Natural Product: NPC12818

Natural Product IDNPC12818
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Onitin
IUPAC Name 4-hydroxy-6-(2-hydroxyethyl)-2,2,5,7-tetramethyl-3H-inden-1-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL261243
PubChem CID 3085044
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0000027] Indanes
        • [CHEMONTID:0001151] Indanones

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 IWRJCMQFEMXOML-UHFFFAOYSA-N
Standard InCHI InChI=1S/C15H20O3/c1-8-10(5-6-16)9(2)13(17)11-7-15(3,4)14(18)12(8)11/h16-17H,5-7H2,1-4H3
SMILES Cc1c(CCO)c(C)c(c2CC(C)(C)C(=O)c12)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   248.14 Volume:   266.708
?
Van der Waals volume.
Dense:   0.93 LogP:   2.028
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.113
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.106
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   11.0
TPSA:   57.53
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   2.0 Rings:   2.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.844 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.946 Fsp3:   0.533
MCE-18:   34.783
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Rejected GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.021 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.52
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.092
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.579 Promiscuous compounds:   0.182

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.94 MDCK Permeability:   -4.717
Pgp-inhibitor:   0.041 Pgp-substrate:   0.179
PAMPA:   0.957
?
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):   0.008
20% Bioavailability (F20%):   0.117 30% Bioavailability (F30%):   0.106
50% Bioavailability (F50%):   0.741

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.297 MRP1:   1.0
Plasma Protein Binding (PPB):   78.173% Volume Distribution (VD):   0.525
Fu: 24.922%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.367
OATP1B3 inhibitor:   0.517 BCRP inhibitor:   0.002
BSEP inhibitor:   0.931

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.003
CYP2C19-inhibitor:   0.971 CYP2C19-substrate:   0.062
CYP2C9-inhibitor:   0.939 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.16 CYP2D6-substrate:   0.004
CYP3A4-inhibitor:   0.985 CYP3A4-substrate:   0.121
CYP2B6-substrate:   0.001 CYP2C8-inhibitor:   0.02
HLM stability:   0.453
?
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):  10.187 Half-life (T1/2):  1.074

ADMET: Toxicity

hERG Blockers:  0.04 hERG Blockers (10um):  0.256
Human Hepatotoxicity (H-HT):  0.726 Drug-induced Liver Injury (DILI):  0.404
AMES Toxicity:  0.766 Rat Oral Acute Toxicity:  0.336
Maximum Recommended Daily Dose:  0.169 Skin Sensitization:  0.977
Carcinogencity:  0.799 Eye Corrosion:  0.133
Eye Irritation:  0.966 Respiratory Toxicity:  0.636
Drug-induced Neurotoxicity:  0.231 Ototoxicity:  0.559
Hematotoxicity:  0.601 Drug-induced Nephrotoxicity:  0.398
Genotoxicity:  0.184 RPMI-8226 Immunitoxicity:  0.114
A549 Cytotoxicity:  0.123 Hek293 Cytotoxicity:  0.243
BCF:   1.078
?
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:   3.65
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.345
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.561
?
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
NPO863 Rhaphidophora decursiva Species Araceae Eukaryota n.a. n.a. n.a. PMID[11421741]
NPO24811 Cibotium barometz Species Cibotiaceae Eukaryota rhizomes n.a. n.a. PMID[19739599]
NPO41007 Phomopsis sp. TJ507A Strain Valsaceae Eukaryota n.a. n.a. n.a. PMID[29771527]
NPO22224 Caragana jubata Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[31577434]
NPO5050 Galium triflorum Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24811 Cibotium barometz Species Cibotiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12472 Buddleja davidii Species Scrophulariaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22224 Caragana jubata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14315 Conostylis setosa Species Haemodoraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15211 Eriogonum brevicaule Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO41007 Phomopsis sp. TJ507A Strain Valsaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13317 Geigeria acaulis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2059 Lactuca denticulata Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15080 Larix kamtschatica Species Pinaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15590 Peperomia tetraphylla Species Piperaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO863 Rhaphidophora decursiva Species Araceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14654 Rhododendron ledebourii Species Ericaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7952 Commelina communis Species Commelinaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7952 Commelina communis Species Commelinaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO12472 Buddleja davidii Species Scrophulariaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO24811 Cibotium barometz Species Cibotiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO22224 Caragana jubata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO10948 Guarea rhopalocarpa Species Meliaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO12472 Buddleja davidii Species Scrophulariaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO10948 Guarea rhopalocarpa Species Meliaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24811 Cibotium barometz Species Cibotiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7952 Commelina communis Species Commelinaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO22224 Caragana jubata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO22224 Caragana jubata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO24811 Cibotium barometz Species Cibotiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO24811 Cibotium barometz Species Cibotiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO7952 Commelina communis Species Commelinaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO8723 Ophiostoma piliferum Species Ophiostomataceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22224 Caragana jubata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24811 Cibotium barometz Species Cibotiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14654 Rhododendron ledebourii Species Ericaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5050 Galium triflorum Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2059 Lactuca denticulata Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10948 Guarea rhopalocarpa Species Meliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO863 Rhaphidophora decursiva Species Araceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14315 Conostylis setosa Species Haemodoraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15080 Larix kamtschatica Species Pinaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15211 Eriogonum brevicaule Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15590 Peperomia tetraphylla Species Piperaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7952 Commelina communis Species Commelinaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13317 Geigeria acaulis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12472 Buddleja davidii Species Scrophulariaceae 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
NPT740 Individual protein Beta-secretase 1 Homo sapiens Inhibition = 19.4 % PMID[29771527]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT2 Others Unspecified n.a. EC50 = 100000.0 nM PMID[17936628]

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 NPC12818 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
0.5778 Remote Similarity NPC112903

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC12818 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