Natural Product: NPC137440

Natural Product IDNPC137440
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 HDQFIVFINXJTNV-LSDHHAIUSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 53359577
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0001392] Lignans, neolignans and related compounds
      • [CHEMONTID:0001969] Dibenzylbutane lignans

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 HDQFIVFINXJTNV-LSDHHAIUSA-N
Standard InCHI InChI=1S/C22H30O5/c1-14(9-16-7-8-18(23)19(11-16)24-3)15(2)10-17-12-20(25-4)22(27-6)21(13-17)26-5/h7-8,11-15,23H,9-10H2,1-6H3/t14-,15+/m0/s1
SMILES C[C@@H](Cc1ccc(c(c1)OC)O)[C@H](C)Cc1cc(c(c(c1)OC)OC)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   374.21 Volume:   400.088
?
Van der Waals volume.
Dense:   0.935 LogP:   3.479
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.11
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.497
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   9.0 Rigid Bonds:   12.0
TPSA:   57.15
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   1.0 Rings:   2.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.701 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.904 Fsp3:   0.455
MCE-18:   30.0
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.202 Fluc inhibitor:   0.031
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.021
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.228
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.416 Promiscuous compounds:   0.214

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.967 MDCK Permeability:   -4.72
Pgp-inhibitor:   0.853 Pgp-substrate:   0.073
PAMPA:   0.0
?
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):   0.003
20% Bioavailability (F20%):   0.584 30% Bioavailability (F30%):   0.886
50% Bioavailability (F50%):   0.99

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.015 MRP1:   0.919
Plasma Protein Binding (PPB):   88.823% Volume Distribution (VD):   -0.174
Fu: 11.689%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.99
OATP1B3 inhibitor:   0.959 BCRP inhibitor:   0.763
BSEP inhibitor:   0.999

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.877
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.006 CYP2C9-substrate:   0.934
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.909
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.854
?
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):  7.133 Half-life (T1/2):  1.119

ADMET: Toxicity

hERG Blockers:  0.312 hERG Blockers (10um):  0.679
Human Hepatotoxicity (H-HT):  0.599 Drug-induced Liver Injury (DILI):  0.363
AMES Toxicity:  0.352 Rat Oral Acute Toxicity:  0.308
Maximum Recommended Daily Dose:  0.463 Skin Sensitization:  0.562
Carcinogencity:  0.394 Eye Corrosion:  0.044
Eye Irritation:  0.796 Respiratory Toxicity:  0.765
Drug-induced Neurotoxicity:  0.672 Ototoxicity:  0.445
Hematotoxicity:  0.443 Drug-induced Nephrotoxicity:  0.443
Genotoxicity:  0.102 RPMI-8226 Immunitoxicity:  0.153
A549 Cytotoxicity:  0.432 Hek293 Cytotoxicity:  0.534
BCF:   1.965
?
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:   4.228
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.341
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.771
?
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
NPO2462 Machilus robusta Species Lauraceae Eukaryota bark n.a. n.a. PMID[21627109]
NPO2462 Machilus robusta Species Lauraceae Eukaryota n.a. bark n.a. PMID[21627109]
NPO2462 Machilus robusta Species Lauraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2462 Machilus robusta Species Lauraceae 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





 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 NPC137440 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
0.8378 Intermediate Similarity NPC165133
0.8378 Intermediate Similarity NPC242885
0.8378 Intermediate Similarity NPC95614
0.8378 Intermediate Similarity NPC232316
0.7857 Intermediate Similarity NPC227217
0.7857 Intermediate Similarity NPC117780
0.7209 Intermediate Similarity NPC56214
0.7073 Intermediate Similarity NPC57490
0.7059 Intermediate Similarity NPC291101
0.7059 Intermediate Similarity NPC266197
0.7021 Intermediate Similarity NPC274356
0.7021 Intermediate Similarity NPC101748
0.6889 Remote Similarity NPC127587
0.6818 Remote Similarity NPC487676
0.641 Remote Similarity NPC156840
0.6279 Remote Similarity NPC85488
0.6275 Remote Similarity NPC284464
0.6226 Remote Similarity NPC106920
0.6226 Remote Similarity NPC15811
0.619 Remote Similarity NPC477886
0.6042 Remote Similarity NPC607444
0.6 Remote Similarity NPC487680
0.5952 Remote Similarity NPC8547
0.5926 Remote Similarity NPC487677
0.5926 Remote Similarity NPC487675
0.5918 Remote Similarity NPC603109
0.587 Remote Similarity NPC31344
0.587 Remote Similarity NPC317769
0.5714 Remote Similarity NPC257124
0.5581 Remote Similarity NPC221049
0.5581 Remote Similarity NPC140359
0.5532 Remote Similarity NPC203133
0.5517 Remote Similarity NPC487679
0.5517 Remote Similarity NPC487678
0.5455 Remote Similarity NPC471693
0.5455 Remote Similarity NPC76451
0.5455 Remote Similarity NPC193544
0.5439 Remote Similarity NPC161249
0.5435 Remote Similarity NPC299406
0.54 Remote Similarity NPC5428
0.5357 Remote Similarity NPC46880
0.5333 Remote Similarity NPC255675
0.5333 Remote Similarity NPC216223
0.5263 Remote Similarity NPC487681
0.5238 Remote Similarity NPC165106
0.5227 Remote Similarity NPC233526
0.5217 Remote Similarity NPC603326
0.5217 Remote Similarity NPC603989
0.5185 Remote Similarity NPC275950
0.5172 Remote Similarity NPC106739
0.5106 Remote Similarity NPC197757
0.5106 Remote Similarity NPC17943
0.5094 Remote Similarity NPC68779
0.5094 Remote Similarity NPC108598
0.5094 Remote Similarity NPC173308
0.5094 Remote Similarity NPC181079
0.5088 Remote Similarity NPC300776
0.5088 Remote Similarity NPC176814
0.5088 Remote Similarity NPC4982
0.5088 Remote Similarity NPC606629
0.5085 Remote Similarity NPC471505

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC137440 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
0.5714 Remote Similarity NPD228 Phase 0
0.5238 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