Natural Product: NPC313004

Natural Product IDNPC313004
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 PBTJWDSMUBVOKC-ZRDIBKRKSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 15875260
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000476] Cinnamic acids and derivatives
        • [CHEMONTID:0001391] Hydroxycinnamic acids and derivatives
          • [CHEMONTID:0000059] Coumaric acids 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 PBTJWDSMUBVOKC-ZRDIBKRKSA-N
Standard InCHI InChI=1S/C18H26O4/c1-3-4-5-6-7-8-13-22-18(20)12-10-15-9-11-16(19)17(14-15)21-2/h9-12,14,19H,3-8,13H2,1-2H3/b12-10+
SMILES CCCCCCCCOC(=O)/C=C/c1ccc(c(c1)OC)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   306.18 Volume:   333.306
?
Van der Waals volume.
Dense:   0.919 LogP:   4.786
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.469
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.747
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   11.0 Rigid Bonds:   8.0
TPSA:   55.76
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   1.0 Rings:   1.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.397 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.011 Fsp3:   0.5
MCE-18:   7.0
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.902 Fluc inhibitor:   0.999
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.211
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.815
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.848 Promiscuous compounds:   0.437

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.929 MDCK Permeability:   -4.686
Pgp-inhibitor:   0.27 Pgp-substrate:   0.033
PAMPA:   0.005
?
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):   0.385
20% Bioavailability (F20%):   0.932 30% Bioavailability (F30%):   0.924
50% Bioavailability (F50%):   0.969

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.014 MRP1:   0.648
Plasma Protein Binding (PPB):   98.845% Volume Distribution (VD):   -0.098
Fu: 0.85%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.986
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.836
BSEP inhibitor:   0.945

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.034 CYP2C19-substrate:   0.149
CYP2C9-inhibitor:   0.74 CYP2C9-substrate:   0.44
CYP2D6-inhibitor:   0.965 CYP2D6-substrate:   0.603
CYP3A4-inhibitor:   0.002 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.016 CYP2C8-inhibitor:   1.0
HLM stability:   0.208
?
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):  6.402 Half-life (T1/2):  0.675

ADMET: Toxicity

hERG Blockers:  0.368 hERG Blockers (10um):  0.708
Human Hepatotoxicity (H-HT):  0.363 Drug-induced Liver Injury (DILI):  0.26
AMES Toxicity:  0.235 Rat Oral Acute Toxicity:  0.143
Maximum Recommended Daily Dose:  0.219 Skin Sensitization:  0.952
Carcinogencity:  0.43 Eye Corrosion:  0.749
Eye Irritation:  0.988 Respiratory Toxicity:  0.54
Drug-induced Neurotoxicity:  0.262 Ototoxicity:  0.148
Hematotoxicity:  0.065 Drug-induced Nephrotoxicity:  0.306
Genotoxicity:  0.001 RPMI-8226 Immunitoxicity:  0.099
A549 Cytotoxicity:  0.282 Hek293 Cytotoxicity:  0.37
BCF:   1.442
?
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:   4.722
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.759
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.434
?
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
NPO11421 Arnebia euchroma Species Boraginaceae Eukaryota n.a. n.a. n.a. PMID[12502328]
NPO26982 Callyspongia siphonella Species Callyspongiidae Eukaryota n.a. n.a. n.a. PMID[17488128]
NPO26982 Callyspongia siphonella Species Callyspongiidae Eukaryota n.a. n.a. n.a. PMID[19534474]
NPO11421 Arnebia euchroma Species Boraginaceae Eukaryota n.a. n.a. n.a. PMID[7775984]
NPO11421 Arnebia euchroma Species Boraginaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26982 Callyspongia siphonella Species Callyspongiidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11300 Eucalyptus coccifera Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9209 Rhizomnium magnifolium Species Mniaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11421 Arnebia euchroma Species Boraginaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO11421 Arnebia euchroma Species Boraginaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO11421 Arnebia euchroma Species Boraginaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO11421 Arnebia euchroma Species Boraginaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO26982 Callyspongia siphonella Species Callyspongiidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11421 Arnebia euchroma Species Boraginaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11300 Eucalyptus coccifera Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9209 Rhizomnium magnifolium Species Mniaceae 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 NPC313004 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 NPC60517
1.0 High Similarity NPC146886
1.0 High Similarity NPC20443
0.9375 High Similarity NPC83062
0.8491 Intermediate Similarity NPC482462
0.7692 Intermediate Similarity NPC70752
0.74 Intermediate Similarity NPC202474
0.7115 Intermediate Similarity NPC273741
0.7115 Intermediate Similarity NPC608423
0.7115 Intermediate Similarity NPC611337
0.6981 Remote Similarity NPC203124
0.6981 Remote Similarity NPC607366
0.6792 Remote Similarity NPC246704
0.6727 Remote Similarity NPC204466
0.6613 Remote Similarity NPC475468
0.66 Remote Similarity NPC107588
0.66 Remote Similarity NPC137537
0.6538 Remote Similarity NPC82731
0.6429 Remote Similarity NPC110313
0.6393 Remote Similarity NPC482043
0.6296 Remote Similarity NPC328593
0.6102 Remote Similarity NPC213552
0.6102 Remote Similarity NPC120225
0.6 Remote Similarity NPC280767
0.6 Remote Similarity NPC135127
0.5926 Remote Similarity NPC33749
0.5902 Remote Similarity NPC110699
0.5902 Remote Similarity NPC106055
0.5763 Remote Similarity NPC15621
0.569 Remote Similarity NPC289459
0.5667 Remote Similarity NPC158949
0.5606 Remote Similarity NPC481915
0.56 Remote Similarity NPC36108
0.56 Remote Similarity NPC233731
0.56 Remote Similarity NPC610203
0.5556 Remote Similarity NPC109275
0.5479 Remote Similarity NPC484274
0.5373 Remote Similarity NPC120852
0.537 Remote Similarity NPC160900
0.5352 Remote Similarity NPC158900
0.5283 Remote Similarity NPC39793
0.5256 Remote Similarity NPC132723
0.5256 Remote Similarity NPC76032
0.5231 Remote Similarity NPC485282
0.5231 Remote Similarity NPC485283
0.5231 Remote Similarity NPC485281
0.5185 Remote Similarity NPC224814
0.5147 Remote Similarity NPC471110
0.5139 Remote Similarity NPC252402
0.5139 Remote Similarity NPC102934
0.5132 Remote Similarity NPC482415
0.5132 Remote Similarity NPC482416
0.5088 Remote Similarity NPC474967
0.5065 Remote Similarity NPC274960

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC313004 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
0.537 Remote Similarity NPD4379 Clinical (unspecified phase)

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