Natural Product: NPC188243

Natural Product IDNPC188243
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 6,4'-Dimethyl-Naringenin
IUPAC Name 7-hydroxy-5-methoxy-2-(4-methoxyphenyl)-2,3-dihydrochromen-4-one
Synonyms 6,4'-Dimethyl-Naringenin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL233063
PubChem CID 21721822
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0002585] O-methylated flavonoids
          • [CHEMONTID:0002590] 5-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 KFGFEKHSEPSVNO-UHFFFAOYSA-N
Standard InCHI InChI=1S/C17H16O5/c1-20-12-5-3-10(4-6-12)14-9-13(19)17-15(21-2)7-11(18)8-16(17)22-14/h3-8,14,18H,9H2,1-2H3
SMILES COc1ccc(cc1)C1CC(=O)c2c(cc(cc2O1)O)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   300.1 Volume:   302.415
?
Van der Waals volume.
Dense:   0.992 LogP:   2.761
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.928
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.15
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   18.0
TPSA:   64.99
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.943 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.679 Fsp3:   0.235
MCE-18:   54.238
?
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:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.335 Fluc inhibitor:   0.493
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.256
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.349
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.334 Promiscuous compounds:   0.019

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.8 MDCK Permeability:   -4.751
Pgp-inhibitor:   0.95 Pgp-substrate:   0.007
PAMPA:   0.012
?
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):   0.027
20% Bioavailability (F20%):   0.012 30% Bioavailability (F30%):   0.27
50% Bioavailability (F50%):   0.908

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.003 MRP1:   0.52
Plasma Protein Binding (PPB):   96.828% Volume Distribution (VD):   0.116
Fu: 2.823%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.937
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.945
BSEP inhibitor:   0.996

ADMET: Metabolism

CYP1A2-inhibitor:   0.997 CYP1A2-substrate:   0.996
CYP2C19-inhibitor:   0.982 CYP2C19-substrate:   0.998
CYP2C9-inhibitor:   0.953 CYP2C9-substrate:   0.002
CYP2D6-inhibitor:   0.739 CYP2D6-substrate:   0.999
CYP3A4-inhibitor:   0.106 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.126
HLM stability:   0.885
?
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):  7.03 Half-life (T1/2):  0.981

ADMET: Toxicity

hERG Blockers:  0.289 hERG Blockers (10um):  0.593
Human Hepatotoxicity (H-HT):  0.672 Drug-induced Liver Injury (DILI):  0.689
AMES Toxicity:  0.739 Rat Oral Acute Toxicity:  0.464
Maximum Recommended Daily Dose:  0.584 Skin Sensitization:  0.343
Carcinogencity:  0.821 Eye Corrosion:  0.04
Eye Irritation:  0.974 Respiratory Toxicity:  0.673
Drug-induced Neurotoxicity:  0.674 Ototoxicity:  0.308
Hematotoxicity:  0.386 Drug-induced Nephrotoxicity:  0.51
Genotoxicity:  0.61 RPMI-8226 Immunitoxicity:  0.094
A549 Cytotoxicity:  0.175 Hek293 Cytotoxicity:  0.609
BCF:   1.313
?
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:   3.888
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.194
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.511
?
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
NPO10494 Alpinia katsumadai Species Staphylinidae Eukaryota n.a. n.a. n.a. PMID[10654416]
NPO10494 Alpinia katsumadai Species Staphylinidae Eukaryota n.a. seed n.a. PMID[14577694]
NPO5878 Etlingera elatior Species Zingiberaceae Eukaryota n.a. rhizome n.a. PMID[15730265]
NPO16039 Scutellaria barbata Species Lamiaceae Eukaryota n.a. whole plant n.a. PMID[16755060]
NPO16039 Scutellaria barbata Species Lamiaceae Eukaryota n.a. aerial part n.a. PMID[17666848]
NPO16039 Scutellaria barbata Species Lamiaceae Eukaryota n.a. aerial part n.a. PMID[18239311]
NPO16039 Scutellaria barbata Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[19785430]
NPO16039 Scutellaria barbata Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[19962306]
NPO10494 Alpinia katsumadai Species Staphylinidae Eukaryota n.a. n.a. n.a. PMID[20014777]
NPO16039 Scutellaria barbata Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[20078074]
NPO10494 Alpinia katsumadai Species Staphylinidae Eukaryota seeds n.a. n.a. PMID[21942765]
NPO10494 Alpinia katsumadai Species Staphylinidae Eukaryota n.a. seed n.a. PMID[21942765]
NPO10494 Alpinia katsumadai Species Staphylinidae Eukaryota n.a. n.a. n.a. PMID[22459211]
NPO16039 Scutellaria barbata Species Lamiaceae Eukaryota whole plants Nanning District, Guangxi Province, China 2012-Sep PMID[25647077]
NPO16039 Scutellaria barbata Species Lamiaceae Eukaryota aerial parts Seoul, Korea n.a. PMID[26331882]
NPO5878 Etlingera elatior Species Zingiberaceae Eukaryota Flowers Johor, Malaysia PMID[26399961]
NPO5878 Etlingera elatior Species Zingiberaceae Eukaryota Flowers Kelantan, Malaysia PMID[26399961]
NPO5878 Etlingera elatior Species Zingiberaceae Eukaryota Flowers Pahang, Malaysia PMID[26399961]
NPO583 Goniothalamus gardneri Species Annonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16039 Scutellaria barbata Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22420 Lignum dalbergiae odoriferae rosewood n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO10494 Alpinia katsumadai Species Staphylinidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO30081 Alpinia speciosa Species Staphylinidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5878 Etlingera elatior Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO583 Goniothalamus gardneri Species Annonaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO16039 Scutellaria barbata Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO10494 Alpinia katsumadai Species Staphylinidae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO2673 Alpinia chinensis Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO30081 Alpinia speciosa Species Staphylinidae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO30081 Alpinia speciosa Species Staphylinidae Eukaryota n.a. n.a. n.a. PMID[Nippon Kogaku Zasshi, 91, (1970), 762]
NPO2673 Alpinia chinensis Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO583 Goniothalamus gardneri Species Annonaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO22420 Lignum dalbergiae odoriferae rosewood n.a. n.a. n.a. n.a. n.a. n.a. Database[TCMID]
NPO16039 Scutellaria barbata Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO10494 Alpinia katsumadai Species Staphylinidae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO5878 Etlingera elatior Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO10494 Alpinia katsumadai Species Staphylinidae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO2673 Alpinia chinensis Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO16039 Scutellaria barbata Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO30081 Alpinia speciosa Species Staphylinidae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO16039 Scutellaria barbata Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO10494 Alpinia katsumadai Species Staphylinidae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO16039 Scutellaria barbata Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5878 Etlingera elatior Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2673 Alpinia chinensis Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10494 Alpinia katsumadai Species Staphylinidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO583 Goniothalamus gardneri Species Annonaceae 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
NPT171 Cell line MRC5 Homo sapiens CC50 = 12000.0 nM PMID[17239594]
NPT1750 Organism Human herpesvirus 5 Human herpesvirus 5 IC50 = 92000.0 nM PMID[17239594]
NPT2 Others Unspecified n.a. Ratio CC50/IC50 = 0.13 n.a. PMID[17239594]

