Natural Product: NPC213730

Natural Product IDNPC213730
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (3R,5R)-1-(4-Hydroxyphenyl)-7-Phenylheptane-3,5-Diol
IUPAC Name (3R,5R)-1-(4-hydroxyphenyl)-7-phenylheptane-3,5-diol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL489757
PubChem CID 13888136
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 GIJBVGHAAVSQGB-RTBURBONSA-N
Standard InCHI InChI=1S/C19H24O3/c20-17-10-6-16(7-11-17)9-13-19(22)14-18(21)12-8-15-4-2-1-3-5-15/h1-7,10-11,18-22H,8-9,12-14H2/t18-,19-/m1/s1
SMILES c1ccc(cc1)CC[C@H](C[C@@H](CCc1ccc(cc1)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   300.17 Volume:   330.619
?
Van der Waals volume.
Dense:   0.908 LogP:   2.69
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.382
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.984
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   8.0 Rigid Bonds:   12.0
TPSA:   60.69
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   3.0 Rings:   2.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.702 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.648 Fsp3:   0.368
MCE-18:   22.0
?
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:   0.314 Fluc inhibitor:   0.005
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.009
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.009
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.705 Promiscuous compounds:   0.361

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.128 MDCK Permeability:   -4.82
Pgp-inhibitor:   0.619 Pgp-substrate:   0.944
PAMPA:   0.156
?
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%):   0.261 30% Bioavailability (F30%):   0.998
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.027
Plasma Protein Binding (PPB):   95.586% Volume Distribution (VD):   -0.012
Fu: 4.625%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.969
OATP1B3 inhibitor:   0.754 BCRP inhibitor:   0.601
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.012
CYP2C19-inhibitor:   0.121 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.042 CYP2C9-substrate:   0.119
CYP2D6-inhibitor:   0.527 CYP2D6-substrate:   0.156
CYP3A4-inhibitor:   0.995 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.106
HLM stability:   0.802
?
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):  13.385 Half-life (T1/2):  1.411

ADMET: Toxicity

hERG Blockers:  0.759 hERG Blockers (10um):  0.9
Human Hepatotoxicity (H-HT):  0.822 Drug-induced Liver Injury (DILI):  0.068
AMES Toxicity:  0.243 Rat Oral Acute Toxicity:  0.08
Maximum Recommended Daily Dose:  0.947 Skin Sensitization:  0.969
Carcinogencity:  0.176 Eye Corrosion:  0.011
Eye Irritation:  0.642 Respiratory Toxicity:  0.57
Drug-induced Neurotoxicity:  0.741 Ototoxicity:  0.807
Hematotoxicity:  0.39 Drug-induced Nephrotoxicity:  0.971
Genotoxicity:  0.034 RPMI-8226 Immunitoxicity:  0.056
A549 Cytotoxicity:  0.908 Hek293 Cytotoxicity:  0.875
BCF:   0.554
?
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:   3.277
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.475
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.868
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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
NPO33450 aplinia officinarum Species n.a. n.a. n.a. n.a. n.a. PMID[12350154]
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

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
NPT673 Organism Gallus gallus Gallus gallus Inhibition = 37.7 % PMID[12350154]





 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 NPC213730 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
0.871 High Similarity NPC91461
0.871 High Similarity NPC7686
0.871 High Similarity NPC40258
0.7742 Intermediate Similarity NPC322515
0.7742 Intermediate Similarity NPC121478
0.7297 Intermediate Similarity NPC179002
0.7297 Intermediate Similarity NPC257430
0.6667 Remote Similarity NPC321252
0.6667 Remote Similarity NPC252544
0.6579 Remote Similarity NPC132078
0.6579 Remote Similarity NPC600556
0.6471 Remote Similarity NPC138117
0.6471 Remote Similarity NPC325292
0.6429 Remote Similarity NPC249435
0.6364 Remote Similarity NPC324571
0.6279 Remote Similarity NPC186843
0.6216 Remote Similarity NPC187583
0.6136 Remote Similarity NPC473853
0.6136 Remote Similarity NPC470212
0.6 Remote Similarity NPC51333
0.5745 Remote Similarity NPC470213
0.5714 Remote Similarity NPC177576
0.5682 Remote Similarity NPC226401
0.5682 Remote Similarity NPC174096
0.54 Remote Similarity NPC154899
0.54 Remote Similarity NPC233396
0.5349 Remote Similarity NPC99482
0.5333 Remote Similarity NPC216468
0.5333 Remote Similarity NPC78119
0.5294 Remote Similarity NPC608485
0.5227 Remote Similarity NPC312675
0.5227 Remote Similarity NPC262156
0.5227 Remote Similarity NPC184651
0.5227 Remote Similarity NPC113865
0.5192 Remote Similarity NPC135464
0.5192 Remote Similarity NPC92623
0.5102 Remote Similarity NPC25689

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC213730 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