Natural Product: NPC69898

Natural Product IDNPC69898
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 4-(2,6,6-Trimethylcyclohexen-1-Yl)But-3-En-2-One
IUPAC Name 4-(2,6,6-trimethylcyclohexen-1-yl)but-3-en-2-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3184146
PubChem CID 26955
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001550] Sesquiterpenoids

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 PSQYTAPXSHCGMF-UHFFFAOYSA-N
Standard InCHI InChI=1S/C13H20O/c1-10-6-5-9-13(3,4)12(10)8-7-11(2)14/h7-8H,5-6,9H2,1-4H3
SMILES CC(=O)C=CC1=C(C)CCCC1(C)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   192.15 Volume:   225.729
?
Van der Waals volume.
Dense:   0.851 LogP:   3.277
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.95
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.973
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   8.0
TPSA:   17.07
?
Topological Polar Surface Area.
 H-Bond Acceptor:   1.0
H-Bond Donor:   0.0 Rings:   1.0
Heavy Atoms:   1.0

MedChem Properties

QED Drug-Likeness Score:   0.61 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.719 Fsp3:   0.615
MCE-18:   12.429
?
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:   Accepted BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.054 Fluc inhibitor:   0.146
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.037
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.016
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.996 Promiscuous compounds:   0.322

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.532 MDCK Permeability:   -4.724
Pgp-inhibitor:   0.186 Pgp-substrate:   0.045
PAMPA:   0.081
?
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):   0.001
20% Bioavailability (F20%):   0.003 30% Bioavailability (F30%):   0.006
50% Bioavailability (F50%):   0.159

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.96 MRP1:   0.956
Plasma Protein Binding (PPB):   94.077% Volume Distribution (VD):   0.432
Fu: 6.78%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.235
OATP1B3 inhibitor:   0.227 BCRP inhibitor:   0.077
BSEP inhibitor:   0.789

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.72
CYP2C19-inhibitor:   0.999 CYP2C19-substrate:   0.07
CYP2C9-inhibitor:   0.968 CYP2C9-substrate:   0.007
CYP2D6-inhibitor:   0.744 CYP2D6-substrate:   0.655
CYP3A4-inhibitor:   0.999 CYP3A4-substrate:   0.999
CYP2B6-substrate:   1.0 CYP2C8-inhibitor:   0.13
HLM stability:   0.97
?
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):  7.656 Half-life (T1/2):  0.232

