Natural Product: NPC219757

Natural Product IDNPC219757
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 RRUHFAXVNXSPNG-TZMCWYRMSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 14213971
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 RRUHFAXVNXSPNG-TZMCWYRMSA-N
Standard InCHI InChI=1S/C15H16O6/c1-15(2)14(18)12(17)11-9(21-15)6-8(19-3)7-4-5-10(16)20-13(7)11/h4-6,12,14,17-18H,1-3H3/t12-,14-/m1/s1
SMILES CC1(C)[C@@H]([C@@H](c2c(cc(c3ccc(=O)oc23)OC)O1)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   292.09 Volume:   281.886
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Van der Waals volume.
Dense:   1.036 LogP:   1.558
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.759
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.333
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The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   17.0
TPSA:   89.13
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Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.772 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.503 Fsp3:   0.4
MCE-18:   65.714
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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:   0.524 Fluc inhibitor:   0.029
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.961
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.131
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.175 Promiscuous compounds:   0.255

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.003 MDCK Permeability:   -4.586
Pgp-inhibitor:   0.068 Pgp-substrate:   0.007
PAMPA:   0.343
?
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):   0.011
20% Bioavailability (F20%):   0.846 30% Bioavailability (F30%):   0.856
50% Bioavailability (F50%):   0.974

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.958
Plasma Protein Binding (PPB):   88.315% Volume Distribution (VD):   0.314
Fu: 13.022%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.021
BSEP inhibitor:   0.998

ADMET: Metabolism

CYP1A2-inhibitor:   0.058 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.179 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.025 CYP2C9-substrate:   0.006
CYP2D6-inhibitor:   0.006 CYP2D6-substrate:   0.028
CYP3A4-inhibitor:   0.22 CYP3A4-substrate:   0.001
CYP2B6-substrate:   0.067 CYP2C8-inhibitor:   0.462
HLM stability:   0.725
?
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):  10.164 Half-life (T1/2):  1.798

ADMET: Toxicity

hERG Blockers:  0.051 hERG Blockers (10um):  0.286
Human Hepatotoxicity (H-HT):  0.435 Drug-induced Liver Injury (DILI):  0.299
AMES Toxicity:  0.58 Rat Oral Acute Toxicity:  0.229
Maximum Recommended Daily Dose:  0.623 Skin Sensitization:  0.337
Carcinogencity:  0.499 Eye Corrosion:  0.031
Eye Irritation:  0.922 Respiratory Toxicity:  0.363
Drug-induced Neurotoxicity:  0.08 Ototoxicity:  0.448
Hematotoxicity:  0.228 Drug-induced Nephrotoxicity:  0.48
Genotoxicity:  0.701 RPMI-8226 Immunitoxicity:  0.072
A549 Cytotoxicity:  0.01 Hek293 Cytotoxicity:  0.171
BCF:   0.315
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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:   2.925
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.65
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.761
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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
NPO18677 Anagallis arvensis Species Primulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19014 Palythoa tuberculosa Species Sphenopidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14773 Uncaria perrottetii Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14773 Uncaria perrottetii Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO18677 Anagallis arvensis Species Primulaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14773 Uncaria perrottetii Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14773 Uncaria perrottetii Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19014 Palythoa tuberculosa Species Sphenopidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18677 Anagallis arvensis Species Primulaceae 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 NPC219757 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
0.7037 Intermediate Similarity NPC225106
0.7037 Intermediate Similarity NPC184861
0.7037 Intermediate Similarity NPC281014
0.7037 Intermediate Similarity NPC212124
0.7037 Intermediate Similarity NPC294456
0.5932 Remote Similarity NPC213173
0.5833 Remote Similarity NPC31849
0.5833 Remote Similarity NPC85085
0.5625 Remote Similarity NPC472525
0.5574 Remote Similarity NPC173350
0.5574 Remote Similarity NPC471826
0.5574 Remote Similarity NPC76753
0.5517 Remote Similarity NPC472518
0.5345 Remote Similarity NPC472517
0.5333 Remote Similarity NPC471828
0.5333 Remote Similarity NPC50896
0.5333 Remote Similarity NPC27671
0.5333 Remote Similarity NPC73413
0.5333 Remote Similarity NPC253616
0.5333 Remote Similarity NPC326600
0.5333 Remote Similarity NPC229128
0.5246 Remote Similarity NPC109675
0.5246 Remote Similarity NPC54503
0.5246 Remote Similarity NPC472515
0.5246 Remote Similarity NPC144418
0.5246 Remote Similarity NPC273772
0.5079 Remote Similarity NPC61499

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC219757 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