Natural Product: NPC540572

Natural Product IDNPC540572
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 1220-77-5
IUPAC Name 6-methyl-8-(2,6,6-trimethylcyclohexen-1-yl)octa-3,5,7-trien-2-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
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 UBTNVRPIHJRBCI-UHFFFAOYSA-N
Standard InCHI InChI=1S/C18H26O/c1-14(8-6-10-16(3)19)11-12-17-15(2)9-7-13-18(17,4)5/h6,8,10-12H,7,9,13H2,1-5H3
SMILES CC(=O)C=CC=C(C)C=CC1=C(C)CCCC1(C)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   258.2 Volume:   306.936
?
Van der Waals volume.
Dense:   0.841 LogP:   4.866
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.71
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.06
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   10.0
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:   0.503 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.034 Fsp3:   0.5
MCE-18:   12.963
?
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:   0.379 Fluc inhibitor:   0.634
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.051
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.013
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.993 Promiscuous compounds:   0.178

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.735 MDCK Permeability:   -4.723
Pgp-inhibitor:   0.269 Pgp-substrate:   0.044
PAMPA:   0.059
?
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):   0.0
20% Bioavailability (F20%):   0.002 30% Bioavailability (F30%):   0.004
50% Bioavailability (F50%):   0.227

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.969 MRP1:   0.961
Plasma Protein Binding (PPB):   94.509% Volume Distribution (VD):   0.413
Fu: 5.843%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.373
OATP1B3 inhibitor:   0.182 BCRP inhibitor:   0.043
BSEP inhibitor:   0.944

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.997
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.361
CYP2C9-inhibitor:   0.995 CYP2C9-substrate:   0.008
CYP2D6-inhibitor:   0.104 CYP2D6-substrate:   0.832
CYP3A4-inhibitor:   0.999 CYP3A4-substrate:   1.0
CYP2B6-substrate:   1.0 CYP2C8-inhibitor:   0.999
HLM stability:   0.989
?
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):  7.587 Half-life (T1/2):  0.188