ADMET: Toxicity

hERG Blockers:  0.072 hERG Blockers (10um):  0.379
Human Hepatotoxicity (H-HT):  0.515 Drug-induced Liver Injury (DILI):  0.2
AMES Toxicity:  0.484 Rat Oral Acute Toxicity:  0.326
Maximum Recommended Daily Dose:  0.428 Skin Sensitization:  0.826
Carcinogencity:  0.466 Eye Corrosion:  0.939
Eye Irritation:  0.985 Respiratory Toxicity:  0.686
Drug-induced Neurotoxicity:  0.493 Ototoxicity:  0.253
Hematotoxicity:  0.35 Drug-induced Nephrotoxicity:  0.371
Genotoxicity:  0.152 RPMI-8226 Immunitoxicity:  0.051
A549 Cytotoxicity:  0.054 Hek293 Cytotoxicity:  0.154
BCF:   2.219
?
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:   3.989
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.843
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.658
?
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
NPO28152 Jacaranda caucana Species Bignoniaceae Eukaryota n.a. n.a. n.a. PMID[19361168]
NPO11450 Pseudoceratina purpurea Species Pseudoceratinidae Eukaryota n.a. n.a. n.a. PMID[26035239]
NPO9396 Carpesium divaricatum Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[31816933]
NPO9396 Carpesium divaricatum Species Asteraceae Eukaryota n.a. aerial part n.a. PMID[9392887]
NPO27219 Gonioma kamassi Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28095 Boronia megastigma Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11450 Pseudoceratina purpurea Species Pseudoceratinidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26838 Adenophora triphylla Species Campanulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27879 Ailanthus triphysa Species Simaroubaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20978 Alternaria cinerariae Species Pleosporaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1650 Boykinia watanabei Species Saxifragaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27588 Carpolobia lutea Species Polygalaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9396 Carpesium divaricatum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27381 Hypselodoris webbi Species Chromodorididae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28152 Jacaranda caucana Species Bignoniaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23311 Libanothamnus tamanus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27948 Licania carii Species Chrysobalanaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27985 Plantago arenaria Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8266 Solanum anguivi Species Solanaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29214 Teucrium massiliense Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28117 Tor sinensis Species Cyprinidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15808 Vibrio gazogenes Species Vibrionaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO11450 Pseudoceratina purpurea Species Pseudoceratinidae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO26838 Adenophora triphylla Species Campanulaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO8266 Solanum anguivi Species Solanaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27948 Licania carii Species Chrysobalanaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27381 Hypselodoris webbi Species Chromodorididae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27985 Plantago arenaria Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11450 Pseudoceratina purpurea Species Pseudoceratinidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1650 Boykinia watanabei Species Saxifragaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29214 Teucrium massiliense Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26838 Adenophora triphylla Species Campanulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28095 Boronia megastigma Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15808 Vibrio gazogenes Species Vibrionaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO27879 Ailanthus triphysa Species Simaroubaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20978 Alternaria cinerariae Species Pleosporaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28117 Tor sinensis Species Cyprinidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27588 Carpolobia lutea Species Polygalaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23311 Libanothamnus tamanus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27219 Gonioma kamassi Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28152 Jacaranda caucana Species Bignoniaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9396 Carpesium divaricatum 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
NPO9396 Carpesium divaricatum Oil n.a. 0.9 n.a. n.a. % PMID[31816933]
NPO9396 Carpesium divaricatum Oil n.a. 1.5 n.a. n.a. % PMID[31816933]

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
NPT163 Individual protein Nuclear factor NF-kappa-B p105 subunit Homo sapiens Potency n.a. 10962.2 nM PubChem BioAssay data set

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT2 Others Unspecified n.a. Potency n.a. 61130.6 nM PubChem BioAssay data set

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
- Rattus norvegicus NOEC = 750.0 mg/kg-day ToxVal
- Rattus norvegicus NOAEL <= 10.0 mg/kg-day ToxVal
- Rattus norvegicus NOAEL >= 8.0 mg/kg-day ToxVal
- Rattus norvegicus LOEL >= 11.6 mg/kg-day ToxVal
- Rattus norvegicus NOAEL = 11.4 mg/kg-day ToxVal
- Rattus norvegicus NOAEL = 11.6 mg/kg-day ToxVal
- Rattus norvegicus LOEL <= 13.1 mg/kg-day ToxVal
- Rattus norvegicus NOAEL = 750.0 mg/kg-day ToxVal
- Rattus norvegicus NOAEL = 1000.0 mg/kg-day ToxVal
- Rattus norvegicus LD50 = 4590.0 mg/kg ToxVal
- Rattus norvegicus LD50 = 3290.0 mg/kg ToxVal
- Mus musculus LD50 = 1.92662077 mg/kg TOXRIC
- Mus musculus LD50 = 2277.0 mg/kg ToxVal
- Mus musculus LD50 > 2000.0 mg/kg ToxVal
- Mus musculus LD50 = 5331.0 mg/kg ToxVal
- Homo sapiens DNEL systemic = 2.498 mg/m3 ToxVal
- Cricetinae NOAEL = 480.0 ppm ToxVal
- Cricetinae NOEC = 480.0 mg/kg-day ToxVal

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 NPC69898 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
1.0 High Similarity NPC295777
0.5135 Remote Similarity NPC22019
0.5135 Remote Similarity NPC281986
0.5135 Remote Similarity NPC321568

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC69898 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