Natural Product: NPC35397

Natural Product IDNPC35397
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Deschloroelatol
IUPAC Name (3S,4R,6R)-4-bromo-5,5,9-trimethyl-1-methylidenespiro[5.5]undec-9-en-3-ol
Synonyms Deschloroelatol
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL513806
PubChem CID 479932
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001550] Sesquiterpenoids
          • [CHEMONTID:0002517] Chamigranes

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 APALGGYWOOAWLG-YDHLFZDLSA-N
Standard InCHI InChI=1S/C15H23BrO/c1-10-5-7-15(8-6-10)11(2)9-12(17)13(16)14(15,3)4/h5,12-13,17H,2,6-9H2,1,3-4H3/t12-,13-,15-/m0/s1
SMILES CC1=CC[C@]2(CC1)C(=C)C[C@@H]([C@@H](C2(C)C)Br)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   298.09 Volume:   273.684
?
Van der Waals volume.
Dense:   1.089 LogP:   3.229
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.121
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.788
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   13.0
TPSA:   20.23
?
Topological Polar Surface Area.
 H-Bond Acceptor:   1.0
H-Bond Donor:   1.0 Rings:   2.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.524 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   5.124 Fsp3:   0.733
MCE-18:   57.846
?
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:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.468 Fluc inhibitor:   0.0
?
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:   0.019
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.928 Promiscuous compounds:   0.171

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.986 MDCK Permeability:   -4.766
Pgp-inhibitor:   0.512 Pgp-substrate:   0.461
PAMPA:   0.772
?
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):   0.008
20% Bioavailability (F20%):   0.336 30% Bioavailability (F30%):   0.324
50% Bioavailability (F50%):   0.752

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.821 MRP1:   0.932
Plasma Protein Binding (PPB):   90.993% Volume Distribution (VD):   0.29
Fu: 8.73%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.884
OATP1B3 inhibitor:   0.363 BCRP inhibitor:   0.142
BSEP inhibitor:   0.659

ADMET: Metabolism

CYP1A2-inhibitor:   0.002 CYP1A2-substrate:   0.732
CYP2C19-inhibitor:   0.488 CYP2C19-substrate:   0.704
CYP2C9-inhibitor:   0.037 CYP2C9-substrate:   0.051
CYP2D6-inhibitor:   0.03 CYP2D6-substrate:   0.239
CYP3A4-inhibitor:   0.006 CYP3A4-substrate:   0.483
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.396
HLM stability:   0.973
?
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):  10.015 Half-life (T1/2):  1.499

ADMET: Toxicity

hERG Blockers:  0.026 hERG Blockers (10um):  0.291
Human Hepatotoxicity (H-HT):  0.425 Drug-induced Liver Injury (DILI):  0.615
AMES Toxicity:  0.508 Rat Oral Acute Toxicity:  0.591
Maximum Recommended Daily Dose:  0.331 Skin Sensitization:  0.98
Carcinogencity:  0.756 Eye Corrosion:  0.631
Eye Irritation:  0.986 Respiratory Toxicity:  0.678
Drug-induced Neurotoxicity:  0.854 Ototoxicity:  0.255
Hematotoxicity:  0.433 Drug-induced Nephrotoxicity:  0.375
Genotoxicity:  0.388 RPMI-8226 Immunitoxicity:  0.094
A549 Cytotoxicity:  0.436 Hek293 Cytotoxicity:  0.359
BCF:   2.378
?
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:   4.078
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.093
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.836
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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
NPO18850 Aplysia dactylomela Species Aplysiidae Eukaryota n.a. tenerife n.a. PMID[10924166]
NPO18850 Aplysia dactylomela Species Aplysiidae Eukaryota n.a. n.a. n.a. PMID[16309323]
NPO18850 Aplysia dactylomela Species Aplysiidae Eukaryota n.a. n.a. n.a. PMID[22220686]
NPO18850 Aplysia dactylomela Species Aplysiidae Eukaryota n.a. n.a. n.a. PMID[24279991]
NPO21610 Laurencia rigida Species Rhodomelaceae Eukaryota n.a. n.a. n.a. PMID[9358636]
NPO18850 Aplysia dactylomela Species Aplysiidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21610 Laurencia rigida Species Rhodomelaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18850 Aplysia dactylomela Species Aplysiidae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO18850 Aplysia dactylomela Species Aplysiidae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21610 Laurencia rigida Species Rhodomelaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18850 Aplysia dactylomela Species Aplysiidae 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
NPT165 Cell line HeLa Homo sapiens IC50 > 67000.0 nM PMID[9358635]
NPT1171 Cell line HEp-2 Homo sapiens IC50 > 67000.0 nM PMID[23758051]
NPT189 Cell line Vero Chlorocebus aethiops IC50 > 67000.0 nM PubChem BioAssay data set
NPT1231 Organism Microbotryum violaceum Microbotryum violaceum IZ = 0.0 mm DOI[10.6019/CHEMBL3301361]
NPT637 Organism Fusarium oxysporum Fusarium oxysporum IZ = 0.0 mm PMID[19822701]
NPT19 Organism Escherichia coli Escherichia coli IZ = 0.0 mm PMID[21652215]
NPT1234 Organism Chlorella fusca Chlorella fusca IZ = 2.0 mm PMID[19103488]
NPT1233 Organism Mycotypha microspora Mycotypha microspora IZ = 20.0 mm DOI[10.6019/CHEMBL3301361]
NPT1232 Organism Eurotium repens Eurotium repens IZ = 18.0 mm PMID[19822701]
NPT1230 Organism Bacillus megaterium Bacillus megaterium IZ = 1.0 mm PMID[21652215]

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 NPC35397 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 NPC474946
0.65 Remote Similarity NPC483534
0.6341 Remote Similarity NPC31330
0.6 Remote Similarity NPC489303
0.5714 Remote Similarity NPC273356
0.5714 Remote Similarity NPC97491
0.5714 Remote Similarity NPC83436
0.5714 Remote Similarity NPC106792
0.5714 Remote Similarity NPC607758
0.5116 Remote Similarity NPC113024
0.5116 Remote Similarity NPC489304
0.5111 Remote Similarity NPC215307
0.5111 Remote Similarity NPC483532
0.5111 Remote Similarity NPC274750
0.5111 Remote Similarity NPC311891

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC35397 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