Natural Product: NPC470460

Natural Product IDNPC470460
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Dodoviscin H
IUPAC Name 5,7-dihydroxy-2-[4-hydroxy-3-(4-hydroxy-3-methylbutyl)-5-(3-methylbut-2-enyl)phenyl]-3-methoxychromen-4-one
Synonyms dodoviscin H
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2037153
PubChem CID 57408288
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0001615] Flavones
          • [CHEMONTID:0003502] 3'-prenylated flavones

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 DJUDTARIJQVMAT-UHFFFAOYSA-N
Standard InCHI InChI=1S/C26H30O7/c1-14(2)5-7-16-9-18(10-17(23(16)30)8-6-15(3)13-27)25-26(32-4)24(31)22-20(29)11-19(28)12-21(22)33-25/h5,9-12,15,27-30H,6-8,13H2,1-4H3
SMILES OCC(CCc1cc(cc(c1O)CC=C(C)C)c1oc2cc(O)cc(c2c(=O)c1OC)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   454.2 Volume:   470.386
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Van der Waals volume.
Dense:   0.966 LogP:   4.956
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.433
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.888
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The logarithm of aqueous solubility value.
Rotatable Bonds:   8.0 Rigid Bonds:   19.0
TPSA:   120.36
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Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   4.0 Rings:   3.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.366 GASA:   1.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.488 Fsp3:   0.346
MCE-18:   44.0
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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:   0 PAINS Alert:   0
Colloidal aggregators:   0.825 Fluc inhibitor:   0.358
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.932
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.847
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.049 Promiscuous compounds:   0.057

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.177 MDCK Permeability:   -4.794
Pgp-inhibitor:   0.725 Pgp-substrate:   0.042
PAMPA:   0.657
?
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):   0.11
20% Bioavailability (F20%):   0.94 30% Bioavailability (F30%):   0.999
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.871
Plasma Protein Binding (PPB):   94.32% Volume Distribution (VD):   0.062
Fu: 4.959%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.033
OATP1B3 inhibitor:   0.836 BCRP inhibitor:   1.0
BSEP inhibitor:   0.987

ADMET: Metabolism

CYP1A2-inhibitor:   0.168 CYP1A2-substrate:   0.998
CYP2C19-inhibitor:   0.907 CYP2C19-substrate:   0.999
CYP2C9-inhibitor:   0.691 CYP2C9-substrate:   0.007
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.995
CYP3A4-inhibitor:   0.251 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):  5.659 Half-life (T1/2):  1.069

ADMET: Toxicity

hERG Blockers:  0.055 hERG Blockers (10um):  0.555
Human Hepatotoxicity (H-HT):  0.653 Drug-induced Liver Injury (DILI):  0.319
AMES Toxicity:  0.369 Rat Oral Acute Toxicity:  0.369
Maximum Recommended Daily Dose:  0.701 Skin Sensitization:  0.935
Carcinogencity:  0.52 Eye Corrosion:  0.001
Eye Irritation:  0.862 Respiratory Toxicity:  0.725
Drug-induced Neurotoxicity:  0.032 Ototoxicity:  0.534
Hematotoxicity:  0.13 Drug-induced Nephrotoxicity:  0.163
Genotoxicity:  0.797 RPMI-8226 Immunitoxicity:  0.071
A549 Cytotoxicity:  0.462 Hek293 Cytotoxicity:  0.648
BCF:   1.726
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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:   4.539
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.97
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.403
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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
NPO12477 Dodonaea viscosa Species Sapindaceae Eukaryota n.a. n.a. n.a. PMID[19719093]
NPO12477 Dodonaea viscosa Species Sapindaceae Eukaryota n.a. n.a. n.a. PMID[22512738]
NPO12477 Dodonaea viscosa Species Sapindaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12477 Dodonaea viscosa Species Sapindaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO12477 Dodonaea viscosa Species Sapindaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12477 Dodonaea viscosa Species Sapindaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO12477 Dodonaea viscosa Species Sapindaceae 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
NPT520 Cell line 3T3-L1 Mus musculus Activity = 263.1 % PMID[24099364]

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 NPC470460 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
0.8154 Intermediate Similarity NPC158874
0.8056 Intermediate Similarity NPC470462
0.7971 Intermediate Similarity NPC470458
0.7671 Intermediate Similarity NPC470461
0.7183 Intermediate Similarity NPC97255
0.6986 Remote Similarity NPC269285
0.6582 Remote Similarity NPC470456
0.6389 Remote Similarity NPC246478
0.6316 Remote Similarity NPC470459
0.6154 Remote Similarity NPC158761
0.6076 Remote Similarity NPC470457
0.5974 Remote Similarity NPC56786
0.5844 Remote Similarity NPC259632
0.5529 Remote Similarity NPC80534
0.5493 Remote Similarity NPC123886
0.5493 Remote Similarity NPC184536
0.5493 Remote Similarity NPC103342
0.5417 Remote Similarity NPC286342
0.5417 Remote Similarity NPC59951
0.5417 Remote Similarity NPC610359
0.5405 Remote Similarity NPC162351
0.5375 Remote Similarity NPC224714
0.527 Remote Similarity NPC82325
0.5256 Remote Similarity NPC205046
0.52 Remote Similarity NPC603596
0.5132 Remote Similarity NPC279989

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC470460 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