Natural Product: NPC292301

Natural Product IDNPC292301
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 DBPWCIPDCMVUFT-GDBMZVCRSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 26183438
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 DBPWCIPDCMVUFT-GDBMZVCRSA-N
Standard InCHI InChI=1S/C16H18O5/c1-9(2)14(18)16(20-4)13-11(19-3)7-5-10-6-8-12(17)21-15(10)13/h5-8,14,16,18H,1H2,2-4H3/t14-,16-/m1/s1
SMILES C=C(C)[C@H]([C@@H](c1c(ccc2ccc(=O)oc12)OC)OC)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   290.12 Volume:   296.312
?
Van der Waals volume.
Dense:   0.979 LogP:   1.847
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.074
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.198
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   13.0
TPSA:   68.9
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   1.0 Rings:   2.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.676 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.601 Fsp3:   0.312
MCE-18:   28.0
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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:   0.589 Fluc inhibitor:   0.01
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.967
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.375
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.212 Promiscuous compounds:   0.219

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.884 MDCK Permeability:   -4.709
Pgp-inhibitor:   0.001 Pgp-substrate:   0.0
PAMPA:   0.453
?
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):   0.005
20% Bioavailability (F20%):   0.787 30% Bioavailability (F30%):   0.918
50% Bioavailability (F50%):   0.827

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.986
Plasma Protein Binding (PPB):   88.803% Volume Distribution (VD):   0.294
Fu: 11.048%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.0
BSEP inhibitor:   0.895

ADMET: Metabolism

CYP1A2-inhibitor:   0.057 CYP1A2-substrate:   0.528
CYP2C19-inhibitor:   0.82 CYP2C19-substrate:   0.024
CYP2C9-inhibitor:   0.691 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.116 CYP2D6-substrate:   0.258
CYP3A4-inhibitor:   0.819 CYP3A4-substrate:   0.049
CYP2B6-substrate:   0.248 CYP2C8-inhibitor:   0.052
HLM stability:   0.963
?
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):  10.519 Half-life (T1/2):  1.227

ADMET: Toxicity

hERG Blockers:  0.079 hERG Blockers (10um):  0.216
Human Hepatotoxicity (H-HT):  0.721 Drug-induced Liver Injury (DILI):  0.834
AMES Toxicity:  0.555 Rat Oral Acute Toxicity:  0.316
Maximum Recommended Daily Dose:  0.489 Skin Sensitization:  0.462
Carcinogencity:  0.444 Eye Corrosion:  0.366
Eye Irritation:  0.985 Respiratory Toxicity:  0.6
Drug-induced Neurotoxicity:  0.413 Ototoxicity:  0.327
Hematotoxicity:  0.334 Drug-induced Nephrotoxicity:  0.283
Genotoxicity:  0.932 RPMI-8226 Immunitoxicity:  0.151
A549 Cytotoxicity:  0.034 Hek293 Cytotoxicity:  0.204
BCF:   0.873
?
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:   3.557
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.944
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.415
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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
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]
NPO24771 Boenninghausenia albiflora Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24771 Boenninghausenia albiflora Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
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 NPC292301 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
0.8679 High Similarity NPC26954
0.8679 High Similarity NPC38099
0.807 Intermediate Similarity NPC484113
0.7018 Intermediate Similarity NPC153818
0.7018 Intermediate Similarity NPC232246
0.6786 Remote Similarity NPC199204
0.6727 Remote Similarity NPC50896
0.6727 Remote Similarity NPC326600
0.5938 Remote Similarity NPC287286
0.5909 Remote Similarity NPC312881
0.5862 Remote Similarity NPC122259
0.5862 Remote Similarity NPC610664
0.5763 Remote Similarity NPC62366
0.5593 Remote Similarity NPC229916
0.5588 Remote Similarity NPC484110
0.5517 Remote Similarity NPC175159
0.55 Remote Similarity NPC185066
0.5484 Remote Similarity NPC168710
0.5424 Remote Similarity NPC80170
0.5424 Remote Similarity NPC96286
0.5385 Remote Similarity NPC479309
0.5373 Remote Similarity NPC129572
0.5333 Remote Similarity NPC225106
0.5333 Remote Similarity NPC184861
0.5333 Remote Similarity NPC281014
0.5333 Remote Similarity NPC212124
0.5333 Remote Similarity NPC294456
0.5312 Remote Similarity NPC167111
0.5312 Remote Similarity NPC318400
0.5303 Remote Similarity NPC469675
0.5303 Remote Similarity NPC479311
0.5278 Remote Similarity NPC471764
0.5246 Remote Similarity NPC188380
0.5246 Remote Similarity NPC224543
0.5238 Remote Similarity NPC605506
0.5167 Remote Similarity NPC55147
0.5167 Remote Similarity NPC472516
0.5167 Remote Similarity NPC271600
0.5156 Remote Similarity NPC479313
0.5147 Remote Similarity NPC166672
0.5147 Remote Similarity NPC479310
0.5079 Remote Similarity NPC31849
0.5079 Remote Similarity NPC85085
0.5072 Remote Similarity NPC479308
0.5068 Remote Similarity NPC484111

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC292301 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