Natural Product: NPC7526

Natural Product IDNPC7526
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 2-[(2S)-7-Oxo-2,3-Dihydrofuro[3,2-G]Chromen-2-Yl]Propan-2-Yl (E)-2-Methylbut-2-Enoate
IUPAC Name 2-[(2S)-7-oxo-2,3-dihydrofuro[3,2-g]chromen-2-yl]propan-2-yl (E)-2-methylbut-2-enoate
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1443379
PubChem CID 906525
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000145] Coumarins and derivatives
        • [CHEMONTID:0000358] Furanocoumarins
          • [CHEMONTID:0002569] Linear furanocoumarins
            • [CHEMONTID:0000202] Psoralens

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 HHNCJFKRMZDTHW-WQRDJFRPSA-N
Standard InCHI InChI=1S/C19H20O5/c1-5-11(2)18(21)24-19(3,4)16-9-13-8-12-6-7-17(20)23-14(12)10-15(13)22-16/h5-8,10,16H,9H2,1-4H3/b11-5+/t16-/m0/s1
SMILES C/C=C(C)/C(=O)OC(C)(C)[C@@H]1Cc2cc3ccc(=O)oc3cc2O1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   328.13 Volume:   337.007
?
Van der Waals volume.
Dense:   0.974 LogP:   3.4
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.096
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.783
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   18.0
TPSA:   65.74
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.491 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.498 Fsp3:   0.368
MCE-18:   63.077
?
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:   0.391 Fluc inhibitor:   0.674
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.977
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.568
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.343 Promiscuous compounds:   0.113

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.786 MDCK Permeability:   -4.644
Pgp-inhibitor:   0.058 Pgp-substrate:   0.0
PAMPA:   0.178
?
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%):   0.69 30% Bioavailability (F30%):   0.582
50% Bioavailability (F50%):   0.476

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   1.0
Plasma Protein Binding (PPB):   95.449% Volume Distribution (VD):   -0.034
Fu: 4.216%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.0
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.112 CYP1A2-substrate:   0.599
CYP2C19-inhibitor:   0.655 CYP2C19-substrate:   0.121
CYP2C9-inhibitor:   0.883 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.001 CYP2D6-substrate:   0.899
CYP3A4-inhibitor:   0.98 CYP3A4-substrate:   0.95
CYP2B6-substrate:   0.051 CYP2C8-inhibitor:   0.995
HLM stability:   0.729
?
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):  5.791 Half-life (T1/2):  0.565

