Natural Product: NPC546625

Natural Product IDNPC546625
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (2~{R},3~{R},4~{S},5~{R},6~{S})-3,4,5-trihydroxy-6-[5-hydroxy-2-(4-hydroxyphenyl)-4-oxo-chromen-7-yl]oxy-tetrahydropyran-2-carboxylic acid
IUPAC Name (2~{R},3~{R},4~{S},5~{R},6~{S})-3,4,5-trihydroxy-6-[5-hydroxy-2-(4-hydroxyphenyl)-4-oxo-chromen-7-yl]oxy-tetrahydropyran-2-carboxylic acid
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]

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 JBFOLLJCGUCDQP-HMPZBHLVSA-N
Standard InCHI InChI=1S/C21H18O11/c22-9-3-1-8(2-4-9)13-7-12(24)15-11(23)5-10(6-14(15)31-13)30-21-18(27)16(25)17(26)19(32-21)20(28)29/h1-7,16-19,21-23,25-27H,(H,28,29)/t16-,17+,18+,19+,21+/m0/s1
SMILES O=C(O)[C@@H]1O[C@@H](OC2=CC(O)=C3C(=O)C=C(C4=CC=C(O)C=C4)OC3=C2)[C@H](O)[C@@H](O)[C@H]1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   446.08 Volume:   410.511
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Van der Waals volume.
Dense:   1.087 LogP:   1.133
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.338
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.416
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The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   25.0
TPSA:   187.12
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Topological Polar Surface Area.
 H-Bond Acceptor:   11.0
H-Bond Donor:   6.0 Rings:   4.0
Heavy Atoms:   11.0

MedChem Properties

QED Drug-Likeness Score:   0.32 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.874 Fsp3:   0.238
MCE-18:   88.0
?
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:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.476 Fluc inhibitor:   0.41
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.949
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.88
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.286 Promiscuous compounds:   0.412

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.327 MDCK Permeability:   -5.159
Pgp-inhibitor:   0.0 Pgp-substrate:   0.579
PAMPA:   1.0
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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):   0.107
20% Bioavailability (F20%):   0.258 30% Bioavailability (F30%):   0.655
50% Bioavailability (F50%):   0.961

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.925
Plasma Protein Binding (PPB):   80.423% Volume Distribution (VD):   -0.089
Fu: 15.087%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.548
OATP1B3 inhibitor:   0.944 BCRP inhibitor:   0.163
BSEP inhibitor:   0.009

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.607 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.005
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.001
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.731
HLM stability:   0.003
?
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):  2.111 Half-life (T1/2):  4.067

ADMET: Toxicity

hERG Blockers:  0.023 hERG Blockers (10um):  0.09
Human Hepatotoxicity (H-HT):  0.429 Drug-induced Liver Injury (DILI):  0.963
AMES Toxicity:  0.491 Rat Oral Acute Toxicity:  0.112
Maximum Recommended Daily Dose:  0.23 Skin Sensitization:  0.65
Carcinogencity:  0.118 Eye Corrosion:  0.0
Eye Irritation:  0.852 Respiratory Toxicity:  0.156
Drug-induced Neurotoxicity:  0.004 Ototoxicity:  0.58
Hematotoxicity:  0.042 Drug-induced Nephrotoxicity:  0.312
Genotoxicity:  0.9 RPMI-8226 Immunitoxicity:  0.058
A549 Cytotoxicity:  0.107 Hek293 Cytotoxicity:  0.266
BCF:   0.273
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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:   2.941
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.227
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.429
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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
NPO25135 Marchantia berteroana Species Marchantiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO47987 Callicarpa japonica Thunb.var.luxurians Rehd. Genus Plumulariidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25135 Marchantia berteroana Species Marchantiaceae 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

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 NPC546625 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
1.0 High Similarity NPC282169
0.8889 High Similarity NPC20505
0.8514 High Similarity NPC608742
0.7792 Intermediate Similarity NPC43211
0.7215 Intermediate Similarity NPC210094
0.6795 Remote Similarity NPC331652
0.679 Remote Similarity NPC237435
0.6782 Remote Similarity NPC64051
0.6709 Remote Similarity NPC39360
0.6709 Remote Similarity NPC29763
0.6709 Remote Similarity NPC210003
0.6707 Remote Similarity NPC610187
0.6522 Remote Similarity NPC253685
0.6471 Remote Similarity NPC600989
0.6463 Remote Similarity NPC27942
0.6386 Remote Similarity NPC135277
0.631 Remote Similarity NPC115760
0.6265 Remote Similarity NPC101191
0.6264 Remote Similarity NPC229409
0.6098 Remote Similarity NPC19709
0.6056 Remote Similarity NPC234133
0.6024 Remote Similarity NPC189142
0.6024 Remote Similarity NPC77660
0.5889 Remote Similarity NPC44931
0.587 Remote Similarity NPC46202
0.5814 Remote Similarity NPC235260
0.5814 Remote Similarity NPC155763
0.5747 Remote Similarity NPC601144
0.5684 Remote Similarity NPC270675
0.5684 Remote Similarity NPC195685
0.5647 Remote Similarity NPC95090
0.5647 Remote Similarity NPC27408
0.5618 Remote Similarity NPC190003
0.5595 Remote Similarity NPC473043
0.5581 Remote Similarity NPC181712
0.5529 Remote Similarity NPC261866
0.551 Remote Similarity NPC472994
0.5506 Remote Similarity NPC311830
0.5495 Remote Similarity NPC606546
0.5484 Remote Similarity NPC65003
0.5455 Remote Similarity NPC49344
0.5408 Remote Similarity NPC101636
0.5408 Remote Similarity NPC298171
0.5385 Remote Similarity NPC222674
0.5341 Remote Similarity NPC138927
0.5333 Remote Similarity NPC108406
0.5319 Remote Similarity NPC210073
0.5294 Remote Similarity NPC472993
0.5222 Remote Similarity NPC22832
0.5222 Remote Similarity NPC243930
0.5222 Remote Similarity NPC264735
0.5172 Remote Similarity NPC249281
0.5172 Remote Similarity NPC108831
0.5172 Remote Similarity NPC182634
0.5161 Remote Similarity NPC8856
0.5155 Remote Similarity NPC65711
0.5152 Remote Similarity NPC479765
0.5114 Remote Similarity NPC93337
0.5114 Remote Similarity NPC297987
0.5114 Remote Similarity NPC146792
0.5114 Remote Similarity NPC323593
0.5114 Remote Similarity NPC203500
0.5104 Remote Similarity NPC122809
0.5102 Remote Similarity NPC210961
0.5067 Remote Similarity NPC127447
0.5067 Remote Similarity NPC29353
0.5056 Remote Similarity NPC105025
0.5056 Remote Similarity NPC610763
0.5051 Remote Similarity NPC479766
0.505 Remote Similarity NPC179862

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC546625 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
0.679 Remote Similarity NPD4338 Clinical (unspecified phase)

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