Natural Product: NPC124302

Natural Product IDNPC124302
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 6,7-Dimethoxy-3-(6-Methyl-7,8-Dihydro-5H-[1,3]Dioxolo[4,5-G]Isoquinolin-5-Yl)-3H-2-Benzofuran-1-One
IUPAC Name 6,7-dimethoxy-3-(6-methyl-7,8-dihydro-5H-[1,3]dioxolo[4,5-g]isoquinolin-5-yl)-3H-2-benzofuran-1-one
Synonyms (+)-Hydrastine
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1256868
PubChem CID 1309
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000279] Alkaloids and derivatives
      • [CHEMONTID:0002188] Phthalide isoquinolines

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 JZUTXVTYJDCMDU-UHFFFAOYSA-N
Standard InCHI InChI=1S/C21H21NO6/c1-22-7-6-11-8-15-16(27-10-26-15)9-13(11)18(22)19-12-4-5-14(24-2)20(25-3)17(12)21(23)28-19/h4-5,8-9,18-19H,6-7,10H2,1-3H3
SMILES CN1CCc2cc3c(cc2C1C1c2ccc(c(c2C(=O)O1)OC)OC)OCO3

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   383.14 Volume:   374.273
?
Van der Waals volume.
Dense:   1.024 LogP:   2.1
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.452
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.923
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The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   26.0
TPSA:   66.46
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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:   0.755 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.416 Fsp3:   0.381
MCE-18:   90.31
?
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:   0.105 Fluc inhibitor:   0.003
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.371
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.204
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.003 Promiscuous compounds:   0.16

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.654 MDCK Permeability:   -4.72
Pgp-inhibitor:   0.281 Pgp-substrate:   0.01
PAMPA:   0.062
?
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%):   0.059 30% Bioavailability (F30%):   0.002
50% Bioavailability (F50%):   0.735

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.992 MRP1:   0.977
Plasma Protein Binding (PPB):   78.739% Volume Distribution (VD):   0.142
Fu: 24.389%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.301
OATP1B3 inhibitor:   0.86 BCRP inhibitor:   0.049
BSEP inhibitor:   0.997

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.999
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.778 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.192 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   0.997 CYP3A4-substrate:   0.997
CYP2B6-substrate:   1.0 CYP2C8-inhibitor:   0.0
HLM stability:   1.0
?
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):  4.723 Half-life (T1/2):  2.646

ADMET: Toxicity

hERG Blockers:  0.239 hERG Blockers (10um):  0.644
Human Hepatotoxicity (H-HT):  0.388 Drug-induced Liver Injury (DILI):  0.292
AMES Toxicity:  0.601 Rat Oral Acute Toxicity:  0.268
Maximum Recommended Daily Dose:  0.655 Skin Sensitization:  0.9
Carcinogencity:  0.774 Eye Corrosion:  0.009
Eye Irritation:  0.351 Respiratory Toxicity:  0.379
Drug-induced Neurotoxicity:  0.753 Ototoxicity:  0.556
Hematotoxicity:  0.3 Drug-induced Nephrotoxicity:  0.67
Genotoxicity:  0.698 RPMI-8226 Immunitoxicity:  0.064
A549 Cytotoxicity:  0.05 Hek293 Cytotoxicity:  0.2
BCF:   1.41
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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:   3.834
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.079
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.836
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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
NPO13757 Coptis japonica Species Ranunculaceae Eukaryota rhizomes n.a. n.a. PMID[11000020]
NPO13757 Coptis japonica Species Ranunculaceae Eukaryota n.a. rhizome n.a. PMID[21401114]
NPO29008 Coptis teeta Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5649 Coptis chinensis Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13757 Coptis japonica Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22622 Coptis deltoidea Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5649 Coptis chinensis Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO22622 Coptis deltoidea Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO13757 Coptis japonica Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO22622 Coptis deltoidea Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO5649 Coptis chinensis Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO13757 Coptis japonica Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO5649 Coptis chinensis Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO5649 Coptis chinensis Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO22622 Coptis deltoidea Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO13757 Coptis japonica Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO29008 Coptis teeta Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO5649 Coptis chinensis Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29008 Coptis teeta Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13757 Coptis japonica Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22622 Coptis deltoidea Species Ranunculaceae 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 = 39810.7 nM PubChem BioAssay data set
NPT109 Individual protein Cytochrome P450 3A4 Homo sapiens Potency = 1258.9 nM PubChem BioAssay data set
NPT10 Individual protein Geminin Homo sapiens Potency n.a. 5804.8 nM PubChem BioAssay data set
NPT713 Individual protein Bile salt export pump Homo sapiens IC50 = 65640.0 nM PMID[22961681]
NPT48 Individual protein Lysine-specific demethylase 4D-like Homo sapiens Potency = 39810.7 nM PubChem BioAssay data set
NPT61 Individual protein Beta-glucocerebrosidase Homo sapiens Potency n.a. 4466.8 nM PubChem BioAssay data set
NPT98 Individual protein HERG Homo sapiens Potency n.a. 15848.9 nM PubChem BioAssay data set
NPT8 Individual protein DNA polymerase iota Homo sapiens Potency n.a. 89125.1 nM PubChem BioAssay data set
NPT56 Individual protein Beta-lactamase AmpC Escherichia coli K-12 Potency = 562.3 nM PubChem BioAssay data set
NPT443 Individual protein Histone acetyltransferase GCN5 Homo sapiens Potency n.a. 39810.7 nM PubChem BioAssay data set
NPT64 Individual protein ATPase family AAA domain-containing protein 5 Homo sapiens Potency n.a. 18348.9 nM PubChem BioAssay data set
NPT49 Individual protein DNA-(apurinic or apyrimidinic site) lyase Homo sapiens Potency n.a. 3981.1 nM PubChem BioAssay data set

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT6 Organism Plasmodium falciparum Plasmodium falciparum Potency n.a. 11689.1 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 5011.9 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 2238.7 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 NPC124302 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
1.0 High Similarity NPC14622
1.0 High Similarity NPC70290
1.0 High Similarity NPC215098
1.0 High Similarity NPC73020
0.8833 High Similarity NPC46744
0.8814 High Similarity NPC120671
0.8814 High Similarity NPC226652
0.8814 High Similarity NPC219113
0.8814 High Similarity NPC72788
0.7812 Intermediate Similarity NPC119818
0.7812 Intermediate Similarity NPC328700
0.7812 Intermediate Similarity NPC202771
0.7812 Intermediate Similarity NPC2173
0.6471 Remote Similarity NPC481429
0.6471 Remote Similarity NPC481428
0.6471 Remote Similarity NPC481449
0.6286 Remote Similarity NPC481430
0.6232 Remote Similarity NPC290525
0.6027 Remote Similarity NPC481431
0.5972 Remote Similarity NPC481432
0.5972 Remote Similarity NPC481433
0.5507 Remote Similarity NPC27887
0.5286 Remote Similarity NPC475959

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC124302 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
1.0 High Similarity NPD4420 Pre-clinical
0.7812 Intermediate Similarity NPD5005 Approved
0.7812 Intermediate Similarity NPD5006 Phase 4

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