Natural Product: NPC110776

Natural Product IDNPC110776
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (S)-5,7-Dihydroxy-8-Methyl-4-Oxo-2-Phenyl-Chroman-6-Carbaldehyde
IUPAC Name (2S)-5,7-dihydroxy-8-methyl-4-oxo-2-phenyl-2,3-dihydrochromene-6-carbaldehyde
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL53757
PubChem CID 503267
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0000337] Flavans
          • [CHEMONTID:0001632] Flavanones

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 OPZHOLABNKMTHG-ZDUSSCGKSA-N
Standard InCHI InChI=1S/C17H14O5/c1-9-15(20)11(8-18)16(21)14-12(19)7-13(22-17(9)14)10-5-3-2-4-6-10/h2-6,8,13,20-21H,7H2,1H3/t13-/m0/s1
SMILES Cc1c(c(C=O)c(c2C(=O)C[C@@H](c3ccccc3)Oc12)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   298.08 Volume:   299.778
?
Van der Waals volume.
Dense:   0.994 LogP:   3.372
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.141
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.35
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The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   19.0
TPSA:   83.83
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.833 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.147 Fsp3:   0.176
MCE-18:   57.6
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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:   Rejected GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.627 Fluc inhibitor:   0.541
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.305
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.465
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.304 Promiscuous compounds:   0.039

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.016 MDCK Permeability:   -4.759
Pgp-inhibitor:   0.67 Pgp-substrate:   0.004
PAMPA:   0.36
?
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%):   0.0 30% Bioavailability (F30%):   0.01
50% Bioavailability (F50%):   0.112

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.442 MRP1:   0.988
Plasma Protein Binding (PPB):   98.227% Volume Distribution (VD):   -0.302
Fu: 1.055%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.379
OATP1B3 inhibitor:   0.544 BCRP inhibitor:   0.037
BSEP inhibitor:   0.913

ADMET: Metabolism

CYP1A2-inhibitor:   0.043 CYP1A2-substrate:   0.993
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.999
CYP2C9-inhibitor:   0.002 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.012
CYP3A4-inhibitor:   0.292 CYP3A4-substrate:   0.991
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.476
HLM stability:   0.839
?
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):  2.67 Half-life (T1/2):  1.338

ADMET: Toxicity

hERG Blockers:  0.056 hERG Blockers (10um):  0.425
Human Hepatotoxicity (H-HT):  0.748 Drug-induced Liver Injury (DILI):  0.521
AMES Toxicity:  0.495 Rat Oral Acute Toxicity:  0.687
Maximum Recommended Daily Dose:  0.662 Skin Sensitization:  0.95
Carcinogencity:  0.186 Eye Corrosion:  0.36
Eye Irritation:  0.996 Respiratory Toxicity:  0.926
Drug-induced Neurotoxicity:  0.758 Ototoxicity:  0.243
Hematotoxicity:  0.123 Drug-induced Nephrotoxicity:  0.545
Genotoxicity:  0.97 RPMI-8226 Immunitoxicity:  0.12
A549 Cytotoxicity:  0.685 Hek293 Cytotoxicity:  0.383
BCF:   1.436
?
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:   4.447
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.917
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.475
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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
NPO33071 desmos spp. Species Annonaceae Eukaryota n.a. n.a. n.a. PMID[12729671]

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
NPT759 Cell line H9 Homo sapiens IC50 = 104.0 ug.mL-1 PMID[12699389]
NPT759 Cell line H9 Homo sapiens EC50 = 2.3 ug.mL-1 PMID[20346682]

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 NPC110776 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
0.7959 Intermediate Similarity NPC2416
0.7872 Intermediate Similarity NPC248372
0.76 Intermediate Similarity NPC271590
0.7551 Intermediate Similarity NPC110038
0.72 Intermediate Similarity NPC215885
0.6939 Remote Similarity NPC213322
0.6731 Remote Similarity NPC476153
0.6538 Remote Similarity NPC482119
0.6538 Remote Similarity NPC482120
0.6471 Remote Similarity NPC482121
0.6471 Remote Similarity NPC270964
0.6346 Remote Similarity NPC167624
0.6346 Remote Similarity NPC166482
0.6226 Remote Similarity NPC296917
0.6226 Remote Similarity NPC170907
0.6111 Remote Similarity NPC485881
0.5926 Remote Similarity NPC194432
0.5818 Remote Similarity NPC324134
0.5818 Remote Similarity NPC192083
0.5818 Remote Similarity NPC40833
0.5741 Remote Similarity NPC312391
0.5741 Remote Similarity NPC177354
0.5588 Remote Similarity NPC481474
0.5588 Remote Similarity NPC481473
0.5556 Remote Similarity NPC603284
0.5536 Remote Similarity NPC480995
0.5536 Remote Similarity NPC480992
0.5536 Remote Similarity NPC477503
0.541 Remote Similarity NPC122894
0.541 Remote Similarity NPC3642
0.5333 Remote Similarity NPC76372
0.5333 Remote Similarity NPC37496
0.5273 Remote Similarity NPC243083
0.5273 Remote Similarity NPC13768
0.5273 Remote Similarity NPC287246
0.5273 Remote Similarity NPC204515
0.5273 Remote Similarity NPC482487
0.5246 Remote Similarity NPC1089
0.5217 Remote Similarity NPC228779
0.5217 Remote Similarity NPC483811
0.5185 Remote Similarity NPC265871
0.5185 Remote Similarity NPC205093
0.5179 Remote Similarity NPC150648
0.5179 Remote Similarity NPC37392
0.5179 Remote Similarity NPC4743
0.5172 Remote Similarity NPC471621
0.5167 Remote Similarity NPC270789
0.5161 Remote Similarity NPC95936
0.5161 Remote Similarity NPC250214
0.5091 Remote Similarity NPC22467
0.5088 Remote Similarity NPC255106
0.5088 Remote Similarity NPC235165
0.5068 Remote Similarity NPC481472
0.5068 Remote Similarity NPC481471

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC110776 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
0.5818 Remote Similarity NPD2393 Clinical (unspecified phase)
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