Natural Product: NPC187885

Natural Product IDNPC187885
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 JJERETZMIHCJOC-SNAWJCMRSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 10611366
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0002341] Phenol ethers

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 JJERETZMIHCJOC-SNAWJCMRSA-N
Standard InCHI InChI=1S/C16H20O3/c1-13(2)10-12-19-16-8-6-15(7-9-16)5-4-11-18-14(3)17/h4-10H,11-12H2,1-3H3/b5-4+
SMILES CC(=CCOc1ccc(/C=C/COC(=O)C)cc1)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   260.14 Volume:   287.288
?
Van der Waals volume.
Dense:   0.906 LogP:   3.862
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.321
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.085
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   9.0
TPSA:   35.53
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   0.0 Rings:   1.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.579 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.27 Fsp3:   0.312
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:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.525 Fluc inhibitor:   0.857
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.009
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.385
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.992 Promiscuous compounds:   0.095

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.511 MDCK Permeability:   -4.651
Pgp-inhibitor:   0.985 Pgp-substrate:   0.023
PAMPA:   0.146
?
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):   0.061
20% Bioavailability (F20%):   0.745 30% Bioavailability (F30%):   0.936
50% Bioavailability (F50%):   0.743

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.041 MRP1:   0.008
Plasma Protein Binding (PPB):   91.518% Volume Distribution (VD):   0.061
Fu: 8.047%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.94
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.864
BSEP inhibitor:   0.999

ADMET: Metabolism

CYP1A2-inhibitor:   0.159 CYP1A2-substrate:   0.706
CYP2C19-inhibitor:   0.165 CYP2C19-substrate:   0.235
CYP2C9-inhibitor:   0.511 CYP2C9-substrate:   0.069
CYP2D6-inhibitor:   0.855 CYP2D6-substrate:   0.011
CYP3A4-inhibitor:   0.026 CYP3A4-substrate:   0.957
CYP2B6-substrate:   0.036 CYP2C8-inhibitor:   1.0
HLM stability:   0.952
?
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):  9.096 Half-life (T1/2):  0.495

ADMET: Toxicity

hERG Blockers:  0.215 hERG Blockers (10um):  0.552
Human Hepatotoxicity (H-HT):  0.489 Drug-induced Liver Injury (DILI):  0.65
AMES Toxicity:  0.775 Rat Oral Acute Toxicity:  0.092
Maximum Recommended Daily Dose:  0.246 Skin Sensitization:  0.77
Carcinogencity:  0.836 Eye Corrosion:  0.056
Eye Irritation:  0.903 Respiratory Toxicity:  0.298
Drug-induced Neurotoxicity:  0.276 Ototoxicity:  0.158
Hematotoxicity:  0.373 Drug-induced Nephrotoxicity:  0.282
Genotoxicity:  0.107 RPMI-8226 Immunitoxicity:  0.051
A549 Cytotoxicity:  0.025 Hek293 Cytotoxicity:  0.125
BCF:   1.708
?
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:   4.017
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.716
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.142
?
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
NPO21908 Corymbia scabrida Species Myrtaceae Eukaryota seeds n.a. n.a. PMID[18771320]
NPO21084 Nymphaea caerulea Species Nymphaeaceae Eukaryota n.a. n.a. n.a. PMID[37894493]
NPO21779 Umbilicaria hypococcinea Species Umbilicariaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21526 Scabiosa rotata Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22301 Pinus hartwegii Species Pinaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21084 Nymphaea caerulea Species Nymphaeaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21337 Libanotis transcaucasica Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20319 Kopsia jasminiflora Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20578 Kallichroma tethys Species Bionectriaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21908 Corymbia scabrida Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21779 Umbilicaria hypococcinea Species Umbilicariaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO21779 Umbilicaria hypococcinea Species Umbilicariaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21084 Nymphaea caerulea Species Nymphaeaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21779 Umbilicaria hypococcinea Species Umbilicariaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO21779 Umbilicaria hypococcinea Species Umbilicariaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21908 Corymbia scabrida Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20578 Kallichroma tethys Species Bionectriaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22301 Pinus hartwegii Species Pinaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21337 Libanotis transcaucasica Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21084 Nymphaea caerulea Species Nymphaeaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21526 Scabiosa rotata Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20319 Kopsia jasminiflora Species Apocynaceae 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 NPC187885 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
0.7 Intermediate Similarity NPC283546
0.6744 Remote Similarity NPC176971
0.6279 Remote Similarity NPC51633
0.6279 Remote Similarity NPC473855
0.5778 Remote Similarity NPC94347
0.575 Remote Similarity NPC252004
0.575 Remote Similarity NPC175393
0.5385 Remote Similarity NPC157473
0.5385 Remote Similarity NPC151530
0.5227 Remote Similarity NPC171843
0.5098 Remote Similarity NPC126220

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC187885 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