Natural Product: NPC498460

Natural Product IDNPC498460
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 2-(4-hydroxy-3-methoxy-phenyl)-7-methoxy-5-[(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-(4-hydroxy-3-methoxy-phenyl)-7-methoxy-5-[(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 UHLWPBYBTUVRPB-DODNOZFWSA-N
Standard InCHI InChI=1S/C23H24O11/c1-30-11-6-16-19(13(26)8-14(32-16)10-3-4-12(25)15(5-10)31-2)17(7-11)33-23-22(29)21(28)20(27)18(9-24)34-23/h3-8,18,20-25,27-29H,9H2,1-2H3/t18-,20-,21+,22-,23-/m1/s1
SMILES COC1=CC(O[C@@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O)=C2C(=O)C=C(C3=CC=C(O)C(OC)=C3)OC2=C1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   476.13 Volume:   447.739
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Van der Waals volume.
Dense:   1.063 LogP:   1.276
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.749
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.378
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The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   24.0
TPSA:   168.28
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Topological Polar Surface Area.
 H-Bond Acceptor:   11.0
H-Bond Donor:   5.0 Rings:   4.0
Heavy Atoms:   11.0

MedChem Properties

QED Drug-Likeness Score:   0.333 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.838 Fsp3:   0.348
MCE-18:   86.387
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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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.63 Fluc inhibitor:   0.288
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.971
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.871
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.091 Promiscuous compounds:   0.435

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.984 MDCK Permeability:   -5.16
Pgp-inhibitor:   0.006 Pgp-substrate:   0.181
PAMPA:   0.601
?
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):   0.525
20% Bioavailability (F20%):   0.218 30% Bioavailability (F30%):   0.918
50% Bioavailability (F50%):   0.993

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.401
Plasma Protein Binding (PPB):   83.77% Volume Distribution (VD):   -0.078
Fu: 17.151%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.984
BSEP inhibitor:   0.198

ADMET: Metabolism

CYP1A2-inhibitor:   0.023 CYP1A2-substrate:   0.002
CYP2C19-inhibitor:   0.144 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.034 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.204 CYP2D6-substrate:   0.885
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.995
HLM stability:   0.116
?
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):  3.08 Half-life (T1/2):  3.633

