Natural Product: NPC186531

Natural Product IDNPC186531
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (2S)-4-Dodec-11-Ynyl-2-Methyl-2H-Furan-5-One
IUPAC Name (2S)-4-dodec-11-ynyl-2-methyl-2H-furan-5-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL477913
PubChem CID 10801466
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0003909] Fatty Acyls
        • [CHEMONTID:0001334] Fatty alcohols
          • [CHEMONTID:0002518] Annonaceous acetogenins

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 KCYNQKJAQXHQLE-HNNXBMFYSA-N
Standard InCHI InChI=1S/C17H26O2/c1-3-4-5-6-7-8-9-10-11-12-13-16-14-15(2)19-17(16)18/h1,14-15H,4-13H2,2H3/t15-/m0/s1
SMILES C#CCCCCCCCCCCC1=C[C@@H](OC1=O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   262.19 Volume:   301.066
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Van der Waals volume.
Dense:   0.871 LogP:   4.211
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.136
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.312
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The logarithm of aqueous solubility value.
Rotatable Bonds:   10.0 Rigid Bonds:   7.0
TPSA:   26.3
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Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   0.0 Rings:   1.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.331 GASA:   1.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.163 Fsp3:   0.706
MCE-18:   12.414
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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:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.19 Fluc inhibitor:   0.307
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.005
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.132
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.974 Promiscuous compounds:   0.107

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.006 MDCK Permeability:   -4.718
Pgp-inhibitor:   0.005 Pgp-substrate:   0.001
PAMPA:   0.041
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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):   0.194
20% Bioavailability (F20%):   0.252 30% Bioavailability (F30%):   0.483
50% Bioavailability (F50%):   0.693

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.102 MRP1:   0.006
Plasma Protein Binding (PPB):   99.104% Volume Distribution (VD):   0.337
Fu: 0.615%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.988
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.742
BSEP inhibitor:   0.774

ADMET: Metabolism

CYP1A2-inhibitor:   0.003 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.004 CYP2C9-substrate:   0.815
CYP2D6-inhibitor:   0.009 CYP2D6-substrate:   0.559
CYP3A4-inhibitor:   0.681 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.777
?
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):  5.163 Half-life (T1/2):  0.584

ADMET: Toxicity

hERG Blockers:  0.021 hERG Blockers (10um):  0.435
Human Hepatotoxicity (H-HT):  0.821 Drug-induced Liver Injury (DILI):  0.065
AMES Toxicity:  0.894 Rat Oral Acute Toxicity:  0.719
Maximum Recommended Daily Dose:  0.821 Skin Sensitization:  1.0
Carcinogencity:  0.83 Eye Corrosion:  0.876
Eye Irritation:  0.949 Respiratory Toxicity:  0.983
Drug-induced Neurotoxicity:  0.573 Ototoxicity:  0.185
Hematotoxicity:  0.209 Drug-induced Nephrotoxicity:  0.991
Genotoxicity:  0.076 RPMI-8226 Immunitoxicity:  0.121
A549 Cytotoxicity:  0.047 Hek293 Cytotoxicity:  0.116
BCF:   1.394
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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:   4.534
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.926
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.731
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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
NPO32807 Hortonia Genus Monimiaceae Eukaryota n.a. n.a. n.a. PMID[11277762]

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

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
- Aedes aegypti LC50 = 0.41 ppm PMID[19739600]

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 NPC186531 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
0.8214 Intermediate Similarity NPC84038
0.697 Remote Similarity NPC218477
0.697 Remote Similarity NPC474705
0.6053 Remote Similarity NPC609415
0.5909 Remote Similarity NPC488224
0.5789 Remote Similarity NPC225272
0.5476 Remote Similarity NPC73310
0.5476 Remote Similarity NPC473529
0.5476 Remote Similarity NPC180363
0.5476 Remote Similarity NPC94875
0.5476 Remote Similarity NPC11332
0.5476 Remote Similarity NPC145914
0.5476 Remote Similarity NPC601174
0.5476 Remote Similarity NPC601403
0.5476 Remote Similarity NPC603568
0.5476 Remote Similarity NPC604330
0.5476 Remote Similarity NPC608300
0.5476 Remote Similarity NPC611200
0.5476 Remote Similarity NPC611571
0.5349 Remote Similarity NPC475947
0.5111 Remote Similarity NPC25764
0.5111 Remote Similarity NPC235809
0.5111 Remote Similarity NPC329829
0.5111 Remote Similarity NPC39279
0.5111 Remote Similarity NPC469483
0.5111 Remote Similarity NPC475159
0.5111 Remote Similarity NPC39167
0.5111 Remote Similarity NPC131002
0.5111 Remote Similarity NPC292809
0.5111 Remote Similarity NPC202055
0.5111 Remote Similarity NPC473780
0.5111 Remote Similarity NPC604521
0.5111 Remote Similarity NPC606804
0.5111 Remote Similarity NPC607425
0.5111 Remote Similarity NPC608574

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC186531 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