Natural Product: NPC271282

Natural Product IDNPC271282
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (9Z,11S,16R)-Dihydroxyoctadeca-9,17-Dien-12,14-Diyn-1-Yl Acetate
IUPAC Name [(9Z,11S,16R)-11,16-dihydroxyoctadeca-9,17-dien-12,14-diynyl] acetate
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL490698
PubChem CID 11652871
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0003909] Fatty Acyls
        • [CHEMONTID:0001334] Fatty alcohols
          • [CHEMONTID:0002951] Long-chain fatty alcohols

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 VVURZXYIXNNJCG-KOIKSQSCSA-N
Standard InCHI InChI=1S/C20H28O4/c1-3-19(22)14-11-12-16-20(23)15-10-8-6-4-5-7-9-13-17-24-18(2)21/h3,10,15,19-20,22-23H,1,4-9,13,17H2,2H3/b15-10-/t19-,20+/m1/s1
SMILES CC(=O)OCCCCCCCC/C=C[C@@H](C#CC#C[C@@H](C=C)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   332.2 Volume:   371.182
?
Van der Waals volume.
Dense:   0.895 LogP:   3.436
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.673
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.459
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The logarithm of aqueous solubility value.
Rotatable Bonds:   12.0 Rigid Bonds:   5.0
TPSA:   66.76
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   2.0 Rings:   0.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.264 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.003 Fsp3:   0.55
MCE-18:   3.0
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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:   0.079 Fluc inhibitor:   0.006
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.039
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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:   0.668 Promiscuous compounds:   0.173

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.771 MDCK Permeability:   -4.618
Pgp-inhibitor:   0.001 Pgp-substrate:   0.0
PAMPA:   1.0
?
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%):   0.0 30% Bioavailability (F30%):   0.0
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.0
Plasma Protein Binding (PPB):   92.368% Volume Distribution (VD):   -0.175
Fu: 3.829%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.0
OATP1B3 inhibitor:   0.0 BCRP inhibitor:   1.0
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.372
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.001 CYP2C9-substrate:   0.082
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.265
CYP3A4-inhibitor:   0.217 CYP3A4-substrate:   0.003
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.895
?
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):  3.486 Half-life (T1/2):  1.205

ADMET: Toxicity

hERG Blockers:  0.039 hERG Blockers (10um):  0.676
Human Hepatotoxicity (H-HT):  0.168 Drug-induced Liver Injury (DILI):  0.143
AMES Toxicity:  0.19 Rat Oral Acute Toxicity:  0.22
Maximum Recommended Daily Dose:  0.497 Skin Sensitization:  0.928
Carcinogencity:  0.44 Eye Corrosion:  0.988
Eye Irritation:  0.996 Respiratory Toxicity:  1.0
Drug-induced Neurotoxicity:  0.105 Ototoxicity:  0.262
Hematotoxicity:  0.002 Drug-induced Nephrotoxicity:  0.042
Genotoxicity:  0.002 RPMI-8226 Immunitoxicity:  0.056
A549 Cytotoxicity:  0.02 Hek293 Cytotoxicity:  0.334
BCF:   1.378
?
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:   4.73
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.255
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.503
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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
NPO21056 Angelica keiskei Species Apiaceae Eukaryota exudates n.a. n.a. PMID[16441065]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota roots purchased from Kiu Shun Trading Ltd., Vancouver, Canada 2000 PMID[16643021]
NPO21056 Angelica keiskei Species Apiaceae Eukaryota stems n.a. n.a. PMID[18558745]
NPO21056 Angelica keiskei Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[21824777]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[25538068]
NPO21056 Angelica keiskei Species Apiaceae Eukaryota stems n.a. n.a. PMID[25891102]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[27400088]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[36838931]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[37480748]
NPO21056 Angelica keiskei Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21056 Angelica keiskei Species Apiaceae Eukaryota n.a. n.a. Database[FooDB]
NPO21056 Angelica keiskei Species Apiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO21056 Angelica keiskei Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO21056 Angelica keiskei Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15462 Angelica sinensis Species Apiaceae 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
NPT1785 Individual protein Serotonin 7 (5-HT7) receptor Homo sapiens IC50 = 118100.0 nM PMID[16643021]
NPT1785 Individual protein Serotonin 7 (5-HT7) receptor Homo sapiens Inhibition = 49.0 % PMID[16643021]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT80 Cell line Raji Homo sapiens Activity = 60.0 % PMID[16441065]
NPT2 Others Unspecified n.a. Activity = 18.7 % PMID[16441065]
NPT2 Others Unspecified n.a. Activity = 53.1 % PMID[16441065]
NPT2 Others Unspecified n.a. Activity = 81.4 % PMID[16441065]
NPT2 Others Unspecified n.a. Activity = 100.0 % PMID[16441065]
NPT2 Others Unspecified n.a. IC50 = 511.0 molar ratio PMID[16441065]
NPT2 Others Unspecified n.a. Ratio = 1.2 n.a. PMID[16441065]

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 NPC271282 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 NPC66460
1.0 High Similarity NPC325929
0.8293 Intermediate Similarity NPC29697
0.7727 Intermediate Similarity NPC484323
0.6809 Remote Similarity NPC484321
0.6667 Remote Similarity NPC91226
0.6667 Remote Similarity NPC243546
0.6667 Remote Similarity NPC31194
0.6667 Remote Similarity NPC248884
0.641 Remote Similarity NPC124183
0.641 Remote Similarity NPC482802
0.5918 Remote Similarity NPC265551
0.5833 Remote Similarity NPC212730
0.575 Remote Similarity NPC207815
0.575 Remote Similarity NPC243813
0.5581 Remote Similarity NPC153538
0.5581 Remote Similarity NPC93639
0.5556 Remote Similarity NPC142092
0.551 Remote Similarity NPC193975
0.5349 Remote Similarity NPC72699
0.5333 Remote Similarity NPC482801
0.5333 Remote Similarity NPC168510
0.5106 Remote Similarity NPC151782

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC271282 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
NPD

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