Natural Product: NPC495416

Natural Product IDNPC495416
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 2-(3,4-dihydroxy-5-methoxy-phenyl)-5-methoxy-7-[(2~{S},3~{R},4~{S},5~{S},6~{R})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-chromen-4-one
IUPAC Name 2-(3,4-dihydroxy-5-methoxy-phenyl)-5-methoxy-7-[(2~{S},3~{R},4~{S},5~{S},6~{R})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-chromen-4-one
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 GFGUBNSRYJIORK-LDBVRRDLSA-N
Standard InCHI InChI=1S/C23H24O12/c1-31-14-5-10(33-23-22(30)21(29)20(28)17(8-24)35-23)6-15-18(14)11(25)7-13(34-15)9-3-12(26)19(27)16(4-9)32-2/h3-7,17,20-24,26-30H,8H2,1-2H3/t17-,20-,21+,22-,23-/m1/s1
SMILES COC1=CC(C2=CC(=O)C3=C(OC)C=C(O[C@@H]4O[C@H](CO)[C@@H](O)[C@H](O)[C@H]4O)C=C3O2)=CC(O)=C1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   492.13 Volume:   456.529
?
Van der Waals volume.
Dense:   1.078 LogP:   0.573
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.102
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.237
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The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   24.0
TPSA:   188.51
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Topological Polar Surface Area.
 H-Bond Acceptor:   12.0
H-Bond Donor:   6.0 Rings:   4.0
Heavy Atoms:   12.0

MedChem Properties

QED Drug-Likeness Score:   0.254 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.988 Fsp3:   0.348
MCE-18:   89.71
?
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:   1 PAINS Alert:   1
Colloidal aggregators:   0.597 Fluc inhibitor:   0.197
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.97
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.901
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.098 Promiscuous compounds:   0.636

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.096 MDCK Permeability:   -5.375
Pgp-inhibitor:   0.001 Pgp-substrate:   0.083
PAMPA:   0.839
?
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):   0.74
20% Bioavailability (F20%):   0.311 30% Bioavailability (F30%):   0.969
50% Bioavailability (F50%):   0.991

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.572
Plasma Protein Binding (PPB):   80.861% Volume Distribution (VD):   -0.105
Fu: 17.6%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.981
BSEP inhibitor:   0.043

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.001 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.004 CYP2D6-substrate:   0.011
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.001
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.561
HLM stability:   0.002
?
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):  3.198 Half-life (T1/2):  4.131

ADMET: Toxicity

hERG Blockers:  0.027 hERG Blockers (10um):  0.126
Human Hepatotoxicity (H-HT):  0.624 Drug-induced Liver Injury (DILI):  0.957
AMES Toxicity:  0.888 Rat Oral Acute Toxicity:  0.031
Maximum Recommended Daily Dose:  0.06 Skin Sensitization:  0.994
Carcinogencity:  0.388 Eye Corrosion:  0.0
Eye Irritation:  0.368 Respiratory Toxicity:  0.02
Drug-induced Neurotoxicity:  0.006 Ototoxicity:  0.902
Hematotoxicity:  0.276 Drug-induced Nephrotoxicity:  0.483
Genotoxicity:  0.842 RPMI-8226 Immunitoxicity:  0.069
A549 Cytotoxicity:  0.397 Hek293 Cytotoxicity:  0.284
BCF:   0.424
?
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:   3.105
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.652
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.829
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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
NPO33342 Bruguiera gymnorrhiza Species Rhizophoraceae Eukaryota stems Xiamen, China 2002-JUN PMID[15387677]
NPO33342 Bruguiera gymnorrhiza Species Rhizophoraceae Eukaryota n.a. n.a. n.a. PMID[16562850]
NPO33342 Bruguiera gymnorrhiza Species Rhizophoraceae 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

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 NPC495416 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
0.7867 Intermediate Similarity NPC610763
0.7792 Intermediate Similarity NPC284960
0.7368 Intermediate Similarity NPC110349
0.7089 Intermediate Similarity NPC182045
0.6667 Remote Similarity NPC222936
0.6235 Remote Similarity NPC311830
0.622 Remote Similarity NPC168822
0.622 Remote Similarity NPC189142
0.622 Remote Similarity NPC77660
0.6145 Remote Similarity NPC58716
0.6145 Remote Similarity NPC45638
0.6118 Remote Similarity NPC22832
0.6071 Remote Similarity NPC201292
0.6024 Remote Similarity NPC95090
0.6024 Remote Similarity NPC27408
0.593 Remote Similarity NPC243930
0.593 Remote Similarity NPC601144
0.5904 Remote Similarity NPC58053
0.5904 Remote Similarity NPC261866
0.5904 Remote Similarity NPC83283
0.5862 Remote Similarity NPC602805
0.5862 Remote Similarity NPC607707
0.5824 Remote Similarity NPC473512
0.5765 Remote Similarity NPC186807
0.5747 Remote Similarity NPC605067
0.5714 Remote Similarity NPC39360
0.5714 Remote Similarity NPC45618
0.5714 Remote Similarity NPC29763
0.5714 Remote Similarity NPC210003
0.5647 Remote Similarity NPC93337
0.5647 Remote Similarity NPC146792
0.5632 Remote Similarity NPC609451
0.5618 Remote Similarity NPC479407
0.5604 Remote Similarity NPC473657
0.5581 Remote Similarity NPC84362
0.5581 Remote Similarity NPC105025
0.5532 Remote Similarity NPC475366
0.5532 Remote Similarity NPC475497
0.5517 Remote Similarity NPC100720
0.5484 Remote Similarity NPC129827
0.5465 Remote Similarity NPC277205
0.5465 Remote Similarity NPC37919
0.5455 Remote Similarity NPC479402
0.5444 Remote Similarity NPC601586
0.5402 Remote Similarity NPC245014
0.5393 Remote Similarity NPC486578
0.5393 Remote Similarity NPC601710
0.5376 Remote Similarity NPC15358
0.5349 Remote Similarity NPC143851
0.5341 Remote Similarity NPC117260
0.5341 Remote Similarity NPC599850
0.5333 Remote Similarity NPC88023
0.5333 Remote Similarity NPC479406
0.5333 Remote Similarity NPC309025
0.5319 Remote Similarity NPC607513
0.5287 Remote Similarity NPC136042
0.5287 Remote Similarity NPC609879
0.5281 Remote Similarity NPC191306
0.5269 Remote Similarity NPC295613
0.5233 Remote Similarity NPC183357
0.5233 Remote Similarity NPC473043
0.5227 Remote Similarity NPC603655
0.5208 Remote Similarity NPC284277
0.5172 Remote Similarity NPC19709
0.5169 Remote Similarity NPC325555
0.5169 Remote Similarity NPC226304
0.5158 Remote Similarity NPC3583
0.5111 Remote Similarity NPC169404
0.5111 Remote Similarity NPC176186
0.5111 Remote Similarity NPC285197
0.5111 Remote Similarity NPC488071
0.5109 Remote Similarity NPC469931
0.5102 Remote Similarity NPC150767
0.5055 Remote Similarity NPC606560

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC495416 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
0.5556 Remote Similarity NPD7472 Pre-clinical

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