Natural Product: NPC477240

Natural Product IDNPC477240
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 1-(2-Methylbutyryl)-phloroglucinol-glucopyranoside
IUPAC Name 1-[2,4-dihydroxy-6-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyphenyl]-2-methylbutan-1-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 25168170
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0004603] Organic oxygen compounds
      • [CHEMONTID:0000323] Organooxygen compounds
        • [CHEMONTID:0000011] Carbohydrates and carbohydrate conjugates
          • [CHEMONTID:0002105] Glycosyl compounds
            • [CHEMONTID:0004165] Phenolic glycosides

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 MMJKSUJYDHTZJV-NZACEUBZSA-N
Standard InCHI InChI=1S/C17H24O9/c1-3-7(2)13(21)12-9(20)4-8(19)5-10(12)25-17-16(24)15(23)14(22)11(6-18)26-17/h4-5,7,11,14-20,22-24H,3,6H2,1-2H3/t7?,11-,14-,15+,16-,17-/m1/s1
SMILES CCC(C)C(=O)C1=C(C=C(C=C1O[C@H]2[C@@H]([C@H]([C@@H]([C@H](O2)CO)O)O)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   372.14 Volume:   354.041
?
Van der Waals volume.
Dense:   1.051 LogP:   0.804
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.439
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.082
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   13.0
TPSA:   156.91
?
Topological Polar Surface Area.
 H-Bond Acceptor:   9.0
H-Bond Donor:   6.0 Rings:   2.0
Heavy Atoms:   9.0

MedChem Properties

QED Drug-Likeness Score:   0.362 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.003 Fsp3:   0.588
MCE-18:   57.296
?
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:   0.592 Fluc inhibitor:   0.058
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.099
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.146
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.306 Promiscuous compounds:   0.317

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.984 MDCK Permeability:   -5.179
Pgp-inhibitor:   0.001 Pgp-substrate:   0.125
PAMPA:   0.823
?
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):   0.232
20% Bioavailability (F20%):   0.053 30% Bioavailability (F30%):   0.976
50% Bioavailability (F50%):   0.988

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.084 MRP1:   0.724
Plasma Protein Binding (PPB):   75.633% Volume Distribution (VD):   -0.176
Fu: 25.25%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.988
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.308
BSEP inhibitor:   0.006

ADMET: Metabolism

CYP1A2-inhibitor:   0.889 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.034 CYP2C19-substrate:   0.004
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.21
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.002
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.994
HLM stability:   0.262
?
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):  3.722 Half-life (T1/2):  2.879

ADMET: Toxicity

hERG Blockers:  0.027 hERG Blockers (10um):  0.16
Human Hepatotoxicity (H-HT):  0.706 Drug-induced Liver Injury (DILI):  0.616
AMES Toxicity:  0.783 Rat Oral Acute Toxicity:  0.028
Maximum Recommended Daily Dose:  0.059 Skin Sensitization:  0.99
Carcinogencity:  0.214 Eye Corrosion:  0.0
Eye Irritation:  0.474 Respiratory Toxicity:  0.074
Drug-induced Neurotoxicity:  0.018 Ototoxicity:  0.895
Hematotoxicity:  0.249 Drug-induced Nephrotoxicity:  0.512
Genotoxicity:  0.196 RPMI-8226 Immunitoxicity:  0.117
A549 Cytotoxicity:  0.344 Hek293 Cytotoxicity:  0.37
BCF:   0.337
?
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:   3.008
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.59
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.81
?
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
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. cone n.a. PMID[10336650]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. PMID[15679315]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. PMID[16252923]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. cone n.a. PMID[17624889]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. PMID[18611049]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. PMID[18768384]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. PMID[19476340]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. PMID[21912858]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. cone n.a. PMID[22111577]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. flower n.a. PMID[22166201]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. PMID[23790907]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. PMID[24948953]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. PMID[25564559]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. PMID[29154541]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. PMID[30384263]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. PMID[37631012]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. PMID[38354824]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. PMID[39199155]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO13879 Humulus lupulus Species Cannabaceae 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
NPT324 Individual protein Cyclooxygenase-1 Ovis aries IC50 = 131300 nM PMID[16252923]

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

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 NPC477240 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
0.8889 High Similarity NPC106025
0.8103 Intermediate Similarity NPC190217
0.7931 Intermediate Similarity NPC199335
0.6716 Remote Similarity NPC259182
0.6522 Remote Similarity NPC257963
0.6471 Remote Similarity NPC88484
0.6377 Remote Similarity NPC26195
0.6271 Remote Similarity NPC214454
0.5968 Remote Similarity NPC23084
0.5593 Remote Similarity NPC152722
0.5542 Remote Similarity NPC168789
0.5522 Remote Similarity NPC475628
0.5479 Remote Similarity NPC127782
0.5417 Remote Similarity NPC169248
0.5417 Remote Similarity NPC72649
0.5397 Remote Similarity NPC40377
0.5373 Remote Similarity NPC97326
0.5352 Remote Similarity NPC177742
0.5345 Remote Similarity NPC142319
0.5278 Remote Similarity NPC271385
0.5278 Remote Similarity NPC5029
0.527 Remote Similarity NPC39351
0.5254 Remote Similarity NPC484157
0.5217 Remote Similarity NPC611586
0.5205 Remote Similarity NPC160156
0.5205 Remote Similarity NPC92565
0.52 Remote Similarity NPC106625
0.5167 Remote Similarity NPC294470
0.5161 Remote Similarity NPC12308
0.5152 Remote Similarity NPC26080
0.5152 Remote Similarity NPC165686
0.5139 Remote Similarity NPC99233
0.5135 Remote Similarity NPC308265
0.5135 Remote Similarity NPC97052
0.5135 Remote Similarity NPC170475
0.5132 Remote Similarity NPC181014
0.5119 Remote Similarity NPC70441
0.5082 Remote Similarity NPC9248
0.5077 Remote Similarity NPC218685
0.507 Remote Similarity NPC121001
0.5068 Remote Similarity NPC601828
0.5067 Remote Similarity NPC219163
0.5067 Remote Similarity NPC471457
0.5065 Remote Similarity NPC300537
0.5065 Remote Similarity NPC5778
0.5063 Remote Similarity NPC259834

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC477240 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