ADMET: Toxicity

hERG Blockers:  0.141 hERG Blockers (10um):  0.505
Human Hepatotoxicity (H-HT):  0.533 Drug-induced Liver Injury (DILI):  0.187
AMES Toxicity:  0.69 Rat Oral Acute Toxicity:  0.519
Maximum Recommended Daily Dose:  0.725 Skin Sensitization:  0.846
Carcinogencity:  0.686 Eye Corrosion:  0.143
Eye Irritation:  0.89 Respiratory Toxicity:  0.758
Drug-induced Neurotoxicity:  0.628 Ototoxicity:  0.354
Hematotoxicity:  0.377 Drug-induced Nephrotoxicity:  0.532
Genotoxicity:  0.334 RPMI-8226 Immunitoxicity:  0.088
A549 Cytotoxicity:  0.098 Hek293 Cytotoxicity:  0.312
BCF:   2.295
?
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:   4.2
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.088
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.91
?
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
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/S0014-5793(03)00033-4]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. DOI[10.1021/ac991142i]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. DOI[10.1034/j.1399-3054.2003.00030.x]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. DOI[10.1046/j.1365-3040.2001.00686.x]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. DOI[10.1074/jbc.274.1.397]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. DOI[10.1074/jbc.M302362200]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. DOI[10.1074/jbc.M314195200]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. DOI[10.1074/jbc.M411109200]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. DOI[10.1104/pp.103.022368]
NPO20081 Mycobacterium tuberculosis Species Mycobacteriaceae Bacteria n.a. n.a. n.a. PMID[10553679]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. leaf n.a. PMID[10952545]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[10952545]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[11005203]
NPO20081 Mycobacterium tuberculosis Species Mycobacteriaceae Bacteria n.a. n.a. n.a. PMID[12055308]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[12637544]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[12805618]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[14745019]
NPO20081 Mycobacterium tuberculosis Species Mycobacteriaceae Bacteria n.a. n.a. n.a. PMID[15070765]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[15280363]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[15820655]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[15834012]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota aerial parts n.a. n.a. PMID[15844959]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[1684022]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[17611796]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[18057039]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[18235971]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[18318836]
NPO20081 Mycobacterium tuberculosis Species Mycobacteriaceae Bacteria n.a. n.a. n.a. PMID[19276083]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. leaf n.a. PMID[19521717]
NPO20081 Mycobacterium tuberculosis Species Mycobacteriaceae Bacteria n.a. n.a. n.a. PMID[20448045]
NPO20081 Mycobacterium tuberculosis Species Mycobacteriaceae Bacteria n.a. n.a. n.a. PMID[20843794]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[21193570]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[21194489]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[21395888]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[21800258]
NPO20081 Mycobacterium tuberculosis Species Mycobacteriaceae Bacteria n.a. n.a. n.a. PMID[22194604]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[23370715]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[23950498]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. root n.a. PMID[24163311]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[24285094]
NPO20081 Mycobacterium tuberculosis Species Mycobacteriaceae Bacteria n.a. n.a. n.a. PMID[24516143]
NPO20081 Mycobacterium tuberculosis Species Mycobacteriaceae Bacteria n.a. n.a. n.a. PMID[25028392]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. root n.a. PMID[25457500]
NPO20081 Mycobacterium tuberculosis Species Mycobacteriaceae Bacteria n.a. n.a. n.a. PMID[26466957]
NPO20081 Mycobacterium tuberculosis Species Mycobacteriaceae Bacteria n.a. n.a. n.a. PMID[26774486]
NPO20081 Mycobacterium tuberculosis Species Mycobacteriaceae Bacteria n.a. n.a. n.a. PMID[27242221]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. root n.a. PMID[27363486]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[27432888]
NPO20081 Mycobacterium tuberculosis Species Mycobacteriaceae Bacteria n.a. n.a. n.a. PMID[27807341]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[8278506]
NPO20081 Mycobacterium tuberculosis Species Mycobacteriaceae Bacteria n.a. n.a. n.a. PMID[8917504]
NPO20081 Mycobacterium tuberculosis Species Mycobacteriaceae Bacteria n.a. n.a. n.a. PMID[97292]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[Article]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO53241 Cucumis melo Inodorus Group Species Cucurbitaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20081 Mycobacterium tuberculosis Species Mycobacteriaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO52184 Novosphingobium aromaticivorans Species Sphingomonadaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[MetaboLights]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. root n.a. Database[MetaboLights]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20081 Mycobacterium tuberculosis Species Mycobacteriaceae Bacteria 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

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 NPC540572 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
0.7059 Intermediate Similarity NPC17810
0.7059 Intermediate Similarity NPC606095
0.7027 Intermediate Similarity NPC22019
0.7027 Intermediate Similarity NPC281986
0.7027 Intermediate Similarity NPC321568
0.6667 Remote Similarity NPC295777
0.6667 Remote Similarity NPC69898
0.6 Remote Similarity NPC55412
0.6 Remote Similarity NPC249645
0.5909 Remote Similarity NPC226066
0.5814 Remote Similarity NPC329416
0.5814 Remote Similarity NPC317025
0.5814 Remote Similarity NPC326645
0.5814 Remote Similarity NPC317177
0.5435 Remote Similarity NPC254886
0.52 Remote Similarity NPC228978
0.52 Remote Similarity NPC600770

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC540572 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
0.7059 Intermediate Similarity NPD8262 Phase 4
0.6 Remote Similarity NPD4219 Phase 4
0.5909 Remote Similarity NPD5325 Clinical (unspecified phase)
0.5814 Remote Similarity NPD4191 Approved
0.5814 Remote Similarity NPD4192 Phase 4
0.5814 Remote Similarity NPD4193 Phase 4
0.5814 Remote Similarity NPD4194 Phase 4
0.52 Remote Similarity NPD8039 Phase 4

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