Natural Product: NPC284820

Natural Product IDNPC284820
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (2S)-6-(Gamma,Gamma-Dimethylallyl)-5-Hydroxy-3',4'-Dimethoxy-6'',6''-Dimethylpyran[2'',3'':7,8]Flavanone
IUPAC Name (2S)-2-(3,4-dimethoxyphenyl)-5-hydroxy-8,8-dimethyl-6-(3-methylbut-2-enyl)-2,3-dihydropyrano[2,3-h]chromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL455606
PubChem CID 44559036
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 FUBFEZXQVKEAMQ-NRFANRHFSA-N
Standard InCHI InChI=1S/C27H30O6/c1-15(2)7-9-17-24(29)23-19(28)14-21(16-8-10-20(30-5)22(13-16)31-6)32-26(23)18-11-12-27(3,4)33-25(17)18/h7-8,10-13,21,29H,9,14H2,1-6H3/t21-/m0/s1
SMILES COc1cc(ccc1OC)[C@@H]1CC(=O)c2c(O1)c1C=CC(Oc1c(c2O)CC=C(C)C)(C)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   450.2 Volume:   470.335
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Van der Waals volume.
Dense:   0.957 LogP:   5.633
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   4.148
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -6.092
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The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   24.0
TPSA:   74.22
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Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   1.0 Rings:   4.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.58 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.541 Fsp3:   0.37
MCE-18:   85.378
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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:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.97 Fluc inhibitor:   0.318
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.755
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.897
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.234 Promiscuous compounds:   0.224

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.929 MDCK Permeability:   -4.718
Pgp-inhibitor:   1.0 Pgp-substrate:   0.003
PAMPA:   0.013
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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):   0.023
20% Bioavailability (F20%):   0.9 30% Bioavailability (F30%):   0.997
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.937
Plasma Protein Binding (PPB):   97.497% Volume Distribution (VD):   0.262
Fu: 2.167%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   0.978 BCRP inhibitor:   0.998
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.024 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.001 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.001 CYP2D6-substrate:   0.982
CYP3A4-inhibitor:   0.88 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.008 CYP2C8-inhibitor:   1.0
HLM stability:   1.0
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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):  6.194 Half-life (T1/2):  1.314

ADMET: Toxicity

hERG Blockers:  0.145 hERG Blockers (10um):  0.476
Human Hepatotoxicity (H-HT):  0.807 Drug-induced Liver Injury (DILI):  0.849
AMES Toxicity:  0.805 Rat Oral Acute Toxicity:  0.881
Maximum Recommended Daily Dose:  0.734 Skin Sensitization:  0.942
Carcinogencity:  0.771 Eye Corrosion:  0.0
Eye Irritation:  0.564 Respiratory Toxicity:  0.959
Drug-induced Neurotoxicity:  0.862 Ototoxicity:  0.633
Hematotoxicity:  0.546 Drug-induced Nephrotoxicity:  0.915
Genotoxicity:  0.891 RPMI-8226 Immunitoxicity:  0.181
A549 Cytotoxicity:  0.594 Hek293 Cytotoxicity:  0.459
BCF:   2.106
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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:   5.014
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   7.318
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   6.616
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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
NPO26220 Lonchocarpus utilis Species Fabaceae Eukaryota n.a. root n.a. PMID[10075742]
NPO4562 Lonchocarpus urucu Species Fabaceae Eukaryota n.a. root n.a. PMID[10075742]
NPO5368 Achillea cretica Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[36408972]
NPO3890 Scopolia japonica Species Solanaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4562 Lonchocarpus urucu Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5368 Achillea cretica Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12750 Cordia americana Species Cordiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6147 Eupatorium riparium Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5753 Glycosmis montana Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2671 Pedicularis semitorta Species Orobanchaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3890 Scopolia japonica Species Solanaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO5753 Glycosmis montana Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO6147 Eupatorium riparium Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO3890 Scopolia japonica Species Solanaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO6147 Eupatorium riparium Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO5753 Glycosmis montana Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO6147 Eupatorium riparium Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO3890 Scopolia japonica Species Solanaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO3890 Scopolia japonica Species Solanaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO26220 Lonchocarpus utilis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12750 Cordia americana Species Cordiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2671 Pedicularis semitorta Species Orobanchaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5368 Achillea cretica Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4562 Lonchocarpus urucu Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5753 Glycosmis montana Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3890 Scopolia japonica Species Solanaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6147 Eupatorium riparium Species Asteraceae 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
NPT2680 Individual protein Ornithine decarboxylase Homo sapiens IC50 = 2200.0 nM PMID[10075742]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT83 Cell line MCF7 Homo sapiens IC50 = 6600.0 nM PMID[10075742]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 8500.0 nM PMID[10075742]
NPT2 Others Unspecified n.a. IC50 = 2100.0 nM PMID[10075742]

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 NPC284820 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
0.8143 Intermediate Similarity NPC119209
0.8 Intermediate Similarity NPC192686
0.7794 Intermediate Similarity NPC246948
0.6986 Remote Similarity NPC214774
0.6986 Remote Similarity NPC40033
0.5921 Remote Similarity NPC142405
0.589 Remote Similarity NPC311741
0.575 Remote Similarity NPC83357
0.5641 Remote Similarity NPC180301
0.5556 Remote Similarity NPC160821
0.55 Remote Similarity NPC67805
0.5432 Remote Similarity NPC195621
0.5405 Remote Similarity NPC265040
0.5405 Remote Similarity NPC148757
0.5366 Remote Similarity NPC54577
0.5333 Remote Similarity NPC310130
0.5333 Remote Similarity NPC610133
0.5316 Remote Similarity NPC39752
0.527 Remote Similarity NPC476342
0.5238 Remote Similarity NPC283234
0.52 Remote Similarity NPC69674
0.52 Remote Similarity NPC250214
0.5195 Remote Similarity NPC608140
0.5185 Remote Similarity NPC161191
0.5181 Remote Similarity NPC101793
0.5132 Remote Similarity NPC176229
0.5125 Remote Similarity NPC483807
0.5119 Remote Similarity NPC132592
0.5063 Remote Similarity NPC473078

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC284820 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