Natural Product: NPC487736

Natural Product IDNPC487736
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 WQIFRGNDJXGCFI-YTXTXJHMSA-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:0002448] Benzenoids
      • [CHEMONTID:0000134] Phenols
        • [CHEMONTID:0004647] 1-hydroxy-4-unsubstituted benzenoids

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 WQIFRGNDJXGCFI-YTXTXJHMSA-N
Standard InCHI InChI=1S/C15H20O/c1-2-3-4-5-6-7-8-10-14-11-9-12-15(16)13-14/h4-7,9,11-13,16H,2-3,8,10H2,1H3/b5-4+,7-6+
SMILES CCC/C=C/C=C/CCc1cccc(c1)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   216.15 Volume:   255.048
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Van der Waals volume.
Dense:   0.847 LogP:   4.42
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.553
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.104
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The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   8.0
TPSA:   20.23
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Topological Polar Surface Area.
 H-Bond Acceptor:   1.0
H-Bond Donor:   1.0 Rings:   1.0
Heavy Atoms:   1.0

MedChem Properties

QED Drug-Likeness Score:   0.705 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.445 Fsp3:   0.333
MCE-18:   5.0
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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:   0.299 Fluc inhibitor:   0.503
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.007
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.268
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.999 Promiscuous compounds:   0.162

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.755 MDCK Permeability:   -4.742
Pgp-inhibitor:   0.427 Pgp-substrate:   0.304
PAMPA:   0.106
?
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%):   0.569 30% Bioavailability (F30%):   0.852
50% Bioavailability (F50%):   0.993

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.011
Plasma Protein Binding (PPB):   98.329% Volume Distribution (VD):   -0.256
Fu: 2.531%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.897
OATP1B3 inhibitor:   0.917 BCRP inhibitor:   0.22
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.798 CYP1A2-substrate:   0.997
CYP2C19-inhibitor:   0.095 CYP2C19-substrate:   0.991
CYP2C9-inhibitor:   0.279 CYP2C9-substrate:   0.855
CYP2D6-inhibitor:   0.857 CYP2D6-substrate:   0.967
CYP3A4-inhibitor:   0.004 CYP3A4-substrate:   0.999
CYP2B6-substrate:   0.007 CYP2C8-inhibitor:   1.0
HLM stability:   0.98
?
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):  9.809 Half-life (T1/2):  0.734

ADMET: Toxicity

hERG Blockers:  0.426 hERG Blockers (10um):  0.681
Human Hepatotoxicity (H-HT):  0.906 Drug-induced Liver Injury (DILI):  0.343
AMES Toxicity:  0.854 Rat Oral Acute Toxicity:  0.109
Maximum Recommended Daily Dose:  0.91 Skin Sensitization:  0.993
Carcinogencity:  0.324 Eye Corrosion:  0.018
Eye Irritation:  0.913 Respiratory Toxicity:  0.923
Drug-induced Neurotoxicity:  0.575 Ototoxicity:  0.539
Hematotoxicity:  0.265 Drug-induced Nephrotoxicity:  0.449
Genotoxicity:  0.254 RPMI-8226 Immunitoxicity:  0.083
A549 Cytotoxicity:  0.127 Hek293 Cytotoxicity:  0.676
BCF:   1.931
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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:   4.59
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.466
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.162
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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
NPO40726 Hormoscilla sp. VPG 16-59 Strain Gomontiellaceae Bacteria n.a. n.a. n.a. PMID[30489078]
NPO40726 Hormoscilla sp. VPG 16-59 Strain Gomontiellaceae Bacteria 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
NPT82 Cell line MDA-MB-231 Homo sapiens IC50 = 42000.0 nM PMID[30489078]
NPT81 Cell line A549 Homo sapiens IC50 = 49000.0 nM PMID[30489078]
NPT393 Cell line HCT-116 Homo sapiens IC50 > 100000.0 nM PMID[30489078]
NPT312 Organism Saccharomyces cerevisiae Saccharomyces cerevisiae MIC > 22.0 ug.mL-1 PMID[30489078]
NPT88 Organism Mycobacterium tuberculosis Mycobacterium tuberculosis MIC > 22.0 ug.mL-1 PMID[30489078]
NPT18 Organism Pseudomonas aeruginosa Pseudomonas aeruginosa MIC > 22.0 ug.mL-1 PMID[30489078]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 22.0 ug.mL-1 PMID[30489078]
NPT314 Organism Bacillus cereus Bacillus cereus MIC = 22.0 ug.mL-1 PMID[30489078]

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 NPC487736 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
0.7105 Intermediate Similarity NPC487946
0.7105 Intermediate Similarity NPC487945
0.6585 Remote Similarity NPC487734
0.6216 Remote Similarity NPC610566
0.6111 Remote Similarity NPC606762
0.6047 Remote Similarity NPC483454
0.6047 Remote Similarity NPC162314
0.5909 Remote Similarity NPC94139
0.5909 Remote Similarity NPC147284
0.587 Remote Similarity NPC210497
0.561 Remote Similarity NPC3358
0.561 Remote Similarity NPC306884
0.561 Remote Similarity NPC603092
0.5429 Remote Similarity NPC27974
0.5333 Remote Similarity NPC487735
0.5238 Remote Similarity NPC113460

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC487736 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