Natural Product: NPC65784

Natural Product IDNPC65784
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Justicidin B
IUPAC Name 4-(1,3-benzodioxol-5-yl)-6,7-dimethoxybenzo[f][1]benzofuran-3-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL149056
PubChem CID 44365806
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0001634] Naphthofurans

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 VKHANCMHYATJMZ-UHFFFAOYSA-N
Standard InCHI InChI=1S/C21H16O6/c1-23-16-6-12-7-19-21(14(22)9-25-19)20(13(12)8-17(16)24-2)11-3-4-15-18(5-11)27-10-26-15/h3-8H,9-10H2,1-2H3
SMILES COc1cc2c(cc1OC)cc1c(c2c2ccc3c(c2)OCO3)C(=O)CO1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   364.09 Volume:   358.003
?
Van der Waals volume.
Dense:   1.017 LogP:   3.555
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.326
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -6.312
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The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   26.0
TPSA:   63.22
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   0.0 Rings:   5.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.704 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.509 Fsp3:   0.19
MCE-18:   56.16
?
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:   0.856 Fluc inhibitor:   0.175
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.954
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.355
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.289 Promiscuous compounds:   0.261

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.864 MDCK Permeability:   -4.702
Pgp-inhibitor:   0.594 Pgp-substrate:   0.0
PAMPA:   0.078
?
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):   0.001
20% Bioavailability (F20%):   0.001 30% Bioavailability (F30%):   0.0
50% Bioavailability (F50%):   0.01

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.017 MRP1:   0.587
Plasma Protein Binding (PPB):   97.548% Volume Distribution (VD):   0.162
Fu: 2.231%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.936
OATP1B3 inhibitor:   0.997 BCRP inhibitor:   0.04
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.767 CYP1A2-substrate:   0.749
CYP2C19-inhibitor:   0.978 CYP2C19-substrate:   0.794
CYP2C9-inhibitor:   0.871 CYP2C9-substrate:   0.869
CYP2D6-inhibitor:   0.971 CYP2D6-substrate:   0.989
CYP3A4-inhibitor:   0.423 CYP3A4-substrate:   0.984
CYP2B6-substrate:   0.096 CYP2C8-inhibitor:   0.145
HLM stability:   0.126
?
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):  4.868 Half-life (T1/2):  1.143

ADMET: Toxicity

hERG Blockers:  0.465 hERG Blockers (10um):  0.581
Human Hepatotoxicity (H-HT):  0.767 Drug-induced Liver Injury (DILI):  0.967
AMES Toxicity:  0.816 Rat Oral Acute Toxicity:  0.565
Maximum Recommended Daily Dose:  0.884 Skin Sensitization:  0.251
Carcinogencity:  0.947 Eye Corrosion:  0.0
Eye Irritation:  0.437 Respiratory Toxicity:  0.765
Drug-induced Neurotoxicity:  0.892 Ototoxicity:  0.577
Hematotoxicity:  0.796 Drug-induced Nephrotoxicity:  0.827
Genotoxicity:  0.883 RPMI-8226 Immunitoxicity:  0.291
A549 Cytotoxicity:  0.472 Hek293 Cytotoxicity:  0.724
BCF:   1.618
?
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:   4.012
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.612
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.852
?
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
NPO16045 Justicia procumbens Species Acanthaceae Eukaryota n.a. n.a. n.a. PMID[11908984]
NPO8188 Hypoestes purpurea Species Acanthaceae Eukaryota n.a. n.a. n.a. PMID[15568798]
NPO25242 Linum leonii Species Linaceae Eukaryota n.a. n.a. n.a. PMID[16872135]
NPO18382 Phyllanthus piscatorum Species Leiothrichidae Eukaryota n.a. n.a. n.a. PMID[19299148]
NPO4373 Phyllanthus acuminatus Species Phyllanthaceae Eukaryota Roots n.a. n.a. PMID[2089115]
NPO40495 Justicia pectoralis Species Acanthaceae Eukaryota n.a. n.a. n.a. PMID[3404155]
NPO16045 Justicia procumbens Species Acanthaceae Eukaryota n.a. n.a. n.a. PMID[3734816]
NPO16045 Justicia procumbens Species Acanthaceae Eukaryota n.a. n.a. n.a. PMID[8988600]
NPO4373 Phyllanthus acuminatus Species Phyllanthaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24771 Boenninghausenia albiflora Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22728 Haplophyllum patavinum Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8188 Hypoestes purpurea Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16045 Justicia procumbens Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO40495 Justicia pectoralis Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23659 Rostellularia procumbens n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO4373 Phyllanthus acuminatus Species Phyllanthaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO18382 Phyllanthus piscatorum Species Leiothrichidae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO22728 Haplophyllum patavinum Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO23659 Rostellularia procumbens n.a. n.a. n.a. n.a. n.a. n.a. Database[HerDing]
NPO8188 Hypoestes purpurea Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO24771 Boenninghausenia albiflora Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO8188 Hypoestes purpurea Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO22728 Haplophyllum patavinum Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO23659 Rostellularia procumbens n.a. n.a. n.a. n.a. n.a. n.a. Database[TCMID]
NPO18382 Phyllanthus piscatorum Species Leiothrichidae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO4373 Phyllanthus acuminatus Species Phyllanthaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24771 Boenninghausenia albiflora Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24771 Boenninghausenia albiflora Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO4373 Phyllanthus acuminatus Species Phyllanthaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO23659 Rostellularia procumbens n.a. n.a. n.a. n.a. n.a. n.a. Database[TCM_Taiwan]
NPO23659 Rostellularia procumbens n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO25242 Linum leonii Species Linaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16045 Justicia procumbens Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8188 Hypoestes purpurea Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18382 Phyllanthus piscatorum Species Leiothrichidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4373 Phyllanthus acuminatus Species Phyllanthaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24771 Boenninghausenia albiflora Species Rutaceae 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
NPT168 Cell line P388 Mus musculus ED50 = 3.3 ug ml-1 PMID[3404155]
NPT1358 Cell line LAMA-84 Homo sapiens IC50 = 1110.0 nM PMID[16872135]
NPT111 Cell line K562 Homo sapiens IC50 = 6080.0 nM PMID[16872135]
NPT6 Organism Plasmodium falciparum Plasmodium falciparum IC50 > 5.0 ug.mL-1 PMID[19299148]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. ED50 = 1.2 10'-2 ug/ml PMID[3404155]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 28.0 ug.mL-1 PMID[3404155]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 1620.0 nM PMID[16872135]
NPT20967 Cell line Platelet n.a. IC50 = 8000.0 nM PMID[8988600]
NPT1795 Organism Murid herpesvirus 1 Murid herpesvirus 1 Inhibition = 14.0 % PMID[9834179]
NPT338 Organism Sindbis virus Sindbis virus Inhibition = 74.0 % PMID[9834179]
NPT195 Organism Vesicular stomatitis virus Vesicular stomatitis virus MIC = 330.0 nM PMID[9834179]

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT29 Organism Rattus norvegicus Rattus norvegicus Control = 47.0 % PMID[8978845]





 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 NPC65784 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
0.5625 Remote Similarity NPC610202
0.5303 Remote Similarity NPC299820
0.5224 Remote Similarity NPC127827
0.5147 Remote Similarity NPC475722

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC65784 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