Natural Product: NPC254412

Natural Product IDNPC254412
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 6,8-Diprenylaromadendrin
IUPAC Name (2R,3R)-3,5,7-trihydroxy-2-(4-hydroxyphenyl)-6,8-bis(3-methylbut-2-enyl)-2,3-dihydrochromen-4-one
Synonyms 6,8-Diprenylaromadendrin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL479131
PubChem CID 10025371
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0000337] Flavans
          • [CHEMONTID:0003642] 8-prenylated flavans
            • [CHEMONTID:0003508] 8-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 KITBJDQJTLGBAY-BJKOFHAPSA-N
Standard InCHI InChI=1S/C25H28O6/c1-13(2)5-11-17-20(27)18(12-6-14(3)4)25-19(21(17)28)22(29)23(30)24(31-25)15-7-9-16(26)10-8-15/h5-10,23-24,26-28,30H,11-12H2,1-4H3/t23-,24+/m0/s1
SMILES CC(=CCc1c2O[C@H](c3ccc(cc3)O)[C@H](C(=O)c2c(c(c1O)CC=C(C)C)O)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   424.19 Volume:   444.3
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Van der Waals volume.
Dense:   0.955 LogP:   4.421
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.408
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.911
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The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   20.0
TPSA:   107.22
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Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   4.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.527 GASA:   1.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.815 Fsp3:   0.32
MCE-18:   68.667
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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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.84 Fluc inhibitor:   0.355
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.655
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.608
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.375 Promiscuous compounds:   0.138

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.441 MDCK Permeability:   -4.787
Pgp-inhibitor:   0.98 Pgp-substrate:   0.035
PAMPA:   0.605
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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):   0.114
20% Bioavailability (F20%):   0.923 30% Bioavailability (F30%):   1.0
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.847
Plasma Protein Binding (PPB):   94.466% Volume Distribution (VD):   0.409
Fu: 6.078%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.973
BSEP inhibitor:   0.825

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.99 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.004 CYP2C9-substrate:   0.006
CYP2D6-inhibitor:   0.144 CYP2D6-substrate:   0.7
CYP3A4-inhibitor:   0.686 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 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):  6.4 Half-life (T1/2):  1.647

ADMET: Toxicity

hERG Blockers:  0.05 hERG Blockers (10um):  0.452
Human Hepatotoxicity (H-HT):  0.943 Drug-induced Liver Injury (DILI):  0.582
AMES Toxicity:  0.705 Rat Oral Acute Toxicity:  0.933
Maximum Recommended Daily Dose:  0.435 Skin Sensitization:  0.999
Carcinogencity:  0.252 Eye Corrosion:  0.0
Eye Irritation:  0.523 Respiratory Toxicity:  0.684
Drug-induced Neurotoxicity:  0.844 Ototoxicity:  0.644
Hematotoxicity:  0.413 Drug-induced Nephrotoxicity:  0.987
Genotoxicity:  0.994 RPMI-8226 Immunitoxicity:  0.156
A549 Cytotoxicity:  0.879 Hek293 Cytotoxicity:  0.804
BCF:   1.909
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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:   5.099
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.752
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   6.174
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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
NPO32704 monotes africanus Species Dipterocarpaceae Eukaryota n.a. n.a. n.a. PMID[11325248]

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
NPT1114 Organism Human immunodeficiency virus Human immunodeficiency virus EC50 = 2.1 ug.mL-1 PMID[23811093]
NPT1114 Organism Human immunodeficiency virus Human immunodeficiency virus IC50 = 4.7 ug.mL-1 DrugMatrix in vitro pharmacology data

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 NPC254412 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
0.8 Intermediate Similarity NPC138288
0.7458 Intermediate Similarity NPC262038
0.7458 Intermediate Similarity NPC319910
0.7333 Intermediate Similarity NPC35567
0.6613 Remote Similarity NPC265040
0.6324 Remote Similarity NPC48579
0.6087 Remote Similarity NPC180301
0.6061 Remote Similarity NPC293286
0.6061 Remote Similarity NPC278476
0.5915 Remote Similarity NPC262039
0.5781 Remote Similarity NPC1486
0.5758 Remote Similarity NPC243171
0.5758 Remote Similarity NPC482705
0.5758 Remote Similarity NPC610133
0.5672 Remote Similarity NPC285555
0.5588 Remote Similarity NPC608140
0.5417 Remote Similarity NPC248793
0.5385 Remote Similarity NPC123544
0.5373 Remote Similarity NPC187282
0.527 Remote Similarity NPC207809
0.527 Remote Similarity NPC259710
0.5256 Remote Similarity NPC259834
0.5205 Remote Similarity NPC488440

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC254412 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