Natural Product: NPC118788

Natural Product IDNPC118788
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 2-(2-Methylbut-3-En-2-Yl)-5-(3-Methylbut-2-Enyl)Cyclohexa-2,5-Diene-1,4-Dione
IUPAC Name 2-(2-methylbut-3-en-2-yl)-5-(3-methylbut-2-enyl)cyclohexa-2,5-diene-1,4-dione
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL403123
PubChem CID 24180642
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001534] Quinone and hydroquinone lipids
          • [CHEMONTID:0002802] Prenylquinones

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 IXIJAOCIIZYSQJ-UHFFFAOYSA-N
Standard InCHI InChI=1S/C16H20O2/c1-6-16(4,5)13-10-14(17)12(9-15(13)18)8-7-11(2)3/h6-7,9-10H,1,8H2,2-5H3
SMILES C=CC(C)(C)C1=CC(=O)C(=CC1=O)CC=C(C)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   244.15 Volume:   278.497
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Van der Waals volume.
Dense:   0.877 LogP:   3.845
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.381
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.967
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The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   10.0
TPSA:   34.14
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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:   0.559 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.477 Fsp3:   0.375
MCE-18:   11.0
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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:   0
Chelating Alert:   0 PAINS Alert:   1
Colloidal aggregators:   0.459 Fluc inhibitor:   0.38
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.376
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.151
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.991 Promiscuous compounds:   0.258

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.78 MDCK Permeability:   -4.69
Pgp-inhibitor:   0.909 Pgp-substrate:   0.002
PAMPA:   0.826
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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):   0.95
20% Bioavailability (F20%):   0.995 30% Bioavailability (F30%):   1.0
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.889
Plasma Protein Binding (PPB):   93.17% Volume Distribution (VD):   0.221
Fu: 7.453%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.645
BSEP inhibitor:   0.892

ADMET: Metabolism

CYP1A2-inhibitor:   0.002 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.999 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.043 CYP2C9-substrate:   0.74
CYP2D6-inhibitor:   0.003 CYP2D6-substrate:   0.447
CYP3A4-inhibitor:   0.913 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.004 CYP2C8-inhibitor:   1.0
HLM stability:   1.0
?
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):  8.696 Half-life (T1/2):  1.047

ADMET: Toxicity

hERG Blockers:  0.053 hERG Blockers (10um):  0.484
Human Hepatotoxicity (H-HT):  0.717 Drug-induced Liver Injury (DILI):  0.638
AMES Toxicity:  0.645 Rat Oral Acute Toxicity:  0.686
Maximum Recommended Daily Dose:  0.7 Skin Sensitization:  0.928
Carcinogencity:  0.712 Eye Corrosion:  0.259
Eye Irritation:  0.97 Respiratory Toxicity:  0.814
Drug-induced Neurotoxicity:  0.753 Ototoxicity:  0.273
Hematotoxicity:  0.613 Drug-induced Nephrotoxicity:  0.354
Genotoxicity:  0.931 RPMI-8226 Immunitoxicity:  0.079
A549 Cytotoxicity:  0.112 Hek293 Cytotoxicity:  0.336
BCF:   1.984
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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:   4.468
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.322
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.819
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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
NPO30938 Perithalia capillaris Species Sporochnaceae Eukaryota n.a. New Zealand n.a. PMID[18052030]
NPO16286 Sporochnus comosus Species Sporochnaceae Eukaryota n.a. n.a. n.a. PMID[21348445]
NPO30938 Perithalia capillaris Species Sporochnaceae Eukaryota n.a. n.a. n.a. PMID[21348445]
NPO1266 Trigonella polycerata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16286 Sporochnus comosus Species Sporochnaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17950 Siphonoglossa ramosa n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO17827 Scutellaria przewalskii Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17845 Rhynchotechum vestitum Species Gesneriaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13944 Parkia speciosa Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5730 Lactuca canadensis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13576 Cordylanthus tenuis Species Orobanchaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17183 Chaetomium coarctatum Species Chaetomiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17714 Blepharispermum zanguebaricum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14726 Alnus subcordata Species Betulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5730 Lactuca canadensis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO17827 Scutellaria przewalskii Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO17845 Rhynchotechum vestitum Species Gesneriaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO17827 Scutellaria przewalskii Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO5730 Lactuca canadensis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO17950 Siphonoglossa ramosa n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO17714 Blepharispermum zanguebaricum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16286 Sporochnus comosus Species Sporochnaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17827 Scutellaria przewalskii Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17845 Rhynchotechum vestitum Species Gesneriaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17183 Chaetomium coarctatum Species Chaetomiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13944 Parkia speciosa Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13576 Cordylanthus tenuis Species Orobanchaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14726 Alnus subcordata Species Betulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1266 Trigonella polycerata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5730 Lactuca canadensis Species Asteraceae 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
NPT116 Cell line HL-60 Homo sapiens IC50 = 340.0 nM PMID[18052030]
NPT395 Cell line SF-268 Homo sapiens GI50 = 17000.0 nM PMID[21348445]
NPT83 Cell line MCF7 Homo sapiens GI50 = 26000.0 nM PMID[21348445]
NPT397 Cell line NCI-H460 Homo sapiens GI50 = 41000.0 nM PMID[21348445]
NPT139 Cell line HT-29 Homo sapiens GI50 = 37000.0 nM PMID[21348445]
NPT913 Cell line CHO-K1 Cricetulus griseus GI50 = 17000.0 nM PMID[21348445]
NPT2 Others Unspecified n.a. IC50 = 2100.0 nM PMID[18052030]

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 NPC118788 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
NPC

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC118788 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