Natural Product: NPC307518

Natural Product IDNPC307518
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Iristectorin A
IUPAC Name 5-hydroxy-3-(3-hydroxy-4-methoxyphenyl)-6-methoxy-7-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxychromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL511453
PubChem CID 11968629
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002506] Isoflavonoids
        • [CHEMONTID:0000507] Isoflavonoid O-glycosides

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 HFODKTZIQVSGJO-ZTATXHNCSA-N
Standard InCHI InChI=1S/C23H24O12/c1-31-12-4-3-9(5-11(12)25)10-8-33-13-6-14(22(32-2)19(28)16(13)17(10)26)34-23-21(30)20(29)18(27)15(7-24)35-23/h3-6,8,15,18,20-21,23-25,27-30H,7H2,1-2H3/t15-,18-,20+,21-,23-/m1/s1
SMILES COc1ccc(cc1O)c1coc2cc(c(c(c2c1=O)O)OC)O[C@H]1[C@@H]([C@H]([C@@H]([C@@H](CO)O1)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   492.13 Volume:   456.529
?
Van der Waals volume.
Dense:   1.078 LogP:   0.492
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.155
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.888
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   24.0
TPSA:   188.51
?
Topological Polar Surface Area.
 H-Bond Acceptor:   12.0
H-Bond Donor:   6.0 Rings:   4.0
Heavy Atoms:   12.0

MedChem Properties

QED Drug-Likeness Score:   0.272 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.024 Fsp3:   0.348
MCE-18:   89.71
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Accepted
Pfizer Rule:   Rejected GSK Rule:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.509 Fluc inhibitor:   0.298
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.836
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.84
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.086 Promiscuous compounds:   0.537

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.187 MDCK Permeability:   -5.44
Pgp-inhibitor:   0.001 Pgp-substrate:   0.33
PAMPA:   0.929
?
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):   0.907
20% Bioavailability (F20%):   0.155 30% Bioavailability (F30%):   0.962
50% Bioavailability (F50%):   0.991

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.009 MRP1:   0.369
Plasma Protein Binding (PPB):   81.709% Volume Distribution (VD):   -0.329
Fu: 15.568%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.353
BSEP inhibitor:   0.001

ADMET: Metabolism

CYP1A2-inhibitor:   0.095 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.166 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   0.002
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.666
HLM stability:   0.08
?
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):  2.405 Half-life (T1/2):  3.677

ADMET: Toxicity

hERG Blockers:  0.029 hERG Blockers (10um):  0.137
Human Hepatotoxicity (H-HT):  0.711 Drug-induced Liver Injury (DILI):  0.956
AMES Toxicity:  0.873 Rat Oral Acute Toxicity:  0.048
Maximum Recommended Daily Dose:  0.087 Skin Sensitization:  0.987
Carcinogencity:  0.368 Eye Corrosion:  0.0
Eye Irritation:  0.217 Respiratory Toxicity:  0.051
Drug-induced Neurotoxicity:  0.019 Ototoxicity:  0.902
Hematotoxicity:  0.294 Drug-induced Nephrotoxicity:  0.684
Genotoxicity:  0.691 RPMI-8226 Immunitoxicity:  0.176
A549 Cytotoxicity:  0.361 Hek293 Cytotoxicity:  0.322
BCF:   0.288
?
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:   2.907
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.386
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.554
?
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]
NPO30734 Belamcanda chinensis Species Iridaceae Eukaryota rhizomes Thai n.a. PMID[15787436]
NPO7528 Belamcanda chinensis Species Iridaceae Eukaryota n.a. n.a. n.a. PMID[21465599]
NPO8881 Centipeda minima Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[23189738]
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]
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]
NPO30734 Belamcanda chinensis Species Iridaceae Eukaryota n.a. n.a. n.a. PMID[36265291]
NPO30734 Belamcanda chinensis Species Iridaceae Eukaryota n.a. n.a. n.a. PMID[9917289]
NPO14417 Iris tectorum Species Iridaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8881 Centipeda minima Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO30734 Belamcanda chinensis Species Iridaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8881 Centipeda minima Species Asteraceae 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]
NPO14417 Iris tectorum Species Iridaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8881 Centipeda minima Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7528 Belamcanda chinensis Species Iridaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8881 Centipeda minima Species Asteraceae 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]
NPO30734 Belamcanda chinensis Species Iridaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO7528 Belamcanda chinensis Species Iridaceae 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]
NPO8881 Centipeda minima Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO14417 Iris tectorum Species Iridaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7528 Belamcanda chinensis Species Iridaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8881 Centipeda minima 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
NPT83 Cell line MCF7 Homo sapiens Activity = 26.1 uM PMID[15787436]

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 NPC307518 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
0.84 Intermediate Similarity NPC224462
0.8077 Intermediate Similarity NPC48773
0.8026 Intermediate Similarity NPC205076
0.7595 Intermediate Similarity NPC229729
0.7 Intermediate Similarity NPC73511
0.6747 Remote Similarity NPC21666
0.642 Remote Similarity NPC135345
0.6265 Remote Similarity NPC105511
0.6265 Remote Similarity NPC156457
0.6235 Remote Similarity NPC481043
0.622 Remote Similarity NPC45165
0.6163 Remote Similarity NPC605067
0.6071 Remote Similarity NPC197896
0.6071 Remote Similarity NPC313163
0.6 Remote Similarity NPC186807
0.5882 Remote Similarity NPC258035
0.5882 Remote Similarity NPC161749
0.5882 Remote Similarity NPC234739
0.5843 Remote Similarity NPC479407
0.5765 Remote Similarity NPC58053
0.5747 Remote Similarity NPC100720
0.5747 Remote Similarity NPC117260
0.5747 Remote Similarity NPC201292
0.573 Remote Similarity NPC602805
0.573 Remote Similarity NPC607201
0.5682 Remote Similarity NPC488071
0.5682 Remote Similarity NPC609451
0.5667 Remote Similarity NPC488072
0.5647 Remote Similarity NPC160515
0.5632 Remote Similarity NPC105025
0.5632 Remote Similarity NPC603655
0.5625 Remote Similarity NPC51326
0.5625 Remote Similarity NPC257714
0.5618 Remote Similarity NPC601607
0.5612 Remote Similarity NPC235575
0.5526 Remote Similarity NPC209487
0.5517 Remote Similarity NPC603782
0.5506 Remote Similarity NPC479402
0.5506 Remote Similarity NPC80140
0.5444 Remote Similarity NPC22832
0.5393 Remote Similarity NPC138540
0.5385 Remote Similarity NPC150442
0.5333 Remote Similarity NPC479401
0.5281 Remote Similarity NPC24043
0.5281 Remote Similarity NPC45638
0.5275 Remote Similarity NPC120099
0.5275 Remote Similarity NPC486578
0.5227 Remote Similarity NPC259070
0.5217 Remote Similarity NPC479406
0.5213 Remote Similarity NPC487212
0.5208 Remote Similarity NPC479405
0.5195 Remote Similarity NPC216769
0.519 Remote Similarity NPC25292
0.5169 Remote Similarity NPC93337
0.5155 Remote Similarity NPC479404
0.5116 Remote Similarity NPC25547
0.5109 Remote Similarity NPC609478
0.5056 Remote Similarity NPC348541

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC307518 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
0.5882 Remote Similarity NPD4381 Clinical (unspecified phase)

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