Natural Product: NPC600941

Natural Product IDNPC600941
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 RCSBILYQLVXLJG-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2229585
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 RCSBILYQLVXLJG-UHFFFAOYSA-N
Standard InCHI InChI=1S/C9H16O2/c1-3-5-6-7-9(10)11-8-4-2/h4H,2-3,5-8H2,1H3
SMILES C=CCOC(=O)CCCCC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   156.12 Volume:   176.528
?
Van der Waals volume.
Dense:   0.884 LogP:   2.987
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.622
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.478
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   2.0
TPSA:   26.3
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   0.0 Rings:   0.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.335 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   1.951 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:   Rejected GSK Rule:   Rejected
Golden Triangle Rule:   Accepted BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.008 Fluc inhibitor:   0.001
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.003
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.002
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   1.0 Promiscuous compounds:   0.049

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.625 MDCK Permeability:   -4.587
Pgp-inhibitor:   0.441 Pgp-substrate:   0.24
PAMPA:   0.075
?
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):   0.018
20% Bioavailability (F20%):   0.442 30% Bioavailability (F30%):   0.579
50% Bioavailability (F50%):   0.575

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.894 MRP1:   0.489
Plasma Protein Binding (PPB):   92.272% Volume Distribution (VD):   -0.556
Fu: 8.55%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.51
OATP1B3 inhibitor:   0.548 BCRP inhibitor:   0.7
BSEP inhibitor:   0.479

ADMET: Metabolism

CYP1A2-inhibitor:   0.016 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.029 CYP2C19-substrate:   0.993
CYP2C9-inhibitor:   0.027 CYP2C9-substrate:   1.0
CYP2D6-inhibitor:   0.38 CYP2D6-substrate:   0.987
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.671
?
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):  7.318 Half-life (T1/2):  0.394

ADMET: Toxicity

hERG Blockers:  0.095 hERG Blockers (10um):  0.597
Human Hepatotoxicity (H-HT):  0.255 Drug-induced Liver Injury (DILI):  0.316
AMES Toxicity:  0.317 Rat Oral Acute Toxicity:  0.451
Maximum Recommended Daily Dose:  0.28 Skin Sensitization:  0.929
Carcinogencity:  0.644 Eye Corrosion:  0.998
Eye Irritation:  0.997 Respiratory Toxicity:  0.768
Drug-induced Neurotoxicity:  0.447 Ototoxicity:  0.154
Hematotoxicity:  0.177 Drug-induced Nephrotoxicity:  0.252
Genotoxicity:  0.008 RPMI-8226 Immunitoxicity:  0.032
A549 Cytotoxicity:  0.042 Hek293 Cytotoxicity:  0.069
BCF:   0.756
?
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:   3.184
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.699
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.456
?
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
NPO10107 Melaleuca alternifolia Species Myrtaceae Eukaryota n.a. leaf n.a. PMID[16418522]
NPO10107 Melaleuca alternifolia Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10107 Melaleuca alternifolia Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO10107 Melaleuca alternifolia Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO10107 Melaleuca alternifolia Species Myrtaceae 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
NPT1637 Organism Cydia pomonella Cydia pomonella Activity n.a. n.a. n.a. PMID[19489625]
NPT4939 Organism Acyrthosiphon pisum Acyrthosiphon pisum Activity n.a. n.a. n.a. DOI[10.1016/j.indcrop.2013.02.019]
NPT1419 Organism Tribolium castaneum Tribolium castaneum Activity n.a. n.a. n.a. DOI[10.1016/j.indcrop.2013.02.019]

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT1637 Organism Cydia pomonella Cydia pomonella mortality = 83.8 % PMID[19489625]
NPT1637 Organism Cydia pomonella Cydia pomonella mortality = 8.4 % PMID[19489625]
NPT1637 Organism Cydia pomonella Cydia pomonella mortality = 13.3 % PMID[19489625]
NPT1637 Organism Cydia pomonella Cydia pomonella mortality = 22.4 % PMID[19489625]
NPT1637 Organism Cydia pomonella Cydia pomonella mortality = 67.8 % PMID[19489625]
NPT1637 Organism Cydia pomonella Cydia pomonella mortality = 98.7 % PMID[19489625]
NPT1637 Organism Cydia pomonella Cydia pomonella mortality = 95.8 % PMID[19489625]
NPT1637 Organism Cydia pomonella Cydia pomonella mortality = 18.9 % PMID[19489625]
NPT1637 Organism Cydia pomonella Cydia pomonella mortality = 51.2 % PMID[19489625]
NPT1637 Organism Cydia pomonella Cydia pomonella mortality = 100.0 % PMID[19489625]
NPT4939 Organism Acyrthosiphon pisum Acyrthosiphon pisum mortality n.a. n.a. n.a. DOI[10.1016/j.indcrop.2013.02.019]
NPT1419 Organism Tribolium castaneum Tribolium castaneum mortality = 45.0 % DOI[10.1016/j.indcrop.2013.02.019]





