Natural Product: NPC11952

Natural Product IDNPC11952
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 NJZFDQRQCKAWQT-HKZYLEAXSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
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 NJZFDQRQCKAWQT-HKZYLEAXSA-N
Standard InCHI InChI=1S/C21H26O5/c1-13(9-15-5-7-17(23-3)19(10-15)24-4)14(2)21(22)16-6-8-18-20(11-16)26-12-25-18/h5-8,10-11,13-14,21-22H,9,12H2,1-4H3/t13-,14+,21-/m1/s1
SMILES C[C@H](Cc1ccc(c(c1)OC)OC)[C@H](C)[C@H](c1ccc2c(c1)OCO2)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   358.18 Volume:   374.235
?
Van der Waals volume.
Dense:   0.957 LogP:   3.427
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.309
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.574
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   16.0
TPSA:   57.15
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.811 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.201 Fsp3:   0.429
MCE-18:   55.2
?
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:   0 PAINS Alert:   0
Colloidal aggregators:   0.345 Fluc inhibitor:   0.508
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.022
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.066
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.189 Promiscuous compounds:   0.09

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.047 MDCK Permeability:   -4.864
Pgp-inhibitor:   0.036 Pgp-substrate:   0.15
PAMPA:   0.126
?
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%):   0.012 30% Bioavailability (F30%):   0.001
50% Bioavailability (F50%):   0.687

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.535 MRP1:   0.217
Plasma Protein Binding (PPB):   88.941% Volume Distribution (VD):   0.451
Fu: 9.407%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.871
OATP1B3 inhibitor:   0.65 BCRP inhibitor:   0.015
BSEP inhibitor:   0.994

ADMET: Metabolism

CYP1A2-inhibitor:   0.572 CYP1A2-substrate:   0.939
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.998
CYP2C9-inhibitor:   0.863 CYP2C9-substrate:   1.0
CYP2D6-inhibitor:   0.976 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   0.994
CYP2B6-substrate:   0.061 CYP2C8-inhibitor:   1.0
HLM stability:   0.999
?
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):  7.117 Half-life (T1/2):  1.885

ADMET: Toxicity

hERG Blockers:  0.319 hERG Blockers (10um):  0.661
Human Hepatotoxicity (H-HT):  0.573 Drug-induced Liver Injury (DILI):  0.589
AMES Toxicity:  0.494 Rat Oral Acute Toxicity:  0.242
Maximum Recommended Daily Dose:  0.447 Skin Sensitization:  0.109
Carcinogencity:  0.632 Eye Corrosion:  0.011
Eye Irritation:  0.815 Respiratory Toxicity:  0.333
Drug-induced Neurotoxicity:  0.569 Ototoxicity:  0.69
Hematotoxicity:  0.39 Drug-induced Nephrotoxicity:  0.654
Genotoxicity:  0.287 RPMI-8226 Immunitoxicity:  0.123
A549 Cytotoxicity:  0.192 Hek293 Cytotoxicity:  0.497
BCF:   1.408
?
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:   3.658
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.252
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.425
?
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]
NPO5146 Tuta absoluta Species Gelechiidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27130 Tsuga sieboldii Species Pinaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27465 Sinularia erecta Species Alcyoniidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27570 Paederia foetida Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26934 Naucleopsis mello-barretoi Species Moraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27742 Mollugo pentaphylla Species Molluginaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27635 Laurencia dendroidea Species Rhodomelaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27339 Lactarius blennius Species Russulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16221 Dolichos kilimandscharicus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27520 Casuarina equisetifolia Species Casuarinaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27777 Artemisia phaeolepis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27593 Silene dioica Species Caryophyllaceae 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]
NPO27130 Tsuga sieboldii Species Pinaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16221 Dolichos kilimandscharicus Species Fabaceae 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

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 NPC11952 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
0.9111 High Similarity NPC104077
0.9111 High Similarity NPC219671
0.9111 High Similarity NPC147616
0.7455 Intermediate Similarity NPC106739
0.7455 Intermediate Similarity NPC161249
0.7174 Intermediate Similarity NPC344161
0.6739 Remote Similarity NPC259742
0.6545 Remote Similarity NPC474808
0.6545 Remote Similarity NPC474017
0.6304 Remote Similarity NPC80241
0.6304 Remote Similarity NPC301641
0.6304 Remote Similarity NPC485483
0.5862 Remote Similarity NPC18576
0.5714 Remote Similarity NPC274356
0.5714 Remote Similarity NPC101748
0.5667 Remote Similarity NPC3982
0.5652 Remote Similarity NPC165106
0.56 Remote Similarity NPC40352
0.56 Remote Similarity NPC213711
0.5574 Remote Similarity NPC474039
0.5556 Remote Similarity NPC249788
0.5556 Remote Similarity NPC485482
0.5556 Remote Similarity NPC196937
0.541 Remote Similarity NPC487677
0.541 Remote Similarity NPC487675
0.5357 Remote Similarity NPC485480
0.5312 Remote Similarity NPC56184
0.52 Remote Similarity NPC477886
0.5161 Remote Similarity NPC46880
0.5098 Remote Similarity NPC604144

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC11952 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
0.5652 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