Natural Product: NPC215885

Natural Product IDNPC215885
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (S)-5-Hydroxy-7-Methoxy-8-Methyl-4-Oxo-2-Phenylchroman-6-Carbaldehyde
IUPAC Name (2S)-5-hydroxy-7-methoxy-8-methyl-4-oxo-2-phenyl-2,3-dihydrochromene-6-carbaldehyde
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1271363
PubChem CID 52945746
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0002585] O-methylated flavonoids
          • [CHEMONTID:0002592] 7-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 HGTSZOYDQGUVER-AWEZNQCLSA-N
Standard InCHI InChI=1S/C18H16O5/c1-10-17(22-2)12(9-19)16(21)15-13(20)8-14(23-18(10)15)11-6-4-3-5-7-11/h3-7,9,14,21H,8H2,1-2H3/t14-/m0/s1
SMILES COc1c(C)c2O[C@@H](CC(=O)c2c(c1C=O)O)c1ccccc1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   312.1 Volume:   317.074
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Van der Waals volume.
Dense:   0.984 LogP:   3.647
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.417
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.017
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The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   19.0
TPSA:   72.83
?
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:   0.881 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.148 Fsp3:   0.222
MCE-18:   57.273
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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:   0 PAINS Alert:   0
Colloidal aggregators:   0.668 Fluc inhibitor:   0.369
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.351
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.537
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.245 Promiscuous compounds:   0.04

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.977 MDCK Permeability:   -4.773
Pgp-inhibitor:   0.996 Pgp-substrate:   0.036
PAMPA:   0.44
?
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%):   0.0 30% Bioavailability (F30%):   0.252
50% Bioavailability (F50%):   0.863

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.225 MRP1:   0.986
Plasma Protein Binding (PPB):   98.574% Volume Distribution (VD):   -0.004
Fu: 1.044%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.961
OATP1B3 inhibitor:   0.997 BCRP inhibitor:   0.936
BSEP inhibitor:   0.986

ADMET: Metabolism

CYP1A2-inhibitor:   0.046 CYP1A2-substrate:   0.927
CYP2C19-inhibitor:   0.002 CYP2C19-substrate:   0.999
CYP2C9-inhibitor:   0.814 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.132
CYP3A4-inhibitor:   0.83 CYP3A4-substrate:   0.8
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.963
HLM stability:   0.323
?
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):  4.395 Half-life (T1/2):  1.008

ADMET: Toxicity

hERG Blockers:  0.067 hERG Blockers (10um):  0.455
Human Hepatotoxicity (H-HT):  0.758 Drug-induced Liver Injury (DILI):  0.251
AMES Toxicity:  0.589 Rat Oral Acute Toxicity:  0.489
Maximum Recommended Daily Dose:  0.571 Skin Sensitization:  0.857
Carcinogencity:  0.496 Eye Corrosion:  0.069
Eye Irritation:  0.993 Respiratory Toxicity:  0.178
Drug-induced Neurotoxicity:  0.891 Ototoxicity:  0.28
Hematotoxicity:  0.227 Drug-induced Nephrotoxicity:  0.737
Genotoxicity:  0.838 RPMI-8226 Immunitoxicity:  0.168
A549 Cytotoxicity:  0.303 Hek293 Cytotoxicity:  0.335
BCF:   1.56
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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:   4.534
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.066
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.543
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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 = 256250.0 nM PMID[20886838]
NPT493 Individual protein Neuraminidase Influenza A virus IC50 = 268590.0 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 NPC215885 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
0.8298 Intermediate Similarity NPC110038
0.76 Intermediate Similarity NPC2416
0.72 Intermediate Similarity NPC194432
0.72 Intermediate Similarity NPC110776
0.7059 Intermediate Similarity NPC476153
0.6923 Remote Similarity NPC271590
0.68 Remote Similarity NPC248372
0.6731 Remote Similarity NPC485881
0.6471 Remote Similarity NPC482121
0.6471 Remote Similarity NPC270964
0.6275 Remote Similarity NPC213322
0.6111 Remote Similarity NPC480992
0.6038 Remote Similarity NPC177354
0.5932 Remote Similarity NPC3642
0.5926 Remote Similarity NPC482119
0.5926 Remote Similarity NPC296917
0.5926 Remote Similarity NPC482120
0.5926 Remote Similarity NPC170907
0.5849 Remote Similarity NPC482487
0.5741 Remote Similarity NPC150648
0.5741 Remote Similarity NPC312391
0.5741 Remote Similarity NPC37392
0.5667 Remote Similarity NPC175504
0.566 Remote Similarity NPC22467
0.5636 Remote Similarity NPC255106
0.5636 Remote Similarity NPC235165
0.55 Remote Similarity NPC109183
0.5472 Remote Similarity NPC265871
0.5472 Remote Similarity NPC205093
0.5455 Remote Similarity NPC167624
0.5455 Remote Similarity NPC166482
0.5439 Remote Similarity NPC471621
0.541 Remote Similarity NPC122894
0.541 Remote Similarity NPC250214
0.5273 Remote Similarity NPC243083
0.5273 Remote Similarity NPC13768
0.5273 Remote Similarity NPC287246
0.5273 Remote Similarity NPC204515
0.5263 Remote Similarity NPC324134
0.5263 Remote Similarity NPC480995
0.5263 Remote Similarity NPC40833
0.5263 Remote Similarity NPC477503
0.5161 Remote Similarity NPC95936
0.5139 Remote Similarity NPC481478
0.5139 Remote Similarity NPC604285
0.5098 Remote Similarity NPC228184
0.5088 Remote Similarity NPC99597
0.5082 Remote Similarity NPC76372
0.5082 Remote Similarity NPC37496
0.5075 Remote Similarity NPC483807

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC215885 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
0.5273 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