Natural Product: NPC250557

Natural Product IDNPC250557
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Irigenin
IUPAC Name 5,7-dihydroxy-3-(3-hydroxy-4,5-dimethoxyphenyl)-6-methoxychromen-4-one
Synonyms Irigenin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL487013
PubChem CID 5464170
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002506] Isoflavonoids
        • [CHEMONTID:0002586] O-methylated isoflavonoids
          • [CHEMONTID:0002606] 4'-O-methylated isoflavonoids
            • [CHEMONTID:0003651] 3'-hydroxy,4'-methoxyisoflavonoids

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 TUGWPJJTQNLKCL-UHFFFAOYSA-N
Standard InCHI InChI=1S/C18H16O8/c1-23-13-5-8(4-10(19)17(13)24-2)9-7-26-12-6-11(20)18(25-3)16(22)14(12)15(9)21/h4-7,19-20,22H,1-3H3
SMILES COc1cc(cc(c1OC)O)c1coc2c(c1=O)c(O)c(c(c2)O)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   360.08 Volume:   343.445
?
Van der Waals volume.
Dense:   1.048 LogP:   1.544
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.758
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.516
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   18.0
TPSA:   118.59
?
Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.65 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.673 Fsp3:   0.167
MCE-18:   20.0
?
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:   1 PAINS Alert:   0
Colloidal aggregators:   0.498 Fluc inhibitor:   0.383
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.837
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.601
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.395 Promiscuous compounds:   0.813

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.177 MDCK Permeability:   -4.788
Pgp-inhibitor:   0.06 Pgp-substrate:   0.447
PAMPA:   0.178
?
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):   0.005
20% Bioavailability (F20%):   0.107 30% Bioavailability (F30%):   0.361
50% Bioavailability (F50%):   0.977

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.176 MRP1:   0.935
Plasma Protein Binding (PPB):   92.505% Volume Distribution (VD):   -0.512
Fu: 8.579%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.908
OATP1B3 inhibitor:   0.969 BCRP inhibitor:   0.859
BSEP inhibitor:   0.227

ADMET: Metabolism

CYP1A2-inhibitor:   0.969 CYP1A2-substrate:   0.867
CYP2C19-inhibitor:   0.004 CYP2C19-substrate:   0.249
CYP2C9-inhibitor:   0.964 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.993 CYP2D6-substrate:   0.409
CYP3A4-inhibitor:   0.004 CYP3A4-substrate:   0.018
CYP2B6-substrate:   0.001 CYP2C8-inhibitor:   0.997
HLM stability:   0.949
?
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):  4.048 Half-life (T1/2):  1.21

