Natural Product: NPC186686

Natural Product IDNPC186686
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-5'-(3-Methylbut-2-Enyl)-2,6'-Bichroman-4-One
IUPAC Name (2S)-5,7-dihydroxy-2-[8-hydroxy-2,2-dimethyl-5-(3-methylbut-2-enyl)chromen-6-yl]-2,3-dihydrochromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL458936
PubChem CID 44589106
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0000337] Flavans
          • [CHEMONTID:0003645] 2'-prenylated flavans
            • [CHEMONTID:0003588] 2'-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 DOHUWPORVBGXGM-NRFANRHFSA-N
Standard InCHI InChI=1S/C25H26O6/c1-13(2)5-6-15-16-7-8-25(3,4)31-24(16)20(29)11-17(15)21-12-19(28)23-18(27)9-14(26)10-22(23)30-21/h5,7-11,21,26-27,29H,6,12H2,1-4H3/t21-/m0/s1
SMILES CC(=CCc1c2C=CC(C)(C)Oc2c(cc1[C@@H]1CC(=O)c2c(cc(cc2O1)O)O)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   422.17 Volume:   435.743
?
Van der Waals volume.
Dense:   0.969 LogP:   5.131
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.97
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.969
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The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   24.0
TPSA:   96.22
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   3.0 Rings:   4.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.588 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.846 Fsp3:   0.32
MCE-18:   85.909
?
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:   1 PAINS Alert:   0
Colloidal aggregators:   0.968 Fluc inhibitor:   0.77
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.886
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.86
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.3 Promiscuous compounds:   0.106

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.081 MDCK Permeability:   -4.801
Pgp-inhibitor:   0.258 Pgp-substrate:   0.122
PAMPA:   0.389
?
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):   0.016
20% Bioavailability (F20%):   0.952 30% Bioavailability (F30%):   1.0
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.002 MRP1:   0.888
Plasma Protein Binding (PPB):   94.723% Volume Distribution (VD):   0.476
Fu: 5.032%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.985
OATP1B3 inhibitor:   0.987 BCRP inhibitor:   0.999
BSEP inhibitor:   0.33

ADMET: Metabolism

CYP1A2-inhibitor:   0.011 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.988 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.032 CYP2C9-substrate:   0.002
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.886
CYP3A4-inhibitor:   0.0 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):  6.046 Half-life (T1/2):  1.318

ADMET: Toxicity

hERG Blockers:  0.084 hERG Blockers (10um):  0.557
Human Hepatotoxicity (H-HT):  0.785 Drug-induced Liver Injury (DILI):  0.81
AMES Toxicity:  0.843 Rat Oral Acute Toxicity:  0.923
Maximum Recommended Daily Dose:  0.92 Skin Sensitization:  0.978
Carcinogencity:  0.679 Eye Corrosion:  0.0
Eye Irritation:  0.684 Respiratory Toxicity:  0.991
Drug-induced Neurotoxicity:  0.734 Ototoxicity:  0.6
Hematotoxicity:  0.166 Drug-induced Nephrotoxicity:  0.856
Genotoxicity:  0.992 RPMI-8226 Immunitoxicity:  0.159
A549 Cytotoxicity:  0.863 Hek293 Cytotoxicity:  0.816
BCF:   2.131
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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:   5.005
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.77
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   6.134
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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 = 13900.0 nM PMID[23672185]

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 NPC186686 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
0.6974 Remote Similarity NPC43319
0.6486 Remote Similarity NPC118256
0.6282 Remote Similarity NPC111786
0.6267 Remote Similarity NPC272502
0.5921 Remote Similarity NPC88964
0.5915 Remote Similarity NPC258630
0.589 Remote Similarity NPC109223
0.589 Remote Similarity NPC10937
0.5811 Remote Similarity NPC106976
0.5733 Remote Similarity NPC85121
0.561 Remote Similarity NPC474024
0.5584 Remote Similarity NPC470890
0.5584 Remote Similarity NPC312973
0.557 Remote Similarity NPC474021
0.5467 Remote Similarity NPC17170
0.5455 Remote Similarity NPC134783
0.5432 Remote Similarity NPC474038
0.5385 Remote Similarity NPC200761
0.5375 Remote Similarity NPC473272
0.5325 Remote Similarity NPC174953
0.5181 Remote Similarity NPC227579
0.5181 Remote Similarity NPC214166
0.5176 Remote Similarity NPC218226
0.506 Remote Similarity NPC267375
0.5059 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 NPC186686 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