Natural Product: NPC474214

Natural Product IDNPC474214
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-(3,4-Dimethoxyphenyl)-7-(4-Methoxyphenyl)Heptane-3,5-Diol
IUPAC Name (3R,5R)-1-(3,4-dimethoxyphenyl)-7-(4-methoxyphenyl)heptane-3,5-diol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL463544
PubChem CID 11143261
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002650] Diarylheptanoids
        • [CHEMONTID:0002651] Linear diarylheptanoids
          • [CHEMONTID:0000356] Curcuminoids

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 CXHGAJKEPFMHME-RTBURBONSA-N
Standard InCHI InChI=1S/C22H30O5/c1-25-20-11-6-16(7-12-20)4-9-18(23)15-19(24)10-5-17-8-13-21(26-2)22(14-17)27-3/h6-8,11-14,18-19,23-24H,4-5,9-10,15H2,1-3H3/t18-,19-/m1/s1
SMILES COC1=CC=C(C=C1)CCC(CC(CCC2=CC(=C(C=C2)OC)OC)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   374.21 Volume:   400.088
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Van der Waals volume.
Dense:   0.935 LogP:   2.355
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.559
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.082
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The logarithm of aqueous solubility value.
Rotatable Bonds:   11.0 Rigid Bonds:   12.0
TPSA:   68.15
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Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   2.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.631 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.726 Fsp3:   0.455
MCE-18:   26.0
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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:   0 PAINS Alert:   0
Colloidal aggregators:   0.334 Fluc inhibitor:   0.002
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.01
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.313
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.497 Promiscuous compounds:   0.095

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.947 MDCK Permeability:   -4.76
Pgp-inhibitor:   0.972 Pgp-substrate:   0.437
PAMPA:   0.01
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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):   0.197
20% Bioavailability (F20%):   0.169 30% Bioavailability (F30%):   0.772
50% Bioavailability (F50%):   0.894

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.097
Plasma Protein Binding (PPB):   85.12% Volume Distribution (VD):   0.074
Fu: 11.569%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.984
OATP1B3 inhibitor:   0.937 BCRP inhibitor:   0.799
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.998 CYP1A2-substrate:   0.027
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.005
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   0.146
CYP2D6-inhibitor:   0.996 CYP2D6-substrate:   0.903
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.994
HLM stability:   0.515
?
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):  9.803 Half-life (T1/2):  1.06

ADMET: Toxicity

hERG Blockers:  0.862 hERG Blockers (10um):  0.873
Human Hepatotoxicity (H-HT):  0.768 Drug-induced Liver Injury (DILI):  0.097
AMES Toxicity:  0.149 Rat Oral Acute Toxicity:  0.016
Maximum Recommended Daily Dose:  0.74 Skin Sensitization:  0.407
Carcinogencity:  0.152 Eye Corrosion:  0.001
Eye Irritation:  0.171 Respiratory Toxicity:  0.554
Drug-induced Neurotoxicity:  0.426 Ototoxicity:  0.962
Hematotoxicity:  0.355 Drug-induced Nephrotoxicity:  0.964
Genotoxicity:  0.013 RPMI-8226 Immunitoxicity:  0.055
A549 Cytotoxicity:  0.248 Hek293 Cytotoxicity:  0.584
BCF:   0.992
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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:   3.753
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.107
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.42
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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
NPO13332 Tacca chantrieri Species Taccaceae Eukaryota rhizomes SiMao City, Yunnan Province, China 1996-OCT PMID[11908966]
NPO13332 Tacca chantrieri Species Taccaceae Eukaryota Rhizomes n.a. n.a. PMID[12350150]
NPO13332 Tacca chantrieri Species Taccaceae Eukaryota n.a. n.a. n.a. PMID[20715765]
NPO13332 Tacca chantrieri Species Taccaceae Eukaryota n.a. n.a. n.a. PMID[33253561]
NPO13332 Tacca chantrieri Species Taccaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13332 Tacca chantrieri Species Taccaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO13332 Tacca chantrieri Species Taccaceae 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
NPT116 Cell line HL-60 Homo sapiens IC50 = 5.5 ug.mL-1 PMID[18973387]
NPT924 Cell line HSC-2 Homo sapiens IC50 = 3.9 ug.mL-1 PMID[11754608]

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 NPC474214 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
0.9167 High Similarity NPC474320
0.8333 Intermediate Similarity NPC474272
0.625 Remote Similarity NPC137685
0.5652 Remote Similarity NPC312675
0.5652 Remote Similarity NPC262156
0.5652 Remote Similarity NPC184651
0.5652 Remote Similarity NPC113865
0.551 Remote Similarity NPC473853
0.551 Remote Similarity NPC470212
0.54 Remote Similarity NPC324571
0.5306 Remote Similarity NPC186843
0.5294 Remote Similarity NPC485986
0.5227 Remote Similarity NPC609746
0.52 Remote Similarity NPC98631
0.52 Remote Similarity NPC206615
0.5192 Remote Similarity NPC244876
0.5128 Remote Similarity NPC321956

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC474214 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