Natural Product: NPC477698

Natural Product IDNPC477698
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (3S,4S)-3-(Hydroxymethyl)-4-[alpha-(4-methoxy-1,3-benzodioxole-6-yl)-3,4,5-trimethoxybenzyl]tetrahydrofuran-2-one
IUPAC Name (3S,4S)-3-(hydroxymethyl)-4-[(7-methoxy-1,3-benzodioxol-5-yl)-(3,4,5-trimethoxyphenyl)methyl]oxolan-2-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 11655244
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000296] Benzodioxoles

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 XQWLRAUXZRVNAY-YNCRUDOASA-N
Standard InCHI InChI=1S/C23H26O9/c1-26-16-5-12(6-17(27-2)21(16)29-4)20(15-10-30-23(25)14(15)9-24)13-7-18(28-3)22-19(8-13)31-11-32-22/h5-8,14-15,20,24H,9-11H2,1-4H3/t14-,15-,20?/m1/s1
SMILES COC1=CC(=CC2=C1OCO2)C([C@@H]3COC(=O)[C@@H]3CO)C4=CC(=C(C(=C4)OC)OC)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   446.16 Volume:   432.795
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Van der Waals volume.
Dense:   1.031 LogP:   2.218
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.517
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.271
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The logarithm of aqueous solubility value.
Rotatable Bonds:   8.0 Rigid Bonds:   22.0
TPSA:   101.91
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Topological Polar Surface Area.
 H-Bond Acceptor:   9.0
H-Bond Donor:   1.0 Rings:   4.0
Heavy Atoms:   9.0

MedChem Properties

QED Drug-Likeness Score:   0.612 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.795 Fsp3:   0.435
MCE-18:   77.818
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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:   0 PAINS Alert:   0
Colloidal aggregators:   0.028 Fluc inhibitor:   0.057
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.029
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.333
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.075 Promiscuous compounds:   0.432

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.009 MDCK Permeability:   -4.756
Pgp-inhibitor:   0.402 Pgp-substrate:   0.003
PAMPA:   0.009
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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):   0.0
20% Bioavailability (F20%):   0.004 30% Bioavailability (F30%):   0.0
50% Bioavailability (F50%):   0.143

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.985 MRP1:   0.999
Plasma Protein Binding (PPB):   91.381% Volume Distribution (VD):   -0.067
Fu: 7.776%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.988
OATP1B3 inhibitor:   0.96 BCRP inhibitor:   0.012
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.007 CYP1A2-substrate:   0.17
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.541 CYP2C9-substrate:   0.003
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.993
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   0.955
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.306
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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):  4.455 Half-life (T1/2):  1.589

ADMET: Toxicity

hERG Blockers:  0.08 hERG Blockers (10um):  0.395
Human Hepatotoxicity (H-HT):  0.867 Drug-induced Liver Injury (DILI):  0.891
AMES Toxicity:  0.509 Rat Oral Acute Toxicity:  0.288
Maximum Recommended Daily Dose:  0.548 Skin Sensitization:  0.861
Carcinogencity:  0.826 Eye Corrosion:  0.009
Eye Irritation:  0.667 Respiratory Toxicity:  0.459
Drug-induced Neurotoxicity:  0.835 Ototoxicity:  0.789
Hematotoxicity:  0.722 Drug-induced Nephrotoxicity:  0.95
Genotoxicity:  0.941 RPMI-8226 Immunitoxicity:  0.32
A549 Cytotoxicity:  0.445 Hek293 Cytotoxicity:  0.398
BCF:   1.209
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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:   3.504
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.133
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.075
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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
NPO27718 Peperomia dindygulensis Species Piperaceae Eukaryota whole plant Yunnan Province, China 2002-FEB PMID[16309318]
NPO27718 Peperomia dindygulensis Species Piperaceae Eukaryota whole plant Yunnan Province, China 2002-FEB PMID[16724842]
NPO27718 Peperomia dindygulensis Species Piperaceae 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
NPT1475 Cell line WI-38 VA13 Homo sapiens IC50 > 224000 nM PMID[16724842]
NPT65 Cell line HepG2 Homo sapiens IC50 > 224000 nM PMID[16724842]
NPT27 Others Unspecified n.a. IC50 > 224000 nM PMID[16724842]
NPT2 Others Unspecified n.a. Activity = 105 % PMID[16724842]
NPT2 Others Unspecified n.a. Activity = 109 % PMID[16724842]
NPT2 Others Unspecified n.a. Activity = 125 % PMID[16724842]
NPT2 Others Unspecified n.a. Activity = 98 % PMID[16724842]
NPT2 Others Unspecified n.a. Activity = 94 % PMID[16724842]
NPT2 Others Unspecified n.a. Activity = 83 % PMID[16724842]

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 NPC477698 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
0.9783 High Similarity NPC164082
0.74 Intermediate Similarity NPC151423
0.72 Intermediate Similarity NPC218841
0.6491 Remote Similarity NPC477695
0.6271 Remote Similarity NPC474965
0.623 Remote Similarity NPC477699
0.6226 Remote Similarity NPC56091
0.6 Remote Similarity NPC44245
0.6 Remote Similarity NPC475000
0.5818 Remote Similarity NPC193779
0.5645 Remote Similarity NPC262455
0.5645 Remote Similarity NPC177476
0.5625 Remote Similarity NPC207584
0.5625 Remote Similarity NPC19947
0.5556 Remote Similarity NPC237946
0.5556 Remote Similarity NPC149505
0.5556 Remote Similarity NPC32373
0.5556 Remote Similarity NPC480477
0.5484 Remote Similarity NPC80230
0.5484 Remote Similarity NPC104024
0.5484 Remote Similarity NPC101755
0.5484 Remote Similarity NPC304687
0.5484 Remote Similarity NPC65574
0.5439 Remote Similarity NPC477696
0.5345 Remote Similarity NPC40237
0.5323 Remote Similarity NPC239890
0.5323 Remote Similarity NPC209411
0.5323 Remote Similarity NPC477700
0.5254 Remote Similarity NPC470811
0.5254 Remote Similarity NPC477697
0.5172 Remote Similarity NPC92693
0.5147 Remote Similarity NPC115281
0.5079 Remote Similarity NPC287124

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC477698 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 NPD4965 Approved
0.5556 Remote Similarity NPD4966 Phase 4
0.5556 Remote Similarity NPD4967 Phase 2

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