Natural Product: NPC311144

Natural Product IDNPC311144
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Cajanol
IUPAC Name (3S)-5-hydroxy-3-(4-hydroxy-2-methoxyphenyl)-7-methoxy-2,3-dihydrochromen-4-one
Synonyms Cajanol
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1689287
PubChem CID 53321436
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002506] Isoflavonoids
        • [CHEMONTID:0002586] O-methylated isoflavonoids
          • [CHEMONTID:0002602] 7-O-methylated isoflavonoids

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 RYYWWFXWFMYKJM-GFCCVEGCSA-N
Standard InCHI InChI=1S/C17H16O6/c1-21-10-6-13(19)16-15(7-10)23-8-12(17(16)20)11-4-3-9(18)5-14(11)22-2/h3-7,12,18-19H,8H2,1-2H3/t12-/m1/s1
SMILES COc1cc(c2c(c1)OC[C@H](c1ccc(cc1OC)O)C2=O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   316.09 Volume:   311.205
?
Van der Waals volume.
Dense:   1.016 LogP:   2.524
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.701
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.291
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   18.0
TPSA:   85.22
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.905 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.945 Fsp3:   0.235
MCE-18:   57.429
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Rejected GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.233 Fluc inhibitor:   0.938
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.185
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.432
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.314 Promiscuous compounds:   0.316

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.9 MDCK Permeability:   -4.777
Pgp-inhibitor:   0.004 Pgp-substrate:   0.168
PAMPA:   0.025
?
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):   0.0
20% Bioavailability (F20%):   0.025 30% Bioavailability (F30%):   0.019
50% Bioavailability (F50%):   0.314

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.088 MRP1:   0.673
Plasma Protein Binding (PPB):   90.892% Volume Distribution (VD):   0.025
Fu: 7.864%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.826
OATP1B3 inhibitor:   0.857 BCRP inhibitor:   0.34
BSEP inhibitor:   0.713

ADMET: Metabolism

CYP1A2-inhibitor:   0.975 CYP1A2-substrate:   0.994
CYP2C19-inhibitor:   0.135 CYP2C19-substrate:   0.913
CYP2C9-inhibitor:   0.997 CYP2C9-substrate:   0.231
CYP2D6-inhibitor:   0.987 CYP2D6-substrate:   0.959
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   0.049
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.606
HLM stability:   0.65
?
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):  8.413 Half-life (T1/2):  1.625

ADMET: Toxicity

hERG Blockers:  0.123 hERG Blockers (10um):  0.521
Human Hepatotoxicity (H-HT):  0.666 Drug-induced Liver Injury (DILI):  0.797
AMES Toxicity:  0.537 Rat Oral Acute Toxicity:  0.535
Maximum Recommended Daily Dose:  0.518 Skin Sensitization:  0.796
Carcinogencity:  0.699 Eye Corrosion:  0.036
Eye Irritation:  0.97 Respiratory Toxicity:  0.937
Drug-induced Neurotoxicity:  0.548 Ototoxicity:  0.383
Hematotoxicity:  0.383 Drug-induced Nephrotoxicity:  0.606
Genotoxicity:  0.855 RPMI-8226 Immunitoxicity:  0.151
A549 Cytotoxicity:  0.506 Hek293 Cytotoxicity:  0.681
BCF:   1.262
?
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:   3.822
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.948
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.158
?
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
NPO64637 Cajanus cajan + Hypocrea lixii symbiont Species n.a. n.a. n.a. n.a. n.a. PMID[ 23495919]
NPO21353 Crotalaria lachnophora Species Fabaceae Eukaryota n.a. whole plant n.a. PMID[21265557]
NPO21353 Crotalaria lachnophora Species Fabaceae Eukaryota whole plant Dschang (west region of Cameroon) 2007-SEP PMID[21265557]
NPO21353 Crotalaria lachnophora 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

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT173 Organism Klebsiella pneumoniae Klebsiella pneumoniae IZ = 9.3 mm PMID[21265557]
NPT19 Organism Escherichia coli Escherichia coli IZ = 7.3 mm PMID[21265557]

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 NPC311144 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 NPC299011
0.5893 Remote Similarity NPC303185
0.5893 Remote Similarity NPC184649
0.5893 Remote Similarity NPC133501
0.5893 Remote Similarity NPC113770
0.5789 Remote Similarity NPC181960
0.569 Remote Similarity NPC482076
0.5636 Remote Similarity NPC316480
0.5614 Remote Similarity NPC255807
0.5614 Remote Similarity NPC31018
0.5593 Remote Similarity NPC469584
0.5536 Remote Similarity NPC202981
0.5536 Remote Similarity NPC488571
0.5517 Remote Similarity NPC129684
0.5517 Remote Similarity NPC299520
0.5333 Remote Similarity NPC32633
0.5254 Remote Similarity NPC260979
0.5238 Remote Similarity NPC469575
0.5217 Remote Similarity NPC308265
0.5167 Remote Similarity NPC488568
0.5091 Remote Similarity NPC26879
0.5085 Remote Similarity NPC469550
0.5082 Remote Similarity NPC39064
0.5082 Remote Similarity NPC47283

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC311144 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