Natural Product: NPC606120

Natural Product IDNPC606120
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 UTLBSLGWELAEAY-MAVJXHJTSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1256584
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 UTLBSLGWELAEAY-MAVJXHJTSA-N
Standard InCHI InChI=1S/C18H34O3/c1-2-17(19)15-13-11-9-7-5-3-4-6-8-10-12-14-16-18(20)21/h3,5,17,19H,2,4,6-16H2,1H3,(H,20,21)/b5-3-/t17-/m1/s1
SMILES CC[C@@H](O)CCCCC/C=CCCCCCCCC(=O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   298.25 Volume:   340.982
?
Van der Waals volume.
Dense:   0.875 LogP:   4.995
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.181
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.913
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   15.0 Rigid Bonds:   2.0
TPSA:   57.53
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   2.0 Rings:   0.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.327 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.709 Fsp3:   0.833
MCE-18:   2.0
?
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:   0.025 Fluc inhibitor:   0.109
?
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:   0.0
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.986 Promiscuous compounds:   0.789

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.128 MDCK Permeability:   -4.848
Pgp-inhibitor:   0.003 Pgp-substrate:   0.001
PAMPA:   0.162
?
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):   0.019
20% Bioavailability (F20%):   0.132 30% Bioavailability (F30%):   0.542
50% Bioavailability (F50%):   0.714

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.023 MRP1:   0.971
Plasma Protein Binding (PPB):   97.04% Volume Distribution (VD):   -0.791
Fu: 1.663%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.023
OATP1B3 inhibitor:   0.745 BCRP inhibitor:   0.689
BSEP inhibitor:   0.992

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.065
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.35
CYP2C9-inhibitor:   0.997 CYP2C9-substrate:   0.132
CYP2D6-inhibitor:   0.293 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.933
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.002
?
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):  4.336 Half-life (T1/2):  0.772

ADMET: Toxicity

hERG Blockers:  0.032 hERG Blockers (10um):  0.122
Human Hepatotoxicity (H-HT):  0.283 Drug-induced Liver Injury (DILI):  0.003
AMES Toxicity:  0.148 Rat Oral Acute Toxicity:  0.03
Maximum Recommended Daily Dose:  0.247 Skin Sensitization:  0.999
Carcinogencity:  0.189 Eye Corrosion:  0.985
Eye Irritation:  0.997 Respiratory Toxicity:  0.462
Drug-induced Neurotoxicity:  0.004 Ototoxicity:  0.344
Hematotoxicity:  0.045 Drug-induced Nephrotoxicity:  0.519
Genotoxicity:  0.0 RPMI-8226 Immunitoxicity:  0.038
A549 Cytotoxicity:  0.093 Hek293 Cytotoxicity:  0.055
BCF:   1.091
?
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:   3.895
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.29
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   2.949
?
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
NPO58920 Paenibacillus sp. BMK771-AF3 Genus Paenibacillaceae Bacteria 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

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT29066 Organism Mannheimia haemolytica Mannheimia haemolytica MIC = 0.78 ug.mL-1 PMID[20728353]
NPT29066 Organism Mannheimia haemolytica Mannheimia haemolytica MIC = 1.56 ug.mL-1 PMID[20728353]
NPT746 Organism Pasteurella multocida Pasteurella multocida MIC = 12.5 ug.mL-1 PMID[20728353]
NPT29053 Organism Histophilus somni Histophilus somni MIC > 50.0 ug.mL-1 PMID[20728353]
NPT746 Organism Pasteurella multocida Pasteurella multocida MIC = 3.13 ug.mL-1 PMID[20728353]
NPT746 Organism Pasteurella multocida Pasteurella multocida MIC > 50.0 ug.mL-1 PMID[20728353]
NPT746 Organism Pasteurella multocida Pasteurella multocida MIC = 6.25 ug.mL-1 PMID[20728353]
NPT18862 Organism Actinobacillus pleuropneumoniae Actinobacillus pleuropneumoniae MIC = 6.25 ug.mL-1 PMID[20728353]

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 NPC606120 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
0.7949 Intermediate Similarity NPC243532
0.7059 Intermediate Similarity NPC281245
0.6944 Remote Similarity NPC324004
0.6944 Remote Similarity NPC328497
0.6857 Remote Similarity NPC424
0.6857 Remote Similarity NPC36061
0.6857 Remote Similarity NPC69510
0.6857 Remote Similarity NPC77272
0.6857 Remote Similarity NPC290563
0.6857 Remote Similarity NPC139029
0.6857 Remote Similarity NPC281972
0.6857 Remote Similarity NPC261831
0.6857 Remote Similarity NPC87564
0.6667 Remote Similarity NPC255863
0.6667 Remote Similarity NPC136164
0.6667 Remote Similarity NPC245947
0.6389 Remote Similarity NPC92114
0.6316 Remote Similarity NPC52955
0.6316 Remote Similarity NPC88966
0.6316 Remote Similarity NPC25417
0.6316 Remote Similarity NPC1813
0.6316 Remote Similarity NPC154245
0.6316 Remote Similarity NPC85813
0.6316 Remote Similarity NPC223697
0.6316 Remote Similarity NPC6095
0.6216 Remote Similarity NPC95145
0.6216 Remote Similarity NPC325642
0.6216 Remote Similarity NPC65174
0.6053 Remote Similarity NPC321062
0.6053 Remote Similarity NPC70387
0.5714 Remote Similarity NPC225929
0.5652 Remote Similarity NPC470320
0.5641 Remote Similarity NPC5413
0.5556 Remote Similarity NPC180534
0.5556 Remote Similarity NPC99619
0.5556 Remote Similarity NPC611531
0.5532 Remote Similarity NPC323045
0.5532 Remote Similarity NPC26500
0.5532 Remote Similarity NPC49863
0.5532 Remote Similarity NPC317881
0.55 Remote Similarity NPC59051
0.5455 Remote Similarity NPC477201
0.5435 Remote Similarity NPC323477
0.5385 Remote Similarity NPC149821
0.5319 Remote Similarity NPC327112
0.5263 Remote Similarity NPC34416
0.525 Remote Similarity NPC91495
0.5238 Remote Similarity NPC601206
0.5152 Remote Similarity NPC214610
0.5152 Remote Similarity NPC118968
0.5152 Remote Similarity NPC183424
0.5152 Remote Similarity NPC294085
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
0.5111 Remote Similarity NPC106851
0.5111 Remote Similarity NPC282788
0.5111 Remote Similarity NPC274927
0.5106 Remote Similarity NPC68343
0.5106 Remote Similarity NPC321838
0.5106 Remote Similarity NPC318420
0.5106 Remote Similarity NPC326268
0.5106 Remote Similarity NPC328089

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC606120 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
0.6857 Remote Similarity NPD3195 Phase 2
0.6857 Remote Similarity NPD3196 Approved
0.65 Remote Similarity NPD3194 Phase 4
0.6316 Remote Similarity NPD3172 Approved
0.6316 Remote Similarity NPD4266 Phase 2
0.5641 Remote Similarity NPD3173 Phase 4
0.5556 Remote Similarity NPD622 Pre-clinical
0.5532 Remote Similarity NPD4247 Clinical (unspecified phase)
0.5319 Remote Similarity NPD4246 Phase 2
0.5152 Remote Similarity NPD9655 Phase 4
0.5143 Remote Similarity NPD2270 Pre-clinical
0.5143 Remote Similarity NPD633 Phase 3
0.5143 Remote Similarity NPD9448 Phase 2
0.5106 Remote Similarity NPD39 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