Natural Product: NPC140120

Natural Product IDNPC140120
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 5-Hydroxy-8,8-Dimethyl-4-Phenyl-6-Propanoyl-9,10-Dihydropyrano[2,3-H]Chromen-2-One
IUPAC Name 5-hydroxy-8,8-dimethyl-4-phenyl-6-propanoyl-9,10-dihydropyrano[2,3-h]chromen-2-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL469714
PubChem CID 11234299
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0001614] Neoflavonoids
        • [CHEMONTID:0003650] Prenylated neoflavonoids

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 SXMWAVZXRLTFTM-UHFFFAOYSA-N
Standard InCHI InChI=1S/C23H22O5/c1-4-16(24)19-20(26)18-15(13-8-6-5-7-9-13)12-17(25)27-21(18)14-10-11-23(2,3)28-22(14)19/h5-9,12,26H,4,10-11H2,1-3H3
SMILES CCC(=O)c1c(c2c(cc(=O)oc2c2CCC(C)(C)Oc12)c1ccccc1)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   378.15 Volume:   392.361
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Van der Waals volume.
Dense:   0.964 LogP:   3.992
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.513
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.099
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The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   24.0
TPSA:   76.74
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Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   1.0 Rings:   4.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.52 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.822 Fsp3:   0.304
MCE-18:   55.0
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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:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.811 Fluc inhibitor:   0.01
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.869
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.825
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.084 Promiscuous compounds:   0.077

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.858 MDCK Permeability:   -4.683
Pgp-inhibitor:   0.875 Pgp-substrate:   0.002
PAMPA:   0.195
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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%):   0.138 30% Bioavailability (F30%):   0.61
50% Bioavailability (F50%):   0.956

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.855 MRP1:   1.0
Plasma Protein Binding (PPB):   98.542% Volume Distribution (VD):   -0.481
Fu: 0.869%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.97
OATP1B3 inhibitor:   0.287 BCRP inhibitor:   0.179
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.987 CYP1A2-substrate:   0.887
CYP2C19-inhibitor:   0.975 CYP2C19-substrate:   0.991
CYP2C9-inhibitor:   0.999 CYP2C9-substrate:   0.07
CYP2D6-inhibitor:   0.023 CYP2D6-substrate:   0.558
CYP3A4-inhibitor:   0.172 CYP3A4-substrate:   0.994
CYP2B6-substrate:   0.351 CYP2C8-inhibitor:   0.991
HLM stability:   0.986
?
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):  4.015 Half-life (T1/2):  0.578

ADMET: Toxicity

hERG Blockers:  0.158 hERG Blockers (10um):  0.415
Human Hepatotoxicity (H-HT):  0.677 Drug-induced Liver Injury (DILI):  0.734
AMES Toxicity:  0.547 Rat Oral Acute Toxicity:  0.539
Maximum Recommended Daily Dose:  0.845 Skin Sensitization:  0.206
Carcinogencity:  0.815 Eye Corrosion:  0.001
Eye Irritation:  0.423 Respiratory Toxicity:  0.761
Drug-induced Neurotoxicity:  0.341 Ototoxicity:  0.283
Hematotoxicity:  0.395 Drug-induced Nephrotoxicity:  0.413
Genotoxicity:  0.981 RPMI-8226 Immunitoxicity:  0.144
A549 Cytotoxicity:  0.197 Hek293 Cytotoxicity:  0.581
BCF:   1.89
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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:   4.805
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.847
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   6.227
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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
NPO33501 marila pluricostata Species Calophyllaceae Eukaryota leaves n.a. n.a. PMID[15787438]

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
NPT83 Cell line MCF7 Homo sapiens GI50 = 4.7 ug.mL-1 DOI[10.6019/CHEMBL1201861]
NPT397 Cell line NCI-H460 Homo sapiens GI50 = 5.7 ug.mL-1 PMID[18299196]
NPT395 Cell line SF-268 Homo sapiens GI50 = 6.8 ug.mL-1 Open TG-GATES in vivo data: Hematology

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 NPC140120 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
0.6812 Remote Similarity NPC131950
0.6267 Remote Similarity NPC129053
0.6267 Remote Similarity NPC290671
0.6267 Remote Similarity NPC108937
0.6133 Remote Similarity NPC474738
0.6053 Remote Similarity NPC57470
0.6 Remote Similarity NPC78554
0.5974 Remote Similarity NPC161864
0.5946 Remote Similarity NPC94794
0.5769 Remote Similarity NPC249942
0.5714 Remote Similarity NPC297886
0.5526 Remote Similarity NPC36181
0.5455 Remote Similarity NPC1886
0.5325 Remote Similarity NPC470296
0.5325 Remote Similarity NPC196459
0.5256 Remote Similarity NPC196137
0.5195 Remote Similarity NPC262011
0.5185 Remote Similarity NPC19238
0.5128 Remote Similarity NPC188632
0.5128 Remote Similarity NPC112791
0.5065 Remote Similarity NPC87609
0.5062 Remote Similarity NPC483434
0.5062 Remote Similarity NPC474735

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC140120 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
NPD

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