 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
- Tribolium castaneum LC50 = 0.2 mg DOI[10.1016/j.indcrop.2013.02.019]
- Tribolium castaneum LC90 = 0.3 mg DOI[10.1016/j.indcrop.2013.02.019]
- Cydia pomonella LC50 = 880.0 ug.mL-1 PMID[19489625]
- Cydia pomonella LC90 = 2.13 mg/ml PMID[19489625]
- Rattus norvegicus LOAEL = 65.0 mg/kg-day ToxVal
- Rattus norvegicus LOEL = 12.0 mg/kg-day ToxVal
- Rattus norvegicus NOEL = 78.0 mg/kg-day ToxVal
- Rattus norvegicus LOAEL = 35.0 mg/kg-day ToxVal
- Rattus norvegicus NOAEL > 195.0 mg/kg-day ToxVal
- Rattus norvegicus NOAEL > 214.0 mg/kg-day ToxVal
- Rattus norvegicus NOEL = 15.0 mg/kg-day ToxVal
- Rattus norvegicus LD50 = 393.0 mg/kg ToxVal
- Rattus norvegicus LD50 = 327.0 mg/kg ToxVal
- Rattus norvegicus LD50 = 276.0 mg/kg ToxVal
- Rattus norvegicus LD50 = 218.0 mg/kg ToxVal
- Rattus norvegicus LEL = 75.0 mg/kg-day ToxVal
- Oryctolagus cuniculus LD50 = 820.0 mg/kg ToxVal
- Oryctolagus cuniculus LD100 = 5000.0 mg/kg ToxVal
- Oryctolagus cuniculus LD50 = 0.3 mL/kg bw ToxVal
- Oryctolagus cuniculus LD50 = 300.0 mg/kg ToxVal
- Homo sapiens ADI <= 0.13 mg/kg ToxVal
- Homo sapiens DNEL systemic = 15.0 mg/m3 ToxVal
- Bos taurus LEL = 50.0 mg/kg-day ToxVal
- Cavia porcellus LD50 = 280.0 mg/kg ToxVal
- Gallus gallus domesticus LEL = 50.0 mg/kg-day ToxVal
- Sus scrofa domesticus LEL = 50.0 mg/kg-day ToxVal

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 NPC600941 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
0.9583 High Similarity NPC310746
0.6538 Remote Similarity NPC250028
0.6538 Remote Similarity NPC236579
0.6538 Remote Similarity NPC80234
0.6538 Remote Similarity NPC203531
0.6538 Remote Similarity NPC256163
0.6538 Remote Similarity NPC40597
0.5862 Remote Similarity NPC80396
0.5862 Remote Similarity NPC154642
0.5862 Remote Similarity NPC603612
0.5806 Remote Similarity NPC128061
0.5769 Remote Similarity NPC53541
0.5667 Remote Similarity NPC149299
0.5625 Remote Similarity NPC163345
0.5556 Remote Similarity NPC2088
0.5484 Remote Similarity NPC26253
0.5357 Remote Similarity NPC81263
0.5312 Remote Similarity NPC488257
0.5312 Remote Similarity NPC469937
0.5312 Remote Similarity NPC94699
0.5312 Remote Similarity NPC320588
0.5312 Remote Similarity NPC53463
0.5294 Remote Similarity NPC223677
0.5294 Remote Similarity NPC28779
0.5185 Remote Similarity NPC201622
0.5185 Remote Similarity NPC305660
0.5185 Remote Similarity NPC12156
0.5185 Remote Similarity NPC161097
0.5185 Remote Similarity NPC28598
0.5185 Remote Similarity NPC22903
0.5185 Remote Similarity NPC54980
0.5172 Remote Similarity NPC476550
0.5152 Remote Similarity NPC55678

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC600941 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
0.5152 Remote Similarity NPD6125 Phase 4

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