Natural Product: NPC282955

Natural Product IDNPC282955
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 CPHXGYQLOSNELY-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 12315460
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0001645] Depsides and depsidones

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 CPHXGYQLOSNELY-UHFFFAOYSA-N
Standard InCHI InChI=1S/C22H26O8/c1-5-7-12-9-14(28-3)11-15(23)17(12)22(27)30-20-16(29-4)10-13(8-6-2)18(19(20)24)21(25)26/h9-11,23-24H,5-8H2,1-4H3,(H,25,26)
SMILES CCCc1cc(cc(c1C(=O)Oc1c(cc(CCC)c(c1O)C(=O)O)OC)O)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   418.16 Volume:   421.185
?
Van der Waals volume.
Dense:   0.993 LogP:   4.329
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.743
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.9
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   10.0 Rigid Bonds:   14.0
TPSA:   122.52
?
Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   3.0 Rings:   2.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.413 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.656 Fsp3:   0.364
MCE-18:   17.0
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.073 Fluc inhibitor:   0.283
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.542
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.721
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.33 Promiscuous compounds:   0.465

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.803 MDCK Permeability:   -4.699
Pgp-inhibitor:   0.963 Pgp-substrate:   0.734
PAMPA:   0.215
?
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):   0.192
20% Bioavailability (F20%):   0.185 30% Bioavailability (F30%):   0.343
50% Bioavailability (F50%):   0.857

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.007 MRP1:   0.914
Plasma Protein Binding (PPB):   97.999% Volume Distribution (VD):   -0.328
Fu: 1.563%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.588
OATP1B3 inhibitor:   0.393 BCRP inhibitor:   0.87
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.001 CYP1A2-substrate:   0.602
CYP2C19-inhibitor:   0.003 CYP2C19-substrate:   0.557
CYP2C9-inhibitor:   0.998 CYP2C9-substrate:   0.02
CYP2D6-inhibitor:   0.012 CYP2D6-substrate:   0.171
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.954
HLM stability:   0.876
?
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):  1.922 Half-life (T1/2):  1.209

ADMET: Toxicity

hERG Blockers:  0.08 hERG Blockers (10um):  0.332
Human Hepatotoxicity (H-HT):  0.406 Drug-induced Liver Injury (DILI):  0.888
AMES Toxicity:  0.076 Rat Oral Acute Toxicity:  0.19
Maximum Recommended Daily Dose:  0.138 Skin Sensitization:  0.767
Carcinogencity:  0.154 Eye Corrosion:  0.257
Eye Irritation:  0.895 Respiratory Toxicity:  0.832
Drug-induced Neurotoxicity:  0.165 Ototoxicity:  0.579
Hematotoxicity:  0.523 Drug-induced Nephrotoxicity:  0.735
Genotoxicity:  0.019 RPMI-8226 Immunitoxicity:  0.069
A549 Cytotoxicity:  0.125 Hek293 Cytotoxicity:  0.084
BCF:   0.889
?
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:   3.761
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.032
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.453
?
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
NPO15002 Amphidinium carterae Species n.a. Eukaryota n.a. n.a. n.a. PMID[20108948]
NPO15002 Amphidinium carterae Species n.a. Eukaryota n.a. n.a. n.a. PMID[24926538]
NPO15002 Amphidinium carterae Species n.a. Eukaryota n.a. n.a. n.a. PMID[29120640]
NPO11114 Phycomyces blakesleeanus Species Phycomycetaceae Eukaryota n.a. n.a. n.a. PMID[9868149]
NPO581 Conyza bonariensis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11114 Phycomyces blakesleeanus Species Phycomycetaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21174 Vigna unguiculata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15002 Amphidinium carterae Species n.a. Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21174 Vigna unguiculata Species Fabaceae Eukaryota n.a. n.a. Database[FooDB]
NPO21174 Vigna unguiculata Species Fabaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO21174 Vigna unguiculata Species Fabaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO3765 Phasianus colchicus Species Phasianidae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO21174 Vigna unguiculata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO8717 Bulbophyllum odoratissimum Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO8717 Bulbophyllum odoratissimum Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21174 Vigna unguiculata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO581 Conyza bonariensis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO3765 Phasianus colchicus Species Phasianidae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO3765 Phasianus colchicus Species Phasianidae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO15002 Amphidinium carterae Species n.a. Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO581 Conyza bonariensis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8717 Bulbophyllum odoratissimum Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11888 Eriostemon buxifolius Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11114 Phycomyces blakesleeanus Species Phycomycetaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3765 Phasianus colchicus Species Phasianidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21174 Vigna unguiculata Species Fabaceae 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

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 NPC282955 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
0.8814 High Similarity NPC606614
0.75 Intermediate Similarity NPC66404
0.6269 Remote Similarity NPC237208
0.5676 Remote Similarity NPC307780
0.5588 Remote Similarity NPC602325
0.5541 Remote Similarity NPC309979
0.5147 Remote Similarity NPC54928
0.5068 Remote Similarity NPC134621

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC282955 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