Natural Product: NPC474520

Natural Product IDNPC474520
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 3-O-Demethyldigicitrin
IUPAC Name 3,5-dihydroxy-2-(3-hydroxy-4,5-dimethoxyphenyl)-6,7,8-trimethoxychromen-4-one
Synonyms 3-O-Demethyldigicitrin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL470678
PubChem CID 44260075
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0001615] Flavones
          • [CHEMONTID:0001136] Flavonols

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 SBECGZQEVBSJHM-UHFFFAOYSA-N
Standard InCHI InChI=1S/C20H20O10/c1-25-10-7-8(6-9(21)16(10)26-2)15-14(24)12(22)11-13(23)18(27-3)20(29-5)19(28-4)17(11)30-15/h6-7,21,23-24H,1-5H3
SMILES COC1=CC(=CC(=C1OC)O)C2=C(C(=O)C3=C(C(=C(C(=C3O2)OC)OC)OC)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   420.11 Volume:   395.617
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Van der Waals volume.
Dense:   1.062 LogP:   1.481
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.66
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.504
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The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   18.0
TPSA:   137.05
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Topological Polar Surface Area.
 H-Bond Acceptor:   10.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   10.0

MedChem Properties

QED Drug-Likeness Score:   0.546 GASA:   1.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.819 Fsp3:   0.25
MCE-18:   22.0
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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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.264 Fluc inhibitor:   0.264
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.663
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.54
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.361 Promiscuous compounds:   0.828

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.356 MDCK Permeability:   -4.854
Pgp-inhibitor:   0.716 Pgp-substrate:   0.084
PAMPA:   0.14
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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):   0.077
20% Bioavailability (F20%):   0.072 30% Bioavailability (F30%):   0.374
50% Bioavailability (F50%):   0.953

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.017 MRP1:   0.967
Plasma Protein Binding (PPB):   96.455% Volume Distribution (VD):   -0.627
Fu: 3.696%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.915
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.953
BSEP inhibitor:   0.768

ADMET: Metabolism

CYP1A2-inhibitor:   0.578 CYP1A2-substrate:   0.098
CYP2C19-inhibitor:   0.019 CYP2C19-substrate:   0.426
CYP2C9-inhibitor:   0.342 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.704 CYP2D6-substrate:   0.824
CYP3A4-inhibitor:   0.495 CYP3A4-substrate:   0.003
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.978
HLM stability:   0.874
?
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):  5.442 Half-life (T1/2):  1.349

ADMET: Toxicity

hERG Blockers:  0.077 hERG Blockers (10um):  0.486
Human Hepatotoxicity (H-HT):  0.461 Drug-induced Liver Injury (DILI):  0.738
AMES Toxicity:  0.266 Rat Oral Acute Toxicity:  0.428
Maximum Recommended Daily Dose:  0.351 Skin Sensitization:  0.681
Carcinogencity:  0.665 Eye Corrosion:  0.183
Eye Irritation:  0.886 Respiratory Toxicity:  0.714
Drug-induced Neurotoxicity:  0.314 Ototoxicity:  0.258
Hematotoxicity:  0.462 Drug-induced Nephrotoxicity:  0.232
Genotoxicity:  0.145 RPMI-8226 Immunitoxicity:  0.168
A549 Cytotoxicity:  0.266 Hek293 Cytotoxicity:  0.367
BCF:   1.293
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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:   3.53
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.688
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.929
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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
NPO32678 acronychia porteri Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[7964782]
NPO33371 zieridium pseudobtusifolium Species n.a. n.a. n.a. n.a. n.a. PMID[7964782]

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
NPT91 Cell line KB Homo sapiens IC50 = 2.0 ug.mL-1 PMID[23398362]

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 NPC474520 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
0.7818 Intermediate Similarity NPC189179
0.75 Intermediate Similarity NPC224137
0.7273 Intermediate Similarity NPC608038
0.7193 Intermediate Similarity NPC235215
0.661 Remote Similarity NPC609179
0.6316 Remote Similarity NPC250822
0.5806 Remote Similarity NPC93376
0.5806 Remote Similarity NPC196439
0.5806 Remote Similarity NPC2476
0.5556 Remote Similarity NPC177298
0.5556 Remote Similarity NPC7846
0.5556 Remote Similarity NPC4481
0.5556 Remote Similarity NPC606638
0.5484 Remote Similarity NPC201136
0.5469 Remote Similarity NPC227325
0.541 Remote Similarity NPC219330
0.5397 Remote Similarity NPC60972
0.5397 Remote Similarity NPC29841
0.5385 Remote Similarity NPC227192
0.5323 Remote Similarity NPC301123
0.5323 Remote Similarity NPC176775
0.5323 Remote Similarity NPC231018
0.5312 Remote Similarity NPC78302
0.5312 Remote Similarity NPC162351
0.5312 Remote Similarity NPC206604
0.5238 Remote Similarity NPC22472
0.5238 Remote Similarity NPC49824
0.5238 Remote Similarity NPC86485
0.5238 Remote Similarity NPC134677
0.5231 Remote Similarity NPC19687
0.5161 Remote Similarity NPC292107
0.5156 Remote Similarity NPC608498
0.5079 Remote Similarity NPC50403
0.5079 Remote Similarity NPC105242
0.5079 Remote Similarity NPC143828

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC474520 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