Natural Product: NPC90665

Natural Product IDNPC90665
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Cajanin
IUPAC Name 3-(2,4-dihydroxyphenyl)-5-hydroxy-7-methoxychromen-4-one
Synonyms Cajanin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL469630
PubChem CID 5281706
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
            • [CHEMONTID:0002689] 7-O-methylisoflavones

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 ALFNTRJPGFNJQV-UHFFFAOYSA-N
Standard InCHI InChI=1S/C16H12O6/c1-21-9-5-13(19)15-14(6-9)22-7-11(16(15)20)10-3-2-8(17)4-12(10)18/h2-7,17-19H,1H3
SMILES COc1cc(O)c2c(c1)occ(c2=O)c1ccc(cc1O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   300.06 Volume:   291.273
?
Van der Waals volume.
Dense:   1.03 LogP:   2.17
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.257
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.989
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   18.0
TPSA:   100.13
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.672 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.45 Fsp3:   0.062
MCE-18:   18.0
?
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:   0.492 Fluc inhibitor:   0.913
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.831
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.498
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.517 Promiscuous compounds:   0.855

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.061 MDCK Permeability:   -4.842
Pgp-inhibitor:   0.085 Pgp-substrate:   0.104
PAMPA:   0.242
?
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):   0.028
20% Bioavailability (F20%):   0.194 30% Bioavailability (F30%):   0.628
50% Bioavailability (F50%):   0.978

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.01 MRP1:   0.473
Plasma Protein Binding (PPB):   93.25% Volume Distribution (VD):   -0.223
Fu: 7.957%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.977
OATP1B3 inhibitor:   0.997 BCRP inhibitor:   0.944
BSEP inhibitor:   0.292

ADMET: Metabolism

CYP1A2-inhibitor:   0.972 CYP1A2-substrate:   0.865
CYP2C19-inhibitor:   0.005 CYP2C19-substrate:   0.17
CYP2C9-inhibitor:   0.999 CYP2C9-substrate:   0.967
CYP2D6-inhibitor:   0.999 CYP2D6-substrate:   0.742
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.059
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.692
HLM stability:   0.591
?
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):  1.724 Half-life (T1/2):  1.695

ADMET: Toxicity

hERG Blockers:  0.093 hERG Blockers (10um):  0.51
Human Hepatotoxicity (H-HT):  0.423 Drug-induced Liver Injury (DILI):  0.676
AMES Toxicity:  0.562 Rat Oral Acute Toxicity:  0.52
Maximum Recommended Daily Dose:  0.777 Skin Sensitization:  0.417
Carcinogencity:  0.632 Eye Corrosion:  0.057
Eye Irritation:  0.991 Respiratory Toxicity:  0.855
Drug-induced Neurotoxicity:  0.14 Ototoxicity:  0.162
Hematotoxicity:  0.083 Drug-induced Nephrotoxicity:  0.14
Genotoxicity:  0.949 RPMI-8226 Immunitoxicity:  0.083
A549 Cytotoxicity:  0.328 Hek293 Cytotoxicity:  0.653
BCF:   1.129
?
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:   3.768
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.33
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.85
?
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
NPO28952 Sapium haematospermum Species Euphorbiaceae Eukaryota n.a. n.a. n.a. PMID[15104489]
NPO28811 Eriophorum scheuchzeri Species Cyperaceae Eukaryota stem n.a. n.a. PMID[16038557]
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]
NPO26559 Glycine soja Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[21545185]
NPO26620 Pulicaria arabica Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[32372353]
NPO24668 Ophiocoma dentata Species Ophiocomidae Eukaryota n.a. n.a. n.a. PMID[8145229]
NPO28952 Sapium haematospermum Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8842 Neurymenia fraxinifolia Species Rhodomelaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10917 Junceella gemmacea Species Ellisellidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26559 Glycine soja Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26722 Dorstenia dinklagei Species Moraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26881 Croton zehntneri Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8308 Bryocaulon pseudosatoanum Species Parmeliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26403 Brachymeris montana n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO26531 Aeschrion excelsa n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO26620 Pulicaria arabica Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27984 Achillea moschata Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO27984 Achillea moschata Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO27984 Achillea moschata Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO8308 Bryocaulon pseudosatoanum Species Parmeliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10917 Junceella gemmacea Species Ellisellidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26881 Croton zehntneri Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8842 Neurymenia fraxinifolia Species Rhodomelaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28952 Sapium haematospermum Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24668 Ophiocoma dentata Species Ophiocomidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26559 Glycine soja Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21353 Crotalaria lachnophora Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26722 Dorstenia dinklagei Species Moraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26403 Brachymeris montana n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO28743 Ticorea longiflora n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO26620 Pulicaria arabica Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28811 Eriophorum scheuchzeri Species Cyperaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26531 Aeschrion excelsa n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO6635 Deamia testudo Species Cactaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27984 Achillea moschata Species Asteraceae 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 = 9.7 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 NPC90665 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
0.7636 Intermediate Similarity NPC303644
0.6842 Remote Similarity NPC116632
0.662 Remote Similarity NPC80140
0.6607 Remote Similarity NPC87545
0.6557 Remote Similarity NPC114192
0.65 Remote Similarity NPC121527
0.6393 Remote Similarity NPC279668
0.6269 Remote Similarity NPC26051
0.6269 Remote Similarity NPC253822
0.5942 Remote Similarity NPC84124
0.5926 Remote Similarity NPC479403
0.5857 Remote Similarity NPC469405
0.5821 Remote Similarity NPC249824
0.5781 Remote Similarity NPC264550
0.5714 Remote Similarity NPC309154
0.5714 Remote Similarity NPC124784
0.5634 Remote Similarity NPC469404
0.5588 Remote Similarity NPC133400
0.5538 Remote Similarity NPC45291
0.5507 Remote Similarity NPC474993
0.55 Remote Similarity NPC235428
0.5493 Remote Similarity NPC15435
0.5432 Remote Similarity NPC480964
0.5397 Remote Similarity NPC216769
0.5397 Remote Similarity NPC294409
0.5397 Remote Similarity NPC490701
0.5385 Remote Similarity NPC12175
0.5352 Remote Similarity NPC488570
0.5333 Remote Similarity NPC234739
0.5312 Remote Similarity NPC19980
0.5301 Remote Similarity NPC480965
0.5294 Remote Similarity NPC203636
0.5278 Remote Similarity NPC488567
0.5217 Remote Similarity NPC268204
0.52 Remote Similarity NPC348541
0.519 Remote Similarity NPC479406
0.5156 Remote Similarity NPC181124
0.5156 Remote Similarity NPC162680
0.5152 Remote Similarity NPC100263
0.5152 Remote Similarity NPC278323
0.5132 Remote Similarity NPC197896
0.5132 Remote Similarity NPC313163
0.5075 Remote Similarity NPC254702
0.5075 Remote Similarity NPC483637
0.5072 Remote Similarity NPC40868
0.5065 Remote Similarity NPC73511

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC90665 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