Natural Product: NPC155264

Natural Product IDNPC155264
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 4,9-Bis(3-Methylbut-2-Enoxy)Furo[3,2-G]Chromen-7-One
IUPAC Name 4,9-bis(3-methylbut-2-enoxy)furo[3,2-g]chromen-7-one
Synonyms 5,8-Diprenyloxypsoralen
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1710181
PubChem CID 10043694
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 HJMDOAWWVCOEDW-UHFFFAOYSA-N
Standard InCHI InChI=1S/C21H22O5/c1-13(2)7-10-23-18-15-5-6-17(22)26-20(15)21(25-11-8-14(3)4)19-16(18)9-12-24-19/h5-9,12H,10-11H2,1-4H3
SMILES CC(=CCOc1c2ccc(=O)oc2c(c2c1cco2)OCC=C(C)C)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   354.15 Volume:   368.962
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Van der Waals volume.
Dense:   0.96 LogP:   5.279
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   4.084
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.066
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The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   18.0
TPSA:   61.81
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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:   0.448 GASA:   1.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.021 Fsp3:   0.286
MCE-18:   18.0
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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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.62 Fluc inhibitor:   0.109
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.719
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.589
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.33 Promiscuous compounds:   0.062

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.619 MDCK Permeability:   -4.655
Pgp-inhibitor:   0.039 Pgp-substrate:   0.014
PAMPA:   0.038
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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):   0.067
20% Bioavailability (F20%):   1.0 30% Bioavailability (F30%):   1.0
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.056
Plasma Protein Binding (PPB):   95.41% Volume Distribution (VD):   0.112
Fu: 4.465%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   1.0
BSEP inhibitor:   0.003

ADMET: Metabolism

CYP1A2-inhibitor:   0.006 CYP1A2-substrate:   0.998
CYP2C19-inhibitor:   0.684 CYP2C19-substrate:   0.955
CYP2C9-inhibitor:   0.002 CYP2C9-substrate:   0.802
CYP2D6-inhibitor:   0.073 CYP2D6-substrate:   0.996
CYP3A4-inhibitor:   0.998 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.031 CYP2C8-inhibitor:   0.996
HLM stability:   0.125
?
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):  9.877 Half-life (T1/2):  0.658

ADMET: Toxicity

hERG Blockers:  0.221 hERG Blockers (10um):  0.592
Human Hepatotoxicity (H-HT):  0.615 Drug-induced Liver Injury (DILI):  0.624
AMES Toxicity:  0.402 Rat Oral Acute Toxicity:  0.49
Maximum Recommended Daily Dose:  0.696 Skin Sensitization:  0.894
Carcinogencity:  0.603 Eye Corrosion:  0.001
Eye Irritation:  0.524 Respiratory Toxicity:  0.675
Drug-induced Neurotoxicity:  0.234 Ototoxicity:  0.228
Hematotoxicity:  0.354 Drug-induced Nephrotoxicity:  0.139
Genotoxicity:  0.947 RPMI-8226 Immunitoxicity:  0.05
A549 Cytotoxicity:  0.054 Hek293 Cytotoxicity:  0.189
BCF:   1.78
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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:   4.624
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.22
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.872
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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
NPO24758 Angelica dahurica Species Apiaceae Eukaryota n.a. root n.a. DOI[10.5012/bkcs.2003.24.11.1699]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota n.a. root n.a. PMID[12510838]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota n.a. root n.a. PMID[15646793]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[21625478]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota n.a. root n.a. PMID[21657081]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[27444348]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota Roots n.a. n.a. PMID[31464439]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO24758 Angelica dahurica Species Apiaceae 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
NPT135 Individual protein Chromobox protein homolog 1 Homo sapiens Potency n.a. 56234.1 nM PubChem BioAssay data set
NPT154 Individual protein Mothers against decapentaplegic homolog 3 Homo sapiens Potency n.a. 35481.3 nM PubChem BioAssay data set
NPT10 Individual protein Geminin Homo sapiens Potency n.a. 5173.5 nM PubChem BioAssay data set
NPT101 Individual protein Glucagon-like peptide 1 receptor Homo sapiens Potency n.a. 31622.8 nM PubChem BioAssay data set
NPT11 Individual protein Guanine nucleotide-binding protein G(s), subunit alpha Homo sapiens Potency n.a. 39810.7 nM PubChem BioAssay data set
NPT740 Individual protein Beta-secretase 1 Homo sapiens IC50 > 500000.0 nM PMID[22222157]
NPT740 Individual protein Beta-secretase 1 Homo sapiens Inhibition = 1.4 % PMID[22222157]
NPT861 Individual protein Isocitrate dehydrogenase [NADP] cytoplasmic Homo sapiens Potency n.a. 39810.7 nM PubChem BioAssay data set
NPT861 Individual protein Isocitrate dehydrogenase [NADP] cytoplasmic Homo sapiens Potency n.a. 18356.4 nM PubChem BioAssay data set
NPT64 Individual protein ATPase family AAA domain-containing protein 5 Homo sapiens Potency n.a. 23099.9 nM PubChem BioAssay data set

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT2 Others Unspecified n.a. Potency n.a. 10000.0 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 NPC155264 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
0.9038 High Similarity NPC67450
0.9038 High Similarity NPC210460
0.8421 Intermediate Similarity NPC478566
0.8276 Intermediate Similarity NPC478570
0.8276 Intermediate Similarity NPC478567
0.8276 Intermediate Similarity NPC478569
0.7419 Intermediate Similarity NPC193881
0.6842 Remote Similarity NPC243509
0.6724 Remote Similarity NPC88445
0.6716 Remote Similarity NPC478568
0.6667 Remote Similarity NPC107244
0.6604 Remote Similarity NPC234536
0.6393 Remote Similarity NPC224165
0.6393 Remote Similarity NPC144288
0.6349 Remote Similarity NPC198876
0.5735 Remote Similarity NPC53917
0.5672 Remote Similarity NPC216092
0.5588 Remote Similarity NPC191104
0.5352 Remote Similarity NPC269495
0.5345 Remote Similarity NPC487850
0.5135 Remote Similarity NPC478632
0.5068 Remote Similarity NPC49009

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC155264 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