Natural Product: NPC134783

Natural Product IDNPC134783
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (S)-5,7,8'-Trihydroxy-2',2'-Dimethyl-2,6'-Bichroman-4,4'-Dione
IUPAC Name 6-[(2S)-5,7-dihydroxy-4-oxo-2,3-dihydrochromen-2-yl]-8-hydroxy-2,2-dimethyl-3H-chromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL458813
PubChem CID 44589231
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 QVJWSGOMMDXZOF-INIZCTEOSA-N
Standard InCHI InChI=1S/C20H18O7/c1-20(2)8-15(25)11-3-9(4-14(24)19(11)27-20)16-7-13(23)18-12(22)5-10(21)6-17(18)26-16/h3-6,16,21-22,24H,7-8H2,1-2H3/t16-/m0/s1
SMILES Oc1cc2O[C@@H](CC(=O)c2c(c1)O)c1cc(O)c2c(c1)C(=O)CC(O2)(C)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   370.11 Volume:   360.69
?
Van der Waals volume.
Dense:   1.026 LogP:   3.002
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.609
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.024
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The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   24.0
TPSA:   113.29
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Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   3.0 Rings:   4.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.706 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.478 Fsp3:   0.3
MCE-18:   86.0
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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:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   1
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.527 Fluc inhibitor:   0.403
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.715
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.553
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.276 Promiscuous compounds:   0.073

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.962 MDCK Permeability:   -4.732
Pgp-inhibitor:   0.94 Pgp-substrate:   0.013
PAMPA:   0.153
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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):   0.002
20% Bioavailability (F20%):   0.048 30% Bioavailability (F30%):   0.908
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.003 MRP1:   0.965
Plasma Protein Binding (PPB):   92.62% Volume Distribution (VD):   0.112
Fu: 7.729%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.994
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.917
BSEP inhibitor:   0.969

ADMET: Metabolism

CYP1A2-inhibitor:   0.948 CYP1A2-substrate:   0.999
CYP2C19-inhibitor:   0.003 CYP2C19-substrate:   0.999
CYP2C9-inhibitor:   0.012 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.97
CYP3A4-inhibitor:   0.592 CYP3A4-substrate:   0.988
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.999
HLM stability:   0.987
?
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):  3.967 Half-life (T1/2):  1.503

ADMET: Toxicity

hERG Blockers:  0.089 hERG Blockers (10um):  0.381
Human Hepatotoxicity (H-HT):  0.863 Drug-induced Liver Injury (DILI):  0.914
AMES Toxicity:  0.87 Rat Oral Acute Toxicity:  0.829
Maximum Recommended Daily Dose:  0.909 Skin Sensitization:  0.94
Carcinogencity:  0.804 Eye Corrosion:  0.0
Eye Irritation:  0.94 Respiratory Toxicity:  0.966
Drug-induced Neurotoxicity:  0.594 Ototoxicity:  0.483
Hematotoxicity:  0.328 Drug-induced Nephrotoxicity:  0.758
Genotoxicity:  0.999 RPMI-8226 Immunitoxicity:  0.238
A549 Cytotoxicity:  0.826 Hek293 Cytotoxicity:  0.732
BCF:   1.654
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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:   4.23
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.228
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.322
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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
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota stem bark n.a. n.a. PMID[17489632]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota n.a. stem n.a. PMID[18484536]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota stem bark Mukono, Uganda 2005-JUN PMID[19008110]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[19299148]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[19836230]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[20337486]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[21116437]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO8526 Erythrina abyssinica Species Fabaceae 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
NPT178 Individual protein Protein-tyrosine phosphatase 1B Homo sapiens IC50 > 60000.0 nM PMID[22037378]

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 NPC134783 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
0.7031 Intermediate Similarity NPC174953
0.6866 Remote Similarity NPC118256
0.6338 Remote Similarity NPC474038
0.6119 Remote Similarity NPC106976
0.6102 Remote Similarity NPC182421
0.6032 Remote Similarity NPC302950
0.6 Remote Similarity NPC258630
0.5738 Remote Similarity NPC32441
0.5738 Remote Similarity NPC243083
0.5738 Remote Similarity NPC13768
0.5738 Remote Similarity NPC287246
0.5738 Remote Similarity NPC79943
0.5735 Remote Similarity NPC109223
0.5735 Remote Similarity NPC10937
0.5714 Remote Similarity NPC321011
0.5714 Remote Similarity NPC294852
0.5714 Remote Similarity NPC188679
0.5634 Remote Similarity NPC470890
0.5634 Remote Similarity NPC312973
0.5616 Remote Similarity NPC474021
0.5556 Remote Similarity NPC274784
0.5556 Remote Similarity NPC338131
0.5556 Remote Similarity NPC473990
0.5556 Remote Similarity NPC20709
0.5507 Remote Similarity NPC17170
0.5455 Remote Similarity NPC186686
0.5417 Remote Similarity NPC200761
0.5417 Remote Similarity NPC475790
0.5405 Remote Similarity NPC473272
0.5373 Remote Similarity NPC236637
0.5325 Remote Similarity NPC74924
0.5316 Remote Similarity NPC602605
0.5238 Remote Similarity NPC295261
0.5238 Remote Similarity NPC296490
0.5238 Remote Similarity NPC12296
0.5195 Remote Similarity NPC475784
0.5143 Remote Similarity NPC477841
0.5139 Remote Similarity NPC474033
0.5139 Remote Similarity NPC85121
0.5128 Remote Similarity NPC111786
0.5077 Remote Similarity NPC107586
0.5067 Remote Similarity NPC272502
0.5063 Remote Similarity NPC474023

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC134783 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
0.6032 Remote Similarity NPD1934 Phase 0
0.5738 Remote Similarity NPD1550 Phase 2
0.5738 Remote Similarity NPD1552 Clinical (unspecified phase)

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