Natural Product: NPC474920

Natural Product IDNPC474920
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Cordiachromene A
IUPAC Name 2-methyl-2-(4-methylpent-3-enyl)chromen-6-ol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL487808
PubChem CID 124963
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000123] Benzopyrans
        • [CHEMONTID:0003410] 1-benzopyrans

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 CEZCHPFUKBTQGN-UHFFFAOYSA-N
Standard InCHI InChI=1S/C16H20O2/c1-12(2)5-4-9-16(3)10-8-13-11-14(17)6-7-15(13)18-16/h5-8,10-11,17H,4,9H2,1-3H3
SMILES CC(=CCCC1(C)C=Cc2cc(ccc2O1)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   244.15 Volume:   272.577
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Van der Waals volume.
Dense:   0.896 LogP:   4.374
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.671
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.988
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The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   12.0
TPSA:   29.46
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Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   1.0 Rings:   2.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.803 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.3 Fsp3:   0.375
MCE-18:   40.182
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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:   Accepted GSK Rule:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.389 Fluc inhibitor:   0.071
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.142
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.324
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.93 Promiscuous compounds:   0.226

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.66 MDCK Permeability:   -4.69
Pgp-inhibitor:   0.095 Pgp-substrate:   0.084
PAMPA:   0.642
?
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):   0.013
20% Bioavailability (F20%):   0.45 30% Bioavailability (F30%):   0.457
50% Bioavailability (F50%):   0.954

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.731 MRP1:   0.803
Plasma Protein Binding (PPB):   93.7% Volume Distribution (VD):   0.321
Fu: 5.663%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.988
OATP1B3 inhibitor:   0.912 BCRP inhibitor:   0.152
BSEP inhibitor:   0.614

ADMET: Metabolism

CYP1A2-inhibitor:   0.003 CYP1A2-substrate:   0.97
CYP2C19-inhibitor:   0.666 CYP2C19-substrate:   0.158
CYP2C9-inhibitor:   0.661 CYP2C9-substrate:   0.297
CYP2D6-inhibitor:   0.198 CYP2D6-substrate:   0.377
CYP3A4-inhibitor:   0.055 CYP3A4-substrate:   0.957
CYP2B6-substrate:   0.223 CYP2C8-inhibitor:   0.994
HLM stability:   0.941
?
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):  11.368 Half-life (T1/2):  1.075