ADMET: Toxicity

hERG Blockers:  0.121 hERG Blockers (10um):  0.534
Human Hepatotoxicity (H-HT):  0.517 Drug-induced Liver Injury (DILI):  0.835
AMES Toxicity:  0.457 Rat Oral Acute Toxicity:  0.522
Maximum Recommended Daily Dose:  0.647 Skin Sensitization:  0.489
Carcinogencity:  0.661 Eye Corrosion:  0.022
Eye Irritation:  0.941 Respiratory Toxicity:  0.733
Drug-induced Neurotoxicity:  0.254 Ototoxicity:  0.329
Hematotoxicity:  0.281 Drug-induced Nephrotoxicity:  0.264
Genotoxicity:  0.531 RPMI-8226 Immunitoxicity:  0.147
A549 Cytotoxicity:  0.346 Hek293 Cytotoxicity:  0.37
BCF:   0.782
?
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:   3.358
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.321
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.784
?
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
NPO30734 Belamcanda chinensis Species Iridaceae Eukaryota n.a. n.a. n.a. DOI[10.1007/s11240-020-01863-w]
NPO14417 Iris tectorum Species Iridaceae Eukaryota n.a. n.a. n.a. PMID[10075762]
NPO1859 Lantana camara Species Verbenaceae Eukaryota aerial parts n.a. n.a. PMID[10869197]
NPO30734 Belamcanda chinensis Species Iridaceae Eukaryota rhizomes Thai n.a. PMID[15787436]
NPO1859 Lantana camara Species Verbenaceae Eukaryota n.a. n.a. n.a. PMID[1812212]
NPO7478 Iris germanica Species Iridaceae Eukaryota n.a. n.a. n.a. PMID[19299148]
NPO7528 Belamcanda chinensis Species Iridaceae Eukaryota n.a. n.a. n.a. PMID[21465599]
NPO7478 Iris germanica Species Iridaceae Eukaryota n.a. rhizome n.a. PMID[22388969]
NPO14417 Iris tectorum Species Iridaceae Eukaryota n.a. n.a. n.a. PMID[24433009]
NPO7528 Belamcanda chinensis Species Iridaceae Eukaryota n.a. n.a. n.a. PMID[25036154]
NPO7478 Iris germanica Species Iridaceae Eukaryota n.a. rhizome n.a. PMID[25204177]
NPO14417 Iris tectorum Species Iridaceae Eukaryota n.a. n.a. n.a. PMID[28032759]
NPO7528 Belamcanda chinensis Species Iridaceae Eukaryota Rhizomes n.a. n.a. PMID[31246464]
NPO1859 Lantana camara Species Verbenaceae Eukaryota n.a. n.a. n.a. PMID[33780581]
NPO30734 Belamcanda chinensis Species Iridaceae Eukaryota n.a. n.a. n.a. PMID[36265291]
NPO1859 Lantana camara Species Verbenaceae Eukaryota n.a. n.a. n.a. PMID[36270431]
NPO1859 Lantana camara Species Verbenaceae Eukaryota n.a. n.a. n.a. PMID[38257257]
NPO1859 Lantana camara Species Verbenaceae Eukaryota n.a. n.a. n.a. PMID[38893531]
NPO1859 Lantana camara Species Verbenaceae Eukaryota n.a. n.a. n.a. PMID[39104562]
NPO1859 Lantana camara Species Verbenaceae Eukaryota leaves n.a. n.a. PMID[9834145]
NPO30734 Belamcanda chinensis Species Iridaceae Eukaryota n.a. n.a. n.a. PMID[9917289]
NPO1859 Lantana camara Species Verbenaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO30734 Belamcanda chinensis Species Iridaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7478 Iris germanica Species Iridaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21346 Eriocaulon buergerianum Species Eriocaulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3733 Senecio triangularis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14417 Iris tectorum Species Iridaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13012 Iris dichotoma Species Iridaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO942 Perophora namei Species Perophoridae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13012 Iris dichotoma Species Iridaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO1859 Lantana camara Species Verbenaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO14417 Iris tectorum Species Iridaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO30734 Belamcanda chinensis Species Iridaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO7478 Iris germanica Species Iridaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO7478 Iris germanica Species Iridaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21346 Eriocaulon buergerianum Species Eriocaulaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO13012 Iris dichotoma Species Iridaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14417 Iris tectorum Species Iridaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO1859 Lantana camara Species Verbenaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7528 Belamcanda chinensis Species Iridaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO2781 Iris kumaonensis Species Tarachodidae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO30734 Belamcanda chinensis Species Iridaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO1859 Lantana camara Species Verbenaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO7478 Iris germanica Species Iridaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO14417 Iris tectorum Species Iridaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO21346 Eriocaulon buergerianum Species Eriocaulaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO13012 Iris dichotoma Species Iridaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO21346 Eriocaulon buergerianum Species Eriocaulaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO1278 Eriocaulon sieboldianum Species Eriocaulaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO14417 Iris tectorum Species Iridaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO7528 Belamcanda chinensis Species Iridaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO2566 Nocardiopsaceae Species Nocardiopsaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO1859 Lantana camara Species Verbenaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7528 Belamcanda chinensis Species Iridaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21346 Eriocaulon buergerianum Species Eriocaulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13012 Iris dichotoma Species Iridaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5561 Thenea muricata Species Theneidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO942 Perophora namei Species Perophoridae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3733 Senecio triangularis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14417 Iris tectorum Species Iridaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6516 Aspidosperma megalocarpon Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2781 Iris kumaonensis Species Tarachodidae 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
NPT1310 Individual protein Xanthine dehydrogenase Bos taurus Inhibition = 0.0 % PMID[3379415]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference

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 NPC250557 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 NPC481044
0.7455 Intermediate Similarity NPC209487
0.7273 Intermediate Similarity NPC245382
0.7091 Intermediate Similarity NPC35763
0.7091 Intermediate Similarity NPC269451
0.6271 Remote Similarity NPC605826
0.5932 Remote Similarity NPC78341
0.5676 Remote Similarity NPC224462
0.5574 Remote Similarity NPC216769
0.5556 Remote Similarity NPC194653
0.5484 Remote Similarity NPC29841
0.5397 Remote Similarity NPC200316
0.5323 Remote Similarity NPC124714
0.5238 Remote Similarity NPC181209
0.5238 Remote Similarity NPC239363
0.5231 Remote Similarity NPC254702
0.5231 Remote Similarity NPC134726
0.5179 Remote Similarity NPC143903
0.5079 Remote Similarity NPC294409
0.5079 Remote Similarity NPC490701

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC250557 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