Natural Product: NPC18284

Natural Product IDNPC18284
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Ichthynone
IUPAC Name 6-methoxy-3-(6-methoxy-1,3-benzodioxol-5-yl)-8,8-dimethylpyrano[2,3-h]chromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3039125
PubChem CID 3428129
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002506] Isoflavonoids
        • [CHEMONTID:0003530] Pyranoisoflavonoids

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 NPYOKEDYJXYSTA-UHFFFAOYSA-N
Standard InCHI InChI=1S/C23H20O7/c1-23(2)6-5-12-21-14(8-19(26-4)22(12)30-23)20(24)15(10-27-21)13-7-17-18(29-11-28-17)9-16(13)25-3/h5-10H,11H2,1-4H3
SMILES COc1cc2c(=O)c(coc2c2c1OC(C)(C)C=C2)c1cc2OCOc2cc1OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   408.12 Volume:   401.385
?
Van der Waals volume.
Dense:   1.017 LogP:   3.44
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.187
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.35
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   27.0
TPSA:   76.36
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   0.0 Rings:   5.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.636 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.981 Fsp3:   0.261
MCE-18:   62.0
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Rejected GSK Rule:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.538 Fluc inhibitor:   0.096
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.804
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.571
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.276 Promiscuous compounds:   0.294

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.81 MDCK Permeability:   -4.743
Pgp-inhibitor:   0.97 Pgp-substrate:   0.015
PAMPA:   0.05
?
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):   0.006
20% Bioavailability (F20%):   0.14 30% Bioavailability (F30%):   0.017
50% Bioavailability (F50%):   0.81

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.202 MRP1:   0.655
Plasma Protein Binding (PPB):   95.218% Volume Distribution (VD):   0.122
Fu: 4.358%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.998
OATP1B3 inhibitor:   0.994 BCRP inhibitor:   0.684
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.925 CYP1A2-substrate:   0.999
CYP2C19-inhibitor:   0.846 CYP2C19-substrate:   0.692
CYP2C9-inhibitor:   0.45 CYP2C9-substrate:   0.313
CYP2D6-inhibitor:   0.208 CYP2D6-substrate:   0.999
CYP3A4-inhibitor:   0.005 CYP3A4-substrate:   0.982
CYP2B6-substrate:   0.131 CYP2C8-inhibitor:   0.068
HLM stability:   0.336
?
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):  4.645 Half-life (T1/2):  0.883

ADMET: Toxicity

hERG Blockers:  0.216 hERG Blockers (10um):  0.517
Human Hepatotoxicity (H-HT):  0.674 Drug-induced Liver Injury (DILI):  0.932
AMES Toxicity:  0.662 Rat Oral Acute Toxicity:  0.651
Maximum Recommended Daily Dose:  0.863 Skin Sensitization:  0.166
Carcinogencity:  0.939 Eye Corrosion:  0.002
Eye Irritation:  0.645 Respiratory Toxicity:  0.673
Drug-induced Neurotoxicity:  0.617 Ototoxicity:  0.369
Hematotoxicity:  0.616 Drug-induced Nephrotoxicity:  0.599
Genotoxicity:  0.86 RPMI-8226 Immunitoxicity:  0.234
A549 Cytotoxicity:  0.145 Hek293 Cytotoxicity:  0.493
BCF:   1.67
?
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:   4.293
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.878
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.63
?
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
NPO29483 Swartzia schomburgkii Species Fabaceae Eukaryota n.a. suriname rainforest n.a. PMID[11087583]
NPO28682 Jatropha multifida Species Euphorbiaceae Eukaryota n.a. n.a. n.a. PMID[19036584]
NPO28682 Jatropha multifida Species Euphorbiaceae Eukaryota stems Botanical Garden, Osmania University, Hyderabad, Andhra Pradesh 2006-AUG PMID[21534583]
NPO28626 Isodon rubescens Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[25590529]
NPO29252 Moneses uniflora Species Ericaceae Eukaryota n.a. n.a. n.a. PMID[8984155]
NPO29132 Agaricus campestris Species Agaricaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28626 Isodon rubescens Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29288 Diplorhynchus condylocarpon Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28682 Jatropha multifida Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28728 Scutellaria planipes Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29339 Didemnum moseleyi Species Didemnidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29022 Sarcococca wallichii Species Buxaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28711 Artabotrys hexapetalus Species Annonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28606 Lemaireocereus thurberi Species Cactaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29252 Moneses uniflora Species Ericaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28711 Artabotrys hexapetalus Species Annonaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO29132 Agaricus campestris Species Agaricaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28626 Isodon rubescens Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28711 Artabotrys hexapetalus Species Annonaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO29132 Agaricus campestris Species Agaricaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO29132 Agaricus campestris Species Agaricaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO28711 Artabotrys hexapetalus Species Annonaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO28626 Isodon rubescens Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO28728 Scutellaria planipes Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28664 Hydrangea arborescens Species Hydrangeaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29252 Moneses uniflora Species Ericaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29164 Lophostemon confertus Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28626 Isodon rubescens Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29483 Swartzia schomburgkii Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29288 Diplorhynchus condylocarpon Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29339 Didemnum moseleyi Species Didemnidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29269 Celsia roripifolia Species Scrophulariaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28682 Jatropha multifida Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28699 Vincetoxicum nigrum Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28798 Calophyllum macrocarpum Species Calophyllaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29022 Sarcococca wallichii Species Buxaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28711 Artabotrys hexapetalus Species Annonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29393 Hapalopilus rutilans Species Phanerochaetaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29132 Agaricus campestris Species Agaricaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28910 Dacus cucumis Species Tephritidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28767 Siparuna apiosyce Species Siparunaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28606 Lemaireocereus thurberi Species Cactaceae 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
NPT72 Individual protein Solute carrier organic anion transporter family member 1B3 Homo sapiens Inhibition = 118.77 % PMID[23571415]
NPT73 Individual protein Solute carrier organic anion transporter family member 1B1 Homo sapiens Inhibition = 105.57 % PMID[23571415]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT1171 Cell line HEp-2 Homo sapiens Activity n.a. n.a. n.a. PMID[38579352]
NPT1171 Cell line HEp-2 Homo sapiens CC50 = 91000.0 nM PMID[38579352]
NPT28912 Organism Human orthopneumovirus Human orthopneumovirus IC50 = 8000.0 nM PMID[38579352]

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 NPC18284 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
0.7826 Intermediate Similarity NPC273021
0.6761 Remote Similarity NPC128961
0.6 Remote Similarity NPC113055
0.5942 Remote Similarity NPC279061
0.5479 Remote Similarity NPC153008
0.5185 Remote Similarity NPC607700
0.5132 Remote Similarity NPC607923
0.5065 Remote Similarity NPC215375

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC18284 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