Natural Product: NPC310854

Natural Product IDNPC310854
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (1S,2S)-2-(4-Hydroxy-2,6-Dimethoxyphenoxy)-1-(4-Hydroxy-3-Methoxyphenyl)Propane-1,3-Diol
IUPAC Name (1S,2S)-2-(4-hydroxy-2,6-dimethoxyphenoxy)-1-(4-hydroxy-3-methoxyphenyl)propane-1,3-diol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1797767
PubChem CID 53356207
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0001392] Lignans, neolignans and related 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 LFLJRVPKZONUDD-IRXDYDNUSA-N
Standard InCHI InChI=1S/C18H22O8/c1-23-13-6-10(4-5-12(13)21)17(22)16(9-19)26-18-14(24-2)7-11(20)8-15(18)25-3/h4-8,16-17,19-22H,9H2,1-3H3/t16-,17-/m0/s1
SMILES OC[C@@H]([C@H](c1ccc(c(c1)OC)O)O)Oc1c(OC)cc(cc1OC)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   366.13 Volume:   357.274
?
Van der Waals volume.
Dense:   1.025 LogP:   0.49
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.854
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.814
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   8.0 Rigid Bonds:   12.0
TPSA:   117.84
?
Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   4.0 Rings:   2.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.556 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.18 Fsp3:   0.333
MCE-18:   30.0
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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:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.48 Fluc inhibitor:   0.276
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.051
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.16
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.287 Promiscuous compounds:   0.561

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.083 MDCK Permeability:   -4.816
Pgp-inhibitor:   0.0 Pgp-substrate:   0.099
PAMPA:   0.526
?
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):   0.002
20% Bioavailability (F20%):   0.194 30% Bioavailability (F30%):   0.198
50% Bioavailability (F50%):   0.979

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.021 MRP1:   0.931
Plasma Protein Binding (PPB):   64.057% Volume Distribution (VD):   0.062
Fu: 37.144%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.978
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.11
BSEP inhibitor:   0.016

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.054 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.553 CYP2C9-substrate:   0.089
CYP2D6-inhibitor:   0.983 CYP2D6-substrate:   0.018
CYP3A4-inhibitor:   0.169 CYP3A4-substrate:   0.006
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.967
HLM stability:   0.385
?
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):  9.596 Half-life (T1/2):  1.99

ADMET: Toxicity

hERG Blockers:  0.067 hERG Blockers (10um):  0.172
Human Hepatotoxicity (H-HT):  0.77 Drug-induced Liver Injury (DILI):  0.376
AMES Toxicity:  0.776 Rat Oral Acute Toxicity:  0.128
Maximum Recommended Daily Dose:  0.223 Skin Sensitization:  0.991
Carcinogencity:  0.491 Eye Corrosion:  0.015
Eye Irritation:  0.943 Respiratory Toxicity:  0.35
Drug-induced Neurotoxicity:  0.807 Ototoxicity:  0.527
Hematotoxicity:  0.25 Drug-induced Nephrotoxicity:  0.59
Genotoxicity:  0.513 RPMI-8226 Immunitoxicity:  0.206
A549 Cytotoxicity:  0.448 Hek293 Cytotoxicity:  0.578
BCF:   0.821
?
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:   3.109
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   3.993
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.536
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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
NPO19192 Sinocalamus affinis Species n.a. n.a. n.a. stem n.a. PMID[21469695]
NPO19192 Sinocalamus affinis Species n.a. n.a. skin-removed stems Pingle Town, Sichuang Province, China 2008-AUG PMID[21469695]
NPO19192 Sinocalamus affinis Species n.a. n.a. n.a. n.a. n.a. PMID[22690646]
NPO19192 Sinocalamus affinis Species n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO19192 Sinocalamus affinis Species n.a. n.a. 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
NPT2 Others Unspecified n.a. Inhibition < 30.0 % PMID[21469695]

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 NPC310854 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
0.717 Intermediate Similarity NPC16208
0.7037 Intermediate Similarity NPC7903
0.7037 Intermediate Similarity NPC160991
0.6909 Remote Similarity NPC75695
0.6786 Remote Similarity NPC267291
0.6786 Remote Similarity NPC481839
0.6481 Remote Similarity NPC9370
0.6481 Remote Similarity NPC287495
0.6441 Remote Similarity NPC470098
0.6441 Remote Similarity NPC473266
0.6316 Remote Similarity NPC111247
0.6316 Remote Similarity NPC292056
0.625 Remote Similarity NPC601893
0.6129 Remote Similarity NPC470097
0.6032 Remote Similarity NPC470826
0.5932 Remote Similarity NPC147821
0.5932 Remote Similarity NPC319625
0.5932 Remote Similarity NPC183181
0.5932 Remote Similarity NPC41706
0.5833 Remote Similarity NPC476387
0.5833 Remote Similarity NPC237594
0.5833 Remote Similarity NPC119060
0.5821 Remote Similarity NPC473236
0.5763 Remote Similarity NPC163332
0.5738 Remote Similarity NPC472969
0.5588 Remote Similarity NPC43065
0.5532 Remote Similarity NPC320987
0.5517 Remote Similarity NPC203831
0.551 Remote Similarity NPC35071
0.551 Remote Similarity NPC177475
0.551 Remote Similarity NPC148615
0.5507 Remote Similarity NPC324517
0.5507 Remote Similarity NPC321972
0.5278 Remote Similarity NPC260397
0.527 Remote Similarity NPC172202
0.527 Remote Similarity NPC284127
0.5263 Remote Similarity NPC35932
0.5263 Remote Similarity NPC184447
0.5246 Remote Similarity NPC291101
0.5246 Remote Similarity NPC266197
0.52 Remote Similarity NPC476343
0.5135 Remote Similarity NPC470769
0.5102 Remote Similarity NPC326599
0.5102 Remote Similarity NPC181969
0.5102 Remote Similarity NPC329595
0.5072 Remote Similarity NPC114119
0.5072 Remote Similarity NPC471415

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC310854 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