Natural Product: NPC201136

Natural Product IDNPC201136
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Sideritiflavone
IUPAC Name 2-(3,4-dihydroxyphenyl)-5-hydroxy-6,7,8-trimethoxychromen-4-one
Synonyms Sideritiflavone
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL312790
PubChem CID 155493
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0002585] O-methylated flavonoids
          • [CHEMONTID:0002593] 8-O-methylated flavonoids

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 UWNUJPINKMRKKR-UHFFFAOYSA-N
Standard InCHI InChI=1S/C18H16O8/c1-23-16-14(22)13-11(21)7-12(8-4-5-9(19)10(20)6-8)26-15(13)17(24-2)18(16)25-3/h4-7,19-20,22H,1-3H3
SMILES COc1c(c2c(=O)cc(c3ccc(c(c3)O)O)oc2c(c1OC)OC)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   360.08 Volume:   343.445
?
Van der Waals volume.
Dense:   1.048 LogP:   2.031
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.033
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.751
?
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:   0.608 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.624 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:   1
Colloidal aggregators:   0.308 Fluc inhibitor:   0.379
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.887
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.626
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.342 Promiscuous compounds:   0.784

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.173 MDCK Permeability:   -4.794
Pgp-inhibitor:   0.036 Pgp-substrate:   0.051
PAMPA:   0.238
?
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):   0.006
20% Bioavailability (F20%):   0.704 30% Bioavailability (F30%):   0.792
50% Bioavailability (F50%):   0.99

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.309 MRP1:   0.991
Plasma Protein Binding (PPB):   97.503% Volume Distribution (VD):   -0.45
Fu: 2.219%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.86
OATP1B3 inhibitor:   0.992 BCRP inhibitor:   0.709
BSEP inhibitor:   0.506

ADMET: Metabolism

CYP1A2-inhibitor:   0.293 CYP1A2-substrate:   0.027
CYP2C19-inhibitor:   0.002 CYP2C19-substrate:   0.054
CYP2C9-inhibitor:   0.025 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.469 CYP2D6-substrate:   0.872
CYP3A4-inhibitor:   0.041 CYP3A4-substrate:   0.325
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.946
HLM stability:   0.688
?
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):  8.816 Half-life (T1/2):  1.555

ADMET: Toxicity

hERG Blockers:  0.081 hERG Blockers (10um):  0.625
Human Hepatotoxicity (H-HT):  0.353 Drug-induced Liver Injury (DILI):  0.739
AMES Toxicity:  0.4 Rat Oral Acute Toxicity:  0.429
Maximum Recommended Daily Dose:  0.582 Skin Sensitization:  0.942
Carcinogencity:  0.631 Eye Corrosion:  0.242
Eye Irritation:  0.966 Respiratory Toxicity:  0.717
Drug-induced Neurotoxicity:  0.07 Ototoxicity:  0.3
Hematotoxicity:  0.147 Drug-induced Nephrotoxicity:  0.055
Genotoxicity:  0.672 RPMI-8226 Immunitoxicity:  0.055
A549 Cytotoxicity:  0.654 Hek293 Cytotoxicity:  0.504
BCF:   1.217
?
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:   3.672
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.687
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.115
?
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
NPO40877 Malagasy connaraceous Species n.a. n.a. n.a. n.a. n.a. PMID[14510616]
NPO33595 Stachys glutinosa Species Lamiaceae Eukaryota aerial parts n.a. n.a. PMID[25562563]
NPO28626 Isodon rubescens Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[25590529]
NPO28865 Hyptis pectinata Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[8496706]
NPO28626 Isodon rubescens Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13857 Mentha canadensis Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23256 Mentha arvensis Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23256 Mentha arvensis Species Lamiaceae Eukaryota Plant n.a. n.a. Database[FooDB]
NPO23256 Mentha arvensis Species Lamiaceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO13857 Mentha canadensis Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28865 Hyptis pectinata Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28626 Isodon rubescens Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28865 Hyptis pectinata Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[Title]
NPO28626 Isodon rubescens Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO23256 Mentha arvensis Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO13857 Mentha canadensis Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO13857 Mentha canadensis Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28865 Hyptis pectinata Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28626 Isodon rubescens Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23256 Mentha arvensis Species Lamiaceae 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
NPT1167 Individual protein Delta opioid receptor Mus musculus Ki = 12500.0 nM PMID[25562563]
NPT1168 Individual protein Mu opioid receptor Mus musculus Ki = 18500.0 nM PMID[25562563]
NPT68 Individual protein Aldose reductase Rattus norvegicus IC50 = 38.9 nM PMID[18585047]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT517 Cell line Panel NCI-60 (60 carcinoma cell lines) Homo sapiens GI50 = 4000.0 nM PMID[9632366]
NPT521 Cell line RBL-2H3 Rattus norvegicus IC50 > 500000.0 nM PMID[14510616]
NPT28438 Unchecked Unchecked n.a. IC50 n.a. n.a. n.a. PMID[35640148]
NPT28438 Unchecked Unchecked n.a. IC50 = 27900.0 nM PMID[35640148]
NPT2 Others Unspecified n.a. Ratio Ki = 0.68 n.a. PMID[25562563]

