Natural Product: NPC473393

Natural Product IDNPC473393
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Acetylbakuchiol
IUPAC Name [4-[(1E,3S)-3-ethenyl-3,7-dimethylocta-1,6-dienyl]phenyl] acetate
Synonyms Acetylbakuchiol
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL408851
PubChem CID 44450293
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001549] Monoterpenoids
          • [CHEMONTID:0000051] Aromatic monoterpenoids

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 KLWKVZWSRSGVHJ-UPTIQUDWSA-N
Standard InCHI InChI=1S/C20H26O2/c1-6-20(5,14-7-8-16(2)3)15-13-18-9-11-19(12-10-18)22-17(4)21/h6,8-13,15H,1,7,14H2,2-5H3/b15-13+/t20-/m1/s1
SMILES C=C[C@@](/C=C/c1ccc(cc1)OC(=O)C)(CCC=C(C)C)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   298.19 Volume:   345.045
?
Van der Waals volume.
Dense:   0.864 LogP:   5.201
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   4.004
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.394
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   8.0 Rigid Bonds:   10.0
TPSA:   26.3
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   0.0 Rings:   1.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.374 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.288 Fsp3:   0.35
MCE-18:   20.0
?
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:   0.942 Fluc inhibitor:   0.547
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.003
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.477
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.966 Promiscuous compounds:   0.13

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.625 MDCK Permeability:   -4.679
Pgp-inhibitor:   0.814 Pgp-substrate:   0.0
PAMPA:   0.004
?
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):   0.088
20% Bioavailability (F20%):   1.0 30% Bioavailability (F30%):   1.0
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.001
Plasma Protein Binding (PPB):   95.117% Volume Distribution (VD):   0.042
Fu: 3.298%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.985
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.082 CYP1A2-substrate:   0.335
CYP2C19-inhibitor:   0.011 CYP2C19-substrate:   0.014
CYP2C9-inhibitor:   0.004 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.656 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.999
CYP2B6-substrate:   0.144 CYP2C8-inhibitor:   1.0
HLM stability:   0.998
?
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):  7.894 Half-life (T1/2):  0.369

ADMET: Toxicity

hERG Blockers:  0.091 hERG Blockers (10um):  0.54
Human Hepatotoxicity (H-HT):  0.472 Drug-induced Liver Injury (DILI):  0.35
AMES Toxicity:  0.144 Rat Oral Acute Toxicity:  0.238
Maximum Recommended Daily Dose:  0.31 Skin Sensitization:  0.987
Carcinogencity:  0.179 Eye Corrosion:  0.922
Eye Irritation:  0.989 Respiratory Toxicity:  0.696
Drug-induced Neurotoxicity:  0.679 Ototoxicity:  0.155
Hematotoxicity:  0.19 Drug-induced Nephrotoxicity:  0.137
Genotoxicity:  0.179 RPMI-8226 Immunitoxicity:  0.042
A549 Cytotoxicity:  0.309 Hek293 Cytotoxicity:  0.163
BCF:   2.215
?
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:   4.741
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.408
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   6.11
?
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]
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]
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]
NPO30150 Psoralea corylifolia Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]

