Natural Product: NPC343720

Natural Product IDNPC343720
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 4-[(3S,5R)-3,5-Dihydroxy-7-(4-Hydroxy-3-Methoxyphenyl)Heptyl]Benzene-1,2-Diol
IUPAC Name 4-[(3S,5R)-3,5-dihydroxy-7-(4-hydroxy-3-methoxyphenyl)heptyl]benzene-1,2-diol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL464199
PubChem CID 11995071
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 RIDWNCYOYKOUAC-JKSUJKDBSA-N
Standard InCHI InChI=1S/C20H26O6/c1-26-20-11-14(5-9-18(20)24)3-7-16(22)12-15(21)6-2-13-4-8-17(23)19(25)10-13/h4-5,8-11,15-16,21-25H,2-3,6-7,12H2,1H3/t15-,16+/m0/s1
SMILES COc1cc(CC[C@H](C[C@H](CCc2ccc(c(c2)O)O)O)O)ccc1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   362.17 Volume:   374.286
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Van der Waals volume.
Dense:   0.968 LogP:   1.773
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.933
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.468
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The logarithm of aqueous solubility value.
Rotatable Bonds:   9.0 Rigid Bonds:   12.0
TPSA:   110.38
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Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   5.0 Rings:   2.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.438 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.041 Fsp3:   0.4
MCE-18:   28.0
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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:   Rejected GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   1
Colloidal aggregators:   0.494 Fluc inhibitor:   0.18
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.013
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.123
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.582 Promiscuous compounds:   0.519

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.273 MDCK Permeability:   -4.964
Pgp-inhibitor:   0.022 Pgp-substrate:   0.96
PAMPA:   0.176
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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%):   0.967 30% Bioavailability (F30%):   1.0
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.192
Plasma Protein Binding (PPB):   72.971% Volume Distribution (VD):   -0.214
Fu: 25.431%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   0.992 BCRP inhibitor:   0.952
BSEP inhibitor:   0.997

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.708 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.998 CYP2C9-substrate:   0.003
CYP2D6-inhibitor:   0.952 CYP2D6-substrate:   0.022
CYP3A4-inhibitor:   0.083 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.979
HLM stability:   0.03
?
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):  13.406 Half-life (T1/2):  2.037

ADMET: Toxicity

hERG Blockers:  0.309 hERG Blockers (10um):  0.786
Human Hepatotoxicity (H-HT):  0.705 Drug-induced Liver Injury (DILI):  0.115
AMES Toxicity:  0.133 Rat Oral Acute Toxicity:  0.037
Maximum Recommended Daily Dose:  0.935 Skin Sensitization:  0.969
Carcinogencity:  0.165 Eye Corrosion:  0.019
Eye Irritation:  0.906 Respiratory Toxicity:  0.324
Drug-induced Neurotoxicity:  0.079 Ototoxicity:  0.884
Hematotoxicity:  0.073 Drug-induced Nephrotoxicity:  0.807
Genotoxicity:  0.061 RPMI-8226 Immunitoxicity:  0.026
A549 Cytotoxicity:  0.763 Hek293 Cytotoxicity:  0.396
BCF:   0.497
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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:   3.09
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.427
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.776
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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
NPO32652 zingiber ottensii Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[17125238]

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
NPT1 Others Radical scavenging activity n.a. IC50 = 24000.0 nM PMID[15387645]

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 NPC343720 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 NPC54872
0.8571 High Similarity NPC312675
0.8571 High Similarity NPC262156
0.8571 High Similarity NPC184651
0.8571 High Similarity NPC113865
0.7826 Intermediate Similarity NPC473853
0.7826 Intermediate Similarity NPC98631
0.7826 Intermediate Similarity NPC206615
0.7826 Intermediate Similarity NPC470212
0.766 Intermediate Similarity NPC324571
0.75 Intermediate Similarity NPC65935
0.75 Intermediate Similarity NPC319282
0.72 Intermediate Similarity NPC311595
0.72 Intermediate Similarity NPC24474
0.6923 Remote Similarity NPC310718
0.6905 Remote Similarity NPC187583
0.6667 Remote Similarity NPC470213
0.6471 Remote Similarity NPC164386
0.6346 Remote Similarity NPC137427
0.6304 Remote Similarity NPC179002
0.6304 Remote Similarity NPC257430
0.62 Remote Similarity NPC186843
0.6 Remote Similarity NPC8547
0.5893 Remote Similarity NPC215941
0.5893 Remote Similarity NPC123196
0.5893 Remote Similarity NPC311419
0.587 Remote Similarity NPC471693
0.5862 Remote Similarity NPC207613
0.5821 Remote Similarity NPC177035
0.58 Remote Similarity NPC56214
0.5789 Remote Similarity NPC275724
0.5789 Remote Similarity NPC244246
0.5789 Remote Similarity NPC611247
0.5778 Remote Similarity NPC257124
0.5769 Remote Similarity NPC481914
0.5745 Remote Similarity NPC255675
0.5556 Remote Similarity NPC485986
0.551 Remote Similarity NPC17943
0.551 Remote Similarity NPC299406
0.537 Remote Similarity NPC212015
0.5357 Remote Similarity NPC481913
0.5333 Remote Similarity NPC156840
0.5319 Remote Similarity NPC221049
0.5306 Remote Similarity NPC474320
0.5294 Remote Similarity NPC177291
0.5294 Remote Similarity NPC127937
0.5273 Remote Similarity NPC303680
0.52 Remote Similarity NPC120982
0.5192 Remote Similarity NPC34634
0.5185 Remote Similarity NPC5018
0.5094 Remote Similarity NPC51840
0.5094 Remote Similarity NPC82679
0.5091 Remote Similarity NPC311680
0.5091 Remote Similarity NPC114298
0.5091 Remote Similarity NPC159968
0.5085 Remote Similarity NPC20287
0.5085 Remote Similarity NPC20404

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC343720 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
0.5778 Remote Similarity NPD228 Phase 0

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