Natural Product: NPC475628

Natural Product IDNPC475628
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Acremonin A Glucoside
IUPAC Name (2R,3S,4S,5R,6S)-2-(hydroxymethyl)-6-[(2-hydroxy-7-prop-1-en-2-yl-5-bicyclo[4.2.0]octa-1,3,5-trienyl)oxy]oxane-3,4,5-triol
Synonyms acremonin A glucoside
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL509625
PubChem CID 11727475
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 GGUZNZRSHSGSBH-RGTJNTCWSA-N
Standard InCHI InChI=1S/C17H22O7/c1-7(2)8-5-9-10(19)3-4-11(13(8)9)23-17-16(22)15(21)14(20)12(6-18)24-17/h3-4,8,12,14-22H,1,5-6H2,2H3/t8?,12-,14-,15+,16-,17-/m1/s1
SMILES OC[C@H]1O[C@@H](Oc2ccc(c3c2C(C3)C(=C)C)O)[C@@H]([C@H]([C@@H]1O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   338.14 Volume:   327.905
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Van der Waals volume.
Dense:   1.031 LogP:   0.827
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.451
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.092
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The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   16.0
TPSA:   119.61
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Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   5.0 Rings:   3.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.482 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.242 Fsp3:   0.529
MCE-18:   70.769
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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:   Rejected GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.48 Fluc inhibitor:   0.017
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.611
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.274
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.166 Promiscuous compounds:   0.106

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.731 MDCK Permeability:   -4.989
Pgp-inhibitor:   0.0 Pgp-substrate:   0.062
PAMPA:   0.942
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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):   0.484
20% Bioavailability (F20%):   0.336 30% Bioavailability (F30%):   0.987
50% Bioavailability (F50%):   0.986

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.216 MRP1:   0.296
Plasma Protein Binding (PPB):   76.901% Volume Distribution (VD):   -0.06
Fu: 23.859%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.033
BSEP inhibitor:   0.004

ADMET: Metabolism

CYP1A2-inhibitor:   0.027 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.005 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.01
CYP3A4-inhibitor:   0.007 CYP3A4-substrate:   0.002
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.326
HLM stability:   0.011
?
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):  4.038 Half-life (T1/2):  3.106

ADMET: Toxicity

hERG Blockers:  0.014 hERG Blockers (10um):  0.121
Human Hepatotoxicity (H-HT):  0.577 Drug-induced Liver Injury (DILI):  0.5
AMES Toxicity:  0.869 Rat Oral Acute Toxicity:  0.048
Maximum Recommended Daily Dose:  0.038 Skin Sensitization:  0.998
Carcinogencity:  0.385 Eye Corrosion:  0.001
Eye Irritation:  0.587 Respiratory Toxicity:  0.081
Drug-induced Neurotoxicity:  0.023 Ototoxicity:  0.933
Hematotoxicity:  0.292 Drug-induced Nephrotoxicity:  0.351
Genotoxicity:  0.235 RPMI-8226 Immunitoxicity:  0.065
A549 Cytotoxicity:  0.176 Hek293 Cytotoxicity:  0.126
BCF:   0.719
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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:   3.385
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.2
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.269
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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
NPO32963 Acremonium sp. Species n.a. Eukaryota n.a. n.a. n.a. PMID[12444684]
NPO32963 Acremonium sp. Species n.a. Eukaryota n.a. n.a. n.a. PMID[16441074]
NPO32963 Acremonium sp. Species n.a. Eukaryota n.a. Australian n.a. PMID[18288804]
NPO32963 Acremonium sp. Species n.a. Eukaryota n.a. n.a. n.a. PMID[19199645]
NPO32963 Acremonium sp. Species n.a. Eukaryota n.a. Mangrove Rhizophora apiculata n.a. PMID[22524636]
NPO32963 Acremonium sp. Species n.a. Eukaryota n.a. n.a. n.a. PMID[22524636]
NPO32963 Acremonium sp. Species n.a. Eukaryota n.a. n.a. n.a. PMID[25689430]
NPO32963 Acremonium sp. Species n.a. Eukaryota n.a. n.a. n.a. PMID[26928174]
NPO32963 Acremonium sp. Species n.a. Eukaryota n.a. n.a. n.a. Database[COCONUT]

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
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = -10.6 % PMID[12444684]
NPT1 Others Radical scavenging activity n.a. Activity = 5.6 % DOI[10.6019/CHEMBL1201861]
NPT1 Others Radical scavenging activity n.a. Activity = 17.5 % PMID[20439614]
NPT1 Others Radical scavenging activity n.a. Activity = 27.7 % PubChem BioAssay data set
NPT1 Others Radical scavenging activity n.a. Activity = 43.0 % PMID[24332631]
NPT1 Others Radical scavenging activity n.a. Activity = 79.9 % PMID[541686]

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 NPC475628 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
0.6029 Remote Similarity NPC177742
0.5909 Remote Similarity NPC611586
0.5846 Remote Similarity NPC97326
0.5692 Remote Similarity NPC106025
0.5645 Remote Similarity NPC40377
0.5616 Remote Similarity NPC56735
0.5616 Remote Similarity NPC147596
0.5522 Remote Similarity NPC477240
0.5395 Remote Similarity NPC476203
0.5345 Remote Similarity NPC142319
0.5294 Remote Similarity NPC199335
0.527 Remote Similarity NPC61594
0.5238 Remote Similarity NPC214454
0.5231 Remote Similarity NPC23084
0.5217 Remote Similarity NPC190217
0.5143 Remote Similarity NPC610808
0.5132 Remote Similarity NPC607365
0.5082 Remote Similarity NPC9248
0.5082 Remote Similarity NPC152722
0.5068 Remote Similarity NPC271385
0.5068 Remote Similarity NPC146837

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC475628 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