Natural Product: NPC54577

Natural Product IDNPC54577
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (-)-(2S)-5,2'-Dihydroxy-6'',6''-Dimethylchromeno-(7,8:2'',3'')-3'-Prenylflavanone
IUPAC Name (2S)-5-hydroxy-2-[2-hydroxy-3-(3-methylbut-2-enyl)phenyl]-8,8-dimethyl-2,3-dihydropyrano[2,3-h]chromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1689203
PubChem CID 51040900
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0000337] Flavans
          • [CHEMONTID:0003643] 3'-prenylated flavans
            • [CHEMONTID:0003506] 3'-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 VPMGXHDHUFGBBL-FQEVSTJZSA-N
Standard InCHI InChI=1S/C25H26O5/c1-14(2)8-9-15-6-5-7-16(23(15)28)20-12-18(26)22-19(27)13-21-17(24(22)29-20)10-11-25(3,4)30-21/h5-8,10-11,13,20,27-28H,9,12H2,1-4H3/t20-/m0/s1
SMILES CC(=CCc1cccc([C@@H]2CC(=O)c3c(cc4c(C=CC(C)(C)O4)c3O2)O)c1O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   406.18 Volume:   426.953
?
Van der Waals volume.
Dense:   0.951 LogP:   5.358
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   4.126
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.045
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   24.0
TPSA:   75.99
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   4.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.659 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.67 Fsp3:   0.32
MCE-18:   82.727
?
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:   0.979 Fluc inhibitor:   0.835
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.727
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.78
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.247 Promiscuous compounds:   0.111

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.959 MDCK Permeability:   -4.712
Pgp-inhibitor:   0.953 Pgp-substrate:   0.018
PAMPA:   0.229
?
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):   0.006
20% Bioavailability (F20%):   0.977 30% Bioavailability (F30%):   0.999
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.021 MRP1:   0.949
Plasma Protein Binding (PPB):   96.894% Volume Distribution (VD):   0.267
Fu: 2.884%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.992
OATP1B3 inhibitor:   0.866 BCRP inhibitor:   0.982
BSEP inhibitor:   0.996

ADMET: Metabolism

CYP1A2-inhibitor:   0.027 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.974 CYP2C19-substrate:   0.999
CYP2C9-inhibitor:   0.156 CYP2C9-substrate:   0.111
CYP2D6-inhibitor:   0.004 CYP2D6-substrate:   0.294
CYP3A4-inhibitor:   0.046 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):  5.239 Half-life (T1/2):  1.212

ADMET: Toxicity

hERG Blockers:  0.118 hERG Blockers (10um):  0.612
Human Hepatotoxicity (H-HT):  0.748 Drug-induced Liver Injury (DILI):  0.781
AMES Toxicity:  0.809 Rat Oral Acute Toxicity:  0.788
Maximum Recommended Daily Dose:  0.68 Skin Sensitization:  0.992
Carcinogencity:  0.43 Eye Corrosion:  0.001
Eye Irritation:  0.784 Respiratory Toxicity:  0.973
Drug-induced Neurotoxicity:  0.737 Ototoxicity:  0.54
Hematotoxicity:  0.189 Drug-induced Nephrotoxicity:  0.919
Genotoxicity:  0.872 RPMI-8226 Immunitoxicity:  0.204
A549 Cytotoxicity:  0.884 Hek293 Cytotoxicity:  0.69
BCF:   2.05
?
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:   4.994
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.964
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   6.261
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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
NPO29456 Theobroma grandiflorum Species Malvaceae Eukaryota n.a. seed n.a. PMID[14640528]
NPO28901 Blighia sapida Species Sapindaceae Eukaryota n.a. fruit n.a. PMID[19653254]
NPO28901 Blighia sapida Species Sapindaceae Eukaryota n.a. fruit n.a. PMID[19653254f]
NPO29014 Dalea boliviana Species Fabaceae Eukaryota n.a. root n.a. PMID[21226489]
NPO29456 Theobroma grandiflorum Species Malvaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29014 Dalea boliviana Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28882 Misopates orontium Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28901 Blighia sapida Species Sapindaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29456 Theobroma grandiflorum Species Malvaceae Eukaryota n.a. n.a. Database[FooDB]
NPO29456 Theobroma grandiflorum Species Malvaceae Eukaryota n.a. n.a. Database[FooDB]
NPO28901 Blighia sapida Species Sapindaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO29014 Dalea boliviana Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28882 Misopates orontium Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28901 Blighia sapida Species Sapindaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29456 Theobroma grandiflorum Species Malvaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29032 Spathiphyllum wallisii Species Araceae 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
NPT43 Individual protein Tyrosinase Agaricus bisporus Inhibition = 6.4 % PMID[21226489]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference

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 NPC54577 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
0.6667 Remote Similarity NPC176229
0.6479 Remote Similarity NPC182852
0.6133 Remote Similarity NPC39752
0.6104 Remote Similarity NPC214774
0.6 Remote Similarity NPC283234
0.6 Remote Similarity NPC301276
0.5897 Remote Similarity NPC267375
0.5897 Remote Similarity NPC67805
0.5714 Remote Similarity NPC246948
0.557 Remote Similarity NPC475052
0.5556 Remote Similarity NPC83357
0.5432 Remote Similarity NPC195621
0.5395 Remote Similarity NPC20488
0.5366 Remote Similarity NPC192686
0.5366 Remote Similarity NPC284820
0.5301 Remote Similarity NPC119209
0.5185 Remote Similarity NPC486093
0.5181 Remote Similarity NPC296998
0.5181 Remote Similarity NPC160821
0.5181 Remote Similarity NPC473077
0.5181 Remote Similarity NPC101793
0.5125 Remote Similarity NPC142405
0.5122 Remote Similarity NPC57313
0.5067 Remote Similarity NPC306829

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC54577 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