Natural Product: NPC305698

Natural Product IDNPC305698
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Asperdiol
IUPAC Name (1R,4E,6S,7R,10E,14R)-4-(hydroxymethyl)-10,14-dimethyl-7-prop-1-en-2-yl-15-oxabicyclo[12.1.0]pentadeca-4,10-dien-6-ol
Synonyms Asperdiol
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1078332
PubChem CID 21582588
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001551] Diterpenoids
          • [CHEMONTID:0000008] Cembrane diterpenoids

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 FLJAFHRJXPAASR-LDTXXPTRSA-N
Standard InCHI InChI=1S/C20H32O3/c1-14(2)17-9-7-15(3)6-5-11-20(4)19(23-20)10-8-16(13-21)12-18(17)22/h6,12,17-19,21-22H,1,5,7-11,13H2,2-4H3/b15-6+,16-12+/t17-,18+,19-,20-/m1/s1
SMILES OC/C/1=C/[C@H](O)[C@H](CC/C(=C/CC[C@@]2([C@@H](CC1)O2)C)/C)C(=C)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   320.24 Volume:   355.825
?
Van der Waals volume.
Dense:   0.9 LogP:   2.523
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.73
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.715
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The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   17.0
TPSA:   52.99
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Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   2.0 Rings:   2.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.599 GASA:   1.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.84 Fsp3:   0.7
MCE-18:   38.824
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Rejected GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.528 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:   0.003
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.014
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.637 Promiscuous compounds:   0.186

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.75 MDCK Permeability:   -4.94
Pgp-inhibitor:   0.356 Pgp-substrate:   0.0
PAMPA:   0.157
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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):   0.39
20% Bioavailability (F20%):   0.415 30% Bioavailability (F30%):   0.893
50% Bioavailability (F50%):   0.979

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.051
Plasma Protein Binding (PPB):   74.114% Volume Distribution (VD):   -0.097
Fu: 24.742%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.011
BSEP inhibitor:   0.907

ADMET: Metabolism

CYP1A2-inhibitor:   0.001 CYP1A2-substrate:   0.001
CYP2C19-inhibitor:   0.928 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.588 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.507 CYP2D6-substrate:   0.025
CYP3A4-inhibitor:   0.105 CYP3A4-substrate:   0.382
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.13
HLM stability:   0.279
?
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):  11.304 Half-life (T1/2):  1.296

ADMET: Toxicity

hERG Blockers:  0.066 hERG Blockers (10um):  0.078
Human Hepatotoxicity (H-HT):  0.533 Drug-induced Liver Injury (DILI):  0.288
AMES Toxicity:  0.111 Rat Oral Acute Toxicity:  0.031
Maximum Recommended Daily Dose:  0.079 Skin Sensitization:  0.972
Carcinogencity:  0.329 Eye Corrosion:  0.348
Eye Irritation:  0.997 Respiratory Toxicity:  0.166
Drug-induced Neurotoxicity:  0.174 Ototoxicity:  0.227
Hematotoxicity:  0.161 Drug-induced Nephrotoxicity:  0.325
Genotoxicity:  0.006 RPMI-8226 Immunitoxicity:  0.046
A549 Cytotoxicity:  0.039 Hek293 Cytotoxicity:  0.303
BCF:   1.913
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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:   3.973
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.408
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.754
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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
NPO11748 Eunicea knighti Species Plexauridae Eukaryota n.a. Santa Marta Bay, Colombian Caribbean 2007-MAY PMID[19778088]
NPO11126 Flindersia ifflaiana Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11748 Eunicea knighti Species Plexauridae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9774 Ceriops roxburghiana Species Rhizophoraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15060 Samia cynthia Species Saturniidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9774 Ceriops roxburghiana Species Rhizophoraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11748 Eunicea knighti Species Plexauridae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15060 Samia cynthia Species Saturniidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11126 Flindersia ifflaiana Species Rutaceae 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
NPT1271 Organism Bacillus sp. Bacillus sp. IZ = 6.0 mm PMID[19778088]
NPT1271 Organism Bacillus sp. Bacillus sp. MIC = 4.0 ug PMID[19778088]
NPT2221 Organism Ochrobactrum pseudogrignonense Ochrobactrum pseudogrignonense IZ = 8.0 mm PMID[19778088]
NPT2221 Organism Ochrobactrum pseudogrignonense Ochrobactrum pseudogrignonense MIC > 30.0 ug PMID[19778088]

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 NPC305698 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
0.7255 Intermediate Similarity NPC259299
0.7018 Intermediate Similarity NPC84360
0.566 Remote Similarity NPC56419
0.5536 Remote Similarity NPC261398
0.5283 Remote Similarity NPC223604
0.5098 Remote Similarity NPC226848
0.5082 Remote Similarity NPC269841

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC305698 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