Natural Product: NPC294432

Natural Product IDNPC294432
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Kayeassamin E
IUPAC Name 6-butanoyl-5,7-dihydroxy-4-[(1S)-1-hydroxypropyl]-8-(3-methylbut-2-enyl)chromen-2-one
Synonyms Kayeassamin E
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL488456
PubChem CID 25141330
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000145] Coumarins and derivatives
        • [CHEMONTID:0002908] Hydroxycoumarins
          • [CHEMONTID:0002909] 7-hydroxycoumarins

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 XJMZUXUWUKIMKA-AWEZNQCLSA-N
Standard InCHI InChI=1S/C21H26O6/c1-5-7-15(23)18-19(25)12(9-8-11(3)4)21-17(20(18)26)13(14(22)6-2)10-16(24)27-21/h8,10,14,22,25-26H,5-7,9H2,1-4H3/t14-/m0/s1
SMILES CCCC(=O)c1c(c(CC=C(C)C)c2c(c(cc(=O)o2)[C@H](CC)O)c1O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   374.17 Volume:   388.945
?
Van der Waals volume.
Dense:   0.962 LogP:   3.124
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.925
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.92
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The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   14.0
TPSA:   107.97
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Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   3.0 Rings:   2.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.382 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.533 Fsp3:   0.429
MCE-18:   34.0
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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:   Rejected GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.523 Fluc inhibitor:   0.04
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.944
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.579
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.1 Promiscuous compounds:   0.243

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.994 MDCK Permeability:   -4.789
Pgp-inhibitor:   0.957 Pgp-substrate:   0.281
PAMPA:   0.434
?
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):   0.009
20% Bioavailability (F20%):   0.177 30% Bioavailability (F30%):   0.523
50% Bioavailability (F50%):   0.958

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.004 MRP1:   0.956
Plasma Protein Binding (PPB):   93.512% Volume Distribution (VD):   -0.003
Fu: 6.834%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.988
OATP1B3 inhibitor:   0.845 BCRP inhibitor:   0.672
BSEP inhibitor:   0.997

ADMET: Metabolism

CYP1A2-inhibitor:   0.001 CYP1A2-substrate:   0.994
CYP2C19-inhibitor:   0.166 CYP2C19-substrate:   0.997
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.264
CYP2D6-inhibitor:   0.022 CYP2D6-substrate:   0.004
CYP3A4-inhibitor:   0.043 CYP3A4-substrate:   0.384
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.999
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):  4.869 Half-life (T1/2):  1.415

ADMET: Toxicity

hERG Blockers:  0.022 hERG Blockers (10um):  0.201
Human Hepatotoxicity (H-HT):  0.54 Drug-induced Liver Injury (DILI):  0.185
AMES Toxicity:  0.443 Rat Oral Acute Toxicity:  0.513
Maximum Recommended Daily Dose:  0.663 Skin Sensitization:  0.735
Carcinogencity:  0.355 Eye Corrosion:  0.001
Eye Irritation:  0.7 Respiratory Toxicity:  0.627
Drug-induced Neurotoxicity:  0.115 Ototoxicity:  0.474
Hematotoxicity:  0.288 Drug-induced Nephrotoxicity:  0.618
Genotoxicity:  0.892 RPMI-8226 Immunitoxicity:  0.13
A549 Cytotoxicity:  0.152 Hek293 Cytotoxicity:  0.339
BCF:   1.221
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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:   3.967
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.507
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.855
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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
NPO4557 Kayea assamica Species Calophyllaceae Eukaryota flower Myanmar n.a. PMID[18640837]
NPO4557 Kayea assamica Species Calophyllaceae Eukaryota flowers Myanmar n.a. PMID[18725180]
NPO32974 mammea siamensis Species Calophyllaceae Eukaryota n.a. n.a. n.a. PMID[22831798]
NPO32974 mammea siamensis Species Calophyllaceae Eukaryota flower n.a. n.a. PMID[23206866]
NPO4557 Kayea assamica Species Calophyllaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4557 Kayea assamica Species Calophyllaceae 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

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT113 Cell line RAW264.7 Mus musculus Inhibition = 38.7 % DOI[10.1007/s00044-009-9198-4]
NPT113 Cell line RAW264.7 Mus musculus Inhibition = 38.8 % PMID[18809934]
NPT113 Cell line RAW264.7 Mus musculus Inhibition = 67.1 % PMID[24694215]
NPT113 Cell line RAW264.7 Mus musculus Inhibition = 63.8 % PMID[23734721]
NPT113 Cell line RAW264.7 Mus musculus Activity = 42.8 % PMID[18487053]
NPT113 Cell line RAW264.7 Mus musculus Activity = 42.2 % PMID[15921418]
NPT113 Cell line RAW264.7 Mus musculus IC50 = 6100.0 nM PMID[22194678]
NPT461 Cell line PANC-1 Homo sapiens Cytotoxicity = 1.0 uM PMID[18725180]

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 NPC294432 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
0.8571 High Similarity NPC184738
0.85 High Similarity NPC96216
0.8033 Intermediate Similarity NPC474939
0.6389 Remote Similarity NPC33653
0.6377 Remote Similarity NPC241975
0.6324 Remote Similarity NPC470909
0.6269 Remote Similarity NPC199458
0.6143 Remote Similarity NPC36181
0.6111 Remote Similarity NPC288910
0.6 Remote Similarity NPC470083
0.5972 Remote Similarity NPC133060
0.5882 Remote Similarity NPC138047
0.5658 Remote Similarity NPC118059
0.5526 Remote Similarity NPC470554
0.52 Remote Similarity NPC1886

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC294432 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