Natural Product: NPC130589

Natural Product IDNPC130589
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Brandisianin C
IUPAC Name 5,7-dihydroxy-3-(4-hydroxy-2,5-dimethoxyphenyl)-8-(3-methylbut-2-enyl)chromen-4-one
Synonyms Brandisianin C
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL403122
PubChem CID 24763482
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 NIJHLDLKJBWHOF-UHFFFAOYSA-N
Standard InCHI InChI=1S/C22H22O7/c1-11(2)5-6-12-15(23)8-17(25)20-21(26)14(10-29-22(12)20)13-7-19(28-4)16(24)9-18(13)27-3/h5,7-10,23-25H,6H2,1-4H3
SMILES COc1cc(O)c(cc1c1coc2c(c1=O)c(O)cc(c2CC=C(C)C)O)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   398.14 Volume:   401.202
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Van der Waals volume.
Dense:   0.992 LogP:   3.124
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.707
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.685
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The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   19.0
TPSA:   109.36
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Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.555 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.882 Fsp3:   0.227
MCE-18:   21.0
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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:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.684 Fluc inhibitor:   0.289
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.944
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.629
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.279 Promiscuous compounds:   0.197

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.043 MDCK Permeability:   -4.749
Pgp-inhibitor:   0.299 Pgp-substrate:   0.084
PAMPA:   0.074
?
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):   0.011
20% Bioavailability (F20%):   0.508 30% Bioavailability (F30%):   0.831
50% Bioavailability (F50%):   0.997

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.958
Plasma Protein Binding (PPB):   94.106% Volume Distribution (VD):   0.061
Fu: 5.532%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.989
BSEP inhibitor:   0.872

ADMET: Metabolism

CYP1A2-inhibitor:   0.029 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.985 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.981 CYP2C9-substrate:   0.474
CYP2D6-inhibitor:   0.995 CYP2D6-substrate:   0.074
CYP3A4-inhibitor:   0.001 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):  3.275 Half-life (T1/2):  1.965

ADMET: Toxicity

hERG Blockers:  0.068 hERG Blockers (10um):  0.53
Human Hepatotoxicity (H-HT):  0.587 Drug-induced Liver Injury (DILI):  0.941
AMES Toxicity:  0.679 Rat Oral Acute Toxicity:  0.782
Maximum Recommended Daily Dose:  0.764 Skin Sensitization:  0.6
Carcinogencity:  0.68 Eye Corrosion:  0.0
Eye Irritation:  0.704 Respiratory Toxicity:  0.958
Drug-induced Neurotoxicity:  0.239 Ototoxicity:  0.336
Hematotoxicity:  0.254 Drug-induced Nephrotoxicity:  0.422
Genotoxicity:  0.935 RPMI-8226 Immunitoxicity:  0.146
A549 Cytotoxicity:  0.431 Hek293 Cytotoxicity:  0.626
BCF:   1.68
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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:   4.468
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.642
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.082
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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[16499318]
NPT165 Cell line HeLa Homo sapiens IC50 = 19100.0 nM PMID[26280920]

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 NPC130589 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 NPC78103
0.7727 Intermediate Similarity NPC610891
0.7313 Intermediate Similarity NPC604255
0.6667 Remote Similarity NPC134287
0.6567 Remote Similarity NPC40868
0.6515 Remote Similarity NPC144118
0.6418 Remote Similarity NPC38545
0.625 Remote Similarity NPC81679
0.6234 Remote Similarity NPC349624
0.6232 Remote Similarity NPC92075
0.6143 Remote Similarity NPC80962
0.6143 Remote Similarity NPC169162
0.5909 Remote Similarity NPC19980
0.5867 Remote Similarity NPC604254
0.5811 Remote Similarity NPC261470
0.5733 Remote Similarity NPC256406
0.5584 Remote Similarity NPC50960
0.5526 Remote Similarity NPC611367
0.5205 Remote Similarity NPC273538
0.5135 Remote Similarity NPC36852
0.5067 Remote Similarity NPC479160
0.5065 Remote Similarity NPC253822

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC130589 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
0.5205 Remote Similarity NPD4378 Phase 3

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