ADMET: Toxicity

hERG Blockers:  0.265 hERG Blockers (10um):  0.636
Human Hepatotoxicity (H-HT):  0.56 Drug-induced Liver Injury (DILI):  0.139
AMES Toxicity:  0.41 Rat Oral Acute Toxicity:  0.341
Maximum Recommended Daily Dose:  0.237 Skin Sensitization:  0.803
Carcinogencity:  0.581 Eye Corrosion:  0.247
Eye Irritation:  0.962 Respiratory Toxicity:  0.699
Drug-induced Neurotoxicity:  0.598 Ototoxicity:  0.317
Hematotoxicity:  0.196 Drug-induced Nephrotoxicity:  0.238
Genotoxicity:  0.113 RPMI-8226 Immunitoxicity:  0.054
A549 Cytotoxicity:  0.103 Hek293 Cytotoxicity:  0.253
BCF:   1.955
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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:   4.547
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.807
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.295
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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
NPO33101 aplidium aff. densum Species Polyclinidae Eukaryota n.a. n.a. n.a. PMID[16180826]
NPO22854 Cordia globifera Species Cordiaceae Eukaryota n.a. n.a. n.a. PMID[19368377]
NPO22854 Cordia globifera Species Cordiaceae Eukaryota n.a. n.a. n.a. PMID[20384317]
NPO40780 Amaroucium multiplicatum Species n.a. n.a. n.a. n.a. n.a. PMID[2607356]
NPO40784 Aplidium antillense Species n.a. n.a. n.a. n.a. n.a. PMID[3404153]
NPO40780 Amaroucium multiplicatum Species n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO40784 Aplidium antillense Species n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO22854 Cordia globifera Species Cordiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22854 Cordia globifera Species Cordiaceae 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
NPT91 Cell line KB Homo sapiens IC50 = 36.0 ug.mL-1 PMID[23145909]
NPT168 Cell line P388 Mus musculus IC50 = 0.5 ug.mL-1 PMID[23145909]
NPT404 Cell line CCRF-CEM Homo sapiens IC50 = 30000.0 nM PMID[21794960]
NPT189 Cell line Vero Chlorocebus aethiops IC50 > 50.0 ug.mL-1 PubChem BioAssay data set
NPT91 Cell line KB Homo sapiens IC50 > 20.0 ug.mL-1 PMID[19901091]
NPT639 Cell line NCI-H187 Homo sapiens IC50 > 20.0 ug.mL-1 PMID[17261619]
NPT172 Organism Proteus mirabilis Proteus mirabilis MIC > 256.0 ug.mL-1 DOI[10.1007/s00044-010-9338-x]
NPT729 Organism Micrococcus luteus Micrococcus luteus MIC = 510000.0 nM PMID[26035018]
NPT1084 Subcellular Liver microsomes Rattus norvegicus IC50 = 0.3 ug.mL-1 PMID[8277308]
NPT173 Organism Klebsiella pneumoniae Klebsiella pneumoniae MIC > 256.0 ug.mL-1 DOI[10.1007/s00044-010-9338-x]
NPT88 Organism Mycobacterium tuberculosis Mycobacterium tuberculosis MIC = 12.5 ug.mL-1 DrugMatrix in vivo data: Pathology
NPT20 Organism Candida albicans Candida albicans IC50 = 11.2 ug.mL-1 PMID[18004813]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 > 20.0 ug.mL-1 PMID[19368377]
NPT18 Organism Pseudomonas aeruginosa Pseudomonas aeruginosa MIC > 256.0 ug.mL-1 DOI[10.1007/s00044-010-9328-z]
NPT19 Organism Escherichia coli Escherichia coli MIC > 256.0 ug.mL-1 DOI[10.1007/s00044-010-9328-z]
NPT3495 Organism Morganella morganii Morganella morganii MIC > 256.0 ug.mL-1 DOI[10.1007/s00044-010-9338-x]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 64.0 ug.mL-1 PMID[15161186]
NPT175 Organism Enterococcus faecalis Enterococcus faecalis MIC = 64.0 ug.mL-1 PMID[15161186]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MBC = 2.0 ug ml-1 PMID[15161186]
NPT175 Organism Enterococcus faecalis Enterococcus faecalis MBC = 1.0 ug ml-1 PMID[19721064]
NPT19 Organism Escherichia coli Escherichia coli MIC > 2000000.0 nM PMID[22705001]
NPT1248 Organism Serratia marcescens Serratia marcescens MIC > 256.0 ug.mL-1 PMID[15161186]
NPT2 Others Unspecified n.a. IC50 = 0.2 ug.mL-1 PMID[8277308]
NPT485 Organism Plasmodium falciparum (isolate K1 / Thailand) Plasmodium falciparum K1 IC50 > 20.0 ug.mL-1 PMID[10869199]

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 NPC474920 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
0.8542 High Similarity NPC476165
0.6667 Remote Similarity NPC473718
0.6604 Remote Similarity NPC479913
0.6 Remote Similarity NPC154256
0.6 Remote Similarity NPC290470
0.5932 Remote Similarity NPC608493
0.5862 Remote Similarity NPC476006
0.55 Remote Similarity NPC74137
0.541 Remote Similarity NPC474481
0.5397 Remote Similarity NPC483636
0.5333 Remote Similarity NPC85895
0.5246 Remote Similarity NPC233059
0.5246 Remote Similarity NPC218753
0.5246 Remote Similarity NPC601175
0.5238 Remote Similarity NPC183107
0.5152 Remote Similarity NPC488702
0.5147 Remote Similarity NPC472633

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC474920 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
0.5082 Remote Similarity NPD6671 Approved

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