Natural Product: NPC252544

Natural Product IDNPC252544
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (5S)-5-Hydroxy-1-(4-Hydroxyphenyl)-7-Phenylheptan-3-One
IUPAC Name (5S)-5-hydroxy-1-(4-hydroxyphenyl)-7-phenylheptan-3-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1824570
PubChem CID 54577336
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 NKSWRYBLSIGGIU-SFHVURJKSA-N
Standard InCHI InChI=1S/C19H22O3/c20-17-10-6-16(7-11-17)9-13-19(22)14-18(21)12-8-15-4-2-1-3-5-15/h1-7,10-11,18,20-21H,8-9,12-14H2/t18-/m0/s1
SMILES O[C@H](CC(=O)CCc1ccc(cc1)O)CCc1ccccc1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   298.16 Volume:   327.983
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Van der Waals volume.
Dense:   0.909 LogP:   3.079
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.603
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.14
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The logarithm of aqueous solubility value.
Rotatable Bonds:   8.0 Rigid Bonds:   13.0
TPSA:   57.53
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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:   0.786 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.384 Fsp3:   0.316
MCE-18:   22.0
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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:   0 PAINS Alert:   0
Colloidal aggregators:   0.388 Fluc inhibitor:   0.01
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.024
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.197
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.709 Promiscuous compounds:   0.296

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.084 MDCK Permeability:   -4.825
Pgp-inhibitor:   1.0 Pgp-substrate:   0.36
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%):   0.06 30% Bioavailability (F30%):   0.997
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.006
Plasma Protein Binding (PPB):   96.389% Volume Distribution (VD):   -0.289
Fu: 4.147%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.994
OATP1B3 inhibitor:   0.954 BCRP inhibitor:   0.818
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.002 CYP1A2-substrate:   0.009
CYP2C19-inhibitor:   0.132 CYP2C19-substrate:   0.005
CYP2C9-inhibitor:   0.071 CYP2C9-substrate:   0.011
CYP2D6-inhibitor:   0.965 CYP2D6-substrate:   0.418
CYP3A4-inhibitor:   0.095 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.526
HLM stability:   0.869
?
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):  11.068 Half-life (T1/2):  0.999

ADMET: Toxicity

hERG Blockers:  0.505 hERG Blockers (10um):  0.812
Human Hepatotoxicity (H-HT):  0.861 Drug-induced Liver Injury (DILI):  0.026
AMES Toxicity:  0.126 Rat Oral Acute Toxicity:  0.065
Maximum Recommended Daily Dose:  0.858 Skin Sensitization:  0.873
Carcinogencity:  0.183 Eye Corrosion:  0.047
Eye Irritation:  0.947 Respiratory Toxicity:  0.193
Drug-induced Neurotoxicity:  0.822 Ototoxicity:  0.681
Hematotoxicity:  0.185 Drug-induced Nephrotoxicity:  0.954
Genotoxicity:  0.033 RPMI-8226 Immunitoxicity:  0.032
A549 Cytotoxicity:  0.215 Hek293 Cytotoxicity:  0.434
BCF:   0.654
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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:   3.337
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.467
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.999
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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
NPO22741 Curcuma kwangsiensis Species Zingiberaceae Eukaryota n.a. rhizome n.a. DOI[10.1021/np100392m]
NPO22741 Curcuma kwangsiensis Species Zingiberaceae Eukaryota Rhizomes n.a. n.a. PMID[20879743]
NPO22741 Curcuma kwangsiensis Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[21807513]
NPO22741 Curcuma kwangsiensis Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22741 Curcuma kwangsiensis Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO22741 Curcuma kwangsiensis Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO22741 Curcuma kwangsiensis Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO22741 Curcuma kwangsiensis Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO22741 Curcuma kwangsiensis 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

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT113 Cell line RAW264.7 Mus musculus IC50 = 75710.0 nM PMID[19211174]

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 NPC252544 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 NPC321252
0.8974 High Similarity NPC177576
0.8205 Intermediate Similarity NPC187725
0.8205 Intermediate Similarity NPC141607
0.8205 Intermediate Similarity NPC310194
0.7778 Intermediate Similarity NPC265454
0.7059 Intermediate Similarity NPC275724
0.7059 Intermediate Similarity NPC244246
0.7059 Intermediate Similarity NPC611247
0.6889 Remote Similarity NPC34634
0.6863 Remote Similarity NPC215941
0.6863 Remote Similarity NPC123196
0.6863 Remote Similarity NPC311419
0.6667 Remote Similarity NPC213730
0.6596 Remote Similarity NPC317305
0.6458 Remote Similarity NPC182240
0.6078 Remote Similarity NPC137427
0.6042 Remote Similarity NPC249435
0.5962 Remote Similarity NPC481913
0.5952 Remote Similarity NPC188677
0.5714 Remote Similarity NPC91461
0.5714 Remote Similarity NPC7686
0.5714 Remote Similarity NPC40258
0.5686 Remote Similarity NPC285350
0.551 Remote Similarity NPC49529
0.5476 Remote Similarity NPC260000
0.5439 Remote Similarity NPC65935
0.5439 Remote Similarity NPC319282
0.5435 Remote Similarity NPC132078
0.5435 Remote Similarity NPC600556
0.5385 Remote Similarity NPC51333
0.5385 Remote Similarity NPC63345
0.5319 Remote Similarity NPC261573
0.5283 Remote Similarity NPC8931
0.5273 Remote Similarity NPC86900
0.5238 Remote Similarity NPC138117
0.5238 Remote Similarity NPC325292
0.5192 Remote Similarity NPC481914
0.5098 Remote Similarity NPC206764

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC252544 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