Natural Product: NPC265871

Natural Product IDNPC265871
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 7-Hydroxy-5-Methoxyflavanone
IUPAC Name 7-hydroxy-5-methoxy-2-phenyl-2,3-dihydrochromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL427218
PubChem CID 4053302
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 QQQCWVDPMPFUGF-UHFFFAOYSA-N
Standard InCHI InChI=1S/C16H14O4/c1-19-14-7-11(17)8-15-16(14)12(18)9-13(20-15)10-5-3-2-4-6-10/h2-8,13,17H,9H2,1H3
SMILES COc1cc(O)cc2c1C(=O)CC(O2)c1ccccc1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   270.09 Volume:   276.329
?
Van der Waals volume.
Dense:   0.977 LogP:   2.777
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.917
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.118
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   18.0
TPSA:   55.76
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.911 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.654 Fsp3:   0.188
MCE-18:   51.368
?
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:   0.378 Fluc inhibitor:   0.513
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.242
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.374
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.415 Promiscuous compounds:   0.011

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.837 MDCK Permeability:   -4.739
Pgp-inhibitor:   0.974 Pgp-substrate:   0.003
PAMPA:   0.033
?
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):   0.001
20% Bioavailability (F20%):   0.004 30% Bioavailability (F30%):   0.298
50% Bioavailability (F50%):   0.946

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.152 MRP1:   0.835
Plasma Protein Binding (PPB):   98.219% Volume Distribution (VD):   0.095
Fu: 1.26%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.839
OATP1B3 inhibitor:   0.995 BCRP inhibitor:   0.901
BSEP inhibitor:   0.998

ADMET: Metabolism

CYP1A2-inhibitor:   0.682 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.263 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.19 CYP2C9-substrate:   0.027
CYP2D6-inhibitor:   0.012 CYP2D6-substrate:   0.986
CYP3A4-inhibitor:   0.074 CYP3A4-substrate:   0.001
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.35
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):  6.07 Half-life (T1/2):  1.109

ADMET: Toxicity

hERG Blockers:  0.274 hERG Blockers (10um):  0.621
Human Hepatotoxicity (H-HT):  0.772 Drug-induced Liver Injury (DILI):  0.516
AMES Toxicity:  0.66 Rat Oral Acute Toxicity:  0.536
Maximum Recommended Daily Dose:  0.621 Skin Sensitization:  0.539
Carcinogencity:  0.752 Eye Corrosion:  0.052
Eye Irritation:  0.979 Respiratory Toxicity:  0.498
Drug-induced Neurotoxicity:  0.67 Ototoxicity:  0.287
Hematotoxicity:  0.344 Drug-induced Nephrotoxicity:  0.51
Genotoxicity:  0.526 RPMI-8226 Immunitoxicity:  0.061
A549 Cytotoxicity:  0.178 Hek293 Cytotoxicity:  0.565
BCF:   1.327
?
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:   3.954
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.254
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.602
?
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]
NPO10494 Alpinia katsumadai Species Staphylinidae Eukaryota n.a. n.a. n.a. PMID[20014777]
NPO10494 Alpinia katsumadai Species Staphylinidae Eukaryota n.a. seed n.a. PMID[21942765]
NPO10494 Alpinia katsumadai Species Staphylinidae Eukaryota seeds n.a. n.a. PMID[21942765]
NPO10494 Alpinia katsumadai Species Staphylinidae Eukaryota n.a. n.a. n.a. PMID[22459211]
NPO18117 Dalbergia odorifera Species Fabaceae Eukaryota heartwood n.a. n.a. PMID[23743282]
NPO18117 Dalbergia odorifera Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[9525107]
NPO30081 Alpinia speciosa Species Staphylinidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10494 Alpinia katsumadai Species Staphylinidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18117 Dalbergia odorifera Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18117 Dalbergia odorifera Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO2673 Alpinia chinensis Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO10494 Alpinia katsumadai Species Staphylinidae 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]
NPO18117 Dalbergia odorifera Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO10494 Alpinia katsumadai Species Staphylinidae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO10494 Alpinia katsumadai Species Staphylinidae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO18117 Dalbergia odorifera Species Fabaceae 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]
NPO2673 Alpinia chinensis Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO10494 Alpinia katsumadai Species Staphylinidae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO18117 Dalbergia odorifera Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO10494 Alpinia katsumadai Species Staphylinidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2673 Alpinia chinensis Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18117 Dalbergia odorifera Species Fabaceae 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
NPT1443 Individual protein Pyruvate dehydrogenase kinase isoform 1 Homo sapiens Inhibition = -0.92 % PMID[28049590]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT71 Cell line HEK293 Homo sapiens FC = 1.0 n.a. PMID[19307119]

