Natural Product: NPC477695

Natural Product IDNPC477695
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-Methyl-4-[alpha-(4-methoxy-1,3-benzodioxole-6-yl)-4-hydroxy-3,5-dimethoxybenzyl]tetrahydrofuran-2-one
IUPAC Name (3S,4S)-4-[(4-hydroxy-3,5-dimethoxyphenyl)-(7-methoxy-1,3-benzodioxol-5-yl)methyl]-3-methyloxolan-2-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 11517262
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0000134] Phenols
        • [CHEMONTID:0000190] Methoxyphenols

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 ZOMWNRBXFSZJFM-WHRCVXDFSA-N
Standard InCHI InChI=1S/C22H24O8/c1-11-14(9-28-22(11)24)19(12-5-15(25-2)20(23)16(6-12)26-3)13-7-17(27-4)21-18(8-13)29-10-30-21/h5-8,11,14,19,23H,9-10H2,1-4H3/t11-,14+,19?/m0/s1
SMILES C[C@H]1[C@@H](COC1=O)C(C2=CC3=C(C(=C2)OC)OCO3)C4=CC(=C(C(=C4)OC)O)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   416.15 Volume:   406.709
?
Van der Waals volume.
Dense:   1.023 LogP:   2.128
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.284
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.261
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   22.0
TPSA:   92.68
?
Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   1.0 Rings:   4.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.719 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.795 Fsp3:   0.409
MCE-18:   78.194
?
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:   0.082 Fluc inhibitor:   0.015
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.036
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.361
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.212 Promiscuous compounds:   0.155

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.226 MDCK Permeability:   -4.82
Pgp-inhibitor:   0.525 Pgp-substrate:   0.044
PAMPA:   0.008
?
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%):   0.006 30% Bioavailability (F30%):   0.0
50% Bioavailability (F50%):   0.403

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.695 MRP1:   0.993
Plasma Protein Binding (PPB):   97.289% Volume Distribution (VD):   -0.206
Fu: 2.474%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   0.937 BCRP inhibitor:   0.094
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.849 CYP1A2-substrate:   0.941
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.519
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.998
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.972
?
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):  3.224 Half-life (T1/2):  1.699

ADMET: Toxicity

hERG Blockers:  0.095 hERG Blockers (10um):  0.402
Human Hepatotoxicity (H-HT):  0.886 Drug-induced Liver Injury (DILI):  0.89
AMES Toxicity:  0.526 Rat Oral Acute Toxicity:  0.377
Maximum Recommended Daily Dose:  0.72 Skin Sensitization:  0.758
Carcinogencity:  0.732 Eye Corrosion:  0.006
Eye Irritation:  0.599 Respiratory Toxicity:  0.45
Drug-induced Neurotoxicity:  0.868 Ototoxicity:  0.562
Hematotoxicity:  0.559 Drug-induced Nephrotoxicity:  0.95
Genotoxicity:  0.947 RPMI-8226 Immunitoxicity:  0.395
A549 Cytotoxicity:  0.379 Hek293 Cytotoxicity:  0.419
BCF:   1.248
?
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:   3.781
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.086
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.421
?
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 = 112000 nM PMID[16724842]
NPT65 Cell line HepG2 Homo sapiens IC50 = 159000 nM PMID[16724842]
NPT27 Others Unspecified n.a. IC50 = 174000 nM PMID[16724842]
NPT2 Others Unspecified n.a. Activity = 99 % PMID[16724842]
NPT2 Others Unspecified n.a. Activity = 104 % PMID[16724842]
NPT2 Others Unspecified n.a. Activity = 107 % PMID[16724842]
NPT2 Others Unspecified n.a. Activity = 93 % PMID[16724842]
NPT2 Others Unspecified n.a. Activity = 90 % PMID[16724842]
NPT2 Others Unspecified n.a. Activity = 71 % 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 NPC477695 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
0.8367 Intermediate Similarity NPC477696
0.8333 Intermediate Similarity NPC218841
0.8163 Intermediate Similarity NPC151423
0.8036 Intermediate Similarity NPC477699
0.7818 Intermediate Similarity NPC474965
0.7018 Intermediate Similarity NPC477700
0.6735 Remote Similarity NPC44245
0.6607 Remote Similarity NPC164082
0.6491 Remote Similarity NPC477698
0.6429 Remote Similarity NPC470811
0.6429 Remote Similarity NPC477697
0.6061 Remote Similarity NPC24425
0.6 Remote Similarity NPC56091
0.5902 Remote Similarity NPC477702
0.5806 Remote Similarity NPC293757
0.5806 Remote Similarity NPC668
0.5614 Remote Similarity NPC193779
0.5517 Remote Similarity NPC475000
0.5455 Remote Similarity NPC30009
0.5455 Remote Similarity NPC103197
0.5424 Remote Similarity NPC185071
0.5373 Remote Similarity NPC91634
0.5373 Remote Similarity NPC150943
0.5373 Remote Similarity NPC268718
0.5373 Remote Similarity NPC212890
0.5303 Remote Similarity NPC76687
0.5147 Remote Similarity NPC32079
0.5147 Remote Similarity NPC136757
0.5143 Remote Similarity NPC163527

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC477695 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