Natural Product: NPC83718

Natural Product IDNPC83718
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 4-Hydroxy-3,5-Bis(3-Methylbut-2-Enyl)Benzoic Acid
IUPAC Name 4-hydroxy-3,5-bis(3-methylbut-2-enyl)benzoic acid
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL500669
PubChem CID 5320129
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0002279] Benzene and substituted derivatives
        • [CHEMONTID:0000176] Benzoic acids and derivatives
          • [CHEMONTID:0001248] Hydroxybenzoic acid derivatives

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 LSVOBJIOONAGLU-UHFFFAOYSA-N
Standard InCHI InChI=1S/C17H22O3/c1-11(2)5-7-13-9-15(17(19)20)10-14(16(13)18)8-6-12(3)4/h5-6,9-10,18H,7-8H2,1-4H3,(H,19,20)
SMILES CC(=CCc1cc(cc(c1O)CC=C(C)C)C(=O)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   274.16 Volume:   304.584
?
Van der Waals volume.
Dense:   0.9 LogP:   4.97
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.146
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.527
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   9.0
TPSA:   57.53
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   2.0 Rings:   1.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.794 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.642 Fsp3:   0.353
MCE-18:   10.0
?
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:   0.092 Fluc inhibitor:   0.159
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.338
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.167
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.827 Promiscuous compounds:   0.207

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.919 MDCK Permeability:   -4.686
Pgp-inhibitor:   0.009 Pgp-substrate:   0.013
PAMPA:   0.993
?
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):   0.859
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:   0.946
Plasma Protein Binding (PPB):   92.35% Volume Distribution (VD):   -0.224
Fu: 8.818%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.246
OATP1B3 inhibitor:   0.959 BCRP inhibitor:   0.973
BSEP inhibitor:   0.013

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.586 CYP2C19-substrate:   0.974
CYP2C9-inhibitor:   0.006 CYP2C9-substrate:   0.002
CYP2D6-inhibitor:   0.012 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.002 CYP2C8-inhibitor:   1.0
HLM stability:   0.993
?
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):  4.302 Half-life (T1/2):  1.669

ADMET: Toxicity

hERG Blockers:  0.029 hERG Blockers (10um):  0.138
Human Hepatotoxicity (H-HT):  0.658 Drug-induced Liver Injury (DILI):  0.685
AMES Toxicity:  0.47 Rat Oral Acute Toxicity:  0.655
Maximum Recommended Daily Dose:  0.225 Skin Sensitization:  0.932
Carcinogencity:  0.261 Eye Corrosion:  0.003
Eye Irritation:  0.787 Respiratory Toxicity:  0.89
Drug-induced Neurotoxicity:  0.525 Ototoxicity:  0.726
Hematotoxicity:  0.461 Drug-induced Nephrotoxicity:  0.861
Genotoxicity:  0.625 RPMI-8226 Immunitoxicity:  0.03
A549 Cytotoxicity:  0.102 Hek293 Cytotoxicity:  0.066
BCF:   1.448
?
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:   4.215
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.754
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.046
?
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
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/j.jarmap.2018.11.004]
NPO1075 Streptomyces natalensis Species Streptomycetaceae Bacteria n.a. n.a. n.a. DOI[10.1074/jbc.M402340200]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota rhizomes n.a. n.a. PMID[18177011]
NPO16463 Piper glabratum Species Piperaceae Eukaryota n.a. leaf n.a. PMID[18712933]
NPO16463 Piper glabratum Species Piperaceae Eukaryota n.a. n.a. n.a. PMID[18712933]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[19271742]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[20590154]
NPO2364 Cornus florida Species Cornaceae Eukaryota n.a. n.a. n.a. PMID[25141901]
NPO2364 Cornus florida Species Cornaceae Eukaryota leaves Timber Lake, Oxford, Mississippi 2011 PMID[25141901]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[32872604]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[36352904]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[39679248]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[39680258]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[8064299]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. rhizome n.a. PMID[8064299]
NPO16463 Piper glabratum Species Piperaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1075 Streptomyces natalensis Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO8980 Teucrium corymbosum Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6778 Suriana maritima Species Surianaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10516 Lactarius piperatus Species Russulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1765 Cirsium lineare Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7299 Swartzia laevicarpa Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. Database[FooDB]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota Root n.a. n.a. Database[FooDB]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota Rhizome n.a. n.a. Database[FooDB]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota Resin, Exudate, Sap n.a. n.a. Database[FooDB]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota Plant n.a. n.a. Database[FooDB]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. Database[FooDB]
NPO1765 Cirsium lineare Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO2524 Liparis nervosa Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO10516 Lactarius piperatus Species Russulaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. Database[Phenol-Explorer]
NPO1765 Cirsium lineare Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO22902.1 Alnus alnobetula subsp. crispa Subspecies Betulaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO2524 Liparis nervosa Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO10516 Lactarius piperatus Species Russulaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO25057 Vespertilio sinensis Species Vespertilionidae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO2524 Liparis nervosa Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO15943 Chicoreus nobilis Species Muricidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16463 Piper glabratum Species Piperaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6778 Suriana maritima Species Surianaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22902.1 Alnus alnobetula subsp. crispa Subspecies Betulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25057 Vespertilio sinensis Species Vespertilionidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9372 Hypericum yezoense Species Hypericaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3483 Bencomia caudata Species Rosaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1075 Streptomyces natalensis Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO7299 Swartzia laevicarpa Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1765 Cirsium lineare Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6397 Schefflera rhododendrifolia Species Araliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2524 Liparis nervosa Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5803 Sedum takesimense Species Crassulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO980 Hedera taurica Species Araliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10516 Lactarius piperatus Species Russulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1435 Staehelina dubia Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7420 Tetraneuris linearifolia Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2222 Litsea wightiana Species Lauraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8980 Teucrium corymbosum Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4270 Cousinia piptocephala Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2364 Cornus florida Species Cornaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7983 Bassia latifolia Species Abylidae 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
NPT6 Organism Plasmodium falciparum Plasmodium falciparum IC50 > 10.0 ug.mL-1 PMID[18712933]
NPT634 Organism Leishmania amazonensis Leishmania amazonensis IC50 = 45.3 ug.mL-1 PMID[18712933]
NPT1208 Organism Leishmania braziliensis Leishmania braziliensis IC50 = 34.1 ug.mL-1 PMID[18712933]
NPT633 Organism Leishmania donovani Leishmania donovani IC50 = 40.0 ug.mL-1 PMID[18712933]
NPT580 Organism Trypanosoma cruzi Trypanosoma cruzi IC50 > 20.0 ug.mL-1 PMID[18712933]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC50 = 7.6 ug.mL-1 PMID[33492131]

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 NPC83718 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
0.7692 Intermediate Similarity NPC475192
0.551 Remote Similarity NPC474890
0.551 Remote Similarity NPC273282
0.5227 Remote Similarity NPC481377

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC83718 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