Natural Product: NPC298134

Natural Product IDNPC298134
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 MCACKYTWGZKQCS-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 71665371
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0002279] Benzene and substituted derivatives
        • [CHEMONTID:0004155] Diphenylethers

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 MCACKYTWGZKQCS-UHFFFAOYSA-N
Standard InCHI InChI=1S/C15H16O3/c1-10-4-12(16)8-14(6-10)18-15-7-11(2)5-13(9-15)17-3/h4-9,16H,1-3H3
SMILES Cc1cc(cc(c1)Oc1cc(C)cc(c1)OC)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   244.11 Volume:   261.435
?
Van der Waals volume.
Dense:   0.934 LogP:   3.852
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.536
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.891
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   12.0
TPSA:   38.69
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   1.0 Rings:   2.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.892 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   1.985 Fsp3:   0.2
MCE-18:   12.0
?
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:   0.358 Fluc inhibitor:   0.233
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.014
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.422
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.809 Promiscuous compounds:   0.373

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.85 MDCK Permeability:   -4.771
Pgp-inhibitor:   0.112 Pgp-substrate:   0.039
PAMPA:   0.023
?
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%):   0.026 30% Bioavailability (F30%):   0.047
50% Bioavailability (F50%):   0.435

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.303 MRP1:   0.786
Plasma Protein Binding (PPB):   97.239% Volume Distribution (VD):   0.238
Fu: 2.971%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.998
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.163
BSEP inhibitor:   0.895

ADMET: Metabolism

CYP1A2-inhibitor:   0.994 CYP1A2-substrate:   0.999
CYP2C19-inhibitor:   0.74 CYP2C19-substrate:   0.981
CYP2C9-inhibitor:   0.982 CYP2C9-substrate:   1.0
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.935
CYP3A4-inhibitor:   0.152 CYP3A4-substrate:   0.78
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.993
HLM stability:   0.927
?
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):  6.805 Half-life (T1/2):  0.882

ADMET: Toxicity

hERG Blockers:  0.38 hERG Blockers (10um):  0.726
Human Hepatotoxicity (H-HT):  0.612 Drug-induced Liver Injury (DILI):  0.517
AMES Toxicity:  0.609 Rat Oral Acute Toxicity:  0.165
Maximum Recommended Daily Dose:  0.542 Skin Sensitization:  0.545
Carcinogencity:  0.836 Eye Corrosion:  0.372
Eye Irritation:  0.991 Respiratory Toxicity:  0.605
Drug-induced Neurotoxicity:  0.634 Ototoxicity:  0.22
Hematotoxicity:  0.253 Drug-induced Nephrotoxicity:  0.229
Genotoxicity:  0.238 RPMI-8226 Immunitoxicity:  0.053
A549 Cytotoxicity:  0.163 Hek293 Cytotoxicity:  0.532
BCF:   1.505
?
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:   3.841
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.695
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.287
?
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
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota rhizosphere Sonoran desert n.a. PMID[15620238]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[17542490]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[17564467]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[19053517]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[21366228]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[21718031]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[21854017]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota healthy leaf of Ginkgo biloba campus of Nanjing University, Nanjing, China 2008-OCT PMID[22196792]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota isolated from the sponge Xestospongia testudinaria n.a. n.a. PMID[22225637]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota Isolated from a sandy-loam soil sample 50 m inland from Waikiki Beach, Honolulu, Hawaii 2010-JUL PMID[22400916]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[22703109]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[23527875]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[24050204]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[25001296]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[25581396]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[26273902]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[31012585]
NPO41083 Trichoderma erinaceum F1-1 Strain Hypocreaceae Eukaryota n.a. n.a. n.a. PMID[31886665]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[33305943]
NPO41083 Trichoderma erinaceum F1-1 Strain Hypocreaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]

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
NPT116 Cell line HL-60 Homo sapiens IC50 > 10000.0 nM PMID[23527875]
NPT111 Cell line K562 Homo sapiens IC50 > 10000.0 nM PMID[23527875]
NPT400 Cell line MDA-MB-435 Homo sapiens IC50 = 41100.0 nM PMID[31886665]
NPT1311 Organism Listonella anguillarum Listonella anguillarum MIC = 25600.0 nM PMID[23527875]
NPT2911 Organism Pseudomonas putida Pseudomonas putida MIC = 51200.0 nM PMID[23527875]
NPT565 Organism Vibrio parahaemolyticus Vibrio parahaemolyticus MIC = 51200.0 nM PMID[23527875]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 51200.0 nM PMID[23527875]
NPT17 Organism Staphylococcus epidermidis Staphylococcus epidermidis MIC = 25600.0 nM PMID[23527875]

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 NPC298134 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
0.7561 Intermediate Similarity NPC487980
0.7209 Intermediate Similarity NPC487984
0.7059 Intermediate Similarity NPC255068
0.7059 Intermediate Similarity NPC481406
0.6596 Remote Similarity NPC487982
0.6429 Remote Similarity NPC216836
0.6111 Remote Similarity NPC164576
0.5556 Remote Similarity NPC116200
0.5455 Remote Similarity NPC481405
0.5227 Remote Similarity NPC145780
0.5122 Remote Similarity NPC487981

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC298134 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