Natural Product: NPC104738

Natural Product IDNPC104738
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 TXJOTIFCEKOXSM-WQPYABEOSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 14376452
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000050] Lactones
        • [CHEMONTID:0001244] Delta valerolactones

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 TXJOTIFCEKOXSM-WQPYABEOSA-N
Standard InCHI InChI=1S/C12H20O3/c1-6-7(2)9-8(3)10(13)12(4,5)11(14)15-9/h6,8-10,13H,1-5H3/b7-6+/t8-,9-,10-/m0/s1
SMILES C/C=C(C)/[C@H]1[C@H](C)[C@@H](C(C)(C)C(=O)O1)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   212.14 Volume:   228.65
?
Van der Waals volume.
Dense:   0.928 LogP:   1.992
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.831
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.239
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   8.0
TPSA:   46.53
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   1.0 Rings:   1.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.533 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.312 Fsp3:   0.75
MCE-18:   26.19
?
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:   0.473 Fluc inhibitor:   0.002
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.028
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.0
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.843 Promiscuous compounds:   0.239

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.006 MDCK Permeability:   -4.688
Pgp-inhibitor:   0.799 Pgp-substrate:   0.805
PAMPA:   0.829
?
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):   0.058
20% Bioavailability (F20%):   0.289 30% Bioavailability (F30%):   0.427
50% Bioavailability (F50%):   0.833

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.02 MRP1:   0.959
Plasma Protein Binding (PPB):   89.137% Volume Distribution (VD):   -0.024
Fu: 10.399%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.679
OATP1B3 inhibitor:   0.191 BCRP inhibitor:   0.188
BSEP inhibitor:   0.619

ADMET: Metabolism

CYP1A2-inhibitor:   0.01 CYP1A2-substrate:   0.331
CYP2C19-inhibitor:   0.523 CYP2C19-substrate:   0.058
CYP2C9-inhibitor:   0.001 CYP2C9-substrate:   0.078
CYP2D6-inhibitor:   0.004 CYP2D6-substrate:   0.384
CYP3A4-inhibitor:   0.958 CYP3A4-substrate:   0.003
CYP2B6-substrate:   0.001 CYP2C8-inhibitor:   0.772
HLM stability:   0.861
?
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):  13.362 Half-life (T1/2):  1.409

ADMET: Toxicity

hERG Blockers:  0.008 hERG Blockers (10um):  0.165
Human Hepatotoxicity (H-HT):  0.677 Drug-induced Liver Injury (DILI):  0.6
AMES Toxicity:  0.389 Rat Oral Acute Toxicity:  0.349
Maximum Recommended Daily Dose:  0.274 Skin Sensitization:  0.994
Carcinogencity:  0.731 Eye Corrosion:  0.075
Eye Irritation:  0.571 Respiratory Toxicity:  0.311
Drug-induced Neurotoxicity:  0.331 Ototoxicity:  0.493
Hematotoxicity:  0.667 Drug-induced Nephrotoxicity:  0.817
Genotoxicity:  0.95 RPMI-8226 Immunitoxicity:  0.147
A549 Cytotoxicity:  0.089 Hek293 Cytotoxicity:  0.175
BCF:   0.28
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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:   2.706
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.019
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.338
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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
NPO996 Acacia confusa Species Fabaceae Eukaryota leaves n.a. n.a. PMID[10843598]
NPO996 Acacia confusa Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[20047272]
NPO41087 Daldinia eschscholtzii HJ004 Strain n.a. Eukaryota n.a. n.a. n.a. PMID[31373815]
NPO5664 Davallia mariesii Species Davalliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO41087 Daldinia eschscholtzii HJ004 Strain n.a. Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2851 Acanthella acuta Species Axinellidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO996 Acacia confusa Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1919 Erica arborea Species Ericaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4725 Isodon lihsienensis Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1919 Erica arborea Species Ericaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO5664 Davallia mariesii Species Davalliaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO5664 Davallia mariesii Species Davalliaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO1919 Erica arborea Species Ericaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO4725 Isodon lihsienensis Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO1919 Erica arborea Species Ericaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO5664 Davallia mariesii Species Davalliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO996 Acacia confusa Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6619 Phoebe clemensii Species Lauraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1919 Erica arborea Species Ericaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2851 Acanthella acuta Species Axinellidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO66 Siphula decumbens Species Icmadophilaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4725 Isodon lihsienensis Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]

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
NPT2 Others Unspecified n.a. IC50 = 16000.0 nM PMID[31373815]

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 NPC104738 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
1.0 High Similarity NPC138965
0.7879 Intermediate Similarity NPC483300
0.7027 Intermediate Similarity NPC483301

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC104738 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