Natural Product: NPC71544

Natural Product IDNPC71544
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 XJDSLGAFRQCARR-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 620900
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000145] Coumarins and derivatives

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 XJDSLGAFRQCARR-UHFFFAOYSA-N
Standard InCHI InChI=1S/C15H14O4/c1-9(2)6-12(16)11-7-10-4-5-15(17)19-13(10)8-14(11)18-3/h4-8H,1-3H3
SMILES CC(=CC(=O)c1cc2ccc(=O)oc2cc1OC)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   258.09 Volume:   267.589
?
Van der Waals volume.
Dense:   0.965 LogP:   2.516
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.553
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.244
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   14.0
TPSA:   56.51
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   0.0 Rings:   2.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.482 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.381 Fsp3:   0.2
MCE-18:   13.0
?
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:   0.113 Fluc inhibitor:   0.547
?
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:   0.542
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.57 Promiscuous compounds:   0.14

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.592 MDCK Permeability:   -4.521
Pgp-inhibitor:   0.008 Pgp-substrate:   0.0
PAMPA:   0.373
?
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%):   0.137 30% Bioavailability (F30%):   0.037
50% Bioavailability (F50%):   0.065

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.997
Plasma Protein Binding (PPB):   95.985% Volume Distribution (VD):   -0.029
Fu: 3.302%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.997
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.0
BSEP inhibitor:   0.976

ADMET: Metabolism

CYP1A2-inhibitor:   0.632 CYP1A2-substrate:   0.028
CYP2C19-inhibitor:   0.991 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.627 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.011 CYP2D6-substrate:   0.085
CYP3A4-inhibitor:   0.961 CYP3A4-substrate:   0.409
CYP2B6-substrate:   0.745 CYP2C8-inhibitor:   0.013
HLM stability:   0.383
?
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):  5.723 Half-life (T1/2):  0.67

ADMET: Toxicity

hERG Blockers:  0.111 hERG Blockers (10um):  0.364
Human Hepatotoxicity (H-HT):  0.552 Drug-induced Liver Injury (DILI):  0.739
AMES Toxicity:  0.556 Rat Oral Acute Toxicity:  0.422
Maximum Recommended Daily Dose:  0.662 Skin Sensitization:  0.334
Carcinogencity:  0.785 Eye Corrosion:  0.246
Eye Irritation:  0.966 Respiratory Toxicity:  0.649
Drug-induced Neurotoxicity:  0.453 Ototoxicity:  0.192
Hematotoxicity:  0.466 Drug-induced Nephrotoxicity:  0.327
Genotoxicity:  0.816 RPMI-8226 Immunitoxicity:  0.102
A549 Cytotoxicity:  0.078 Hek293 Cytotoxicity:  0.208
BCF:   0.98
?
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:   3.877
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.812
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.492
?
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
NPO24758 Angelica dahurica Species Apiaceae Eukaryota n.a. root n.a. DOI[10.5012/bkcs.2003.24.11.1699]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota n.a. root n.a. PMID[12510838]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota n.a. root n.a. PMID[15646793]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[21625478]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota n.a. root n.a. PMID[21657081]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[27444348]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota Roots n.a. n.a. PMID[31464439]
NPO24771 Boenninghausenia albiflora Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24771 Boenninghausenia albiflora Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO24771 Boenninghausenia albiflora Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24771 Boenninghausenia albiflora Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24771 Boenninghausenia albiflora Species Rutaceae 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 NPC71544 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
0.8043 Intermediate Similarity NPC605579
0.7115 Intermediate Similarity NPC36414
0.6604 Remote Similarity NPC248429
0.6182 Remote Similarity NPC72281
0.5965 Remote Similarity NPC204353
0.5789 Remote Similarity NPC601133
0.5789 Remote Similarity NPC608534
0.5455 Remote Similarity NPC151946
0.5439 Remote Similarity NPC137669
0.5439 Remote Similarity NPC253616
0.54 Remote Similarity NPC265547
0.54 Remote Similarity NPC240722
0.5345 Remote Similarity NPC257188
0.5345 Remote Similarity NPC234109
0.5345 Remote Similarity NPC188327
0.5323 Remote Similarity NPC76657
0.5263 Remote Similarity NPC201667
0.5224 Remote Similarity NPC155963
0.5172 Remote Similarity NPC111347
0.5167 Remote Similarity NPC76753
0.5098 Remote Similarity NPC87563
0.5088 Remote Similarity NPC281356
0.5085 Remote Similarity NPC253574
0.5085 Remote Similarity NPC98179
0.5075 Remote Similarity NPC14248
0.5075 Remote Similarity NPC207002
0.5075 Remote Similarity NPC133956

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC71544 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