Natural Product: NPC142985

Natural Product IDNPC142985
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (3R,4S)-4-(4-Hydroxy-3-Methoxyphenyl)-4-Methoxy-3-Methylbutan-2-One
IUPAC Name (3R,4S)-4-(4-hydroxy-3-methoxyphenyl)-4-methoxy-3-methylbutan-2-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1075663
PubChem CID 44613168
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 WLUGKAVAULDYKC-SDBXPKJASA-N
Standard InCHI InChI=1S/C13H18O4/c1-8(9(2)14)13(17-4)10-5-6-11(15)12(7-10)16-3/h5-8,13,15H,1-4H3/t8-,13-/m0/s1
SMILES C[C@@H](C(=O)C)[C@@H](c1ccc(c(c1)OC)O)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   238.12 Volume:   249.463
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Van der Waals volume.
Dense:   0.955 LogP:   1.172
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.048
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.519
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The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   7.0
TPSA:   55.76
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Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   1.0 Rings:   1.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.855 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.112 Fsp3:   0.462
MCE-18:   18.0
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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:   0.085 Fluc inhibitor:   0.004
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.017
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.039
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.838 Promiscuous compounds:   0.225

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.034 MDCK Permeability:   -4.831
Pgp-inhibitor:   0.02 Pgp-substrate:   0.016
PAMPA:   0.381
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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%):   0.008 30% Bioavailability (F30%):   0.051
50% Bioavailability (F50%):   0.788

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.618
Plasma Protein Binding (PPB):   73.123% Volume Distribution (VD):   0.033
Fu: 27.808%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.777
OATP1B3 inhibitor:   0.964 BCRP inhibitor:   0.031
BSEP inhibitor:   0.333

ADMET: Metabolism

CYP1A2-inhibitor:   0.705 CYP1A2-substrate:   0.217
CYP2C19-inhibitor:   0.97 CYP2C19-substrate:   0.542
CYP2C9-inhibitor:   0.03 CYP2C9-substrate:   0.005
CYP2D6-inhibitor:   0.912 CYP2D6-substrate:   0.221
CYP3A4-inhibitor:   0.933 CYP3A4-substrate:   0.111
CYP2B6-substrate:   0.001 CYP2C8-inhibitor:   0.357
HLM stability:   0.294
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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):  8.853 Half-life (T1/2):  1.305

ADMET: Toxicity

hERG Blockers:  0.115 hERG Blockers (10um):  0.448
Human Hepatotoxicity (H-HT):  0.67 Drug-induced Liver Injury (DILI):  0.358
AMES Toxicity:  0.596 Rat Oral Acute Toxicity:  0.317
Maximum Recommended Daily Dose:  0.398 Skin Sensitization:  0.663
Carcinogencity:  0.64 Eye Corrosion:  0.286
Eye Irritation:  0.97 Respiratory Toxicity:  0.438
Drug-induced Neurotoxicity:  0.487 Ototoxicity:  0.421
Hematotoxicity:  0.51 Drug-induced Nephrotoxicity:  0.505
Genotoxicity:  0.74 RPMI-8226 Immunitoxicity:  0.058
A549 Cytotoxicity:  0.109 Hek293 Cytotoxicity:  0.284
BCF:   0.494
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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:   2.874
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   3.909
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.212
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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
NPO23895 Machilus wangchiana Species Lauraceae Eukaryota bark n.a. n.a. PMID[19916529]
NPO23895 Machilus wangchiana Species Lauraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23895 Machilus wangchiana Species Lauraceae 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
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 67.0 % PMID[19916529]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 47.0 % PMID[19916529]

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 NPC142985 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
0.8293 Intermediate Similarity NPC469480
0.7073 Intermediate Similarity NPC282703
0.7073 Intermediate Similarity NPC184733
0.7073 Intermediate Similarity NPC128208
0.7073 Intermediate Similarity NPC129570
0.7073 Intermediate Similarity NPC63238
0.7073 Intermediate Similarity NPC602603
0.6667 Remote Similarity NPC147379
0.64 Remote Similarity NPC488988
0.6383 Remote Similarity NPC11258
0.6383 Remote Similarity NPC21867
0.6383 Remote Similarity NPC487683
0.6383 Remote Similarity NPC45774
0.6383 Remote Similarity NPC74914
0.6364 Remote Similarity NPC115207
0.6364 Remote Similarity NPC158079
0.6364 Remote Similarity NPC228346
0.6364 Remote Similarity NPC242807
0.6364 Remote Similarity NPC40432
0.6364 Remote Similarity NPC161557
0.6364 Remote Similarity NPC153739
0.6 Remote Similarity NPC43514
0.5833 Remote Similarity NPC126409
0.5833 Remote Similarity NPC99572
0.58 Remote Similarity NPC27843
0.58 Remote Similarity NPC478955
0.58 Remote Similarity NPC478700
0.58 Remote Similarity NPC488986
0.58 Remote Similarity NPC7171
0.5769 Remote Similarity NPC142547
0.5769 Remote Similarity NPC228469
0.5714 Remote Similarity NPC159418
0.5577 Remote Similarity NPC223185
0.5577 Remote Similarity NPC610778
0.5556 Remote Similarity NPC606519
0.5472 Remote Similarity NPC480701
0.5439 Remote Similarity NPC471505
0.5435 Remote Similarity NPC209567
0.5435 Remote Similarity NPC195292
0.5306 Remote Similarity NPC470804
0.5273 Remote Similarity NPC88640
0.5273 Remote Similarity NPC101153
0.5273 Remote Similarity NPC193666
0.5273 Remote Similarity NPC123526
0.5273 Remote Similarity NPC608725
0.5263 Remote Similarity NPC67247
0.5254 Remote Similarity NPC471988
0.5238 Remote Similarity NPC32163
0.5217 Remote Similarity NPC224814
0.5208 Remote Similarity NPC4940
0.5185 Remote Similarity NPC181049
0.5179 Remote Similarity NPC481088
0.5179 Remote Similarity NPC610652
0.5106 Remote Similarity NPC160900
0.5091 Remote Similarity NPC471942
0.5088 Remote Similarity NPC145144

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC142985 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
0.5333 Remote Similarity NPD824 Phase 4
0.5106 Remote Similarity NPD4379 Clinical (unspecified phase)

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