Natural Product: NPC98392

Natural Product IDNPC98392
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Alliodorin
IUPAC Name (2E,6E)-8-(2,5-dihydroxyphenyl)-2,6-dimethylocta-2,6-dienal
Synonyms Alliodorin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL257343
PubChem CID 11747343
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001534] Quinone and hydroquinone lipids
          • [CHEMONTID:0002801] Prenylated hydroquinones

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 SMWFREPIBWIJGX-YKNDAMCPSA-N
Standard InCHI InChI=1S/C16H20O3/c1-12(4-3-5-13(2)11-17)6-7-14-10-15(18)8-9-16(14)19/h5-6,8-11,18-19H,3-4,7H2,1-2H3/b12-6+,13-5+
SMILES O=C/C(=C/CC/C(=C/Cc1cc(O)ccc1O)/C)/C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   260.14 Volume:   287.288
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Van der Waals volume.
Dense:   0.906 LogP:   3.818
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.102
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.728
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The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   9.0
TPSA:   57.53
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Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   2.0 Rings:   1.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.356 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.844 Fsp3:   0.312
MCE-18:   8.0
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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:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.486 Fluc inhibitor:   0.024
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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:   0.144
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.893 Promiscuous compounds:   0.163

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.868 MDCK Permeability:   -4.739
Pgp-inhibitor:   0.475 Pgp-substrate:   0.001
PAMPA:   0.089
?
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):   0.123
20% Bioavailability (F20%):   0.999 30% Bioavailability (F30%):   1.0
50% Bioavailability (F50%):   0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.11
Plasma Protein Binding (PPB):   97.367% Volume Distribution (VD):   0.038
Fu: 2.64%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.952
OATP1B3 inhibitor:   0.996 BCRP inhibitor:   0.817
BSEP inhibitor:   0.921

ADMET: Metabolism

CYP1A2-inhibitor:   0.001 CYP1A2-substrate:   0.87
CYP2C19-inhibitor:   0.812 CYP2C19-substrate:   0.988
CYP2C9-inhibitor:   0.973 CYP2C9-substrate:   0.03
CYP2D6-inhibitor:   0.976 CYP2D6-substrate:   0.024
CYP3A4-inhibitor:   0.004 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.001 CYP2C8-inhibitor:   1.0
HLM stability:   0.997
?
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):  14.177 Half-life (T1/2):  1.306

ADMET: Toxicity

hERG Blockers:  0.114 hERG Blockers (10um):  0.589
Human Hepatotoxicity (H-HT):  0.71 Drug-induced Liver Injury (DILI):  0.265
AMES Toxicity:  0.467 Rat Oral Acute Toxicity:  0.371
Maximum Recommended Daily Dose:  0.718 Skin Sensitization:  0.982
Carcinogencity:  0.291 Eye Corrosion:  0.016
Eye Irritation:  0.952 Respiratory Toxicity:  0.868
Drug-induced Neurotoxicity:  0.258 Ototoxicity:  0.364
Hematotoxicity:  0.204 Drug-induced Nephrotoxicity:  0.371
Genotoxicity:  0.892 RPMI-8226 Immunitoxicity:  0.099
A549 Cytotoxicity:  0.526 Hek293 Cytotoxicity:  0.596
BCF:   1.747
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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:   4.887
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.844
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.475
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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
NPO6865 Cordia fragrantissima Species Cordiaceae Eukaryota n.a. Myanmar n.a. PMID[18088097]
NPO22854 Cordia globifera Species Cordiaceae Eukaryota n.a. n.a. n.a. PMID[19368377]
NPO22854 Cordia globifera Species Cordiaceae Eukaryota n.a. n.a. n.a. PMID[20384317]
NPO6865 Cordia fragrantissima Species Cordiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22854 Cordia globifera Species Cordiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6865 Cordia fragrantissima Species Cordiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22854 Cordia globifera Species Cordiaceae 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
NPT1229 Cell line Huh-7 Homo sapiens IC50 = 44.8 ug.mL-1 PMID[23164712]
NPT189 Cell line Vero Chlorocebus aethiops IC50 = 14.1 ug.mL-1 PMID[17877337]
NPT91 Cell line KB Homo sapiens IC50 = 12.0 ug.mL-1 PMID[15332848]
NPT639 Cell line NCI-H187 Homo sapiens IC50 = 2.2 ug.mL-1 PMID[19928832]
NPT3632 Organism Leishmania panamensis Leishmania panamensis IC50 = 1.8 ug.mL-1 PMID[25766629]
NPT88 Organism Mycobacterium tuberculosis Mycobacterium tuberculosis MIC = 12.5 ug.mL-1 PMID[20384296]
NPT20 Organism Candida albicans Candida albicans IC50 > 20.0 ug.mL-1 PMID[23734634]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 10.3 ug.mL-1 PMID[19368377]
NPT3631 Organism Leishmania guyanensis Leishmania guyanensis IC50 = 2.0 ug.mL-1 PMID[25316316]
NPT841 Organism Leishmania major Leishmania major IC50 = 7.0 ug.mL-1 PMID[23265253]
NPT485 Organism Plasmodium falciparum (isolate K1 / Thailand) Plasmodium falciparum K1 IC50 = 3.1 ug.mL-1 PMID[22545792]

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 NPC98392 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
0.7907 Intermediate Similarity NPC152097
0.7556 Intermediate Similarity NPC260775
0.7556 Intermediate Similarity NPC130756
0.7556 Intermediate Similarity NPC70677
0.7556 Intermediate Similarity NPC12931
0.6182 Remote Similarity NPC155072
0.5814 Remote Similarity NPC609473
0.5439 Remote Similarity NPC85342
0.5439 Remote Similarity NPC206207
0.5424 Remote Similarity NPC228609
0.5385 Remote Similarity NPC76400
0.5263 Remote Similarity NPC320439
0.5192 Remote Similarity NPC269414
0.5192 Remote Similarity NPC477685
0.5172 Remote Similarity NPC95305
0.5161 Remote Similarity NPC197513

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC98392 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