Natural Product: NPC161249

Natural Product IDNPC161249
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 ROSZLESPLNBVCZ-MTJIALIYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 11791717
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 ROSZLESPLNBVCZ-MTJIALIYSA-N
Standard InCHI InChI=1S/C20H24O5/c1-12(8-14-4-6-16(21)18(9-14)23-3)13(2)20(22)15-5-7-17-19(10-15)25-11-24-17/h4-7,9-10,12-13,20-22H,8,11H2,1-3H3/t12-,13+,20-/m1/s1
SMILES C[C@H](Cc1ccc(c(c1)OC)O)[C@H](C)[C@H](c1ccc2c(c1)OCO2)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   344.16 Volume:   356.939
?
Van der Waals volume.
Dense:   0.964 LogP:   3.326
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.104
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.462
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   16.0
TPSA:   68.15
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.837 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.3 Fsp3:   0.4
MCE-18:   55.286
?
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:   0.53 Fluc inhibitor:   0.352
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.026
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.068
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.189 Promiscuous compounds:   0.354

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.076 MDCK Permeability:   -4.886
Pgp-inhibitor:   0.005 Pgp-substrate:   0.156
PAMPA:   0.144
?
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):   0.0
20% Bioavailability (F20%):   0.042 30% Bioavailability (F30%):   0.011
50% Bioavailability (F50%):   0.957

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.16 MRP1:   0.213
Plasma Protein Binding (PPB):   89.113% Volume Distribution (VD):   0.11
Fu: 11.421%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.983
OATP1B3 inhibitor:   0.914 BCRP inhibitor:   0.016
BSEP inhibitor:   0.936

ADMET: Metabolism

CYP1A2-inhibitor:   0.05 CYP1A2-substrate:   0.948
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.999
CYP2C9-inhibitor:   0.874 CYP2C9-substrate:   1.0
CYP2D6-inhibitor:   0.987 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   0.998 CYP3A4-substrate:   0.997
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.998
?
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):  7.02 Half-life (T1/2):  1.605

ADMET: Toxicity

hERG Blockers:  0.271 hERG Blockers (10um):  0.685
Human Hepatotoxicity (H-HT):  0.543 Drug-induced Liver Injury (DILI):  0.471
AMES Toxicity:  0.51 Rat Oral Acute Toxicity:  0.248
Maximum Recommended Daily Dose:  0.505 Skin Sensitization:  0.179
Carcinogencity:  0.554 Eye Corrosion:  0.007
Eye Irritation:  0.86 Respiratory Toxicity:  0.345
Drug-induced Neurotoxicity:  0.412 Ototoxicity:  0.65
Hematotoxicity:  0.273 Drug-induced Nephrotoxicity:  0.613
Genotoxicity:  0.387 RPMI-8226 Immunitoxicity:  0.129
A549 Cytotoxicity:  0.308 Hek293 Cytotoxicity:  0.621
BCF:   0.933
?
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:   3.552
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.976
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.277
?
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
NPO27465 Sinularia erecta Species Alcyoniidae Eukaryota n.a. n.a. n.a. PMID[27142697]
NPO40344 Schisandra bicolor var. tuberculata Strain Schisandraceae Eukaryota Fruits n.a. n.a. PMID[28333453]
NPO27339 Lactarius blennius Species Russulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27593 Silene dioica Species Caryophyllaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27777 Artemisia phaeolepis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27520 Casuarina equisetifolia Species Casuarinaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16221 Dolichos kilimandscharicus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27635 Laurencia dendroidea Species Rhodomelaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27742 Mollugo pentaphylla Species Molluginaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26934 Naucleopsis mello-barretoi Species Moraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27570 Paederia foetida Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27465 Sinularia erecta Species Alcyoniidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27130 Tsuga sieboldii Species Pinaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5146 Tuta absoluta Species Gelechiidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27520 Casuarina equisetifolia Species Casuarinaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO27742 Mollugo pentaphylla Species Molluginaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO27520 Casuarina equisetifolia Species Casuarinaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO27742 Mollugo pentaphylla Species Molluginaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO27520 Casuarina equisetifolia Species Casuarinaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO16221 Dolichos kilimandscharicus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27130 Tsuga sieboldii Species Pinaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27339 Lactarius blennius Species Russulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27635 Laurencia dendroidea Species Rhodomelaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27570 Paederia foetida Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27742 Mollugo pentaphylla Species Molluginaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27593 Silene dioica Species Caryophyllaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27465 Sinularia erecta Species Alcyoniidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26934 Naucleopsis mello-barretoi Species Moraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5146 Tuta absoluta Species Gelechiidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27777 Artemisia phaeolepis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27520 Casuarina equisetifolia Species Casuarinaceae 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
NPT519 Cell line SH-SY5Y Homo sapiens Activity > 15.0 % PMID[28333453]
NPT519 Cell line SH-SY5Y Homo sapiens Activity = 76.6 % PMID[28333453]
NPT519 Cell line SH-SY5Y Homo sapiens Activity = 83.3 % PMID[28333453]
NPT519 Cell line SH-SY5Y Homo sapiens Activity = 81.6 % PMID[28333453]

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 NPC161249 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
0.8545 High Similarity NPC106739
0.7407 Intermediate Similarity NPC274356
0.7407 Intermediate Similarity NPC101748
0.7358 Intermediate Similarity NPC104077
0.7358 Intermediate Similarity NPC219671
0.7358 Intermediate Similarity NPC147616
0.6949 Remote Similarity NPC487677
0.6949 Remote Similarity NPC487675
0.6441 Remote Similarity NPC474808
0.629 Remote Similarity NPC487681
0.625 Remote Similarity NPC487679
0.625 Remote Similarity NPC487678
0.6167 Remote Similarity NPC284464
0.6129 Remote Similarity NPC46880
0.5962 Remote Similarity NPC259742
0.5893 Remote Similarity NPC227217
0.5893 Remote Similarity NPC117780
0.5846 Remote Similarity NPC471505
0.5769 Remote Similarity NPC165133
0.5769 Remote Similarity NPC242885
0.5769 Remote Similarity NPC95614
0.5769 Remote Similarity NPC232316
0.5672 Remote Similarity NPC169973
0.5645 Remote Similarity NPC474017
0.5538 Remote Similarity NPC474039
0.5517 Remote Similarity NPC249788
0.5441 Remote Similarity NPC282291
0.5441 Remote Similarity NPC166137
0.5439 Remote Similarity NPC487676
0.5254 Remote Similarity NPC127587
0.5179 Remote Similarity NPC344161
0.5172 Remote Similarity NPC56214
0.5167 Remote Similarity NPC607444
0.5161 Remote Similarity NPC487680
0.5077 Remote Similarity NPC18576
0.5075 Remote Similarity NPC291101
0.5075 Remote Similarity NPC266197

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC161249 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