Natural Product: NPC501836

Natural Product IDNPC501836
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 16-Hexadecanolide
IUPAC Name oxacycloheptadecan-2-one
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 LOKPJYNMYCVCRM-UHFFFAOYSA-N
Standard InCHI InChI=1S/C16H30O2/c17-16-14-12-10-8-6-4-2-1-3-5-7-9-11-13-15-18-16/h1-15H2
SMILES O=C1CCCCCCCCCCCCCCCO1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   254.22 Volume:   291.68
?
Van der Waals volume.
Dense:   0.872 LogP:   5.354
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.574
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.423
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   18.0
TPSA:   26.3
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   0.0 Rings:   1.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.568 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.316 Fsp3:   0.938
MCE-18:   7.871
?
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:   0.056 Fluc inhibitor:   0.203
?
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:   0.007
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.997 Promiscuous compounds:   0.657

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.958 MDCK Permeability:   -4.89
Pgp-inhibitor:   0.741 Pgp-substrate:   0.0
PAMPA:   0.0
?
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):   0.0
20% Bioavailability (F20%):   0.001 30% Bioavailability (F30%):   0.01
50% Bioavailability (F50%):   0.016

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.991 MRP1:   0.923
Plasma Protein Binding (PPB):   78.733% Volume Distribution (VD):   0.043
Fu: 8.14%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.741
OATP1B3 inhibitor:   0.936 BCRP inhibitor:   0.054
BSEP inhibitor:   0.926

ADMET: Metabolism

CYP1A2-inhibitor:   0.437 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.022
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.008
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.003 CYP2C8-inhibitor:   0.428
HLM stability:   1.0
?
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):  5.298 Half-life (T1/2):  0.221

ADMET: Toxicity

hERG Blockers:  0.338 hERG Blockers (10um):  0.69
Human Hepatotoxicity (H-HT):  0.113 Drug-induced Liver Injury (DILI):  0.073
AMES Toxicity:  0.007 Rat Oral Acute Toxicity:  0.012
Maximum Recommended Daily Dose:  0.613 Skin Sensitization:  0.811
Carcinogencity:  0.061 Eye Corrosion:  0.908
Eye Irritation:  0.993 Respiratory Toxicity:  0.265
Drug-induced Neurotoxicity:  0.112 Ototoxicity:  0.131
Hematotoxicity:  0.078 Drug-induced Nephrotoxicity:  0.059
Genotoxicity:  0.0 RPMI-8226 Immunitoxicity:  0.055
A549 Cytotoxicity:  0.192 Hek293 Cytotoxicity:  0.179
BCF:   1.711
?
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:   2.94
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.086
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.477
?
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
NPO13182 Achillea wilhelmsii Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[38783072]
NPO42417 Achillea vermicularis Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[38783072]
NPO64307 Achillea tenuifolia Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[38783072]
NPO13182 Achillea wilhelmsii Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[39349567]
NPO13182 Achillea wilhelmsii Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13182 Achillea wilhelmsii Species Asteraceae 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
NPO13182 Achillea wilhelmsii Oil n.a. 1.11 n.a. n.a. % PMID[38783072]
NPO13182 Achillea wilhelmsii Oil n.a. 2.09 n.a. n.a. % PMID[38783072]
NPO13182 Achillea wilhelmsii Oil n.a. 2.6 n.a. n.a. % PMID[38783072]
NPO13182 Achillea wilhelmsii Oil n.a. 1.64 n.a. n.a. % PMID[38783072]
NPO13182 Achillea wilhelmsii Oil n.a. 1.84 n.a. n.a. % PMID[38783072]
NPO13182 Achillea wilhelmsii Oil n.a. 7.43 n.a. n.a. % PMID[38783072]
NPO13182 Achillea wilhelmsii Oil n.a. 4.47 n.a. n.a. % PMID[38783072]
NPO13182 Achillea wilhelmsii Oil n.a. 2.14 n.a. n.a. % PMID[38783072]
NPO42417 Achillea vermicularis Oil n.a. 1.18 n.a. n.a. % PMID[38783072]
NPO42417 Achillea vermicularis Oil n.a. 1.9 n.a. n.a. % PMID[38783072]
NPO42417 Achillea vermicularis Oil n.a. 0 n.a. n.a. % PMID[38783072]
NPO42417 Achillea vermicularis Oil n.a. 2.03 n.a. n.a. % PMID[38783072]
NPO42417 Achillea vermicularis Oil n.a. 17.16 n.a. n.a. % PMID[38783072]
NPO42417 Achillea vermicularis Oil n.a. 1.77 n.a. n.a. % PMID[38783072]
NPO42417 Achillea vermicularis Oil n.a. 0.72 n.a. n.a. % PMID[38783072]
NPO42417 Achillea vermicularis Oil n.a. 1.21 n.a. n.a. % PMID[38783072]
NPO42417 Achillea vermicularis Oil n.a. 1.48 n.a. n.a. % PMID[38783072]
NPO42417 Achillea vermicularis Oil n.a. 0.84 n.a. n.a. % PMID[38783072]
NPO64307 Achillea tenuifolia Oil n.a. 0.77 n.a. n.a. % PMID[38783072]
NPO64307 Achillea tenuifolia Oil n.a. 0.96 n.a. n.a. % PMID[38783072]
NPO64307 Achillea tenuifolia Oil n.a. 0.47 n.a. n.a. % PMID[38783072]
NPO64307 Achillea tenuifolia Oil n.a. 0 n.a. n.a. % PMID[38783072]

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
- Rattus norvegicus LD50 > 5000.0 mg/kg ToxVal
- Oryctolagus cuniculus LD50 > 5000.0 mg/kg 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 NPC501836 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 NPC223249
0.875 High Similarity NPC149299
0.8333 Intermediate Similarity NPC80396
0.7778 Intermediate Similarity NPC71761
0.76 Intermediate Similarity NPC154642
0.76 Intermediate Similarity NPC80641
0.76 Intermediate Similarity NPC603612
0.72 Intermediate Similarity NPC154396
0.72 Intermediate Similarity NPC286695
0.7143 Intermediate Similarity NPC99700
0.68 Remote Similarity NPC12904
0.68 Remote Similarity NPC476550
0.625 Remote Similarity NPC53541
0.619 Remote Similarity NPC327450
0.619 Remote Similarity NPC234005
0.6154 Remote Similarity NPC322892
0.6129 Remote Similarity NPC223677
0.5769 Remote Similarity NPC250028
0.5769 Remote Similarity NPC236579
0.5769 Remote Similarity NPC80234
0.5769 Remote Similarity NPC86545
0.5769 Remote Similarity NPC286498
0.5769 Remote Similarity NPC223374
0.5769 Remote Similarity NPC203531
0.5769 Remote Similarity NPC196442
0.5769 Remote Similarity NPC256163
0.5769 Remote Similarity NPC301398
0.5769 Remote Similarity NPC40597
0.5769 Remote Similarity NPC608162
0.5769 Remote Similarity NPC609004
0.5517 Remote Similarity NPC223675
0.5517 Remote Similarity NPC68577
0.5484 Remote Similarity NPC163345
0.5385 Remote Similarity NPC40965
0.5185 Remote Similarity NPC81263

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC501836 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
0.6 Remote Similarity NPD900 Pre-clinical
0.5758 Remote Similarity NPD631 Phase 4
0.5588 Remote Similarity NPD630 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