Natural Product: NPC51633

Natural Product IDNPC51633
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Evofolin C
IUPAC Name (E)-3-[4-(3-methylbut-2-enoxy)phenyl]prop-2-en-1-ol
Synonyms Evofolin C
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL251915
PubChem CID 44445795
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002754] Cinnamyl alcohols

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 ROCWIPIJKMWFFA-ONEGZZNKSA-N
Standard InCHI InChI=1S/C14H18O2/c1-12(2)9-11-16-14-7-5-13(6-8-14)4-3-10-15/h3-9,15H,10-11H2,1-2H3/b4-3+
SMILES OC/C=C/c1ccc(cc1)OCC=C(C)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   218.13 Volume:   246.542
?
Van der Waals volume.
Dense:   0.885 LogP:   3.551
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.185
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.482
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   8.0
TPSA:   29.46
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   1.0 Rings:   1.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.77 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.248 Fsp3:   0.286
MCE-18:   6.0
?
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:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.425 Fluc inhibitor:   0.654
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.004
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.333
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.984 Promiscuous compounds:   0.156

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.502 MDCK Permeability:   -4.703
Pgp-inhibitor:   0.896 Pgp-substrate:   0.009
PAMPA:   0.241
?
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):   0.239
20% Bioavailability (F20%):   0.942 30% Bioavailability (F30%):   0.99
50% Bioavailability (F50%):   0.859

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.052 MRP1:   0.001
Plasma Protein Binding (PPB):   84.76% Volume Distribution (VD):   0.196
Fu: 14.732%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.908
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.863
BSEP inhibitor:   0.999

ADMET: Metabolism

CYP1A2-inhibitor:   0.01 CYP1A2-substrate:   0.477
CYP2C19-inhibitor:   0.148 CYP2C19-substrate:   0.052
CYP2C9-inhibitor:   0.284 CYP2C9-substrate:   0.152
CYP2D6-inhibitor:   0.999 CYP2D6-substrate:   0.001
CYP3A4-inhibitor:   0.162 CYP3A4-substrate:   0.328
CYP2B6-substrate:   0.002 CYP2C8-inhibitor:   0.999
HLM stability:   0.902
?
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):  11.934 Half-life (T1/2):  1.024

