Natural Product: NPC183192

Natural Product IDNPC183192
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 MVQOWXHYPYRBOE-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 5316872
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 MVQOWXHYPYRBOE-UHFFFAOYSA-N
Standard InCHI InChI=1S/C19H18O4/c1-21-18-11-15-16(20)10-14(23-17(15)12-19(18)22-2)9-8-13-6-4-3-5-7-13/h3-7,10-12H,8-9H2,1-2H3
SMILES COc1cc2c(=O)cc(CCc3ccccc3)oc2cc1OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   310.12 Volume:   325.58
?
Van der Waals volume.
Dense:   0.953 LogP:   3.449
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.141
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.558
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   18.0
TPSA:   48.67
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.722 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.002 Fsp3:   0.211
MCE-18:   16.0
?
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:   0.435 Fluc inhibitor:   0.236
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.721
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.637
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.315 Promiscuous compounds:   0.338

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.969 MDCK Permeability:   -4.704
Pgp-inhibitor:   1.0 Pgp-substrate:   0.016
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):   0.013
20% Bioavailability (F20%):   0.153 30% Bioavailability (F30%):   0.197
50% Bioavailability (F50%):   0.539

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.023 MRP1:   0.69
Plasma Protein Binding (PPB):   98.522% Volume Distribution (VD):   0.329
Fu: 1.771%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.993
OATP1B3 inhibitor:   0.995 BCRP inhibitor:   0.864
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.545 CYP1A2-substrate:   0.938
CYP2C19-inhibitor:   0.954 CYP2C19-substrate:   0.702
CYP2C9-inhibitor:   0.571 CYP2C9-substrate:   0.023
CYP2D6-inhibitor:   0.531 CYP2D6-substrate:   0.895
CYP3A4-inhibitor:   0.972 CYP3A4-substrate:   0.722
CYP2B6-substrate:   0.175 CYP2C8-inhibitor:   0.983
HLM stability:   0.907
?
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):  7.182 Half-life (T1/2):  1.297

ADMET: Toxicity

hERG Blockers:  0.429 hERG Blockers (10um):  0.764
Human Hepatotoxicity (H-HT):  0.843 Drug-induced Liver Injury (DILI):  0.414
AMES Toxicity:  0.585 Rat Oral Acute Toxicity:  0.256
Maximum Recommended Daily Dose:  0.871 Skin Sensitization:  0.179
Carcinogencity:  0.616 Eye Corrosion:  0.003
Eye Irritation:  0.281 Respiratory Toxicity:  0.432
Drug-induced Neurotoxicity:  0.756 Ototoxicity:  0.453
Hematotoxicity:  0.576 Drug-induced Nephrotoxicity:  0.643
Genotoxicity:  0.957 RPMI-8226 Immunitoxicity:  0.112
A549 Cytotoxicity:  0.267 Hek293 Cytotoxicity:  0.714
BCF:   1.753
?
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:   4.184
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.158
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.813
?
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
NPO2715 Murraya paniculata Species Rutaceae Eukaryota n.a. twig n.a. PMID[24354205]
NPO2715 Murraya paniculata Species Rutaceae Eukaryota n.a. leaf n.a. PMID[24354205]
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]
NPO2715 Murraya paniculata Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[34964904]
NPO2715 Murraya paniculata Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[36529712]
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]
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]
NPO2715 Murraya paniculata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14558 Aquilaria sinensis Species Thymelaeaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO2715 Murraya paniculata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO2715 Murraya paniculata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14558 Aquilaria sinensis Species Thymelaeaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO2715 Murraya paniculata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO14558 Aquilaria sinensis Species Thymelaeaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO14558 Aquilaria sinensis Species Thymelaeaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO2715 Murraya paniculata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO14558 Aquilaria sinensis Species Thymelaeaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2715 Murraya paniculata Species Rutaceae 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
NPT29671 Protein complex group Nuclear factor NF-kappa-B complex Homo sapiens IC = 0.31 uM PMID[35472851]

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 NPC183192 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
0.8235 Intermediate Similarity NPC9038
0.7407 Intermediate Similarity NPC129443
0.7358 Intermediate Similarity NPC38790
0.6538 Remote Similarity NPC54243
0.614 Remote Similarity NPC7569
0.5645 Remote Similarity NPC227172
0.5424 Remote Similarity NPC39753
0.5246 Remote Similarity NPC480152
0.5085 Remote Similarity NPC472884

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC183192 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