Natural Product: NPC244246

Natural Product IDNPC244246
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 5-Hydroxy-7-(4-Hydroxy-3-Methoxyphenyl)-1-Phenylheptan-3-One
IUPAC Name 5-hydroxy-7-(4-hydroxy-3-methoxyphenyl)-1-phenylheptan-3-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1506910
PubChem CID 5318228
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002650] Diarylheptanoids
        • [CHEMONTID:0002651] Linear diarylheptanoids

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 JHJPDDBIHSFERA-UHFFFAOYSA-N
Standard InCHI InChI=1S/C20H24O4/c1-24-20-13-16(9-12-19(20)23)8-11-18(22)14-17(21)10-7-15-5-3-2-4-6-15/h2-6,9,12-13,18,22-23H,7-8,10-11,14H2,1H3
SMILES COc1cc(CCC(CC(=O)CCc2ccccc2)O)ccc1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   328.17 Volume:   354.069
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Van der Waals volume.
Dense:   0.927 LogP:   3.231
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.001
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.644
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The logarithm of aqueous solubility value.
Rotatable Bonds:   9.0 Rigid Bonds:   13.0
TPSA:   66.76
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Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   2.0 Rings:   2.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.741 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.486 Fsp3:   0.35
MCE-18:   24.0
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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:   1 PAINS Alert:   0
Colloidal aggregators:   0.116 Fluc inhibitor:   0.006
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.038
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.395
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.406 Promiscuous compounds:   0.13

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.033 MDCK Permeability:   -4.735
Pgp-inhibitor:   1.0 Pgp-substrate:   0.04
PAMPA:   0.012
?
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%):   0.046 30% Bioavailability (F30%):   0.848
50% Bioavailability (F50%):   0.976

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.018
Plasma Protein Binding (PPB):   96.55% Volume Distribution (VD):   -0.29
Fu: 3.066%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.928
OATP1B3 inhibitor:   0.985 BCRP inhibitor:   0.826
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.772 CYP1A2-substrate:   0.05
CYP2C19-inhibitor:   0.986 CYP2C19-substrate:   0.004
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   0.004
CYP2D6-inhibitor:   0.147 CYP2D6-substrate:   0.021
CYP3A4-inhibitor:   0.645 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.001 CYP2C8-inhibitor:   0.981
HLM stability:   0.048
?
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):  8.175 Half-life (T1/2):  1.026

ADMET: Toxicity

hERG Blockers:  0.538 hERG Blockers (10um):  0.828
Human Hepatotoxicity (H-HT):  0.701 Drug-induced Liver Injury (DILI):  0.025
AMES Toxicity:  0.171 Rat Oral Acute Toxicity:  0.055
Maximum Recommended Daily Dose:  0.639 Skin Sensitization:  0.768
Carcinogencity:  0.132 Eye Corrosion:  0.011
Eye Irritation:  0.616 Respiratory Toxicity:  0.398
Drug-induced Neurotoxicity:  0.5 Ototoxicity:  0.819
Hematotoxicity:  0.276 Drug-induced Nephrotoxicity:  0.869
Genotoxicity:  0.049 RPMI-8226 Immunitoxicity:  0.029
A549 Cytotoxicity:  0.087 Hek293 Cytotoxicity:  0.392
BCF:   0.803
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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:   3.494
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.727
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.224
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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
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. root n.a. PMID[18484537]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. rhizome n.a. PMID[18484537]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota rhizomes n.a. n.a. PMID[19615910]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[29323912]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. rhizome n.a. PMID[731398]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. root n.a. PMID[731398]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO23911 Alpinia officinarum Species Zingiberaceae 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
NPT531 Individual protein Nuclear receptor ROR-gamma Mus musculus Potency = 11220.2 nM PubChem BioAssay data set
NPT60 Individual protein Lysosomal alpha-glucosidase Homo sapiens Potency = 25118.9 nM PubChem BioAssay data set
NPT59 Individual protein DNA polymerase beta Homo sapiens Potency = 25118.9 nM PubChem BioAssay data set
NPT8 Individual protein DNA polymerase iota Homo sapiens Potency n.a. 79432.8 nM PubChem BioAssay data set
NPT472 Individual protein Vanilloid receptor Homo sapiens Potency n.a. 816.2 nM PubChem BioAssay data set
NPT472 Individual protein Vanilloid receptor Homo sapiens Potency n.a. 2022.7 nM PubChem BioAssay data set
NPT49 Individual protein DNA-(apurinic or apyrimidinic site) lyase Homo sapiens Potency n.a. 14125.4 nM PubChem BioAssay data set

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT83 Cell line MCF7 Homo sapiens IC50 = 97200.0 nM PMID[33587631]
NPT6 Organism Plasmodium falciparum Plasmodium falciparum Potency n.a. 16511.3 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 1122.0 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

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 NPC244246 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 NPC275724
1.0 High Similarity NPC611247
0.8958 High Similarity NPC137427
0.8627 High Similarity NPC215941
0.8627 High Similarity NPC123196
0.8627 High Similarity NPC311419
0.7963 Intermediate Similarity NPC65935
0.7963 Intermediate Similarity NPC319282
0.7959 Intermediate Similarity NPC481914
0.7692 Intermediate Similarity NPC481913
0.7451 Intermediate Similarity NPC324571
0.7059 Intermediate Similarity NPC321252
0.7059 Intermediate Similarity NPC252544
0.6964 Remote Similarity NPC20287
0.6964 Remote Similarity NPC20404
0.6842 Remote Similarity NPC12022
0.6842 Remote Similarity NPC278308
0.6786 Remote Similarity NPC229497
0.6667 Remote Similarity NPC187725
0.6667 Remote Similarity NPC141607
0.6667 Remote Similarity NPC310194
0.6471 Remote Similarity NPC312675
0.6471 Remote Similarity NPC262156
0.6471 Remote Similarity NPC127937
0.6471 Remote Similarity NPC184651
0.6471 Remote Similarity NPC113865
0.6316 Remote Similarity NPC179777
0.6296 Remote Similarity NPC473853
0.6296 Remote Similarity NPC470212
0.6275 Remote Similarity NPC177576
0.6078 Remote Similarity NPC299406
0.6 Remote Similarity NPC98631
0.6 Remote Similarity NPC206615
0.5893 Remote Similarity NPC53305
0.5789 Remote Similarity NPC164386
0.5789 Remote Similarity NPC343720
0.5789 Remote Similarity NPC201777
0.5789 Remote Similarity NPC54872
0.5789 Remote Similarity NPC604524
0.5763 Remote Similarity NPC257589
0.5741 Remote Similarity NPC34634
0.5614 Remote Similarity NPC265454
0.5593 Remote Similarity NPC311595
0.5593 Remote Similarity NPC24474
0.5593 Remote Similarity NPC163083
0.5517 Remote Similarity NPC303680
0.5439 Remote Similarity NPC182240
0.5439 Remote Similarity NPC5018
0.541 Remote Similarity NPC310718
0.5345 Remote Similarity NPC114298
0.5333 Remote Similarity NPC123228
0.5333 Remote Similarity NPC123722
0.5323 Remote Similarity NPC304622
0.5312 Remote Similarity NPC207613
0.5294 Remote Similarity NPC8547
0.5254 Remote Similarity NPC4181
0.5238 Remote Similarity NPC84076
0.5082 Remote Similarity NPC164778
0.5077 Remote Similarity NPC90128

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC244246 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