Natural Product: NPC64915

Natural Product IDNPC64915
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 4'-O-Methylbonannione A
IUPAC Name (2S)-6-[(2E)-3,7-dimethylocta-2,6-dienyl]-5,7-dihydroxy-2-(4-methoxyphenyl)-2,3-dihydrochromen-4-one
Synonyms 4'-O-Methylbonannione A
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL479870
PubChem CID 11750568
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0000337] Flavans
          • [CHEMONTID:0003646] 6-prenylated flavans
            • [CHEMONTID:0003507] 6-prenylated flavanones

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 LKAFYCSXBIOTDY-KUCZMUFWSA-N
Standard InCHI InChI=1S/C26H30O5/c1-16(2)6-5-7-17(3)8-13-20-21(27)14-24-25(26(20)29)22(28)15-23(31-24)18-9-11-19(30-4)12-10-18/h6,8-12,14,23,27,29H,5,7,13,15H2,1-4H3/b17-8+/t23-/m0/s1
SMILES CC(=CCC/C(=C/Cc1c(cc2c(C(=O)C[C@@H](c3ccc(cc3)OC)O2)c1O)O)/C)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   422.21 Volume:   452.806
?
Van der Waals volume.
Dense:   0.932 LogP:   6.554
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   4.346
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.874
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   20.0
TPSA:   75.99
?
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:   0.531 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.296 Fsp3:   0.346
MCE-18:   62.286
?
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:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.985 Fluc inhibitor:   0.925
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.525
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.685
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.357 Promiscuous compounds:   0.147

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.861 MDCK Permeability:   -4.661
Pgp-inhibitor:   1.0 Pgp-substrate:   0.001
PAMPA:   0.002
?
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):   0.004
20% Bioavailability (F20%):   0.01 30% Bioavailability (F30%):   0.35
50% Bioavailability (F50%):   0.955

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.504
Plasma Protein Binding (PPB):   97.224% Volume Distribution (VD):   0.17
Fu: 2.367%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.998
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.872
BSEP inhibitor:   0.999

ADMET: Metabolism

CYP1A2-inhibitor:   0.133 CYP1A2-substrate:   0.995
CYP2C19-inhibitor:   0.975 CYP2C19-substrate:   0.969
CYP2C9-inhibitor:   0.974 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.987 CYP2D6-substrate:   0.056
CYP3A4-inhibitor:   0.007 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.999
?
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):  6.485 Half-life (T1/2):  0.845

ADMET: Toxicity

hERG Blockers:  0.146 hERG Blockers (10um):  0.557
Human Hepatotoxicity (H-HT):  0.876 Drug-induced Liver Injury (DILI):  0.92
AMES Toxicity:  0.461 Rat Oral Acute Toxicity:  0.732
Maximum Recommended Daily Dose:  0.671 Skin Sensitization:  0.952
Carcinogencity:  0.323 Eye Corrosion:  0.001
Eye Irritation:  0.874 Respiratory Toxicity:  0.991
Drug-induced Neurotoxicity:  0.739 Ototoxicity:  0.567
Hematotoxicity:  0.36 Drug-induced Nephrotoxicity:  0.888
Genotoxicity:  0.939 RPMI-8226 Immunitoxicity:  0.312
A549 Cytotoxicity:  0.839 Hek293 Cytotoxicity:  0.587
BCF:   2.138
?
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:   5.241
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   7.063
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   6.571
?
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
NPO16269 Schizolaena hystrix Species Sarcolaenaceae Eukaryota n.a. Madagascar rainforest n.a. PMID[15787448]
NPO16269 Schizolaena hystrix Species Sarcolaenaceae Eukaryota n.a. fruit n.a. PMID[15787448]
NPO16269 Schizolaena hystrix Species Sarcolaenaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16269 Schizolaena hystrix Species Sarcolaenaceae 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
NPT179 Cell line A2780 Homo sapiens IC50 = 17.0 ug.mL-1 PMID[25681711]

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 NPC64915 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
0.8636 High Similarity NPC226025
0.8358 Intermediate Similarity NPC278778
0.8333 Intermediate Similarity NPC164272
0.8333 Intermediate Similarity NPC470327
0.8308 Intermediate Similarity NPC228504
0.806 Intermediate Similarity NPC470328
0.806 Intermediate Similarity NPC209614
0.791 Intermediate Similarity NPC213896
0.7857 Intermediate Similarity NPC195796
0.7761 Intermediate Similarity NPC290133
0.7681 Intermediate Similarity NPC185276
0.7606 Intermediate Similarity NPC45849
0.7606 Intermediate Similarity NPC472626
0.7324 Intermediate Similarity NPC298692
0.6923 Remote Similarity NPC1089
0.6892 Remote Similarity NPC210459
0.6667 Remote Similarity NPC488557
0.6575 Remote Similarity NPC488556
0.6533 Remote Similarity NPC472628
0.6533 Remote Similarity NPC488554
0.6486 Remote Similarity NPC472627
0.6479 Remote Similarity NPC35038
0.64 Remote Similarity NPC488558
0.6377 Remote Similarity NPC125855
0.6316 Remote Similarity NPC472630
0.6267 Remote Similarity NPC58805
0.6267 Remote Similarity NPC261063
0.6234 Remote Similarity NPC282009
0.6234 Remote Similarity NPC472631
0.6216 Remote Similarity NPC472629
0.6203 Remote Similarity NPC474055
0.6184 Remote Similarity NPC321779
0.6184 Remote Similarity NPC470326
0.6125 Remote Similarity NPC472634
0.6076 Remote Similarity NPC488555
0.6076 Remote Similarity NPC484418
0.6049 Remote Similarity NPC321399
0.6 Remote Similarity NPC279650
0.5949 Remote Similarity NPC27337
0.5949 Remote Similarity NPC472598
0.5921 Remote Similarity NPC262039
0.5915 Remote Similarity NPC223500
0.589 Remote Similarity NPC223787
0.5875 Remote Similarity NPC287328
0.5844 Remote Similarity NPC22192
0.5811 Remote Similarity NPC477242
0.5694 Remote Similarity NPC166689
0.5641 Remote Similarity NPC299436
0.557 Remote Similarity NPC201800
0.5526 Remote Similarity NPC166934
0.5455 Remote Similarity NPC96408
0.5455 Remote Similarity NPC610511
0.5417 Remote Similarity NPC148757
0.5375 Remote Similarity NPC67396
0.5373 Remote Similarity NPC274784
0.5373 Remote Similarity NPC20709
0.5357 Remote Similarity NPC293319
0.5303 Remote Similarity NPC6407
0.5303 Remote Similarity NPC545184
0.5217 Remote Similarity NPC469758
0.5211 Remote Similarity NPC25287
0.5205 Remote Similarity NPC95936
0.5205 Remote Similarity NPC69674
0.5195 Remote Similarity NPC24136
0.5195 Remote Similarity NPC36275
0.5147 Remote Similarity NPC482119
0.5147 Remote Similarity NPC482120
0.5135 Remote Similarity NPC220998
0.5125 Remote Similarity NPC267375
0.5063 Remote Similarity NPC484416

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC64915 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