Natural Product: NPC489114

Natural Product IDNPC489114
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 FGBQMZDQNSRMSZ-RAKGIWIYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 132525259
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0002319] Phenol esters

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 FGBQMZDQNSRMSZ-RAKGIWIYSA-N
Standard InCHI InChI=1S/C23H32O3/c1-15-7-6-8-21-22(15,4)12-11-16(2)23(21,5)14-18-13-19(25)9-10-20(18)26-17(3)24/h9-10,13,16,21,25H,1,6-8,11-12,14H2,2-5H3/t16-,21+,22+,23+/m0/s1
SMILES C=C1CCC[C@@H]2[C@]1(C)CC[C@H](C)[C@@]2(C)Cc1cc(ccc1OC(=O)C)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   356.24 Volume:   393.883
?
Van der Waals volume.
Dense:   0.904 LogP:   3.923
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.537
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.037
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   19.0
TPSA:   46.53
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.432 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.969 Fsp3:   0.609
MCE-18:   76.703
?
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:   0.276 Fluc inhibitor:   0.003
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.012
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.031
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.295 Promiscuous compounds:   0.095

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.63 MDCK Permeability:   -4.723
Pgp-inhibitor:   0.082 Pgp-substrate:   0.001
PAMPA:   0.038
?
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):   0.0
20% Bioavailability (F20%):   0.156 30% Bioavailability (F30%):   0.637
50% Bioavailability (F50%):   0.859

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.319 MRP1:   0.368
Plasma Protein Binding (PPB):   92.58% Volume Distribution (VD):   0.34
Fu: 6.318%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.744
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.227 CYP1A2-substrate:   0.884
CYP2C19-inhibitor:   0.966 CYP2C19-substrate:   0.006
CYP2C9-inhibitor:   0.029 CYP2C9-substrate:   0.122
CYP2D6-inhibitor:   0.135 CYP2D6-substrate:   0.077
CYP3A4-inhibitor:   0.831 CYP3A4-substrate:   0.999
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.992
HLM stability:   1.0
?
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):  6.8 Half-life (T1/2):  0.376

ADMET: Toxicity

hERG Blockers:  0.077 hERG Blockers (10um):  0.408
Human Hepatotoxicity (H-HT):  0.563 Drug-induced Liver Injury (DILI):  0.441
AMES Toxicity:  0.359 Rat Oral Acute Toxicity:  0.34
Maximum Recommended Daily Dose:  0.483 Skin Sensitization:  0.927
Carcinogencity:  0.54 Eye Corrosion:  0.569
Eye Irritation:  0.965 Respiratory Toxicity:  0.737
Drug-induced Neurotoxicity:  0.451 Ototoxicity:  0.202
Hematotoxicity:  0.432 Drug-induced Nephrotoxicity:  0.15
Genotoxicity:  0.116 RPMI-8226 Immunitoxicity:  0.037
A549 Cytotoxicity:  0.551 Hek293 Cytotoxicity:  0.554
BCF:   2.079
?
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:   4.934
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.053
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.669
?
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
NPO32617 dysidea sp. Species Dysideidae Eukaryota n.a. n.a. n.a. PMID[11374954]
NPO32617 dysidea sp. Species Dysideidae Eukaryota n.a. n.a. n.a. PMID[15921404]
NPO32617 dysidea sp. Species Dysideidae Eukaryota n.a. n.a. n.a. PMID[1593283]
NPO32617 dysidea sp. Species Dysideidae Eukaryota n.a. n.a. n.a. PMID[18198840]
NPO32617 dysidea sp. Species Dysideidae Eukaryota n.a. at 1020 m depth from Chuuk Atoll, Federated States of Micronesia n.a. PMID[18824352]
NPO32617 dysidea sp. Species Dysideidae Eukaryota n.a. n.a. n.a. PMID[20230038]
NPO32617 dysidea sp. Species Dysideidae Eukaryota n.a. n.a. n.a. PMID[26551342]
NPO32617 dysidea sp. Species Dysideidae Eukaryota n.a. n.a. n.a. PMID[26863083]
NPO32617 dysidea sp. Species Dysideidae Eukaryota n.a. n.a. n.a. PMID[27336796]
NPO32617 dysidea sp. Species Dysideidae Eukaryota n.a. n.a. n.a. PMID[32243140]
NPO32617 dysidea sp. Species Dysideidae Eukaryota n.a. Indo-Pacific n.a. PMID[7494145]
NPO32617 dysidea sp. Species Dysideidae Eukaryota n.a. n.a. n.a. PMID[9748373]

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
NPT178 Individual protein Protein-tyrosine phosphatase 1B Homo sapiens IC50 = 6500.0 nM PMID[27336796]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT913 Cell line CHO-K1 Cricetulus griseus IC50 > 27300.0 nM PMID[31253530]
NPT2 Others Unspecified n.a. IC50 = 11900.0 nM PMID[31253530]
NPT2 Others Unspecified n.a. IC50 > 27300.0 nM PMID[31253530]

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 NPC489114 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
0.7143 Intermediate Similarity NPC489113
0.6935 Remote Similarity NPC489118
0.6364 Remote Similarity NPC176590
0.6212 Remote Similarity NPC489120
0.6129 Remote Similarity NPC77772
0.6129 Remote Similarity NPC53548
0.5821 Remote Similarity NPC489119
0.5479 Remote Similarity NPC475848
0.5479 Remote Similarity NPC474306
0.5429 Remote Similarity NPC600514
0.5352 Remote Similarity NPC290286
0.5211 Remote Similarity NPC75295
0.5211 Remote Similarity NPC481954
0.5205 Remote Similarity NPC604728
0.5139 Remote Similarity NPC609727
0.5135 Remote Similarity NPC124842
0.5132 Remote Similarity NPC470042

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC489114 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