Natural Product: NPC99597

Natural Product IDNPC99597
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (2S)-7-Hydroxy-6-Methoxyflavanone
IUPAC Name (2S)-7-hydroxy-6-methoxy-2-phenyl-2,3-dihydrochromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL402528
PubChem CID 25022738
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0002585] O-methylated flavonoids
          • [CHEMONTID:0002591] 6-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 WCXMGPNELNHROM-AWEZNQCLSA-N
Standard InCHI InChI=1S/C16H14O4/c1-19-16-7-11-12(17)8-14(10-5-3-2-4-6-10)20-15(11)9-13(16)18/h2-7,9,14,18H,8H2,1H3/t14-/m0/s1
SMILES COc1cc2C(=O)C[C@H](Oc2cc1O)c1ccccc1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   270.09 Volume:   276.329
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Van der Waals volume.
Dense:   0.977 LogP:   3.009
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.002
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.202
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The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   18.0
TPSA:   55.76
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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:   2.59 Fsp3:   0.188
MCE-18:   51.368
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MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   1
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.487 Fluc inhibitor:   0.711
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.595
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.365
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.407 Promiscuous compounds:   0.078

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.84 MDCK Permeability:   -4.747
Pgp-inhibitor:   0.832 Pgp-substrate:   0.015
PAMPA:   0.046
?
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):   0.0
20% Bioavailability (F20%):   0.003 30% Bioavailability (F30%):   0.028
50% Bioavailability (F50%):   0.403

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.077 MRP1:   0.867
Plasma Protein Binding (PPB):   98.367% Volume Distribution (VD):   -0.215
Fu: 1.266%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.494
OATP1B3 inhibitor:   0.936 BCRP inhibitor:   0.509
BSEP inhibitor:   0.956

ADMET: Metabolism

CYP1A2-inhibitor:   0.004 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.981
CYP2C9-inhibitor:   0.002 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.035
CYP3A4-inhibitor:   0.017 CYP3A4-substrate:   0.989
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.996
HLM stability:   0.938
?
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):  4.478 Half-life (T1/2):  1.966

ADMET: Toxicity

hERG Blockers:  0.241 hERG Blockers (10um):  0.541
Human Hepatotoxicity (H-HT):  0.852 Drug-induced Liver Injury (DILI):  0.692
AMES Toxicity:  0.623 Rat Oral Acute Toxicity:  0.711
Maximum Recommended Daily Dose:  0.719 Skin Sensitization:  0.818
Carcinogencity:  0.307 Eye Corrosion:  0.093
Eye Irritation:  0.982 Respiratory Toxicity:  0.854
Drug-induced Neurotoxicity:  0.943 Ototoxicity:  0.378
Hematotoxicity:  0.319 Drug-induced Nephrotoxicity:  0.821
Genotoxicity:  0.873 RPMI-8226 Immunitoxicity:  0.117
A549 Cytotoxicity:  0.544 Hek293 Cytotoxicity:  0.401
BCF:   1.098
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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:   3.77
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.943
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.388
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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
NPO33288 Brazilian Red Propolis Strain n.a. n.a. n.a. Brazilian n.a. PMID[17950610]
NPO33288 Brazilian Red Propolis Strain n.a. n.a. n.a. Brazilian n.a. PMID[18440233]
NPO33288 Brazilian Red Propolis Strain n.a. n.a. n.a. n.a. n.a. PMID[26938776]
NPO33288 Brazilian Red Propolis Strain n.a. n.a. n.a. n.a. n.a. PMID[32525315]
NPO33288 Brazilian Red Propolis Strain n.a. n.a. n.a. n.a. n.a. Database[COCONUT]

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
NPT461 Cell line PANC-1 Homo sapiens CD100 = 50.0 uM DOI[10.1016/j.bmcl.2004.08.026]
NPT81 Cell line A549 Homo sapiens IC50 = 8600.0 nM PMID[23570790]
NPT165 Cell line HeLa Homo sapiens IC50 = 5600.0 nM DrugMatrix in vitro pharmacology data
NPT453 Cell line HT-1080 Homo sapiens IC50 = 7900.0 nM PMID[19105653]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 5900.0 nM PMID[18440233]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 6700.0 nM PMID[18440233]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 9300.0 nM PMID[18440233]

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 NPC99597 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
0.7755 Intermediate Similarity NPC486095
0.66 Remote Similarity NPC476480
0.66 Remote Similarity NPC84585
0.6538 Remote Similarity NPC255106
0.6538 Remote Similarity NPC235165
0.64 Remote Similarity NPC265871
0.64 Remote Similarity NPC205093
0.6111 Remote Similarity NPC308992
0.6038 Remote Similarity NPC150648
0.5882 Remote Similarity NPC485642
0.5882 Remote Similarity NPC611561
0.5833 Remote Similarity NPC314329
0.5833 Remote Similarity NPC603208
0.5741 Remote Similarity NPC37392
0.5741 Remote Similarity NPC177354
0.5714 Remote Similarity NPC228184
0.5636 Remote Similarity NPC194432
0.5577 Remote Similarity NPC329225
0.5577 Remote Similarity NPC147686
0.5556 Remote Similarity NPC243083
0.5556 Remote Similarity NPC13768
0.5556 Remote Similarity NPC287246
0.5556 Remote Similarity NPC204515
0.5536 Remote Similarity NPC210084
0.5517 Remote Similarity NPC474836
0.5455 Remote Similarity NPC312391
0.5439 Remote Similarity NPC599987
0.537 Remote Similarity NPC225153
0.537 Remote Similarity NPC188243
0.537 Remote Similarity NPC479876
0.537 Remote Similarity NPC110228
0.5357 Remote Similarity NPC482119
0.5357 Remote Similarity NPC482120
0.5273 Remote Similarity NPC482487
0.5263 Remote Similarity NPC606248
0.5167 Remote Similarity NPC236637
0.5088 Remote Similarity NPC215885
0.5088 Remote Similarity NPC110038

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC99597 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
0.5833 Remote Similarity NPD1547 Clinical (unspecified phase)
0.5577 Remote Similarity NPD1549 Phase 2
0.5556 Remote Similarity NPD1550 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