ADMET: Toxicity

hERG Blockers:  0.03 hERG Blockers (10um):  0.125
Human Hepatotoxicity (H-HT):  0.634 Drug-induced Liver Injury (DILI):  0.96
AMES Toxicity:  0.901 Rat Oral Acute Toxicity:  0.048
Maximum Recommended Daily Dose:  0.122 Skin Sensitization:  0.991
Carcinogencity:  0.5 Eye Corrosion:  0.0
Eye Irritation:  0.472 Respiratory Toxicity:  0.063
Drug-induced Neurotoxicity:  0.013 Ototoxicity:  0.794
Hematotoxicity:  0.285 Drug-induced Nephrotoxicity:  0.467
Genotoxicity:  0.732 RPMI-8226 Immunitoxicity:  0.106
A549 Cytotoxicity:  0.289 Hek293 Cytotoxicity:  0.418
BCF:   0.459
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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:   3.087
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.465
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.727
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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
NPO22441 Senna spectabilis Species Fabaceae Eukaryota flowers n.a. n.a. PMID[30413343]
NPO22441 Senna spectabilis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4718 Daphne sericea Species Thymelaeaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22441 Senna spectabilis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4718 Daphne sericea Species Thymelaeaceae 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 NPC498460 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
0.7895 Intermediate Similarity NPC610763
0.7821 Intermediate Similarity NPC284960
0.7792 Intermediate Similarity NPC182045
0.7722 Intermediate Similarity NPC311830
0.7632 Intermediate Similarity NPC110349
0.7284 Intermediate Similarity NPC602805
0.716 Intermediate Similarity NPC601144
0.6707 Remote Similarity NPC222936
0.6548 Remote Similarity NPC601710
0.6543 Remote Similarity NPC83283
0.6353 Remote Similarity NPC606560
0.6222 Remote Similarity NPC129827
0.6207 Remote Similarity NPC479407
0.6207 Remote Similarity NPC601586
0.6163 Remote Similarity NPC22832
0.6163 Remote Similarity NPC243930
0.6145 Remote Similarity NPC39360
0.6145 Remote Similarity NPC29763
0.6145 Remote Similarity NPC210003
0.6092 Remote Similarity NPC607707
0.6071 Remote Similarity NPC93337
0.6071 Remote Similarity NPC168822
0.6071 Remote Similarity NPC95090
0.6071 Remote Similarity NPC27408
0.6071 Remote Similarity NPC189142
0.6071 Remote Similarity NPC77660
0.6023 Remote Similarity NPC488072
0.6 Remote Similarity NPC105025
0.6 Remote Similarity NPC45638
0.5977 Remote Similarity NPC101026
0.5977 Remote Similarity NPC488077
0.5952 Remote Similarity NPC58053
0.593 Remote Similarity NPC201292
0.5909 Remote Similarity NPC206123
0.5882 Remote Similarity NPC146792
0.587 Remote Similarity NPC473512
0.5862 Remote Similarity NPC609451
0.5843 Remote Similarity NPC203050
0.5843 Remote Similarity NPC469931
0.5843 Remote Similarity NPC225434
0.5833 Remote Similarity NPC195257
0.5833 Remote Similarity NPC183357
0.5814 Remote Similarity NPC186807
0.5814 Remote Similarity NPC58716
0.5795 Remote Similarity NPC605067
0.5745 Remote Similarity NPC284277
0.5652 Remote Similarity NPC295613
0.5591 Remote Similarity NPC15358
0.5584 Remote Similarity NPC606105
0.5581 Remote Similarity NPC261866
0.5581 Remote Similarity NPC45618
0.5556 Remote Similarity NPC88023
0.5556 Remote Similarity NPC309025
0.5455 Remote Similarity NPC84362
0.5444 Remote Similarity NPC197285
0.5435 Remote Similarity NPC4390
0.5417 Remote Similarity NPC475366
0.5417 Remote Similarity NPC475497
0.5402 Remote Similarity NPC143851
0.5393 Remote Similarity NPC100720
0.5385 Remote Similarity NPC150442
0.5341 Remote Similarity NPC259152
0.5333 Remote Similarity NPC191306
0.5333 Remote Similarity NPC169404
0.5333 Remote Similarity NPC176186
0.5319 Remote Similarity NPC473657
0.5281 Remote Similarity NPC22195
0.5281 Remote Similarity NPC21190
0.5275 Remote Similarity NPC486578
0.5256 Remote Similarity NPC179126
0.5222 Remote Similarity NPC599850
0.5217 Remote Similarity NPC479406
0.5217 Remote Similarity NPC111249
0.519 Remote Similarity NPC137062
0.5169 Remote Similarity NPC297987
0.5169 Remote Similarity NPC277205
0.5169 Remote Similarity NPC37919
0.5169 Remote Similarity NPC136042
0.5169 Remote Similarity NPC323593
0.5169 Remote Similarity NPC203500
0.5169 Remote Similarity NPC609879
0.5165 Remote Similarity NPC479402
0.5161 Remote Similarity NPC48773
0.5128 Remote Similarity NPC20830
0.5125 Remote Similarity NPC473045
0.5114 Remote Similarity NPC331652
0.5111 Remote Similarity NPC24043
0.5111 Remote Similarity NPC488080
0.5111 Remote Similarity NPC169977
0.5111 Remote Similarity NPC603655
0.5056 Remote Similarity NPC95855
0.5056 Remote Similarity NPC19709
0.5055 Remote Similarity NPC42773
0.5055 Remote Similarity NPC475942
0.5055 Remote Similarity NPC27942
0.5055 Remote Similarity NPC45522
0.5055 Remote Similarity NPC117260
0.5052 Remote Similarity NPC607513

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC498460 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
0.5446 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