Natural Product: NPC108141

Natural Product IDNPC108141
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Blumenol C-Glucoside
IUPAC Name (4R)-3,5,5-trimethyl-4-[(3S)-3-[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxybutyl]cyclohex-2-en-1-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3400306
PubChem CID 38346961
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0003909] Fatty Acyls
        • [CHEMONTID:0001766] Fatty acyl glycosides
          • [CHEMONTID:0003861] Fatty acyl glycosides of mono- and disaccharides

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 NYLNHNDMNOPWAZ-CODAKJSOSA-N
Standard InCHI InChI=1S/C19H32O7/c1-10-7-12(21)8-19(3,4)13(10)6-5-11(2)25-18-17(24)16(23)15(22)14(9-20)26-18/h7,11,13-18,20,22-24H,5-6,8-9H2,1-4H3/t11-,13-,14+,15+,16-,17+,18+/m0/s1
SMILES CC1=CC(=O)CC(C)(C)[C@H]1CC[C@H](C)O[C@H]1[C@@H]([C@H]([C@@H]([C@@H](CO)O1)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   372.21 Volume:   376.326
?
Van der Waals volume.
Dense:   0.989 LogP:   0.685
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.013
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.885
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   13.0
TPSA:   116.45
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   4.0 Rings:   2.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.537 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.534 Fsp3:   0.842
MCE-18:   44.229
?
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:   0.522 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.046
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.001
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.239 Promiscuous compounds:   0.333

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.581 MDCK Permeability:   -5.0
Pgp-inhibitor:   0.009 Pgp-substrate:   0.429
PAMPA:   0.919
?
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):   0.066
20% Bioavailability (F20%):   0.011 30% Bioavailability (F30%):   0.114
50% Bioavailability (F50%):   0.905

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.152 MRP1:   0.191
Plasma Protein Binding (PPB):   46.247% Volume Distribution (VD):   -0.521
Fu: 52.088%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.03
BSEP inhibitor:   0.024

ADMET: Metabolism

CYP1A2-inhibitor:   0.278 CYP1A2-substrate:   0.024
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.083
CYP2C9-inhibitor:   0.001 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.046
CYP3A4-inhibitor:   0.991 CYP3A4-substrate:   0.672
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.972
HLM stability:   0.991
?
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):  3.388 Half-life (T1/2):  1.636

ADMET: Toxicity

hERG Blockers:  0.02 hERG Blockers (10um):  0.124
Human Hepatotoxicity (H-HT):  0.641 Drug-induced Liver Injury (DILI):  0.699
AMES Toxicity:  0.888 Rat Oral Acute Toxicity:  0.094
Maximum Recommended Daily Dose:  0.028 Skin Sensitization:  0.997
Carcinogencity:  0.327 Eye Corrosion:  0.006
Eye Irritation:  0.395 Respiratory Toxicity:  0.036
Drug-induced Neurotoxicity:  0.084 Ototoxicity:  0.888
Hematotoxicity:  0.646 Drug-induced Nephrotoxicity:  0.742
Genotoxicity:  0.335 RPMI-8226 Immunitoxicity:  0.108
A549 Cytotoxicity:  0.181 Hek293 Cytotoxicity:  0.176
BCF:   0.487
?
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:   3.17
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.729
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.793
?
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
NPO17799 Siraitia grosvenorii Species Cucurbitaceae Eukaryota n.a. fruit n.a. PMID[16268506]
NPO14254 Kandelia candel Species Rhizophoraceae Eukaryota n.a. n.a. n.a. PMID[17944538]
NPO17799 Siraitia grosvenorii Species Cucurbitaceae Eukaryota n.a. n.a. n.a. PMID[21893415]
NPO14254 Kandelia candel Species Rhizophoraceae Eukaryota n.a. n.a. n.a. PMID[22823026]
NPO14254 Kandelia candel Species Rhizophoraceae Eukaryota leaves and stems Ha Long, Quang Ninh province, Vietnam 2014-Jul PMID[25769817]
NPO17799 Siraitia grosvenorii Species Cucurbitaceae Eukaryota n.a. n.a. n.a. PMID[28448136]
NPO14254 Kandelia candel Species Rhizophoraceae Eukaryota n.a. n.a. n.a. PMID[29792702]
NPO14254 Kandelia candel Species Rhizophoraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17799 Siraitia grosvenorii Species Cucurbitaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9231 Mikania mendocina Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14254 Kandelia candel Species Rhizophoraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO17799 Siraitia grosvenorii Species Cucurbitaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14254 Kandelia candel Species Rhizophoraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO6341 Magonia glabrata Species Sapindaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17799 Siraitia grosvenorii Species Cucurbitaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14254 Kandelia candel Species Rhizophoraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9231 Mikania mendocina Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16285 Stachys byzantina Species Lamiaceae 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
NPT2 Others Unspecified n.a. IC50 > 50000.0 nM PMID[25769817]

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 NPC108141 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 NPC56071
0.75 Intermediate Similarity NPC70733
0.6852 Remote Similarity NPC25701
0.6852 Remote Similarity NPC2003
0.6429 Remote Similarity NPC71381
0.6429 Remote Similarity NPC263407
0.6207 Remote Similarity NPC223834
0.6129 Remote Similarity NPC278506
0.5965 Remote Similarity NPC471756
0.5517 Remote Similarity NPC308489
0.549 Remote Similarity NPC114236
0.5455 Remote Similarity NPC198422
0.5455 Remote Similarity NPC40182
0.52 Remote Similarity NPC37757
0.5161 Remote Similarity NPC169468
0.5161 Remote Similarity NPC81483
0.5161 Remote Similarity NPC307517
0.5161 Remote Similarity NPC61630
0.5156 Remote Similarity NPC610039

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC108141 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