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
NPT196 Cell line AGS Homo sapiens IC50 = 26800.0 nM DOI[10.1016/j.jssas.2011.10.002]
NPT165 Cell line HeLa Homo sapiens IC50 = 18100.0 nM PMID[26684850]
NPT382 Cell line OVCAR-5 Homo sapiens GI = 71.0 % PMID[7908950]
NPT744 Cell line IMR-32 Homo sapiens GI = 71.0 % DOI[10.6019/CHEMBL1201861]
NPT165 Cell line HeLa Homo sapiens GI = 63.0 % PMID[23820574]
NPT1970 Cell line THP-1 Homo sapiens GI = 81.0 % PMID[11975501]
NPT81 Cell line A549 Homo sapiens GI = 1.0 % PMID[11430005]
NPT306 Cell line PC-3 Homo sapiens GI = 45.0 % DrugMatrix in vitro pharmacology data
NPT744 Cell line IMR-32 Homo sapiens GI = 48.0 % PMID[11929285]
NPT1970 Cell line THP-1 Homo sapiens GI = 50.0 % PMID[11929285]
NPT83 Cell line MCF7 Homo sapiens GI = 56.0 % PMID[4851320]
NPT81 Cell line A549 Homo sapiens GI = 60.0 % PubChem BioAssay data set
NPT306 Cell line PC-3 Homo sapiens GI = 60.0 % PMID[23376010]
NPT382 Cell line OVCAR-5 Homo sapiens GI = 62.0 % PMID[23647825]
NPT744 Cell line IMR-32 Homo sapiens GI = 59.0 % PMID[16919944]
NPT165 Cell line HeLa Homo sapiens GI = 45.0 % PMID[16919944]
NPT1970 Cell line THP-1 Homo sapiens GI = 63.0 % PMID[8759172]
NPT83 Cell line MCF7 Homo sapiens GI = 31.0 % PMID[12762801]
NPT83 Cell line MCF7 Homo sapiens GI = 15.0 % PMID[18412396]
NPT1171 Cell line HEp-2 Homo sapiens GI = 52.0 % PMID[18640035]
NPT1171 Cell line HEp-2 Homo sapiens GI = 51.0 % PMID[22779787]
NPT1171 Cell line HEp-2 Homo sapiens GI = 46.0 % PMID[25838141]
NPT1171 Cell line HEp-2 Homo sapiens GI = 30.0 % PMID[25537529]
NPT1171 Cell line HEp-2 Homo sapiens GI = 14.0 % PMID[25537529]
NPT81 Cell line A549 Homo sapiens GI = 22.0 % PMID[23006147]
NPT81 Cell line A549 Homo sapiens GI = 13.0 % PMID[12088422]
NPT90 Cell line DU-145 Homo sapiens GI = 42.0 % PMID[22037378]
NPT90 Cell line DU-145 Homo sapiens GI = 29.0 % PMID[20857959]
NPT90 Cell line DU-145 Homo sapiens GI = 19.0 % PMID[21036050]
NPT1970 Cell line THP-1 Homo sapiens GI = 44.0 % PMID[20863701]
NPT1970 Cell line THP-1 Homo sapiens GI = 34.0 % PubChem BioAssay data set
NPT306 Cell line PC-3 Homo sapiens GI = 32.0 % PubChem BioAssay data set
NPT306 Cell line PC-3 Homo sapiens GI = 21.0 % PubChem BioAssay data set
NPT744 Cell line IMR-32 Homo sapiens GI = 34.0 % PubChem BioAssay data set
NPT744 Cell line IMR-32 Homo sapiens GI = 27.0 % DrugMatrix in vitro pharmacology data
NPT148 Cell line HCT-15 Homo sapiens GI = 57.0 % DrugMatrix in vitro pharmacology data
NPT148 Cell line HCT-15 Homo sapiens GI = 46.0 % DrugMatrix in vitro pharmacology data
NPT148 Cell line HCT-15 Homo sapiens GI = 31.0 % PubChem BioAssay data set
NPT1970 Cell line THP-1 Homo sapiens IC50 = 18000.0 nM PubChem BioAssay data set
NPT90 Cell line DU-145 Homo sapiens IC50 = 26000.0 nM PMID[19093800]
NPT306 Cell line PC-3 Homo sapiens IC50 = 23000.0 nM PMID[24508135]
NPT1171 Cell line HEp-2 Homo sapiens IC50 = 20000.0 nM PMID[16643047]
NPT83 Cell line MCF7 Homo sapiens IC50 = 25000.0 nM PMID[25798528]
NPT81 Cell line A549 Homo sapiens IC50 = 40000.0 nM PMID[14518939]
NPT399 Cell line SF-295 Homo sapiens IC50 = 8000.0 nM PMID[14518939]
NPT148 Cell line HCT-15 Homo sapiens IC50 = 11000.0 nM PMID[12662097]
NPT83 Cell line MCF7 Homo sapiens GI = 44.0 % PMID[16124786]
NPT83 Cell line MCF7 Homo sapiens GI = 75.0 % PMID[12662101]
NPT81 Cell line A549 Homo sapiens GI = 72.0 % PMID[26546220]
NPT306 Cell line PC-3 Homo sapiens GI = 67.0 % PMID[12105963]
NPT878 Organism Streptococcus mutans Streptococcus mutans MIC = 128.0 ug.mL-1 PMID[22652254]
NPT878 Organism Streptococcus mutans Streptococcus mutans MBC > 128.0 ug ml-1 PMID[15958589]
NPT1172 Organism Streptococcus sanguinis Streptococcus sanguinis MIC = 16.0 ug.mL-1 PMID[15958589]
NPT1172 Organism Streptococcus sanguinis Streptococcus sanguinis MBC = 16.0 ug ml-1 PMID[15958589]
NPT1484 Organism Fusobacterium nucleatum Fusobacterium nucleatum MIC > 128.0 ug.mL-1 PMID[22652254]
NPT1484 Organism Fusobacterium nucleatum Fusobacterium nucleatum MBC > 128.0 ug ml-1 PMID[15958589]
NPT1128 Organism Prevotella intermedia Prevotella intermedia MIC = 64.0 ug.mL-1 PMID[15958589]
NPT1128 Organism Prevotella intermedia Prevotella intermedia MBC = 64.0 ug ml-1 PMID[15958589]
NPT1127 Organism Porphyromonas gingivalis Porphyromonas gingivalis MIC = 8.0 ug.mL-1 PubChem BioAssay data set
NPT1127 Organism Porphyromonas gingivalis Porphyromonas gingivalis MBC = 8.0 ug ml-1 PubChem BioAssay data set
NPT21802 Protein family Hypoxia inducible factors; HIF-1-alpha, HIF-2-alpha Homo sapiens IC50 = 5700.0 nM PMID[18359631]
NPT2 Others Unspecified n.a. IC50 = 5700.0 nM PMID[26684850]
NPT1129 Organism Actinomyces viscosus Actinomyces viscosus MIC = 32.0 ug.mL-1 PMID[15958589]
NPT1129 Organism Actinomyces viscosus Actinomyces viscosus MBC = 64.0 ug ml-1 PMID[15958589]

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 NPC473393 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
0.8095 Intermediate Similarity NPC471581
0.7907 Intermediate Similarity NPC471576
0.5745 Remote Similarity NPC98772
0.5667 Remote Similarity NPC163036

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC473393 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