ADMET: Toxicity

hERG Blockers:  0.214 hERG Blockers (10um):  0.455
Human Hepatotoxicity (H-HT):  0.791 Drug-induced Liver Injury (DILI):  0.343
AMES Toxicity:  0.603 Rat Oral Acute Toxicity:  0.067
Maximum Recommended Daily Dose:  0.273 Skin Sensitization:  0.905
Carcinogencity:  0.554 Eye Corrosion:  0.134
Eye Irritation:  0.974 Respiratory Toxicity:  0.651
Drug-induced Neurotoxicity:  0.421 Ototoxicity:  0.301
Hematotoxicity:  0.235 Drug-induced Nephrotoxicity:  0.203
Genotoxicity:  0.107 RPMI-8226 Immunitoxicity:  0.041
A549 Cytotoxicity:  0.066 Hek293 Cytotoxicity:  0.119
BCF:   1.611
?
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:   3.854
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.384
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.697
?
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
NPO21390 Zanthoxylum integrifoliolum Species Rutaceae Eukaryota fruit Lanyu Island, Taitung County, Taiwan n.a. PMID[10395498]
NPO13278 Strychnos spinosa Species Loganiaceae Eukaryota Leaves n.a. n.a. PMID[17637068]
NPO21390 Zanthoxylum integrifoliolum Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[17822293]
NPO15233 Balanophora japonica Species Balanophoraceae Eukaryota n.a. n.a. n.a. PMID[18302336]
NPO21908 Corymbia scabrida Species Myrtaceae Eukaryota seeds n.a. n.a. PMID[18771320]
NPO5470 Cynoglossum amabile Species Boraginaceae Eukaryota n.a. n.a. n.a. PMID[22432912]
NPO2330 Alchornea cordifolia Species Euphorbiaceae Eukaryota n.a. stem n.a. PMID[26724423]
NPO2330 Alchornea cordifolia Species Euphorbiaceae Eukaryota n.a. root n.a. PMID[26724423]
NPO21084 Nymphaea caerulea Species Nymphaeaceae Eukaryota n.a. n.a. n.a. PMID[37894493]
NPO21908 Corymbia scabrida Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20578 Kallichroma tethys Species Bionectriaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20319 Kopsia jasminiflora Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21337 Libanotis transcaucasica Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21084 Nymphaea caerulea Species Nymphaeaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22301 Pinus hartwegii Species Pinaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21526 Scabiosa rotata Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21779 Umbilicaria hypococcinea Species Umbilicariaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2330 Alchornea cordifolia Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1759 Alexandrium excavatum Species Gonyaulacaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6906 Atalantia wightii Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13848 Amomum daniellii Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3761 Plectosphaerella cucumerina Species Plectosphaerellaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21390 Zanthoxylum integrifoliolum Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23772 Tetradium glabrifolium Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13278 Strychnos spinosa Species Loganiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18873.2 Salmonella enterica subsp. enterica serovar bovismorbificans Subspecies Enterobacteriaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO15329 Rhizoplaca baranowii Species Lecanoraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15145 Rauvolfia salicifolia Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14526 Plectranthus caninus Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15233 Balanophora japonica Species Balanophoraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5398 Peucedanum oroselinum Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14947 Lathyrus tingitanus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12487 Juniperus horizontalis Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11430 Inula grantioides Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7521 Hygrophorus eburneus Species Hygrophoraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10098 Glycosmis pseudoracemosa Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5470 Cynoglossum amabile Species Boraginaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16801 Cota tinctoria Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3965 Corynanthe pachyceras Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1109 Corydalis persica Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13647 Calcarisporium thermophilum Species n.a. Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5470 Cynoglossum amabile Species Boraginaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO15233 Balanophora japonica Species Balanophoraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO21779 Umbilicaria hypococcinea Species Umbilicariaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO13278 Strychnos spinosa Species Loganiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO5470 Cynoglossum amabile Species Boraginaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO10098 Glycosmis pseudoracemosa Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12487 Juniperus horizontalis Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO13278 Strychnos spinosa Species Loganiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21779 Umbilicaria hypococcinea Species Umbilicariaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21084 Nymphaea caerulea Species Nymphaeaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO23772 Tetradium glabrifolium Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15233 Balanophora japonica Species Balanophoraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21390 Zanthoxylum integrifoliolum Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21779 Umbilicaria hypococcinea Species Umbilicariaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO5470 Cynoglossum amabile Species Boraginaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO15233 Balanophora japonica Species Balanophoraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12487 Juniperus horizontalis Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3965 Corynanthe pachyceras Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15145 Rauvolfia salicifolia Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23772 Tetradium glabrifolium Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18873.2 Salmonella enterica subsp. enterica serovar bovismorbificans Subspecies Enterobacteriaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO21779 Umbilicaria hypococcinea Species Umbilicariaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20319 Kopsia jasminiflora Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3761 Plectosphaerella cucumerina Species Plectosphaerellaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6906 Atalantia wightii Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14947 Lathyrus tingitanus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2330 Alchornea cordifolia Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13647 Calcarisporium thermophilum Species n.a. Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15329 Rhizoplaca baranowii Species Lecanoraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10098 Glycosmis pseudoracemosa Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16801 Cota tinctoria Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21526 Scabiosa rotata Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14526 Plectranthus caninus Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13848 Amomum daniellii Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21084 Nymphaea caerulea Species Nymphaeaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5398 Peucedanum oroselinum Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7521 Hygrophorus eburneus Species Hygrophoraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11430 Inula grantioides Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1759 Alexandrium excavatum Species Gonyaulacaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1109 Corydalis persica Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21390 Zanthoxylum integrifoliolum Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21337 Libanotis transcaucasica Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13278 Strychnos spinosa Species Loganiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22301 Pinus hartwegii Species Pinaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20578 Kallichroma tethys Species Bionectriaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21908 Corymbia scabrida Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5470 Cynoglossum amabile Species Boraginaceae 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
NPT2740 Cell line Neutrophils n.a. IC50 = 9640.0 nM PMID[17822293]

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 NPC51633 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
0.75 Intermediate Similarity NPC192596
0.6818 Remote Similarity NPC55300
0.6667 Remote Similarity NPC46844
0.6486 Remote Similarity NPC4718
0.6341 Remote Similarity NPC38079
0.6279 Remote Similarity NPC176971
0.6053 Remote Similarity NPC252004
0.5909 Remote Similarity NPC108875
0.537 Remote Similarity NPC165646
0.5217 Remote Similarity NPC261718
0.5111 Remote Similarity NPC473855

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC51633 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