Natural Product: NPC167055

Natural Product IDNPC167055
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Merulinic Acid B
IUPAC Name 2-hydroxy-6-[(Z)-16-hydroxyheptadec-8-enyl]benzoic acid
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL518757
PubChem CID 44575583
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0003909] Fatty Acyls
        • [CHEMONTID:0001334] Fatty alcohols
          • [CHEMONTID:0002951] Long-chain fatty alcohols

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 IKOVEXGXUDELJW-IHWYPQMZSA-N
Standard InCHI InChI=1S/C24H38O4/c1-20(25)16-13-11-9-7-5-3-2-4-6-8-10-12-14-17-21-18-15-19-22(26)23(21)24(27)28/h2-3,15,18-20,25-26H,4-14,16-17H2,1H3,(H,27,28)/b3-2-
SMILES CC(CCCCCC/C=CCCCCCCCc1cccc(c1C(=O)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   390.28 Volume:   437.082
?
Van der Waals volume.
Dense:   0.893 LogP:   6.322
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.604
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.872
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   16.0 Rigid Bonds:   8.0
TPSA:   77.76
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   3.0 Rings:   1.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.23 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.906 Fsp3:   0.625
MCE-18:   16.0
?
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:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.266 Fluc inhibitor:   0.087
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.027
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.228
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.398 Promiscuous compounds:   0.246

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.101 MDCK Permeability:   -4.701
Pgp-inhibitor:   0.889 Pgp-substrate:   0.001
PAMPA:   0.012
?
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):   0.019
20% Bioavailability (F20%):   0.043 30% Bioavailability (F30%):   0.643
50% Bioavailability (F50%):   0.446

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.002 MRP1:   0.976
Plasma Protein Binding (PPB):   98.372% Volume Distribution (VD):   -0.756
Fu: 0.854%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.01
OATP1B3 inhibitor:   0.621 BCRP inhibitor:   0.479
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.001 CYP1A2-substrate:   0.998
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.073
CYP2C9-inhibitor:   0.95 CYP2C9-substrate:   0.003
CYP2D6-inhibitor:   0.316 CYP2D6-substrate:   0.774
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   0.23
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.402
?
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):  2.433 Half-life (T1/2):  1.095

ADMET: Toxicity

hERG Blockers:  0.107 hERG Blockers (10um):  0.245
Human Hepatotoxicity (H-HT):  0.356 Drug-induced Liver Injury (DILI):  0.019
AMES Toxicity:  0.159 Rat Oral Acute Toxicity:  0.048
Maximum Recommended Daily Dose:  0.156 Skin Sensitization:  1.0
Carcinogencity:  0.051 Eye Corrosion:  0.933
Eye Irritation:  0.995 Respiratory Toxicity:  0.883
Drug-induced Neurotoxicity:  0.003 Ototoxicity:  0.502
Hematotoxicity:  0.036 Drug-induced Nephrotoxicity:  0.726
Genotoxicity:  0.0 RPMI-8226 Immunitoxicity:  0.043
A549 Cytotoxicity:  0.431 Hek293 Cytotoxicity:  0.078
BCF:   1.446
?
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:   4.796
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.056
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.414
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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
NPO22584 Thelephora vialis Species Thelephoraceae Eukaryota n.a. n.a. n.a. PMID[16901696]
NPO22584 Thelephora vialis Species Thelephoraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16152 Phlebia radiata Species Meruliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22584 Thelephora vialis Species Thelephoraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO22584 Thelephora vialis Species Thelephoraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO16152 Phlebia radiata Species Meruliaceae Eukaryota n.a. n.a. n.a. Database[Title]
NPO32809 merulius tremellosus Species Meruliaceae Eukaryota n.a. n.a. n.a. Database[Title]
NPO16152 Phlebia radiata Species Meruliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22584 Thelephora vialis Species Thelephoraceae 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
NPT1388 Organism Arthrobacter citreus Arthrobacter citreus MIC = 0.4 ug.mL-1 PMID[14987072]
NPT1390 Organism Kocuria rosea Kocuria rosea MIC = 0.4 ug.mL-1 PMID[14987072]
NPT729 Organism Micrococcus luteus Micrococcus luteus MIC = 0.4 ug.mL-1 PMID[14987072]
NPT79 Organism Bacillus subtilis Bacillus subtilis MIC = 0.4 ug.mL-1 PMID[14987072]
NPT1389 Organism Clavibacter michiganensis subsp. insidiosus Clavibacter michiganensis subsp. insidiosus MIC = 0.4 ug.mL-1 PMID[14987072]

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 NPC167055 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
0.86 High Similarity NPC238531
0.86 High Similarity NPC178395
0.8431 Intermediate Similarity NPC244994
0.8431 Intermediate Similarity NPC222876
0.8431 Intermediate Similarity NPC292665
0.8431 Intermediate Similarity NPC179092
0.84 Intermediate Similarity NPC483452
0.8214 Intermediate Similarity NPC240744
0.7963 Intermediate Similarity NPC115188
0.7963 Intermediate Similarity NPC159760
0.7963 Intermediate Similarity NPC301987
0.7963 Intermediate Similarity NPC26433
0.7636 Intermediate Similarity NPC184579
0.7636 Intermediate Similarity NPC233165
0.7255 Intermediate Similarity NPC483451
0.7255 Intermediate Similarity NPC227450
0.7255 Intermediate Similarity NPC272454
0.7255 Intermediate Similarity NPC35856
0.7255 Intermediate Similarity NPC609957
0.6727 Remote Similarity NPC605990
0.6545 Remote Similarity NPC244351
0.6545 Remote Similarity NPC483453
0.5932 Remote Similarity NPC17840
0.5932 Remote Similarity NPC247477
0.5323 Remote Similarity NPC486906

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC167055 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