Natural Product: NPC177354

Natural Product IDNPC177354
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (S)-7-Hydroxy-5-Methoxy-8-Methyl-2-Phenylchroman-4-One
IUPAC Name (2S)-7-hydroxy-5-methoxy-8-methyl-2-phenyl-2,3-dihydrochromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1269826
PubChem CID 52943439
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 VQRIOVIKJMGUNI-AWEZNQCLSA-N
Standard InCHI InChI=1S/C17H16O4/c1-10-12(18)8-15(20-2)16-13(19)9-14(21-17(10)16)11-6-4-3-5-7-11/h3-8,14,18H,9H2,1-2H3/t14-/m0/s1
SMILES Cc1c(cc(c2C(=O)C[C@@H](c3ccccc3)Oc12)OC)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   284.1 Volume:   293.625
?
Van der Waals volume.
Dense:   0.968 LogP:   3.472
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.225
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.064
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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:   0.918 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.804 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:   Accepted GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.482 Fluc inhibitor:   0.691
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.4
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.337
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.276 Promiscuous compounds:   0.03

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.866 MDCK Permeability:   -4.759
Pgp-inhibitor:   0.991 Pgp-substrate:   0.02
PAMPA:   0.243
?
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%):   0.001 30% Bioavailability (F30%):   0.439
50% Bioavailability (F50%):   0.958

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.056 MRP1:   0.969
Plasma Protein Binding (PPB):   98.247% Volume Distribution (VD):   0.053
Fu: 1.423%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.998
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.938
BSEP inhibitor:   0.989

ADMET: Metabolism

CYP1A2-inhibitor:   0.893 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.936 CYP2C19-substrate:   0.999
CYP2C9-inhibitor:   0.197 CYP2C9-substrate:   0.047
CYP2D6-inhibitor:   0.004 CYP2D6-substrate:   0.993
CYP3A4-inhibitor:   0.499 CYP3A4-substrate:   0.969
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.625
HLM stability:   0.977
?
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):  5.091 Half-life (T1/2):  1.059

ADMET: Toxicity

hERG Blockers:  0.117 hERG Blockers (10um):  0.496
Human Hepatotoxicity (H-HT):  0.835 Drug-induced Liver Injury (DILI):  0.251
AMES Toxicity:  0.676 Rat Oral Acute Toxicity:  0.513
Maximum Recommended Daily Dose:  0.488 Skin Sensitization:  0.824
Carcinogencity:  0.569 Eye Corrosion:  0.083
Eye Irritation:  0.993 Respiratory Toxicity:  0.176
Drug-induced Neurotoxicity:  0.914 Ototoxicity:  0.331
Hematotoxicity:  0.363 Drug-induced Nephrotoxicity:  0.649
Genotoxicity:  0.7 RPMI-8226 Immunitoxicity:  0.116
A549 Cytotoxicity:  0.164 Hek293 Cytotoxicity:  0.319
BCF:   1.481
?
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:   4.076
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.681
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.841
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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
NPO30425 Cleistocalyx operculatus n.a. n.a. n.a. n.a. flower bud n.a. DOI[10.1021/np1002753]
NPO30425 Cleistocalyx operculatus n.a. n.a. n.a. n.a. n.a. n.a. PMID[20886838]
NPO30425 Cleistocalyx operculatus n.a. 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
NPT493 Individual protein Neuraminidase Influenza A virus IC50 > 500000.0 nM PMID[20886838]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference

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 NPC177354 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
0.7347 Intermediate Similarity NPC194432
0.7234 Intermediate Similarity NPC265871
0.7234 Intermediate Similarity NPC205093
0.6964 Remote Similarity NPC316816
0.6863 Remote Similarity NPC476153
0.6429 Remote Similarity NPC109183
0.64 Remote Similarity NPC22467
0.64 Remote Similarity NPC213322
0.6346 Remote Similarity NPC110038
0.617 Remote Similarity NPC228184
0.6154 Remote Similarity NPC150648
0.6154 Remote Similarity NPC312391
0.6154 Remote Similarity NPC37392
0.6111 Remote Similarity NPC2416
0.6078 Remote Similarity NPC225153
0.6078 Remote Similarity NPC188243
0.6078 Remote Similarity NPC479876
0.6078 Remote Similarity NPC110228
0.6038 Remote Similarity NPC215885
0.6034 Remote Similarity NPC175504
0.5962 Remote Similarity NPC248372
0.5833 Remote Similarity NPC76338
0.5833 Remote Similarity NPC250242
0.5741 Remote Similarity NPC99597
0.5741 Remote Similarity NPC255106
0.5741 Remote Similarity NPC482119
0.5741 Remote Similarity NPC235165
0.5741 Remote Similarity NPC482120
0.5741 Remote Similarity NPC110776
0.5667 Remote Similarity NPC470133
0.566 Remote Similarity NPC243083
0.566 Remote Similarity NPC13768
0.566 Remote Similarity NPC482121
0.566 Remote Similarity NPC287246
0.566 Remote Similarity NPC270964
0.5614 Remote Similarity NPC259685
0.5593 Remote Similarity NPC87486
0.5593 Remote Similarity NPC124780
0.5536 Remote Similarity NPC271590
0.55 Remote Similarity NPC3642
0.5472 Remote Similarity NPC476480
0.5472 Remote Similarity NPC84585
0.541 Remote Similarity NPC176229
0.537 Remote Similarity NPC204515
0.537 Remote Similarity NPC482487
0.5333 Remote Similarity NPC608647
0.5224 Remote Similarity NPC485619
0.5179 Remote Similarity NPC296917
0.5179 Remote Similarity NPC170907
0.5094 Remote Similarity NPC485642
0.5094 Remote Similarity NPC611561
0.5091 Remote Similarity NPC6407
0.5091 Remote Similarity NPC545184
0.5091 Remote Similarity NPC603284
0.5088 Remote Similarity NPC485881
0.5082 Remote Similarity NPC1089
0.5082 Remote Similarity NPC39045

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC177354 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
0.566 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