Natural Product: NPC511977

Natural Product IDNPC511977
Common Name
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The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Trans-3,4-bis(3,4-dimethoxybenzyl)tetrahydrofuran
IUPAC Name (3~{R},4~{R})-3,4-bis[(3,4-dimethoxyphenyl)methyl]tetrahydrofuran
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]

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 DMDLIQAXFOCGBP-ROUUACIJSA-N
Standard InCHI InChI=1S/C22H28O5/c1-23-19-7-5-15(11-21(19)25-3)9-17-13-27-14-18(17)10-16-6-8-20(24-2)22(12-16)26-4/h5-8,11-12,17-18H,9-10,13-14H2,1-4H3/t17-,18-/m0/s1
SMILES COC1=CC=C(C[C@H]2COC[C@@H]2CC2=CC=C(OC)C(OC)=C2)C=C1OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   372.19 Volume:   391.531
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Van der Waals volume.
Dense:   0.951 LogP:   2.499
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.658
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.295
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The logarithm of aqueous solubility value.
Rotatable Bonds:   8.0 Rigid Bonds:   17.0
TPSA:   46.15
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Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.706 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.968 Fsp3:   0.455
MCE-18:   55.25
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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:   0.204 Fluc inhibitor:   0.276
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.022
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.161
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.327 Promiscuous compounds:   0.109

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.56 MDCK Permeability:   -4.674
Pgp-inhibitor:   0.974 Pgp-substrate:   0.79
PAMPA:   0.005
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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):   0.008
20% Bioavailability (F20%):   0.355 30% Bioavailability (F30%):   0.18
50% Bioavailability (F50%):   0.431

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.031 MRP1:   0.839
Plasma Protein Binding (PPB):   88.752% Volume Distribution (VD):   0.219
Fu: 9.983%
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The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.982
OATP1B3 inhibitor:   0.95 BCRP inhibitor:   0.57
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.998 CYP1A2-substrate:   0.769
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.247 CYP2C9-substrate:   0.032
CYP2D6-inhibitor:   0.975 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   0.434
CYP2B6-substrate:   0.75 CYP2C8-inhibitor:   1.0
HLM stability:   0.967
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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):  9.07 Half-life (T1/2):  1.787

ADMET: Toxicity

hERG Blockers:  0.346 hERG Blockers (10um):  0.489
Human Hepatotoxicity (H-HT):  0.956 Drug-induced Liver Injury (DILI):  0.988
AMES Toxicity:  0.753 Rat Oral Acute Toxicity:  0.254
Maximum Recommended Daily Dose:  0.258 Skin Sensitization:  0.965
Carcinogencity:  0.694 Eye Corrosion:  0.028
Eye Irritation:  0.947 Respiratory Toxicity:  0.503
Drug-induced Neurotoxicity:  0.969 Ototoxicity:  0.735
Hematotoxicity:  0.445 Drug-induced Nephrotoxicity:  0.906
Genotoxicity:  0.559 RPMI-8226 Immunitoxicity:  0.179
A549 Cytotoxicity:  0.182 Hek293 Cytotoxicity:  0.402
BCF:   2.314
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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:   4.325
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.512
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.076
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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
NPO54104 Flindersia brassii Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]

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





 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 NPC511977 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
0.8529 High Similarity NPC81067
0.8529 High Similarity NPC602945
0.7179 Intermediate Similarity NPC600801
0.6977 Remote Similarity NPC192255
0.6667 Remote Similarity NPC223807
0.6389 Remote Similarity NPC165106
0.6364 Remote Similarity NPC482890
0.6087 Remote Similarity NPC211386
0.6042 Remote Similarity NPC206882
0.5814 Remote Similarity NPC31344
0.5814 Remote Similarity NPC317769
0.575 Remote Similarity NPC477886
0.5714 Remote Similarity NPC205915
0.5682 Remote Similarity NPC476748
0.5625 Remote Similarity NPC143895
0.5405 Remote Similarity NPC292792
0.5349 Remote Similarity NPC344161
0.5283 Remote Similarity NPC5310
0.5283 Remote Similarity NPC300776
0.5283 Remote Similarity NPC176814
0.5283 Remote Similarity NPC4982
0.5283 Remote Similarity NPC606629
0.5273 Remote Similarity NPC40094
0.5192 Remote Similarity NPC18576
0.5128 Remote Similarity NPC254625
0.5128 Remote Similarity NPC120075

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC511977 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
0.6389 Remote Similarity NPD5283 Phase 2

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