Natural Product: NPC529876

Natural Product IDNPC529876
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 3-Methyl-3-butenyl hexanoate
IUPAC Name 3-methylbut-3-enyl hexanoate
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0003909] Fatty Acyls
        • [CHEMONTID:0000324] Fatty acid esters

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 PFKCNOUVNPEGIF-UHFFFAOYSA-N
Standard InCHI InChI=1S/C11H20O2/c1-4-5-6-7-11(12)13-9-8-10(2)3/h2,4-9H2,1,3H3
SMILES C=C(C)CCOC(=O)CCCCC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   184.15 Volume:   211.12
?
Van der Waals volume.
Dense:   0.872 LogP:   3.423
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.926
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.046
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The logarithm of aqueous solubility value.
Rotatable Bonds:   8.0 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:   0.345 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.132 Fsp3:   0.727
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:   Rejected
Golden Triangle Rule:   Accepted BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.003 Fluc inhibitor:   0.0
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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:   0.006
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   1.0 Promiscuous compounds:   0.126

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.706 MDCK Permeability:   -4.591
Pgp-inhibitor:   0.054 Pgp-substrate:   0.017
PAMPA:   0.073
?
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):   0.014
20% Bioavailability (F20%):   0.208 30% Bioavailability (F30%):   0.304
50% Bioavailability (F50%):   0.777

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.946 MRP1:   0.786
Plasma Protein Binding (PPB):   92.822% Volume Distribution (VD):   -0.137
Fu: 8.687%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.531
OATP1B3 inhibitor:   0.942 BCRP inhibitor:   0.308
BSEP inhibitor:   0.837

ADMET: Metabolism

CYP1A2-inhibitor:   0.004 CYP1A2-substrate:   0.986
CYP2C19-inhibitor:   0.756 CYP2C19-substrate:   0.899
CYP2C9-inhibitor:   0.013 CYP2C9-substrate:   0.197
CYP2D6-inhibitor:   0.014 CYP2D6-substrate:   0.86
CYP3A4-inhibitor:   0.017 CYP3A4-substrate:   0.995
CYP2B6-substrate:   0.23 CYP2C8-inhibitor:   0.975
HLM stability:   0.926
?
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):  7.08 Half-life (T1/2):  0.426

ADMET: Toxicity

hERG Blockers:  0.069 hERG Blockers (10um):  0.459
Human Hepatotoxicity (H-HT):  0.318 Drug-induced Liver Injury (DILI):  0.194
AMES Toxicity:  0.193 Rat Oral Acute Toxicity:  0.198
Maximum Recommended Daily Dose:  0.179 Skin Sensitization:  0.909
Carcinogencity:  0.671 Eye Corrosion:  0.991
Eye Irritation:  0.996 Respiratory Toxicity:  0.592
Drug-induced Neurotoxicity:  0.403 Ototoxicity:  0.19
Hematotoxicity:  0.29 Drug-induced Nephrotoxicity:  0.243
Genotoxicity:  0.002 RPMI-8226 Immunitoxicity:  0.037
A549 Cytotoxicity:  0.025 Hek293 Cytotoxicity:  0.041
BCF:   0.929
?
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:   3.401
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.03
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.669
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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
NPO4323 Morinda citrifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/j.jarmap.2018.11.004]
NPO4323 Morinda citrifolia Species Rubiaceae Eukaryota n.a. leaf n.a. PMID[11348221]
NPO4323 Morinda citrifolia Species Rubiaceae Eukaryota fruit n.a. n.a. PMID[15844957]
NPO4323 Morinda citrifolia Species Rubiaceae Eukaryota fruits n.a. n.a. PMID[16378361]
NPO4323 Morinda citrifolia Species Rubiaceae Eukaryota fruits Tahiti n.a. PMID[17378609]
NPO4323 Morinda citrifolia Species Rubiaceae Eukaryota Fruits n.a. n.a. PMID[17480098]
NPO4323 Morinda citrifolia Species Rubiaceae Eukaryota roots n.a. n.a. PMID[18076142]
NPO4323 Morinda citrifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. PMID[24224843]
NPO4323 Morinda citrifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. PMID[27196335]
NPO4323 Morinda citrifolia Species Rubiaceae Eukaryota Fruits n.a. n.a. PMID[32083868]
NPO4323 Morinda citrifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. PMID[36014413]
NPO4323 Morinda citrifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4323 Morinda citrifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO4323 Morinda citrifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO4323 Morinda citrifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO4323 Morinda citrifolia Species Rubiaceae 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 NPC529876 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
0.7037 Intermediate Similarity NPC80396
0.7037 Intermediate Similarity NPC154642
0.7037 Intermediate Similarity NPC603612
0.6786 Remote Similarity NPC149299
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
0.6429 Remote Similarity NPC600941
0.6296 Remote Similarity NPC476550
0.6207 Remote Similarity NPC310746
0.6129 Remote Similarity NPC163345
0.6071 Remote Similarity NPC154396
0.6071 Remote Similarity NPC286695
0.5862 Remote Similarity NPC80641
0.5769 Remote Similarity NPC53541
0.5769 Remote Similarity NPC201622
0.5769 Remote Similarity NPC305660
0.5769 Remote Similarity NPC161097
0.5769 Remote Similarity NPC28598
0.5769 Remote Similarity NPC326758
0.5769 Remote Similarity NPC22903
0.5769 Remote Similarity NPC54980
0.5758 Remote Similarity NPC223677
0.5714 Remote Similarity NPC223249
0.5714 Remote Similarity NPC12904
0.5484 Remote Similarity NPC26253
0.5357 Remote Similarity NPC81263
0.5357 Remote Similarity NPC178643
0.5312 Remote Similarity NPC488257
0.5312 Remote Similarity NPC469937
0.5312 Remote Similarity NPC94699
0.5312 Remote Similarity NPC128061
0.5312 Remote Similarity NPC320588
0.5312 Remote Similarity NPC53463
0.52 Remote Similarity NPC40805
0.52 Remote Similarity NPC99700
0.5185 Remote Similarity NPC12156
0.5172 Remote Similarity NPC322892
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 NPC529876 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
0.5556 Remote Similarity NPD900 Pre-clinical
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