Natural Product: NPC72455

Natural Product IDNPC72455
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Pachyrrizine
IUPAC Name 6-(6-methoxy-1,3-benzodioxol-5-yl)furo[3,2-g]chromen-7-one
Synonyms Pachyrrizine
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL479689
PubChem CID 101277
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002506] Isoflavonoids
        • [CHEMONTID:0002819] Isoflav-3-enes
          • [CHEMONTID:0002820] Isoflav-3-enones

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 PENSQRMNZZWMGV-UHFFFAOYSA-N
Standard InCHI InChI=1S/C19H12O6/c1-21-16-8-18-17(23-9-24-18)6-12(16)13-5-11-4-10-2-3-22-14(10)7-15(11)25-19(13)20/h2-8H,9H2,1H3
SMILES COc1cc2OCOc2cc1c1cc2cc3ccoc3cc2oc1=O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   336.06 Volume:   323.411
?
Van der Waals volume.
Dense:   1.039 LogP:   2.963
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.986
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.666
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   26.0
TPSA:   71.04
?
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:   0.516 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.579 Fsp3:   0.105
MCE-18:   52.381
?
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:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.83 Fluc inhibitor:   0.875
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.995
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.666
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.266 Promiscuous compounds:   0.388

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.699 MDCK Permeability:   -4.633
Pgp-inhibitor:   0.027 Pgp-substrate:   0.0
PAMPA:   0.243
?
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%):   0.217 30% Bioavailability (F30%):   0.002
50% Bioavailability (F50%):   0.036

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.004 MRP1:   0.99
Plasma Protein Binding (PPB):   97.09% Volume Distribution (VD):   -0.101
Fu: 2.837%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.995
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.001
BSEP inhibitor:   0.999

ADMET: Metabolism

CYP1A2-inhibitor:   0.677 CYP1A2-substrate:   0.914
CYP2C19-inhibitor:   0.325 CYP2C19-substrate:   0.686
CYP2C9-inhibitor:   0.989 CYP2C9-substrate:   0.576
CYP2D6-inhibitor:   0.971 CYP2D6-substrate:   0.984
CYP3A4-inhibitor:   0.013 CYP3A4-substrate:   0.994
CYP2B6-substrate:   0.988 CYP2C8-inhibitor:   0.164
HLM stability:   0.407
?
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):  4.11 Half-life (T1/2):  1.052

ADMET: Toxicity

hERG Blockers:  0.251 hERG Blockers (10um):  0.415
Human Hepatotoxicity (H-HT):  0.548 Drug-induced Liver Injury (DILI):  0.991
AMES Toxicity:  0.685 Rat Oral Acute Toxicity:  0.733
Maximum Recommended Daily Dose:  0.893 Skin Sensitization:  0.044
Carcinogencity:  0.966 Eye Corrosion:  0.005
Eye Irritation:  0.91 Respiratory Toxicity:  0.714
Drug-induced Neurotoxicity:  0.177 Ototoxicity:  0.196
Hematotoxicity:  0.33 Drug-induced Nephrotoxicity:  0.226
Genotoxicity:  0.966 RPMI-8226 Immunitoxicity:  0.127
A549 Cytotoxicity:  0.168 Hek293 Cytotoxicity:  0.488
BCF:   1.351
?
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:   4.003
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.484
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.909
?
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
NPO29463 Pogostemon cablin Species Lamiaceae Eukaryota n.a. stem n.a. PMID[12575075]
NPO29463 Pogostemon cablin Species Lamiaceae Eukaryota n.a. leaf n.a. PMID[12575075]
NPO29463 Pogostemon cablin Species Lamiaceae Eukaryota n.a. whole plant n.a. PMID[15577255]
NPO24293 Neorautanenia mitis Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[16562843]
NPO29463 Pogostemon cablin Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[30188125]
NPO3392 Agastache rugosus Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6470 Pachyrhizus erosus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4333 Neorautanenia edulis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24293 Neorautanenia mitis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24667 Pachyrrhizus erosus n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO29463 Pogostemon cablin Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6470 Pachyrhizus erosus Species Fabaceae Eukaryota Tuber n.a. n.a. Database[FooDB]
NPO6470 Pachyrhizus erosus Species Fabaceae Eukaryota Plant n.a. n.a. Database[FooDB]
NPO6470 Pachyrhizus erosus Species Fabaceae Eukaryota n.a. n.a. Database[FooDB]
NPO29463 Pogostemon cablin Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO13860 Solanum pubescens Species Solanaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO3392 Agastache rugosus Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO6470 Pachyrhizus erosus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO19015 Begonia glabra Species Begoniaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO24667 Pachyrrhizus erosus n.a. n.a. n.a. n.a. n.a. n.a. Database[HerDing]
NPO13860 Solanum pubescens Species Solanaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO6470 Pachyrhizus erosus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO3392 Agastache rugosus Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO29463 Pogostemon cablin Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24667 Pachyrrhizus erosus n.a. n.a. n.a. n.a. n.a. n.a. Database[TCMID]
NPO4333 Neorautanenia edulis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24293 Neorautanenia mitis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO19015 Begonia glabra Species Begoniaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO13860 Solanum pubescens Species Solanaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO6470 Pachyrhizus erosus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO19015 Begonia glabra Species Begoniaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO29463 Pogostemon cablin Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO29463 Pogostemon cablin Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO6470 Pachyrhizus erosus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13860 Solanum pubescens Species Solanaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29463 Pogostemon cablin Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4333 Neorautanenia edulis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24667 Pachyrrhizus erosus n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO19015 Begonia glabra Species Begoniaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24293 Neorautanenia mitis Species Fabaceae 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
NPT149 Individual protein Endoplasmic reticulum-associated amyloid beta-peptide-binding protein Homo sapiens Potency = 31622.8 nM PubChem BioAssay data set
NPT1226 Individual protein Caspase-7 Homo sapiens Potency = 19952.6 nM PubChem BioAssay data set
NPT277 Individual protein Caspase-1 Homo sapiens Potency = 31622.8 nM PubChem BioAssay data set
NPT109 Individual protein Cytochrome P450 3A4 Homo sapiens Potency = 398.1 nM PubChem BioAssay data set
NPT199 Individual protein DNA polymerase kappa Homo sapiens Potency n.a. 15848.9 nM PubChem BioAssay data set
NPT72 Individual protein Solute carrier organic anion transporter family member 1B3 Homo sapiens Inhibition = 121.35 % PMID[23571415]
NPT444 Individual protein Ubiquitin carboxyl-terminal hydrolase 1 Homo sapiens Potency n.a. 50118.7 nM PubChem BioAssay data set
NPT73 Individual protein Solute carrier organic anion transporter family member 1B1 Homo sapiens Inhibition = 139.6 % PMID[23571415]
NPT442 Individual protein Ferritin light chain Equus caballus Potency = 50118.7 nM PubChem BioAssay data set

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT81 Cell line A549 Homo sapiens IC50 > 5.0 ug.mL-1 PMID[16562843]
NPT83 Cell line MCF7 Homo sapiens IC50 = 3.6 ug.mL-1 PMID[16562843]
NPT20555 Organism SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 IC50 > 20000.0 nM DOI[10.6019/CHEMBL4651402]
NPT20555 Organism SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 IC50 > 19952.62 nM DOI[10.6019/CHEMBL4651402]
NPT2 Others Unspecified n.a. Potency = 31622.8 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 3162.3 nM PubChem BioAssay data set

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 NPC72455 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
0.5522 Remote Similarity NPC65846

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC72455 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