Natural Product: NPC124024

Natural Product IDNPC124024
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 WGBFEDHNTNVZGG-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 5320811
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 WGBFEDHNTNVZGG-UHFFFAOYSA-N
Standard InCHI InChI=1S/C16H16O6/c1-8(17)20-15-13(19)12-10(22-16(15,2)3)6-4-9-5-7-11(18)21-14(9)12/h4-7,13,15,19H,1-3H3
SMILES CC(=O)OC1C(c2c(ccc3ccc(=O)oc23)OC1(C)C)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   304.09 Volume:   296.545
?
Van der Waals volume.
Dense:   1.025 LogP:   1.631
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.52
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.554
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   18.0
TPSA:   85.97
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.64 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.496 Fsp3:   0.375
MCE-18:   65.455
?
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:   0.227 Fluc inhibitor:   0.004
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.99
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.216
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.199 Promiscuous compounds:   0.189

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.168 MDCK Permeability:   -4.725
Pgp-inhibitor:   0.019 Pgp-substrate:   0.0
PAMPA:   0.361
?
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):   0.001
20% Bioavailability (F20%):   0.695 30% Bioavailability (F30%):   0.76
50% Bioavailability (F50%):   0.618

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.002 MRP1:   0.999
Plasma Protein Binding (PPB):   78.222% Volume Distribution (VD):   0.235
Fu: 25.176%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.996
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.0
BSEP inhibitor:   0.998

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.413
CYP2C19-inhibitor:   0.187 CYP2C19-substrate:   0.03
CYP2C9-inhibitor:   0.585 CYP2C9-substrate:   0.099
CYP2D6-inhibitor:   0.019 CYP2D6-substrate:   0.552
CYP3A4-inhibitor:   0.749 CYP3A4-substrate:   0.128
CYP2B6-substrate:   1.0 CYP2C8-inhibitor:   0.998
HLM stability:   0.544
?
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):  2.846 Half-life (T1/2):  1.374

ADMET: Toxicity

hERG Blockers:  0.072 hERG Blockers (10um):  0.349
Human Hepatotoxicity (H-HT):  0.436 Drug-induced Liver Injury (DILI):  0.754
AMES Toxicity:  0.639 Rat Oral Acute Toxicity:  0.461
Maximum Recommended Daily Dose:  0.506 Skin Sensitization:  0.109
Carcinogencity:  0.673 Eye Corrosion:  0.154
Eye Irritation:  0.909 Respiratory Toxicity:  0.474
Drug-induced Neurotoxicity:  0.227 Ototoxicity:  0.277
Hematotoxicity:  0.196 Drug-induced Nephrotoxicity:  0.194
Genotoxicity:  0.613 RPMI-8226 Immunitoxicity:  0.051
A549 Cytotoxicity:  0.032 Hek293 Cytotoxicity:  0.181
BCF:   0.878
?
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:   3.518
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.622
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.979
?
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
NPO4340 Peucedanum praeruptorum Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4340 Peucedanum praeruptorum Species Apiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO4340 Peucedanum praeruptorum Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO4340 Peucedanum praeruptorum Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO4340 Peucedanum praeruptorum Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO4340 Peucedanum praeruptorum Species Apiaceae 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 NPC124024 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
0.8276 Intermediate Similarity NPC195357
0.8276 Intermediate Similarity NPC152771
0.6207 Remote Similarity NPC225106
0.6207 Remote Similarity NPC184861
0.6207 Remote Similarity NPC281014
0.6207 Remote Similarity NPC212124
0.6207 Remote Similarity NPC294456
0.6154 Remote Similarity NPC86892
0.6129 Remote Similarity NPC167111
0.6129 Remote Similarity NPC318400
0.5909 Remote Similarity NPC166672
0.5909 Remote Similarity NPC129572
0.5909 Remote Similarity NPC471909
0.5882 Remote Similarity NPC476455
0.5781 Remote Similarity NPC472424
0.5781 Remote Similarity NPC281241
0.5758 Remote Similarity NPC476457
0.5652 Remote Similarity NPC128529
0.5652 Remote Similarity NPC319859
0.5652 Remote Similarity NPC198381
0.5652 Remote Similarity NPC127888
0.5522 Remote Similarity NPC260265
0.5507 Remote Similarity NPC195343
0.5507 Remote Similarity NPC267412
0.5507 Remote Similarity NPC149320
0.5507 Remote Similarity NPC160727
0.5507 Remote Similarity NPC177281
0.5507 Remote Similarity NPC74655
0.5507 Remote Similarity NPC471910
0.5429 Remote Similarity NPC84894
0.5429 Remote Similarity NPC18804
0.5429 Remote Similarity NPC164269
0.5429 Remote Similarity NPC287182
0.5429 Remote Similarity NPC55615
0.5417 Remote Similarity NPC471625
0.541 Remote Similarity NPC50896
0.541 Remote Similarity NPC229916
0.541 Remote Similarity NPC326600
0.5405 Remote Similarity NPC469701
0.5342 Remote Similarity NPC169510
0.5323 Remote Similarity NPC188380
0.5323 Remote Similarity NPC224543
0.5294 Remote Similarity NPC287286
0.5246 Remote Similarity NPC80170
0.5231 Remote Similarity NPC153818
0.5231 Remote Similarity NPC232246
0.5211 Remote Similarity NPC296624
0.5205 Remote Similarity NPC87950
0.52 Remote Similarity NPC471630
0.5079 Remote Similarity NPC33986
0.507 Remote Similarity NPC312881

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC124024 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