Natural Product: NPC47333

Natural Product IDNPC47333
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (Z,2R,3R)-2-Aminotetradec-7-Ene-1,3-Diol
IUPAC Name (Z,2R,3R)-2-aminotetradec-7-ene-1,3-diol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL509810
PubChem CID 10562206
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0004707] Organic nitrogen compounds
      • [CHEMONTID:0000278] Organonitrogen compounds
        • [CHEMONTID:0002449] Amines
          • [CHEMONTID:0002460] Alkanolamines
            • [CHEMONTID:0001897] 1,2-aminoalcohols

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 GAPOVTCESQJLFA-JUBSNLHESA-N
Standard InCHI InChI=1S/C14H29NO2/c1-2-3-4-5-6-7-8-9-10-11-14(17)13(15)12-16/h7-8,13-14,16-17H,2-6,9-12,15H2,1H3/b8-7-/t13-,14-/m1/s1
SMILES CCCCCC/C=CCCC[C@H]([C@@H](CO)N)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   243.22 Volume:   276.641
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Van der Waals volume.
Dense:   0.879 LogP:   3.111
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.61
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.643
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The logarithm of aqueous solubility value.
Rotatable Bonds:   11.0 Rigid Bonds:   1.0
TPSA:   66.48
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Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   4.0 Rings:   0.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.385 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.238 Fsp3:   0.857
MCE-18:   2.0
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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:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.269 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:   0.0
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.476 Promiscuous compounds:   0.262

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.243 MDCK Permeability:   -4.836
Pgp-inhibitor:   0.008 Pgp-substrate:   0.017
PAMPA:   0.036
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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):   0.282
20% Bioavailability (F20%):   0.523 30% Bioavailability (F30%):   0.9
50% Bioavailability (F50%):   0.957

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.005 MRP1:   0.649
Plasma Protein Binding (PPB):   97.412% Volume Distribution (VD):   -0.224
Fu: 2.891%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.01
OATP1B3 inhibitor:   0.803 BCRP inhibitor:   0.083
BSEP inhibitor:   0.217

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.264 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.001 CYP2C9-substrate:   0.977
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.986
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.538
HLM stability:   0.0
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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):  6.173 Half-life (T1/2):  1.024

ADMET: Toxicity

hERG Blockers:  0.175 hERG Blockers (10um):  0.506
Human Hepatotoxicity (H-HT):  0.352 Drug-induced Liver Injury (DILI):  0.005
AMES Toxicity:  0.289 Rat Oral Acute Toxicity:  0.069
Maximum Recommended Daily Dose:  0.111 Skin Sensitization:  0.999
Carcinogencity:  0.102 Eye Corrosion:  0.972
Eye Irritation:  0.942 Respiratory Toxicity:  0.259
Drug-induced Neurotoxicity:  0.042 Ototoxicity:  0.471
Hematotoxicity:  0.056 Drug-induced Nephrotoxicity:  0.442
Genotoxicity:  0.0 RPMI-8226 Immunitoxicity:  0.04
A549 Cytotoxicity:  0.307 Hek293 Cytotoxicity:  0.168
BCF:   2.004
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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:   4.342
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.344
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.861
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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
NPO8164 Haliclona vansoesti Species Chalinidae Eukaryota n.a. caribbean n.a. PMID[10924178]
NPO8164 Haliclona vansoesti Species Chalinidae 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
- Artemia LD50 = 9.0 mg/L PMID[10879539]

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 NPC47333 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
0.75 Intermediate Similarity NPC123814
0.6452 Remote Similarity NPC604436
0.6364 Remote Similarity NPC55068
0.625 Remote Similarity NPC478318
0.6061 Remote Similarity NPC603231
0.5833 Remote Similarity NPC113224
0.5833 Remote Similarity NPC601273
0.5714 Remote Similarity NPC485043
0.5333 Remote Similarity NPC478319
0.5333 Remote Similarity NPC121062
0.5333 Remote Similarity NPC29222
0.5333 Remote Similarity NPC96966
0.5333 Remote Similarity NPC602997
0.5161 Remote Similarity NPC76976
0.5152 Remote Similarity NPC168308
0.5152 Remote Similarity NPC8979
0.5152 Remote Similarity NPC302569
0.5143 Remote Similarity NPC485042
0.5111 Remote Similarity NPC212008
0.5111 Remote Similarity NPC140327
0.5111 Remote Similarity NPC62293
0.5111 Remote Similarity NPC51055

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC47333 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
0.75 Intermediate Similarity NPD3215 Phase 2
0.6364 Remote Similarity NPD3210 Clinical (unspecified phase)
0.5333 Remote Similarity NPD3214 Discontinued

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