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 NPC265871 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 NPC205093
0.8372 Intermediate Similarity NPC225153
0.8372 Intermediate Similarity NPC188243
0.8372 Intermediate Similarity NPC479876
0.8372 Intermediate Similarity NPC110228
0.7234 Intermediate Similarity NPC177354
0.6977 Remote Similarity NPC228184
0.6809 Remote Similarity NPC476480
0.6809 Remote Similarity NPC84585
0.6667 Remote Similarity NPC243083
0.6667 Remote Similarity NPC13768
0.6667 Remote Similarity NPC287246
0.6531 Remote Similarity NPC150648
0.64 Remote Similarity NPC99597
0.64 Remote Similarity NPC255106
0.64 Remote Similarity NPC235165
0.6275 Remote Similarity NPC476153
0.62 Remote Similarity NPC37392
0.6078 Remote Similarity NPC194432
0.6 Remote Similarity NPC476182
0.6 Remote Similarity NPC204515
0.5926 Remote Similarity NPC35150
0.5926 Remote Similarity NPC106328
0.5882 Remote Similarity NPC312391
0.5862 Remote Similarity NPC316816
0.58 Remote Similarity NPC22467
0.5769 Remote Similarity NPC274784
0.5769 Remote Similarity NPC482119
0.5769 Remote Similarity NPC20709
0.5769 Remote Similarity NPC482120
0.5769 Remote Similarity NPC110038
0.5714 Remote Similarity NPC485642
0.5714 Remote Similarity NPC329225
0.5714 Remote Similarity NPC147686
0.5714 Remote Similarity NPC611561
0.5686 Remote Similarity NPC482487
0.5652 Remote Similarity NPC314329
0.5652 Remote Similarity NPC603208
0.5625 Remote Similarity NPC99854
0.5614 Remote Similarity NPC109183
0.5556 Remote Similarity NPC2416
0.549 Remote Similarity NPC213322
0.5472 Remote Similarity NPC215885
0.5472 Remote Similarity NPC329203
0.5472 Remote Similarity NPC156057
0.5472 Remote Similarity NPC222342
0.5385 Remote Similarity NPC248372
0.5385 Remote Similarity NPC32441
0.5385 Remote Similarity NPC6407
0.5385 Remote Similarity NPC79943
0.5385 Remote Similarity NPC545184
0.537 Remote Similarity NPC606248
0.5273 Remote Similarity NPC599987
0.5254 Remote Similarity NPC175504
0.5185 Remote Similarity NPC338131
0.5185 Remote Similarity NPC110776
0.5179 Remote Similarity NPC302950
0.5167 Remote Similarity NPC470133
0.5094 Remote Similarity NPC264083
0.5094 Remote Similarity NPC482121
0.5094 Remote Similarity NPC270964
0.5091 Remote Similarity NPC210084
0.5091 Remote Similarity NPC475267
0.5088 Remote Similarity NPC259685
0.5085 Remote Similarity NPC1089
0.5085 Remote Similarity NPC87486
0.5085 Remote Similarity NPC39045
0.5085 Remote Similarity NPC124780
0.5082 Remote Similarity NPC76338
0.5082 Remote Similarity NPC250242
0.5077 Remote Similarity NPC169248
0.5077 Remote Similarity NPC72649

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC265871 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
0.6667 Remote Similarity NPD1550 Phase 2
0.5714 Remote Similarity NPD1549 Phase 2
0.5652 Remote Similarity NPD1547 Clinical (unspecified phase)
0.5385 Remote Similarity NPD1552 Clinical (unspecified phase)
0.5179 Remote Similarity NPD1934 Phase 0

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