Natural Product: NPC215392

Natural Product IDNPC215392
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 2,4,6-Trihydroxy-3-(3,3-Dimethylallyl)Acetophenone
IUPAC Name 1-[2,4,6-trihydroxy-3-(3-methylbut-2-enyl)phenyl]ethanone
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1241050
PubChem CID 11687311
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0004603] Organic oxygen compounds
      • [CHEMONTID:0000323] Organooxygen compounds
        • [CHEMONTID:0001831] Carbonyl compounds
          • [CHEMONTID:0000118] Ketones
            • [CHEMONTID:0003670] Aryl ketones
              • [CHEMONTID:0004296] Phenylketones
                • [CHEMONTID:0004298] Alkyl-phenylketones

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 VSODLHSFRVYYBZ-UHFFFAOYSA-N
Standard InCHI InChI=1S/C13H16O4/c1-7(2)4-5-9-10(15)6-11(16)12(8(3)14)13(9)17/h4,6,15-17H,5H2,1-3H3
SMILES CC(=CCc1c(O)cc(c(c1O)C(=O)C)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   236.1 Volume:   246.826
?
Van der Waals volume.
Dense:   0.957 LogP:   2.742
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.751
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.799
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   8.0
TPSA:   77.76
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   3.0 Rings:   1.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.556 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.673 Fsp3:   0.308
MCE-18:   10.0
?
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:   0.382 Fluc inhibitor:   0.042
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.618
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.173
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.885 Promiscuous compounds:   0.192

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.014 MDCK Permeability:   -4.729
Pgp-inhibitor:   0.297 Pgp-substrate:   0.042
PAMPA:   0.368
?
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):   0.063
20% Bioavailability (F20%):   0.434 30% Bioavailability (F30%):   0.829
50% Bioavailability (F50%):   0.988

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.142 MRP1:   0.927
Plasma Protein Binding (PPB):   86.298% Volume Distribution (VD):   0.237
Fu: 12.909%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.989
OATP1B3 inhibitor:   0.993 BCRP inhibitor:   0.617
BSEP inhibitor:   0.192

ADMET: Metabolism

CYP1A2-inhibitor:   0.849 CYP1A2-substrate:   0.997
CYP2C19-inhibitor:   0.76 CYP2C19-substrate:   0.984
CYP2C9-inhibitor:   0.653 CYP2C9-substrate:   0.938
CYP2D6-inhibitor:   0.967 CYP2D6-substrate:   0.23
CYP3A4-inhibitor:   0.963 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.006 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):  6.195 Half-life (T1/2):  1.076

