Natural Product: NPC472918

Natural Product IDNPC472918
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 MYJSUEBYZUYQNB-KRWDZBQOSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3594096
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002507] Homoisoflavonoids
        • [CHEMONTID:0002508] Homoisoflavans

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 MYJSUEBYZUYQNB-KRWDZBQOSA-N
Standard InCHI InChI=1S/C17H16O6/c1-22-12-6-13(19)15-14(7-12)23-9-17(21,16(15)20)8-10-2-4-11(18)5-3-10/h2-7,18-19,21H,8-9H2,1H3/t17-/m0/s1
SMILES COc1cc(O)c2c(c1)OC[C@@](C2=O)(O)Cc1ccc(cc1)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   316.09 Volume:   311.205
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Van der Waals volume.
Dense:   1.016 LogP:   1.933
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.183
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.538
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The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   18.0
TPSA:   96.22
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Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.797 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.158 Fsp3:   0.235
MCE-18:   60.619
?
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:   0.123 Fluc inhibitor:   0.347
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.297
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.328
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.231 Promiscuous compounds:   0.183

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.104 MDCK Permeability:   -4.811
Pgp-inhibitor:   0.097 Pgp-substrate:   0.584
PAMPA:   0.821
?
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):   0.0
20% Bioavailability (F20%):   0.132 30% Bioavailability (F30%):   0.097
50% Bioavailability (F50%):   0.973

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.023 MRP1:   0.656
Plasma Protein Binding (PPB):   89.251% Volume Distribution (VD):   0.116
Fu: 12.758%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.993
OATP1B3 inhibitor:   0.986 BCRP inhibitor:   0.676
BSEP inhibitor:   0.989

ADMET: Metabolism

CYP1A2-inhibitor:   0.98 CYP1A2-substrate:   0.185
CYP2C19-inhibitor:   0.735 CYP2C19-substrate:   0.099
CYP2C9-inhibitor:   0.783 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.581 CYP2D6-substrate:   0.901
CYP3A4-inhibitor:   0.009 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.017
HLM stability:   0.547
?
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):  10.827 Half-life (T1/2):  1.525

ADMET: Toxicity

hERG Blockers:  0.086 hERG Blockers (10um):  0.368
Human Hepatotoxicity (H-HT):  0.781 Drug-induced Liver Injury (DILI):  0.334
AMES Toxicity:  0.464 Rat Oral Acute Toxicity:  0.237
Maximum Recommended Daily Dose:  0.866 Skin Sensitization:  0.632
Carcinogencity:  0.642 Eye Corrosion:  0.0
Eye Irritation:  0.839 Respiratory Toxicity:  0.132
Drug-induced Neurotoxicity:  0.075 Ototoxicity:  0.406
Hematotoxicity:  0.225 Drug-induced Nephrotoxicity:  0.491
Genotoxicity:  0.987 RPMI-8226 Immunitoxicity:  0.151
A549 Cytotoxicity:  0.071 Hek293 Cytotoxicity:  0.749
BCF:   1.001
?
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:   3.53
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.634
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.816
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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
NPO33045 bellevalia eigii Species Hyacinthaceae Eukaryota Bulbs Irbid, Jordan n.a. PMID[26147490]
NPO33045 bellevalia eigii Species Hyacinthaceae 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
NPT400 Cell line MDA-MB-435 Homo sapiens IC50 > 20000.0 nM DOI[10.6019/CHEMBL1201861]
NPT139 Cell line HT-29 Homo sapiens IC50 > 20000.0 nM PMID[20585136]

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 NPC472918 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
0.8367 Intermediate Similarity NPC45544
0.6852 Remote Similarity NPC482955
0.6852 Remote Similarity NPC48204
0.6731 Remote Similarity NPC229190
0.6429 Remote Similarity NPC152904
0.5862 Remote Similarity NPC284550
0.5833 Remote Similarity NPC67876
0.569 Remote Similarity NPC141212
0.5536 Remote Similarity NPC18877
0.5085 Remote Similarity NPC303255

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC472918 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