Natural Product: NPC63083

Natural Product IDNPC63083
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 3-(3,4,5-Trimethoxyphenyl)Propan-1-Ol
IUPAC Name 3-(3,4,5-trimethoxyphenyl)propan-1-ol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2088632
PubChem CID 6428843
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0002341] Phenol ethers
        • [CHEMONTID:0000138] Anisoles

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 IBRWTCISGCXHQZ-UHFFFAOYSA-N
Standard InCHI InChI=1S/C12H18O4/c1-14-10-7-9(5-4-6-13)8-11(15-2)12(10)16-3/h7-8,13H,4-6H2,1-3H3
SMILES COc1cc(CCCO)cc(c1OC)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   226.12 Volume:   234.803
?
Van der Waals volume.
Dense:   0.963 LogP:   1.369
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.643
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.944
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   6.0
TPSA:   47.92
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   1.0 Rings:   1.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.801 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   1.782 Fsp3:   0.5
MCE-18:   7.0
?
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:   0.043 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.018
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.156
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.659 Promiscuous compounds:   0.143

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.797 MDCK Permeability:   -4.691
Pgp-inhibitor:   0.342 Pgp-substrate:   0.385
PAMPA:   0.149
?
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):   0.037
20% Bioavailability (F20%):   0.129 30% Bioavailability (F30%):   0.071
50% Bioavailability (F50%):   0.348

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.735 MRP1:   0.889
Plasma Protein Binding (PPB):   56.06% Volume Distribution (VD):   -0.357
Fu: 42.911%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.874
OATP1B3 inhibitor:   0.832 BCRP inhibitor:   0.104
BSEP inhibitor:   0.962

ADMET: Metabolism

CYP1A2-inhibitor:   0.483 CYP1A2-substrate:   0.001
CYP2C19-inhibitor:   0.99 CYP2C19-substrate:   0.005
CYP2C9-inhibitor:   0.977 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.134 CYP2D6-substrate:   0.245
CYP3A4-inhibitor:   0.964 CYP3A4-substrate:   0.005
CYP2B6-substrate:   0.034 CYP2C8-inhibitor:   0.947
HLM stability:   0.039
?
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):  6.892 Half-life (T1/2):  1.124

ADMET: Toxicity

hERG Blockers:  0.176 hERG Blockers (10um):  0.524
Human Hepatotoxicity (H-HT):  0.538 Drug-induced Liver Injury (DILI):  0.205
AMES Toxicity:  0.25 Rat Oral Acute Toxicity:  0.147
Maximum Recommended Daily Dose:  0.123 Skin Sensitization:  0.618
Carcinogencity:  0.469 Eye Corrosion:  0.861
Eye Irritation:  0.983 Respiratory Toxicity:  0.604
Drug-induced Neurotoxicity:  0.461 Ototoxicity:  0.457
Hematotoxicity:  0.389 Drug-induced Nephrotoxicity:  0.431
Genotoxicity:  0.011 RPMI-8226 Immunitoxicity:  0.059
A549 Cytotoxicity:  0.097 Hek293 Cytotoxicity:  0.157
BCF:   0.535
?
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:   2.591
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   3.861
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.226
?
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
NPO8666 Acorus tatarinowii Species Acoraceae Eukaryota n.a. n.a. n.a. PMID[20476749]
NPO5681 Acorus gramineus Species Acoraceae Eukaryota n.a. rhizome n.a. PMID[21936523]
NPO5681 Acorus gramineus Species Acoraceae Eukaryota Rhizomes n.a. n.a. PMID[21936523]
NPO5681 Acorus gramineus Species Acoraceae Eukaryota rhizomes n.a. n.a. PMID[22951040]
NPO8666 Acorus tatarinowii Species Acoraceae Eukaryota n.a. rhizome n.a. PMID[23713285]
NPO8666 Acorus tatarinowii Species Acoraceae Eukaryota rhizomes n.a. n.a. PMID[26296476]
NPO8666 Acorus tatarinowii Species Acoraceae Eukaryota n.a. n.a. n.a. PMID[26305406]
NPO8666 Acorus tatarinowii Species Acoraceae Eukaryota Rhizomes n.a. n.a. PMID[29116780]
NPO8666 Acorus tatarinowii Species Acoraceae Eukaryota n.a. n.a. n.a. PMID[32807141]
NPO8666 Acorus tatarinowii Species Acoraceae Eukaryota n.a. n.a. n.a. PMID[38821245]
NPO8666 Acorus tatarinowii Species Acoraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5681 Acorus gramineus Species Acoraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5681 Acorus gramineus Species Acoraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO8666 Acorus tatarinowii Species Acoraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO5681 Acorus gramineus Species Acoraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8666 Acorus tatarinowii Species Acoraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8666 Acorus tatarinowii Species Acoraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO5681 Acorus gramineus Species Acoraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO8666 Acorus tatarinowii Species Acoraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO8666 Acorus tatarinowii Species Acoraceae 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
NPT34 Cell line BV-2 Mus musculus Activity = 96.3 % PMID[22951040]
NPT34 Cell line BV-2 Mus musculus IC50 = 141740.0 nM PMID[22951040]
NPT81 Cell line A549 Homo sapiens IC50 > 30000.0 nM PMID[22951040]
NPT146 Cell line SK-OV-3 Homo sapiens IC50 > 30000.0 nM PMID[22951040]
NPT147 Cell line SK-MEL-2 Homo sapiens IC50 > 30000.0 nM PMID[22951040]
NPT148 Cell line HCT-15 Homo sapiens IC50 > 30000.0 nM PMID[22951040]

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 NPC63083 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
0.6667 Remote Similarity NPC49341
0.6667 Remote Similarity NPC137685
0.6111 Remote Similarity NPC486042
0.5952 Remote Similarity NPC469612
0.5952 Remote Similarity NPC469614
0.5862 Remote Similarity NPC603667
0.5714 Remote Similarity NPC600726
0.5556 Remote Similarity NPC3439
0.5556 Remote Similarity NPC285339
0.5435 Remote Similarity NPC215833
0.5385 Remote Similarity NPC472968
0.5312 Remote Similarity NPC204120
0.5312 Remote Similarity NPC609116
0.5208 Remote Similarity NPC469613
0.5208 Remote Similarity NPC30043
0.5208 Remote Similarity NPC469625
0.5152 Remote Similarity NPC105513
0.5116 Remote Similarity NPC71090
0.5102 Remote Similarity NPC16208

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC63083 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