ADMET: Toxicity

hERG Blockers:  0.019 hERG Blockers (10um):  0.52
Human Hepatotoxicity (H-HT):  0.436 Drug-induced Liver Injury (DILI):  0.268
AMES Toxicity:  0.628 Rat Oral Acute Toxicity:  0.486
Maximum Recommended Daily Dose:  0.309 Skin Sensitization:  0.941
Carcinogencity:  0.239 Eye Corrosion:  0.025
Eye Irritation:  0.985 Respiratory Toxicity:  0.984
Drug-induced Neurotoxicity:  0.163 Ototoxicity:  0.293
Hematotoxicity:  0.193 Drug-induced Nephrotoxicity:  0.452
Genotoxicity:  0.806 RPMI-8226 Immunitoxicity:  0.125
A549 Cytotoxicity:  0.45 Hek293 Cytotoxicity:  0.504
BCF:   1.686
?
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:   3.925
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.385
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.649
?
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
NPO25763 Miconia lepidota Species Melastomataceae Eukaryota n.a. n.a. n.a. PMID[11170656]
NPO25763 Miconia lepidota Species Melastomataceae Eukaryota n.a. Suriname rainforest n.a. PMID[11170656]
NPO10501 Mitrephora glabra Species Annonaceae Eukaryota stem bark n.a. n.a. PMID[19874044]
NPO5744 Galipea panamensis Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[20423106]
NPO12221 Acacia saligna Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[25183120]
NPO26454 Acacia oswaldii Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12221 Acacia saligna Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5298 Anastrepha ludens Species Tephritidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6956 Citrus limonia Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26697 Dracocephalum moldavicum Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13782 Dicranopteris pedata Species Gleicheniaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28056 Drepanospora viridis Species n.a. Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24789 Opuntia elatior Species Cactaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO660 Elephas maximus Species Elephantidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5744 Galipea panamensis Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25082 Glycine canescens Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7038 Helichrysum oreophilum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25109 Paenibacillus polymyxa Species Paenibacillaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO7231 Vernonia polyanthes Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8166 Polygala paniculata Species Polygalaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1363 Photinia glabra Species Rosaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4930 Philodendron guttiferum Species Araceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2000 Helichrysum stenopterum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1992 Ophiura leptoctenia Species Ophiuridae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10501 Mitrephora glabra Species Annonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24800 Mentha crispa Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4288 Lambertella hicoriae Species Rutstroemiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13782 Dicranopteris pedata Species Gleicheniaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO23541 Smilax sieboldii Species Smilacaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO6956 Citrus limonia Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO26697 Dracocephalum moldavicum Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO660 Elephas maximus Species Elephantidae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO13782 Dicranopteris pedata Species Gleicheniaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO6956 Citrus limonia Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO26697 Dracocephalum moldavicum Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO660 Elephas maximus Species Elephantidae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO23541 Smilax sieboldii Species Smilacaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO23541 Smilax sieboldii Species Smilacaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO26697 Dracocephalum moldavicum Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO6956 Citrus limonia Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO25987 Euphorbia obtusifolia Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4288 Lambertella hicoriae Species Rutstroemiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26454 Acacia oswaldii Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6956 Citrus limonia Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13782 Dicranopteris pedata Species Gleicheniaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5744 Galipea panamensis Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25763 Miconia lepidota Species Melastomataceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28056 Drepanospora viridis Species n.a. Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8166 Polygala paniculata Species Polygalaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25109 Paenibacillus polymyxa Species Paenibacillaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO12221 Acacia saligna Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1992 Ophiura leptoctenia Species Ophiuridae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4930 Philodendron guttiferum Species Araceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2000 Helichrysum stenopterum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7231 Vernonia polyanthes Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26734 Cupaniopsis azantha Species Sapindaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8394 Ramalina geniculata Species Ramalinaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25082 Glycine canescens Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23541 Smilax sieboldii Species Smilacaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7038 Helichrysum oreophilum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO660 Elephas maximus Species Elephantidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25724 Mya arenaria Species Myidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1363 Photinia glabra Species Rosaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26672 Matricaria tenuifolia Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24789 Opuntia elatior Species Cactaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26697 Dracocephalum moldavicum Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5298 Anastrepha ludens Species Tephritidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24800 Mentha crispa Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10501 Mitrephora glabra Species Annonaceae 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
NPT956 Individual protein Prostaglandin E synthase Homo sapiens IC50 > 10000.0 nM PMID[28240894]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT165 Cell line HeLa Homo sapiens IC50 = 30000.0 nM PMID[20619940]
NPT81 Cell line A549 Homo sapiens IC50 = 29000.0 nM PMID[20619940]
NPT139 Cell line HT-29 Homo sapiens IC50 = 28000.0 nM PMID[20619940]
NPT116 Cell line HL-60 Homo sapiens IC50 = 32000.0 nM PMID[20619940]
NPT6 Organism Plasmodium falciparum Plasmodium falciparum IC50 > 20000.0 nM PMID[27228055]

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 NPC215392 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
0.725 Intermediate Similarity NPC91105
0.6444 Remote Similarity NPC98254
0.6222 Remote Similarity NPC65761
0.6129 Remote Similarity NPC226275
0.6087 Remote Similarity NPC472029
0.5366 Remote Similarity NPC481376
0.5283 Remote Similarity NPC483966
0.5263 Remote Similarity NPC480241
0.5208 Remote Similarity NPC166480
0.5185 Remote Similarity NPC23126

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC215392 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