Natural Product: NPC141194

Natural Product IDNPC141194
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 RRHCDWLSHIIIIT-GHAIFCDISA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 668079
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000145] Coumarins and derivatives
        • [CHEMONTID:0003484] Pyranocoumarins
          • [CHEMONTID:0003485] Angular pyranocoumarins

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 RRHCDWLSHIIIIT-GHAIFCDISA-N
Standard InCHI InChI=1S/C19H20O5/c1-5-11(2)18(21)22-15-10-13-14(24-19(15,3)4)8-6-12-7-9-16(20)23-17(12)13/h5-9,15H,10H2,1-4H3/b11-5-/t15-/m0/s1
SMILES C/C=C(/C)C(=O)O[C@H]1Cc2c(ccc3ccc(=O)oc23)OC1(C)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   328.13 Volume:   337.007
?
Van der Waals volume.
Dense:   0.974 LogP:   2.825
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.879
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.19
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   19.0
TPSA:   65.74
?
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:   0.48 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.466 Fsp3:   0.368
MCE-18:   64.615
?
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:   0.491 Fluc inhibitor:   0.459
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.979
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.598
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.332 Promiscuous compounds:   0.131

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.768 MDCK Permeability:   -4.652
Pgp-inhibitor:   0.13 Pgp-substrate:   0.0
PAMPA:   0.455
?
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%):   0.976 30% Bioavailability (F30%):   0.984
50% Bioavailability (F50%):   0.957

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.992
Plasma Protein Binding (PPB):   98.051% Volume Distribution (VD):   -0.008
Fu: 1.759%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.0
BSEP inhibitor:   0.999

ADMET: Metabolism

CYP1A2-inhibitor:   0.009 CYP1A2-substrate:   0.99
CYP2C19-inhibitor:   0.853 CYP2C19-substrate:   0.879
CYP2C9-inhibitor:   0.958 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.003 CYP2D6-substrate:   0.949
CYP3A4-inhibitor:   0.992 CYP3A4-substrate:   0.994
CYP2B6-substrate:   0.862 CYP2C8-inhibitor:   0.995
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):  5.272 Half-life (T1/2):  0.648

ADMET: Toxicity

hERG Blockers:  0.07 hERG Blockers (10um):  0.33
Human Hepatotoxicity (H-HT):  0.561 Drug-induced Liver Injury (DILI):  0.866
AMES Toxicity:  0.681 Rat Oral Acute Toxicity:  0.635
Maximum Recommended Daily Dose:  0.752 Skin Sensitization:  0.776
Carcinogencity:  0.84 Eye Corrosion:  0.635
Eye Irritation:  0.97 Respiratory Toxicity:  0.65
Drug-induced Neurotoxicity:  0.244 Ototoxicity:  0.126
Hematotoxicity:  0.183 Drug-induced Nephrotoxicity:  0.414
Genotoxicity:  0.902 RPMI-8226 Immunitoxicity:  0.062
A549 Cytotoxicity:  0.096 Hek293 Cytotoxicity:  0.325
BCF:   1.58
?
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:   4.473
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.611
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   6.046
?
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
NPO16675 Peucedanum japonicum Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[1453177]
NPO26621 Streptomyces uncialis Species Streptomycetaceae Bacteria n.a. n.a. n.a. PMID[18646774]
NPO23122 Trichoderma citrinoviride Species Hypocreaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16675 Peucedanum japonicum Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10678 Anemia phyllitidis Species Anemiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13650 Dysidea frondosa Species Dysideidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26365 Gomphidius glutinosus Species Gomphidiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25369 Levisticum officinale Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6020 Termitomyces titanicus Species Lyophyllaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26621 Streptomyces uncialis Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO25369 Levisticum officinale Species Apiaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO25369 Levisticum officinale Species Apiaceae Eukaryota Plant n.a. n.a. Database[FooDB]
NPO25369 Levisticum officinale Species Apiaceae Eukaryota n.a. n.a. Database[FooDB]
NPO25369 Levisticum officinale Species Apiaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO25369 Levisticum officinale Species Apiaceae Eukaryota Root n.a. n.a. Database[FooDB]
NPO25369 Levisticum officinale Species Apiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO25369 Levisticum officinale Species Apiaceae Eukaryota n.a. n.a. Database[Phenol-Explorer]
NPO25369 Levisticum officinale Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO16675 Peucedanum japonicum Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO16675 Peucedanum japonicum Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO9129 Ircinia campana Species Irciniidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16675 Peucedanum japonicum Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26621 Streptomyces uncialis Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO6534 Taraxacum alpinum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26014 Amphidinium corpulentum Species Gymnodiniaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25369 Levisticum officinale Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6020 Termitomyces titanicus Species Lyophyllaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8094 Cotoneaster veitchii Species Rosaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26092 Agathosma abrupta Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26365 Gomphidius glutinosus Species Gomphidiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13650 Dysidea frondosa Species Dysideidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10678 Anemia phyllitidis Species Anemiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9816 Polyporus porrectus Species Polyporaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23122 Trichoderma citrinoviride Species Hypocreaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8376 Dryopteris wallichiana Species Dryopteridaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26830 Hyaena hyaena Species Hyaenidae 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 NPC141194 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
1.0 High Similarity NPC260265
0.7797 Intermediate Similarity NPC472424
0.7797 Intermediate Similarity NPC281241
0.6875 Remote Similarity NPC55149
0.6818 Remote Similarity NPC47163
0.6667 Remote Similarity NPC195357
0.6667 Remote Similarity NPC152771
0.6567 Remote Similarity NPC195343
0.6567 Remote Similarity NPC267412
0.6567 Remote Similarity NPC74655
0.6471 Remote Similarity NPC84894
0.6471 Remote Similarity NPC18804
0.6471 Remote Similarity NPC164269
0.6471 Remote Similarity NPC287182
0.6441 Remote Similarity NPC80170
0.6232 Remote Similarity NPC319859
0.6232 Remote Similarity NPC198381
0.6232 Remote Similarity NPC127888
0.6197 Remote Similarity NPC471625
0.6111 Remote Similarity NPC100986
0.5972 Remote Similarity NPC87950
0.5972 Remote Similarity NPC211110
0.5946 Remote Similarity NPC471630
0.5556 Remote Similarity NPC104796
0.5522 Remote Similarity NPC167111
0.5522 Remote Similarity NPC318400
0.5469 Remote Similarity NPC188380
0.5469 Remote Similarity NPC224543
0.5469 Remote Similarity NPC33986
0.5455 Remote Similarity NPC168710
0.5417 Remote Similarity NPC207002
0.5417 Remote Similarity NPC133956
0.5417 Remote Similarity NPC312881
0.5417 Remote Similarity NPC471910
0.5397 Remote Similarity NPC96286
0.5352 Remote Similarity NPC166672
0.5342 Remote Similarity NPC307412
0.5342 Remote Similarity NPC296624
0.5342 Remote Similarity NPC606124
0.5211 Remote Similarity NPC476457
0.5205 Remote Similarity NPC149320
0.5205 Remote Similarity NPC160727
0.5205 Remote Similarity NPC177281
0.5152 Remote Similarity NPC199204
0.5139 Remote Similarity NPC119640
0.5139 Remote Similarity NPC183646
0.5139 Remote Similarity NPC86892
0.5139 Remote Similarity NPC471909
0.5135 Remote Similarity NPC128529
0.5135 Remote Similarity NPC55615
0.5065 Remote Similarity NPC279573

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC141194 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