Natural Product: NPC56232

Natural Product IDNPC56232
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 8-C-Beta-D-Digitoxopyranosylapigenin
IUPAC Name 8-[(2R,4S,5S,6R)-4,5-dihydroxy-6-methyloxan-2-yl]-5,7-dihydroxy-2-(4-hydroxyphenyl)chromen-4-one
Synonyms 7-De-O-methylaciculatin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2011650
PubChem CID 57332512
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0001111] Flavonoid glycosides
          • [CHEMONTID:0001737] Flavonoid C-glycosides
            • [CHEMONTID:0003535] Flavonoid 8-C-glycosides

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 BZHMTPJDQAFTNF-YKRGOEPUSA-N
Standard InCHI InChI=1S/C21H20O8/c1-9-20(27)15(26)8-17(28-9)19-13(24)6-12(23)18-14(25)7-16(29-21(18)19)10-2-4-11(22)5-3-10/h2-7,9,15,17,20,22-24,26-27H,8H2,1H3/t9-,15+,17-,20-/m1/s1
SMILES Oc1ccc(cc1)c1cc(=O)c2c(o1)c([C@H]1C[C@H](O)[C@@H]([C@H](O1)C)O)c(cc2O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   400.12 Volume:   386.776
?
Van der Waals volume.
Dense:   1.034 LogP:   1.473
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.624
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.886
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   24.0
TPSA:   140.59
?
Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   5.0 Rings:   4.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.441 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.971 Fsp3:   0.286
MCE-18:   84.259
?
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:   0 PAINS Alert:   0
Colloidal aggregators:   0.562 Fluc inhibitor:   0.304
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.853
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.895
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.163 Promiscuous compounds:   0.662

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.831 MDCK Permeability:   -4.935
Pgp-inhibitor:   0.001 Pgp-substrate:   0.756
PAMPA:   0.933
?
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):   0.001
20% Bioavailability (F20%):   0.276 30% Bioavailability (F30%):   0.816
50% Bioavailability (F50%):   0.996

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.002 MRP1:   0.942
Plasma Protein Binding (PPB):   93.896% Volume Distribution (VD):   -0.055
Fu: 7.058%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.968
OATP1B3 inhibitor:   0.94 BCRP inhibitor:   0.502
BSEP inhibitor:   0.66

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.003
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.003
CYP2C9-inhibitor:   0.066 CYP2C9-substrate:   0.034
CYP2D6-inhibitor:   0.002 CYP2D6-substrate:   0.237
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.957
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.999
HLM stability:   0.58
?
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):  4.121 Half-life (T1/2):  2.48

ADMET: Toxicity

hERG Blockers:  0.071 hERG Blockers (10um):  0.403
Human Hepatotoxicity (H-HT):  0.633 Drug-induced Liver Injury (DILI):  0.858
AMES Toxicity:  0.84 Rat Oral Acute Toxicity:  0.753
Maximum Recommended Daily Dose:  0.945 Skin Sensitization:  0.922
Carcinogencity:  0.533 Eye Corrosion:  0.0
Eye Irritation:  0.856 Respiratory Toxicity:  0.884
Drug-induced Neurotoxicity:  0.032 Ototoxicity:  0.198
Hematotoxicity:  0.176 Drug-induced Nephrotoxicity:  0.192
Genotoxicity:  0.995 RPMI-8226 Immunitoxicity:  0.192
A549 Cytotoxicity:  0.803 Hek293 Cytotoxicity:  0.886
BCF:   0.99
?
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:   3.775
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.746
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.268
?
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
NPO32718 chrysopogon aciculatis Species n.a. n.a. n.a. n.a. n.a. PMID[22272829]

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
NPT83 Cell line MCF7 Homo sapiens IC50 = 6350.0 nM PMID[11575968]
NPT397 Cell line NCI-H460 Homo sapiens IC50 = 18250.0 nM PMID[25050172]
NPT139 Cell line HT-29 Homo sapiens IC50 = 25290.0 nM PMID[23850570]
NPT404 Cell line CCRF-CEM Homo sapiens IC50 = 4420.0 nM PMID[24087924]

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 NPC56232 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
1.0 High Similarity NPC150123
1.0 High Similarity NPC608009
0.7123 Intermediate Similarity NPC607327
0.6806 Remote Similarity NPC611357
0.6575 Remote Similarity NPC209846
0.6164 Remote Similarity NPC477897
0.6024 Remote Similarity NPC44947
0.5823 Remote Similarity NPC111341
0.5714 Remote Similarity NPC190393
0.5641 Remote Similarity NPC117418
0.5493 Remote Similarity NPC220062
0.5402 Remote Similarity NPC605855
0.5185 Remote Similarity NPC112701
0.5135 Remote Similarity NPC609354
0.5054 Remote Similarity NPC124155

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC56232 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