Natural Product: NPC114740

Natural Product IDNPC114740
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Haploperoside
IUPAC Name 6-methoxy-7-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-[[(2R,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxymethyl]oxan-2-yl]oxychromen-2-one
Synonyms Haploperoside
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1928410
PubChem CID 21607625
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000145] Coumarins and derivatives
        • [CHEMONTID:0001743] Coumarin 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 FCIZPHNZRNLUJD-HLUXVQISSA-N
Standard InCHI InChI=1S/C22H28O13/c1-8-15(24)17(26)19(28)21(32-8)31-7-13-16(25)18(27)20(29)22(35-13)34-12-6-10-9(5-11(12)30-2)3-4-14(23)33-10/h3-6,8,13,15-22,24-29H,7H2,1-2H3/t8-,13+,15-,16+,17+,18-,19+,20+,21+,22+/m0/s1
SMILES COc1cc2ccc(=O)oc2cc1O[C@@H]1O[C@H](CO[C@@H]2O[C@@H](C)[C@@H]([C@H]([C@H]2O)O)O)[C@H]([C@@H]([C@H]1O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   500.15 Volume:   455.933
?
Van der Waals volume.
Dense:   1.097 LogP:   -1.659
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   -0.463
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.103
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   24.0
TPSA:   197.74
?
Topological Polar Surface Area.
 H-Bond Acceptor:   13.0
H-Bond Donor:   6.0 Rings:   4.0
Heavy Atoms:   13.0

MedChem Properties

QED Drug-Likeness Score:   0.235 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.43 Fsp3:   0.591
MCE-18:   96.429
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Accepted
Pfizer Rule:   Rejected GSK Rule:   Accepted
Golden Triangle Rule:   Accepted BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.641 Fluc inhibitor:   0.158
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.888
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.186
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.076 Promiscuous compounds:   0.061

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.172 MDCK Permeability:   -5.243
Pgp-inhibitor:   0.0 Pgp-substrate:   0.015
PAMPA:   0.998
?
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):   0.108
20% Bioavailability (F20%):   0.251 30% Bioavailability (F30%):   0.741
50% Bioavailability (F50%):   0.45

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.934
Plasma Protein Binding (PPB):   62.506% Volume Distribution (VD):   -0.44
Fu: 37.063%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.0
BSEP inhibitor:   0.075

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.147
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.252
HLM stability:   0.015
?
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):  1.435 Half-life (T1/2):  4.066

ADMET: Toxicity

hERG Blockers:  0.03 hERG Blockers (10um):  0.128
Human Hepatotoxicity (H-HT):  0.333 Drug-induced Liver Injury (DILI):  0.796
AMES Toxicity:  0.823 Rat Oral Acute Toxicity:  0.011
Maximum Recommended Daily Dose:  0.018 Skin Sensitization:  0.701
Carcinogencity:  0.06 Eye Corrosion:  0.0
Eye Irritation:  0.089 Respiratory Toxicity:  0.002
Drug-induced Neurotoxicity:  0.002 Ototoxicity:  0.948
Hematotoxicity:  0.175 Drug-induced Nephrotoxicity:  0.574
Genotoxicity:  0.348 RPMI-8226 Immunitoxicity:  0.176
A549 Cytotoxicity:  0.07 Hek293 Cytotoxicity:  0.155
BCF:   0.102
?
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:   2.559
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.108
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.239
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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
NPO1762 Citropsis articulata Species Rutaceae Eukaryota Root Bark n.a. n.a. PMID[21985060]
NPO1762 Citropsis articulata Species Rutaceae Eukaryota n.a. root n.a. PMID[21985060]
NPO1762 Citropsis articulata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1762 Citropsis articulata Species Rutaceae 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
NPT189 Cell line Vero Chlorocebus aethiops IC50 > 50.0 ug.mL-1 PMID[21985060]
NPT1225 Organism Plasmodium falciparum (isolate FcB1 / Columbia) Plasmodium falciparum FcB1/Columbia IC50 > 100.0 ug.mL-1 PMID[21985060]
NPT633 Organism Leishmania donovani Leishmania donovani EC50 > 125.0 ug.mL-1 PMID[21985060]
NPT471 Organism Trypanosoma brucei brucei Trypanosoma brucei brucei EC50 > 125.0 ug.mL-1 PMID[21985060]

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 NPC114740 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
0.6812 Remote Similarity NPC96294
0.6118 Remote Similarity NPC485744
0.6047 Remote Similarity NPC485745
0.6 Remote Similarity NPC84482
0.5955 Remote Similarity NPC485746
0.5875 Remote Similarity NPC476442
0.5875 Remote Similarity NPC215512
0.5833 Remote Similarity NPC99957
0.5658 Remote Similarity NPC479450
0.5467 Remote Similarity NPC469622
0.5444 Remote Similarity NPC475155
0.5385 Remote Similarity NPC204693
0.5349 Remote Similarity NPC284810
0.5233 Remote Similarity NPC485743
0.5172 Remote Similarity NPC181616
0.5161 Remote Similarity NPC475366
0.5109 Remote Similarity NPC22062
0.5109 Remote Similarity NPC473634
0.5109 Remote Similarity NPC138811
0.5063 Remote Similarity NPC469621

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC114740 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