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 NPC188243 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
1.0 High Similarity NPC110228
0.8372 Intermediate Similarity NPC265871
0.8372 Intermediate Similarity NPC205093
0.8182 Intermediate Similarity NPC225153
0.8182 Intermediate Similarity NPC479876
0.6939 Remote Similarity NPC274784
0.6939 Remote Similarity NPC20709
0.6889 Remote Similarity NPC99854
0.66 Remote Similarity NPC156057
0.6531 Remote Similarity NPC6407
0.6531 Remote Similarity NPC545184
0.6122 Remote Similarity NPC135616
0.6078 Remote Similarity NPC177354
0.5769 Remote Similarity NPC150648
0.5769 Remote Similarity NPC162869
0.5745 Remote Similarity NPC228184
0.5741 Remote Similarity NPC469758
0.5686 Remote Similarity NPC476480
0.5686 Remote Similarity NPC84585
0.566 Remote Similarity NPC296917
0.566 Remote Similarity NPC329203
0.566 Remote Similarity NPC222342
0.566 Remote Similarity NPC170907
0.56 Remote Similarity NPC329225
0.56 Remote Similarity NPC147686
0.5577 Remote Similarity NPC243083
0.5577 Remote Similarity NPC13768
0.5577 Remote Similarity NPC36016
0.5577 Remote Similarity NPC287246
0.5472 Remote Similarity NPC20354
0.5455 Remote Similarity NPC599987
0.537 Remote Similarity NPC99597
0.537 Remote Similarity NPC255106
0.537 Remote Similarity NPC235165
0.5357 Remote Similarity NPC302950
0.5294 Remote Similarity NPC485642
0.5294 Remote Similarity NPC611561
0.5283 Remote Similarity NPC32441
0.5283 Remote Similarity NPC79943
0.5273 Remote Similarity NPC476153
0.5273 Remote Similarity NPC606248
0.5185 Remote Similarity NPC37392
0.5179 Remote Similarity NPC18727
0.5091 Remote Similarity NPC194432
0.5091 Remote Similarity NPC73028
0.5091 Remote Similarity NPC480993
0.5091 Remote Similarity NPC338131
0.5082 Remote Similarity NPC470133
0.5072 Remote Similarity NPC5778

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC188243 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
0.56 Remote Similarity NPD1549 Phase 2
0.5577 Remote Similarity NPD1550 Phase 2
0.5357 Remote Similarity NPD1934 Phase 0
0.5283 Remote Similarity NPD1552 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