Natural Product: NPC78103

Natural Product IDNPC78103
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Brandisianin E
IUPAC Name 5,7-dihydroxy-3-(4-hydroxy-2,5-dimethoxyphenyl)-8-[(E)-4-hydroxy-3-methylbut-2-enyl]chromen-4-one
Synonyms Brandisianin E
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL250889
PubChem CID 24763560
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002506] Isoflavonoids
        • [CHEMONTID:0002586] O-methylated isoflavonoids
          • [CHEMONTID:0002605] 3'-O-methylated isoflavonoids
            • [CHEMONTID:0002690] 3'-O-methylisoflavones

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 NQIJCWMTBNAWNQ-NYYWCZLTSA-N
Standard InCHI InChI=1S/C22H22O8/c1-11(9-23)4-5-12-15(24)7-17(26)20-21(27)14(10-30-22(12)20)13-6-19(29-3)16(25)8-18(13)28-2/h4,6-8,10,23-26H,5,9H2,1-3H3/b11-4+
SMILES OC/C(=C/Cc1c(O)cc(c2c1occ(c2=O)c1cc(OC)c(cc1OC)O)O)/C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   414.13 Volume:   409.992
?
Van der Waals volume.
Dense:   1.01 LogP:   1.84
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.008
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.686
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   19.0
TPSA:   129.59
?
Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   4.0 Rings:   3.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.453 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.005 Fsp3:   0.227
MCE-18:   21.0
?
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:   1 PAINS Alert:   0
Colloidal aggregators:   0.619 Fluc inhibitor:   0.264
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.918
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.594
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.116 Promiscuous compounds:   0.435

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.195 MDCK Permeability:   -4.823
Pgp-inhibitor:   0.648 Pgp-substrate:   0.073
PAMPA:   0.031
?
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):   0.066
20% Bioavailability (F20%):   0.675 30% Bioavailability (F30%):   0.936
50% Bioavailability (F50%):   0.992

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.618
Plasma Protein Binding (PPB):   94.761% Volume Distribution (VD):   -0.06
Fu: 4.468%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.99
BSEP inhibitor:   0.837

ADMET: Metabolism

CYP1A2-inhibitor:   0.009 CYP1A2-substrate:   0.988
CYP2C19-inhibitor:   0.173 CYP2C19-substrate:   0.881
CYP2C9-inhibitor:   0.97 CYP2C9-substrate:   0.828
CYP2D6-inhibitor:   0.744 CYP2D6-substrate:   0.06
CYP3A4-inhibitor:   0.007 CYP3A4-substrate:   0.997
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.777
?
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):  3.227 Half-life (T1/2):  1.876

ADMET: Toxicity

hERG Blockers:  0.056 hERG Blockers (10um):  0.501
Human Hepatotoxicity (H-HT):  0.704 Drug-induced Liver Injury (DILI):  0.949
AMES Toxicity:  0.438 Rat Oral Acute Toxicity:  0.656
Maximum Recommended Daily Dose:  0.666 Skin Sensitization:  0.688
Carcinogencity:  0.545 Eye Corrosion:  0.0
Eye Irritation:  0.724 Respiratory Toxicity:  0.977
Drug-induced Neurotoxicity:  0.305 Ototoxicity:  0.335
Hematotoxicity:  0.269 Drug-induced Nephrotoxicity:  0.414
Genotoxicity:  0.982 RPMI-8226 Immunitoxicity:  0.215
A549 Cytotoxicity:  0.32 Hek293 Cytotoxicity:  0.659
BCF:   1.181
?
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:   3.791
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.236
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.408
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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
NPO24609 Millettia brandisiana Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[18039011]
NPO24609 Millettia brandisiana Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[19124248]
NPO24609 Millettia brandisiana Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24609 Millettia brandisiana 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

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT579 Cell line DLD-1 Homo sapiens IC50 > 25000.0 nM PMID[20727622]
NPT165 Cell line HeLa Homo sapiens IC50 = 21700.0 nM PubChem BioAssay data set

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 NPC78103 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
0.873 High Similarity NPC130589
0.6806 Remote Similarity NPC610891
0.6438 Remote Similarity NPC604255
0.5921 Remote Similarity NPC81679
0.5867 Remote Similarity NPC134287
0.5769 Remote Similarity NPC604254
0.5753 Remote Similarity NPC40868
0.5732 Remote Similarity NPC349624
0.5696 Remote Similarity NPC50960
0.5694 Remote Similarity NPC144118
0.5616 Remote Similarity NPC38545
0.5571 Remote Similarity NPC19980
0.5513 Remote Similarity NPC261470
0.5467 Remote Similarity NPC92075
0.5443 Remote Similarity NPC611367
0.5395 Remote Similarity NPC80962
0.5395 Remote Similarity NPC169162
0.5062 Remote Similarity NPC256406

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC78103 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