Natural Product: NPC38790

Natural Product IDNPC38790
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 JOYYVGVYUHRBAE-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 5319482
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000123] Benzopyrans
        • [CHEMONTID:0003410] 1-benzopyrans
          • [CHEMONTID:0000144] Chromones

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 JOYYVGVYUHRBAE-UHFFFAOYSA-N
Standard InCHI InChI=1S/C18H16O3/c1-20-14-9-10-18-16(11-14)17(19)12-15(21-18)8-7-13-5-3-2-4-6-13/h2-6,9-12H,7-8H2,1H3
SMILES COc1ccc2c(c1)c(=O)cc(CCc1ccccc1)o2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   280.11 Volume:   299.494
?
Van der Waals volume.
Dense:   0.935 LogP:   4.008
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.589
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.454
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   18.0
TPSA:   39.44
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.733 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   1.917 Fsp3:   0.167
MCE-18:   15.0
?
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:   0 PAINS Alert:   0
Colloidal aggregators:   0.625 Fluc inhibitor:   0.851
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.716
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.687
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.503 Promiscuous compounds:   0.346

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.972 MDCK Permeability:   -4.651
Pgp-inhibitor:   0.999 Pgp-substrate:   0.015
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):   0.012
20% Bioavailability (F20%):   0.188 30% Bioavailability (F30%):   0.401
50% Bioavailability (F50%):   0.461

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.298 MRP1:   0.534
Plasma Protein Binding (PPB):   98.521% Volume Distribution (VD):   0.328
Fu: 1.395%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.949
OATP1B3 inhibitor:   0.897 BCRP inhibitor:   0.199
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.988 CYP1A2-substrate:   0.989
CYP2C19-inhibitor:   0.997 CYP2C19-substrate:   0.734
CYP2C9-inhibitor:   0.864 CYP2C9-substrate:   0.198
CYP2D6-inhibitor:   0.489 CYP2D6-substrate:   0.985
CYP3A4-inhibitor:   0.002 CYP3A4-substrate:   0.098
CYP2B6-substrate:   0.461 CYP2C8-inhibitor:   0.986
HLM stability:   0.997
?
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):  7.192 Half-life (T1/2):  0.668

ADMET: Toxicity

hERG Blockers:  0.544 hERG Blockers (10um):  0.776
Human Hepatotoxicity (H-HT):  0.868 Drug-induced Liver Injury (DILI):  0.581
AMES Toxicity:  0.689 Rat Oral Acute Toxicity:  0.213
Maximum Recommended Daily Dose:  0.887 Skin Sensitization:  0.128
Carcinogencity:  0.726 Eye Corrosion:  0.001
Eye Irritation:  0.265 Respiratory Toxicity:  0.508
Drug-induced Neurotoxicity:  0.779 Ototoxicity:  0.482
Hematotoxicity:  0.545 Drug-induced Nephrotoxicity:  0.765
Genotoxicity:  0.968 RPMI-8226 Immunitoxicity:  0.109
A549 Cytotoxicity:  0.272 Hek293 Cytotoxicity:  0.748
BCF:   1.779
?
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:   4.334
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.472
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.07
?
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
NPO14558 Aquilaria sinensis Species Thymelaeaceae Eukaryota n.a. n.a. n.a. PMID[27128895]
NPO1692 Aquilaria malaccensis Species Thymelaeaceae Eukaryota Seeds n.a. n.a. PMID[28445049]
NPO1692 Aquilaria malaccensis Species Thymelaeaceae Eukaryota Agarwood n.a. n.a. PMID[29083898]
NPO14558 Aquilaria sinensis Species Thymelaeaceae Eukaryota Resinous Wood n.a. n.a. PMID[29227647]
NPO1692 Aquilaria malaccensis Species Thymelaeaceae Eukaryota n.a. n.a. n.a. PMID[30672698]
NPO14558 Aquilaria sinensis Species Thymelaeaceae Eukaryota n.a. n.a. n.a. PMID[38792158]
NPO1692 Aquilaria malaccensis Species Thymelaeaceae Eukaryota n.a. n.a. n.a. PMID[7320738]
NPO23275 Galeola faberi Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29756 Aquilaria agallocha Species Thymelaeaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12265 Aquilaria agallochum Species Thymelaeaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1692 Aquilaria malaccensis Species Thymelaeaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14558 Aquilaria sinensis Species Thymelaeaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14558 Aquilaria sinensis Species Thymelaeaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO29756 Aquilaria agallocha Species Thymelaeaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO23275 Galeola faberi Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO23275 Galeola faberi Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12265 Aquilaria agallochum Species Thymelaeaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14558 Aquilaria sinensis Species Thymelaeaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14558 Aquilaria sinensis Species Thymelaeaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO29756 Aquilaria agallocha Species Thymelaeaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO12265 Aquilaria agallochum Species Thymelaeaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO14558 Aquilaria sinensis Species Thymelaeaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO12265 Aquilaria agallochum Species Thymelaeaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23275 Galeola faberi Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14558 Aquilaria sinensis Species Thymelaeaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1692 Aquilaria malaccensis Species Thymelaeaceae 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
NPT99 Individual protein Peroxisome proliferator-activated receptor gamma Homo sapiens Inhibition = 52.8 % PMID[30672698]
NPT99 Individual protein Peroxisome proliferator-activated receptor gamma Homo sapiens Ki = 18100.0 nM PMID[30672698]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT2 Others Unspecified n.a. EC50 = 16200.0 nM PMID[30672698]

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 NPC38790 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
0.7407 Intermediate Similarity NPC129443
0.7358 Intermediate Similarity NPC183192
0.72 Intermediate Similarity NPC54243
0.6607 Remote Similarity NPC9038
0.6441 Remote Similarity NPC227172
0.6429 Remote Similarity NPC7569
0.575 Remote Similarity NPC478386
0.569 Remote Similarity NPC39753
0.561 Remote Similarity NPC478384
0.561 Remote Similarity NPC478385
0.55 Remote Similarity NPC480152
0.5345 Remote Similarity NPC472882

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC38790 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