ADMET: Toxicity

hERG Blockers:  0.152 hERG Blockers (10um):  0.33
Human Hepatotoxicity (H-HT):  0.536 Drug-induced Liver Injury (DILI):  0.928
AMES Toxicity:  0.694 Rat Oral Acute Toxicity:  0.727
Maximum Recommended Daily Dose:  0.916 Skin Sensitization:  0.716
Carcinogencity:  0.876 Eye Corrosion:  0.04
Eye Irritation:  0.917 Respiratory Toxicity:  0.797
Drug-induced Neurotoxicity:  0.581 Ototoxicity:  0.224
Hematotoxicity:  0.282 Drug-induced Nephrotoxicity:  0.665
Genotoxicity:  0.989 RPMI-8226 Immunitoxicity:  0.105
A549 Cytotoxicity:  0.151 Hek293 Cytotoxicity:  0.391
BCF:   1.183
?
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:   3.864
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.164
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.816
?
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
NPO16675 Peucedanum japonicum Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[1453177]
NPO16755 Saposhnikovia divaricata Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[17703773]
NPO15394 Angelica decursiva Species Apiaceae Eukaryota n.a. root n.a. PMID[22784551]
NPO15394 Angelica decursiva Species Apiaceae Eukaryota n.a. root n.a. PMID[25068578]
NPO16755 Saposhnikovia divaricata Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[38830452]
NPO16755 Saposhnikovia divaricata Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16675 Peucedanum japonicum Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12008 Aplidium californicum Species Polyclinidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15394 Angelica decursiva Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26235 Achillea ageratum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17866 Peucedanum rubricaule Species Apiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO16755 Saposhnikovia divaricata Species Apiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO15394 Angelica decursiva Species Apiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO17866 Peucedanum rubricaule Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO16755 Saposhnikovia divaricata Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15394 Angelica decursiva Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO16675 Peucedanum japonicum Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15394 Angelica decursiva Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO17866 Peucedanum rubricaule Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO16675 Peucedanum japonicum Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO15394 Angelica decursiva Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO16755 Saposhnikovia divaricata Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO15394 Angelica decursiva Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12008 Aplidium californicum Species Polyclinidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26235 Achillea ageratum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16675 Peucedanum japonicum Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12370 Pulmonaria officinalis Species Boraginaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8979 Strychnos malacoclados Species Loganiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21159 Monoon membranifolium Species Annonaceae 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
NPT154 Individual protein Mothers against decapentaplegic homolog 3 Homo sapiens Potency n.a. 6309.6 nM PubChem BioAssay data set
NPT101 Individual protein Glucagon-like peptide 1 receptor Homo sapiens Potency n.a. 14125.4 nM PubChem BioAssay data set
NPT204 Individual protein Acetylcholinesterase Homo sapiens IC50 > 100000.0 nM PMID[23746477]
NPT7 Individual protein Thioredoxin reductase 1, cytoplasmic Rattus norvegicus Potency n.a. 31622.8 nM PubChem BioAssay data set
NPT535 Individual protein Parathyroid hormone receptor Homo sapiens Potency n.a. 112201.8 nM PubChem BioAssay data set
NPT864 Individual protein Lethal(3)malignant brain tumor-like protein 1 Homo sapiens Potency = 8912.5 nM PubChem BioAssay data set
NPT539 Individual protein Cellular tumor antigen p53 Homo sapiens Potency n.a. 35481.3 nM PubChem BioAssay data set
NPT64 Individual protein ATPase family AAA domain-containing protein 5 Homo sapiens Potency n.a. 651.0 nM PubChem BioAssay data set

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT65 Cell line HepG2 Homo sapiens Potency n.a. 6309.6 nM PubChem BioAssay data set
NPT393 Cell line HCT-116 Homo sapiens IC50 = 7600.0 nM PMID[23746477]
NPT139 Cell line HT-29 Homo sapiens IC50 = 930.0 nM PMID[23746477]
NPT6 Organism Plasmodium falciparum Plasmodium falciparum Potency n.a. 2936.2 nM PubChem BioAssay data set
NPT6 Organism Plasmodium falciparum Plasmodium falciparum Potency n.a. 1168.9 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 39810.7 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 11220.2 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 NPC7526 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 NPC222036
0.8095 Intermediate Similarity NPC14248
0.7077 Intermediate Similarity NPC55149
0.6765 Remote Similarity NPC47163
0.619 Remote Similarity NPC234109
0.619 Remote Similarity NPC188327
0.6 Remote Similarity NPC131296
0.6 Remote Similarity NPC326489
0.6 Remote Similarity NPC283331
0.5946 Remote Similarity NPC211110
0.5938 Remote Similarity NPC253574
0.5938 Remote Similarity NPC98179
0.5921 Remote Similarity NPC296377
0.5833 Remote Similarity NPC207002
0.5833 Remote Similarity NPC133956
0.5811 Remote Similarity NPC488325
0.5571 Remote Similarity NPC603073
0.5556 Remote Similarity NPC119640
0.5556 Remote Similarity NPC183646
0.5455 Remote Similarity NPC279573
0.5385 Remote Similarity NPC488332
0.5333 Remote Similarity NPC151946
0.5316 Remote Similarity NPC488333
0.5303 Remote Similarity NPC248429
0.5132 Remote Similarity NPC155963
0.5132 Remote Similarity NPC606124
0.5075 Remote Similarity NPC111347

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC7526 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