Natural Product: NPC110969

Natural Product IDNPC110969
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Bavachinin
IUPAC Name 2-(4-hydroxyphenyl)-7-methoxy-6-(3-methylbut-2-enyl)chromen-4-one
Synonyms Bavachinin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL458053
PubChem CID 44584224
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0001615] Flavones
          • [CHEMONTID:0003503] 6-prenylated flavones

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 BVTZAHKRSBADDO-UHFFFAOYSA-N
Standard InCHI InChI=1S/C21H20O4/c1-13(2)4-5-15-10-17-18(23)11-20(14-6-8-16(22)9-7-14)25-21(17)12-19(15)24-3/h4,6-12,22H,5H2,1-3H3
SMILES CC(=CCc1cc2c(=O)cc(c3ccc(cc3)O)oc2cc1OC)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   336.14 Volume:   357.536
?
Van der Waals volume.
Dense:   0.94 LogP:   4.478
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.733
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.179
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   19.0
TPSA:   59.67
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.703 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.415 Fsp3:   0.19
MCE-18:   18.0
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.965 Fluc inhibitor:   0.907
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.994
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.832
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.298 Promiscuous compounds:   0.081

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.698 MDCK Permeability:   -4.689
Pgp-inhibitor:   0.12 Pgp-substrate:   0.034
PAMPA:   0.635
?
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):   0.056
20% Bioavailability (F20%):   0.977 30% Bioavailability (F30%):   0.983
50% Bioavailability (F50%):   0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.002 MRP1:   0.954
Plasma Protein Binding (PPB):   95.729% Volume Distribution (VD):   0.168
Fu: 3.404%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.97
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.982
BSEP inhibitor:   0.855

ADMET: Metabolism

CYP1A2-inhibitor:   0.001 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.967 CYP2C19-substrate:   0.729
CYP2C9-inhibitor:   0.047 CYP2C9-substrate:   0.501
CYP2D6-inhibitor:   0.891 CYP2D6-substrate:   0.994
CYP3A4-inhibitor:   0.02 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.994
?
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):  9.652 Half-life (T1/2):  1.288

ADMET: Toxicity

hERG Blockers:  0.142 hERG Blockers (10um):  0.528
Human Hepatotoxicity (H-HT):  0.525 Drug-induced Liver Injury (DILI):  0.747
AMES Toxicity:  0.607 Rat Oral Acute Toxicity:  0.669
Maximum Recommended Daily Dose:  0.84 Skin Sensitization:  0.658
Carcinogencity:  0.773 Eye Corrosion:  0.01
Eye Irritation:  0.912 Respiratory Toxicity:  0.772
Drug-induced Neurotoxicity:  0.389 Ototoxicity:  0.203
Hematotoxicity:  0.203 Drug-induced Nephrotoxicity:  0.2
Genotoxicity:  0.988 RPMI-8226 Immunitoxicity:  0.05
A549 Cytotoxicity:  0.256 Hek293 Cytotoxicity:  0.733
BCF:   1.735
?
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:   4.686
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.851
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.422
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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
NPO30150 Psoralea corylifolia Species Fabaceae Eukaryota seeds n.a. n.a. PMID[18359631]
NPO28809 Cullen corylifolium Species Fabaceae Eukaryota n.a. fruit n.a. PMID[20663508]
NPO28809 Cullen corylifolium Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[24507928]
NPO30150 Psoralea corylifolia Species Fabaceae Eukaryota Fruits n.a. n.a. PMID[25710081]
NPO30150 Psoralea corylifolia Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[3069958]
NPO30150 Psoralea corylifolia Species Fabaceae Eukaryota n.a. seed n.a. PMID[8759164]
NPO28809 Cullen corylifolium Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[9544566]
NPO28809 Cullen corylifolium Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1470 Fructus psoraleae corylifoliae n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO30150 Psoralea corylifolia Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO30150 Psoralea corylifolia Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO1470 Fructus psoraleae corylifoliae n.a. n.a. n.a. n.a. n.a. n.a. Database[TCMID]
NPO28809 Cullen corylifolium Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO30150 Psoralea corylifolia Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO28809 Cullen corylifolium Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO28809 Cullen corylifolium 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
NPT99 Individual protein Peroxisome proliferator-activated receptor gamma Homo sapiens Ki = 175.5 nM PMID[25978962]
NPT99 Individual protein Peroxisome proliferator-activated receptor gamma Homo sapiens IC50 = 488.8 nM PMID[25978962]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT111 Cell line K562 Homo sapiens IC50 > 10000.0 nM PMID[25710081]
NPT81 Cell line A549 Homo sapiens IC50 > 10000.0 nM PMID[25710081]
NPT2 Others Unspecified n.a. IC50 = 3200.0 nM PMID[8882428]

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 NPC110969 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 NPC270883
0.6129 Remote Similarity NPC250266
0.6032 Remote Similarity NPC78913
0.5672 Remote Similarity NPC284220
0.5588 Remote Similarity NPC172986
0.5469 Remote Similarity NPC47815
0.5385 Remote Similarity NPC198826
0.5385 Remote Similarity NPC234133
0.5385 Remote Similarity NPC120163
0.5352 Remote Similarity NPC265932
0.5294 Remote Similarity NPC220062
0.5231 Remote Similarity NPC241498
0.5211 Remote Similarity NPC476185
0.5211 Remote Similarity NPC261227
0.5143 Remote Similarity NPC482709
0.5077 Remote Similarity NPC226973
0.507 Remote Similarity NPC37226
0.5067 Remote Similarity NPC602497

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC110969 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