. IC50 = 0.77 ug.mL-1 PMID[26900657]
NPT1531 Organism Enterococcus faecium Enterococcus faecium MIC > 100.0 ug.mL-1 Open TG-GATES in vivo data: Hematology

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 NPC470412 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 NPC470410
0.62 Remote Similarity NPC470411
0.6042 Remote Similarity NPC187777
0.5833 Remote Similarity NPC274290
0.5625 Remote Similarity NPC28205
0.54 Remote Similarity NPC473863
0.5319 Remote Similarity NPC18357
0.5294 Remote Similarity NPC54766
0.5227 Remote Similarity NPC73245
0.52 Remote Similarity NPC179764
0.5192 Remote Similarity NPC226592
0.5116 Remote Similarity NPC281245

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC470412 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