Natural Product: NPC487561

Natural Product IDNPC487561
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 SPOAYCLWQFBLTG-PKNBQFBNSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]

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 SPOAYCLWQFBLTG-PKNBQFBNSA-N
Standard InCHI InChI=1S/C15H26O2/c1-3-4-5-6-7-8-9-11-14(2)12-10-13-15(16)17/h9,11H,2-8,10,12-13H2,1H3,(H,16,17)/b11-9+
SMILES CCCCCCC/C=C/C(=C)CCCC(=O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   238.19 Volume:   277.667
?
Van der Waals volume.
Dense:   0.858 LogP:   4.696
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.207
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.106
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The logarithm of aqueous solubility value.
Rotatable Bonds:   11.0 Rigid Bonds:   3.0
TPSA:   37.3
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   1.0 Rings:   0.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.418 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.447 Fsp3:   0.667
MCE-18:   0.0
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.012 Fluc inhibitor:   0.012
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.004
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.026
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.998 Promiscuous compounds:   0.31

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.145 MDCK Permeability:   -4.978
Pgp-inhibitor:   0.0 Pgp-substrate:   0.002
PAMPA:   0.445
?
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):   0.077
20% Bioavailability (F20%):   0.097 30% Bioavailability (F30%):   0.693
50% Bioavailability (F50%):   0.182

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.014 MRP1:   0.818
Plasma Protein Binding (PPB):   98.069% Volume Distribution (VD):   -0.655
Fu: 1.011%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.281
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.014
BSEP inhibitor:   0.905

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.562
CYP2C19-inhibitor:   0.004 CYP2C19-substrate:   0.01
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   0.428
CYP2D6-inhibitor:   0.836 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.606 CYP2C8-inhibitor:   1.0
HLM stability:   0.005
?
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):  5.729 Half-life (T1/2):  0.525

ADMET: Toxicity

hERG Blockers:  0.113 hERG Blockers (10um):  0.238
Human Hepatotoxicity (H-HT):  0.403 Drug-induced Liver Injury (DILI):  0.035
AMES Toxicity:  0.189 Rat Oral Acute Toxicity:  0.073
Maximum Recommended Daily Dose:  0.096 Skin Sensitization:  0.969
Carcinogencity:  0.137 Eye Corrosion:  0.987
Eye Irritation:  0.998 Respiratory Toxicity:  0.771
Drug-induced Neurotoxicity:  0.048 Ototoxicity:  0.252
Hematotoxicity:  0.134 Drug-induced Nephrotoxicity:  0.322
Genotoxicity:  0.0 RPMI-8226 Immunitoxicity:  0.04
A549 Cytotoxicity:  0.083 Hek293 Cytotoxicity:  0.041
BCF:   1.214
?
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:   3.935
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.219
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.318
?
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
NPO40121 Eremophila oppositifolia subsp. Angustifolia Strain Scrophulariaceae Eukaryota n.a. n.a. n.a. PMID[32255628]
NPO40121 Eremophila oppositifolia subsp. Angustifolia Strain Scrophulariaceae Eukaryota 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
NPT178 Individual protein Protein-tyrosine phosphatase 1B Homo sapiens IC50 = 144000.0 nM PMID[32255628]

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 NPC487561 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
0.6389 Remote Similarity NPC424
0.6389 Remote Similarity NPC36061
0.6389 Remote Similarity NPC69510
0.6389 Remote Similarity NPC77272
0.6389 Remote Similarity NPC290563
0.6389 Remote Similarity NPC139029
0.6389 Remote Similarity NPC281972
0.6389 Remote Similarity NPC92114
0.6389 Remote Similarity NPC261831
0.6389 Remote Similarity NPC87564
0.6216 Remote Similarity NPC95145
0.6216 Remote Similarity NPC325642
0.6216 Remote Similarity NPC65174
0.6111 Remote Similarity NPC281245
0.5897 Remote Similarity NPC154245
0.5897 Remote Similarity NPC85813
0.5897 Remote Similarity NPC223697
0.5897 Remote Similarity NPC59051
0.5897 Remote Similarity NPC6095
0.5641 Remote Similarity NPC321062
0.5641 Remote Similarity NPC91495
0.5641 Remote Similarity NPC5413
0.5143 Remote Similarity NPC171736
0.5143 Remote Similarity NPC301585
0.5143 Remote Similarity NPC261080
0.5143 Remote Similarity NPC132565
0.5143 Remote Similarity NPC209970
0.5143 Remote Similarity NPC216630
0.5143 Remote Similarity NPC201844
0.5143 Remote Similarity NPC301696
0.5143 Remote Similarity NPC196924
0.5143 Remote Similarity NPC307783
0.5143 Remote Similarity NPC154186
0.5143 Remote Similarity NPC149184
0.5143 Remote Similarity NPC279026
0.5143 Remote Similarity NPC113928
0.5143 Remote Similarity NPC14227
0.5135 Remote Similarity NPC180534
0.5135 Remote Similarity NPC611531
0.5122 Remote Similarity NPC52955
0.5122 Remote Similarity NPC88966
0.5122 Remote Similarity NPC25417
0.5122 Remote Similarity NPC1813
0.5116 Remote Similarity NPC487562
0.5111 Remote Similarity NPC106851
0.5111 Remote Similarity NPC282788
0.5111 Remote Similarity NPC274927
0.5111 Remote Similarity NPC477201

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC487561 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
0.6389 Remote Similarity NPD3195 Phase 2
0.6389 Remote Similarity NPD3196 Approved
0.5897 Remote Similarity NPD4266 Phase 2
0.5641 Remote Similarity NPD3173 Phase 4
0.5349 Remote Similarity NPD3194 Phase 4
0.5143 Remote Similarity NPD2270 Pre-clinical
0.5143 Remote Similarity NPD633 Phase 3
0.5143 Remote Similarity NPD9448 Phase 2
0.5135 Remote Similarity NPD622 Pre-clinical
0.5122 Remote Similarity NPD3172 Approved

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