Natural Product: NPC294741

Natural Product IDNPC294741
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Kneglomeratanol
IUPAC Name 3-[(10S)-10-hydroxy-10-phenyldecyl]phenol
Synonyms Kneglomeratanol
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL513977
PubChem CID 11723929
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0003909] Fatty Acyls
        • [CHEMONTID:0001334] 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 MFDBSKOHHOKJHW-QFIPXVFZSA-N
Standard InCHI InChI=1S/C22H30O2/c23-21-16-11-13-19(18-21)12-7-4-2-1-3-5-10-17-22(24)20-14-8-6-9-15-20/h6,8-9,11,13-16,18,22-24H,1-5,7,10,12,17H2/t22-/m0/s1
SMILES C(CCCCc1cccc(c1)O)CCCC[C@@H](c1ccccc1)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   326.22 Volume:   373.717
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Van der Waals volume.
Dense:   0.873 LogP:   4.517
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.357
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.538
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The logarithm of aqueous solubility value.
Rotatable Bonds:   11.0 Rigid Bonds:   12.0
TPSA:   40.46
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Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   2.0 Rings:   2.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.513 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.331 Fsp3:   0.455
MCE-18:   20.0
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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:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.719 Fluc inhibitor:   0.044
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.008
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.164
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.47 Promiscuous compounds:   0.158

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.153 MDCK Permeability:   -4.731
Pgp-inhibitor:   0.132 Pgp-substrate:   0.126
PAMPA:   0.16
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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):   0.003
20% Bioavailability (F20%):   0.53 30% Bioavailability (F30%):   0.954
50% Bioavailability (F50%):   0.957

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.034 MRP1:   0.45
Plasma Protein Binding (PPB):   98.499% Volume Distribution (VD):   0.725
Fu: 1.629%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.171
OATP1B3 inhibitor:   0.761 BCRP inhibitor:   0.353
BSEP inhibitor:   0.85

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.414
CYP2C19-inhibitor:   0.004 CYP2C19-substrate:   0.576
CYP2C9-inhibitor:   0.008 CYP2C9-substrate:   0.45
CYP2D6-inhibitor:   0.252 CYP2D6-substrate:   0.933
CYP3A4-inhibitor:   0.337 CYP3A4-substrate:   0.985
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.962
HLM stability:   0.964
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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):  5.123 Half-life (T1/2):  0.336

ADMET: Toxicity

hERG Blockers:  0.521 hERG Blockers (10um):  0.794
Human Hepatotoxicity (H-HT):  0.591 Drug-induced Liver Injury (DILI):  0.035
AMES Toxicity:  0.184 Rat Oral Acute Toxicity:  0.144
Maximum Recommended Daily Dose:  0.446 Skin Sensitization:  0.979
Carcinogencity:  0.241 Eye Corrosion:  0.701
Eye Irritation:  0.994 Respiratory Toxicity:  0.797
Drug-induced Neurotoxicity:  0.288 Ototoxicity:  0.14
Hematotoxicity:  0.048 Drug-induced Nephrotoxicity:  0.28
Genotoxicity:  0.001 RPMI-8226 Immunitoxicity:  0.042
A549 Cytotoxicity:  0.857 Hek293 Cytotoxicity:  0.511
BCF:   2.118
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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:   5.38
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.275
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.992
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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
NPO11253 Knema glomerata Species Myristicaceae Eukaryota n.a. n.a. n.a. PMID[8201311]
NPO5999 Schinopsis balansae Species Anacardiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5999 Schinopsis balansae Species Anacardiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7853 Baphia racemosa Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11253 Knema glomerata Species Myristicaceae 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
NPT81 Cell line A549 Homo sapiens ED50 = 5.99 ug ml-1 PMID[8201311]
NPT83 Cell line MCF7 Homo sapiens ED50 = 2.32 ug ml-1 PMID[8201311]
NPT139 Cell line HT-29 Homo sapiens ED50 = 9.33 ug ml-1 PMID[8201311]
NPT141 Organism Agrobacterium tumefaciens Agrobacterium tumefaciens T/C = 29.0 % PMID[8201311]

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
- Artemia LC50 = 0.21 ug.mL-1 PMID[8201311]

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 NPC294741 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
0.725 Intermediate Similarity NPC76938
0.725 Intermediate Similarity NPC32714
0.6429 Remote Similarity NPC3358
0.6429 Remote Similarity NPC306884
0.6429 Remote Similarity NPC603092
0.5745 Remote Similarity NPC483454
0.5745 Remote Similarity NPC162314
0.5682 Remote Similarity NPC241891
0.5682 Remote Similarity NPC134829
0.5625 Remote Similarity NPC94139
0.5625 Remote Similarity NPC147284
0.551 Remote Similarity NPC475018
0.5476 Remote Similarity NPC610566
0.5455 Remote Similarity NPC474073
0.5294 Remote Similarity NPC210497
0.5294 Remote Similarity NPC192
0.5208 Remote Similarity NPC487734
0.5102 Remote Similarity NPC487735

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC294741 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