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 NPC201136 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
0.8235 Intermediate Similarity NPC231018
0.7778 Intermediate Similarity NPC196439
0.7636 Intermediate Similarity NPC227325
0.7547 Intermediate Similarity NPC176775
0.75 Intermediate Similarity NPC250822
0.7143 Intermediate Similarity NPC2476
0.7091 Intermediate Similarity NPC22472
0.7037 Intermediate Similarity NPC138360
0.6964 Remote Similarity NPC183878
0.6786 Remote Similarity NPC25270
0.6607 Remote Similarity NPC188203
0.6552 Remote Similarity NPC92659
0.6379 Remote Similarity NPC608498
0.6316 Remote Similarity NPC100887
0.614 Remote Similarity NPC71334
0.6034 Remote Similarity NPC105242
0.5932 Remote Similarity NPC108406
0.5932 Remote Similarity NPC162313
0.5862 Remote Similarity NPC275836
0.5738 Remote Similarity NPC128863
0.569 Remote Similarity NPC226973
0.569 Remote Similarity NPC607196
0.5667 Remote Similarity NPC604569
0.5645 Remote Similarity NPC19687
0.5593 Remote Similarity NPC292107
0.5574 Remote Similarity NPC146165
0.55 Remote Similarity NPC120163
0.55 Remote Similarity NPC143828
0.55 Remote Similarity NPC608038
0.5484 Remote Similarity NPC189179
0.5484 Remote Similarity NPC4455
0.5484 Remote Similarity NPC235215
0.5484 Remote Similarity NPC474520
0.5484 Remote Similarity NPC4481
0.5424 Remote Similarity NPC602963
0.541 Remote Similarity NPC50715
0.541 Remote Similarity NPC605047
0.5345 Remote Similarity NPC279121
0.5333 Remote Similarity NPC274327
0.5333 Remote Similarity NPC301323
0.5333 Remote Similarity NPC306821
0.5323 Remote Similarity NPC280339
0.5323 Remote Similarity NPC167815
0.5312 Remote Similarity NPC258331
0.5263 Remote Similarity NPC17286
0.5238 Remote Similarity NPC224137
0.5238 Remote Similarity NPC160951
0.5238 Remote Similarity NPC7846
0.5172 Remote Similarity NPC275772
0.5167 Remote Similarity NPC75279
0.5161 Remote Similarity NPC18772
0.5161 Remote Similarity NPC607913
0.5156 Remote Similarity NPC47781
0.5082 Remote Similarity NPC241498
0.5082 Remote Similarity NPC239128
0.5079 Remote Similarity NPC183597
0.5067 Remote Similarity NPC45638

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC201136 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
0.5345 Remote Similarity NPD1511 Phase 2

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