Natural Product: NPC87609

Natural Product IDNPC87609
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Isomesuol
IUPAC Name 5,7-dihydroxy-6-(3-methylbut-2-enyl)-8-(2-methylpropanoyl)-4-phenylchromen-2-one
Synonyms Isomesuol
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL383592
PubChem CID 5277587
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0001614] Neoflavonoids
        • [CHEMONTID:0003650] Prenylated neoflavonoids

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 HFESPLMGUIFVMR-UHFFFAOYSA-N
Standard InCHI InChI=1S/C24H24O5/c1-13(2)10-11-16-22(27)19-17(15-8-6-5-7-9-15)12-18(25)29-24(19)20(23(16)28)21(26)14(3)4/h5-10,12,14,27-28H,11H2,1-4H3
SMILES CC(=CCc1c(O)c2c(cc(=O)oc2c(c1O)C(=O)C(C)C)c1ccccc1)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   392.16 Volume:   415.577
?
Van der Waals volume.
Dense:   0.944 LogP:   4.902
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.721
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.713
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   20.0
TPSA:   87.74
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.353 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.782 Fsp3:   0.25
MCE-18:   21.0
?
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:   0.809 Fluc inhibitor:   0.034
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.875
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.71
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.217 Promiscuous compounds:   0.055

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.034 MDCK Permeability:   -4.693
Pgp-inhibitor:   0.995 Pgp-substrate:   0.014
PAMPA:   0.029
?
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):   0.002
20% Bioavailability (F20%):   0.335 30% Bioavailability (F30%):   0.845
50% Bioavailability (F50%):   0.986

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.026 MRP1:   1.0
Plasma Protein Binding (PPB):   98.309% Volume Distribution (VD):   0.017
Fu: 1.32%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.966
OATP1B3 inhibitor:   0.732 BCRP inhibitor:   0.241
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.786 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.998 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.289 CYP2C9-substrate:   0.998
CYP2D6-inhibitor:   0.001 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.999 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.702 CYP2C8-inhibitor:   1.0
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):  3.862 Half-life (T1/2):  0.794

ADMET: Toxicity

hERG Blockers:  0.075 hERG Blockers (10um):  0.386
Human Hepatotoxicity (H-HT):  0.698 Drug-induced Liver Injury (DILI):  0.9
AMES Toxicity:  0.471 Rat Oral Acute Toxicity:  0.685
Maximum Recommended Daily Dose:  0.783 Skin Sensitization:  0.528
Carcinogencity:  0.589 Eye Corrosion:  0.0
Eye Irritation:  0.466 Respiratory Toxicity:  0.882
Drug-induced Neurotoxicity:  0.282 Ototoxicity:  0.415
Hematotoxicity:  0.392 Drug-induced Nephrotoxicity:  0.768
Genotoxicity:  0.99 RPMI-8226 Immunitoxicity:  0.108
A549 Cytotoxicity:  0.254 Hek293 Cytotoxicity:  0.625
BCF:   1.706
?
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:   4.852
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.517
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   6.121
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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
NPO33501 marila pluricostata Species Calophyllaceae Eukaryota leaves n.a. n.a. PMID[15787438]

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
NPT459 Individual protein Human immunodeficiency virus type 1 reverse transcriptase Human immunodeficiency virus 1 IC50 = 31900.0 nM DOI[10.6019/CHEMBL1201861]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT165 Cell line HeLa Homo sapiens Inhibition = 36.7 % DOI[10.6019/CHEMBL1201861]
NPT165 Cell line HeLa Homo sapiens Inhibition = 34.3 % DOI[10.1007/s00044-011-9611-7]
NPT460 Cell line MT2 Homo sapiens Cell death = 11.5 % PMID[16137881]
NPT83 Cell line MCF7 Homo sapiens GI50 = 0.7 ug.mL-1 PMID[950643]
NPT397 Cell line NCI-H460 Homo sapiens GI50 = 0.6 ug.mL-1 PMID[17438057]
NPT395 Cell line SF-268 Homo sapiens GI50 = 0.6 ug.mL-1 PMID[15217297]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 67.0 % PMID[16137881]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 67.1 % PMID[16137881]
NPT24 Organism Human immunodeficiency virus 1 Human immunodeficiency virus 1 IC50 = 2000.0 nM PMID[27484512]

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 NPC87609 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
0.9 High Similarity NPC188632
0.9 High Similarity NPC112791
0.8333 Intermediate Similarity NPC178627
0.8254 Intermediate Similarity NPC196137
0.7879 Intermediate Similarity NPC483434
0.7681 Intermediate Similarity NPC469935
0.7083 Intermediate Similarity NPC181388
0.6765 Remote Similarity NPC470296
0.6765 Remote Similarity NPC196459
0.6765 Remote Similarity NPC94794
0.6429 Remote Similarity NPC1886
0.6286 Remote Similarity NPC36181
0.6081 Remote Similarity NPC19238
0.5972 Remote Similarity NPC73776
0.5821 Remote Similarity NPC32463
0.56 Remote Similarity NPC36705
0.5507 Remote Similarity NPC154217
0.5479 Remote Similarity NPC204088
0.5479 Remote Similarity NPC262011
0.5467 Remote Similarity NPC78554
0.5395 Remote Similarity NPC321372
0.5325 Remote Similarity NPC470322
0.5325 Remote Similarity NPC474735
0.5278 Remote Similarity NPC131782
0.5278 Remote Similarity NPC474624
0.5195 Remote Similarity NPC474738
0.5195 Remote Similarity NPC297886
0.5135 Remote Similarity NPC470909
0.5128 Remote Similarity NPC290671
0.5067 Remote Similarity NPC219584
0.5065 Remote Similarity NPC140120

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC87609 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