Natural Product: NPC191037

Natural Product IDNPC191037
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Machilin D
IUPAC Name 4-[(1S,2S)-1-hydroxy-2-[2-methoxy-4-[(E)-prop-1-enyl]phenoxy]propyl]-2-methoxyphenol
Synonyms Machilin D
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL185692
PubChem CID 904797
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 WCFYXOLUODJLKB-QONXFYDISA-N
Standard InCHI InChI=1S/C20H24O5/c1-5-6-14-7-10-17(19(11-14)24-4)25-13(2)20(22)15-8-9-16(21)18(12-15)23-3/h5-13,20-22H,1-4H3/b6-5+/t13-,20+/m0/s1
SMILES C/C=C/c1ccc(c(c1)OC)O[C@@H](C)[C@H](c1ccc(c(c1)OC)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   344.16 Volume:   362.859
?
Van der Waals volume.
Dense:   0.948 LogP:   2.709
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.842
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.897
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   13.0
TPSA:   68.15
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   2.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.796 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.071 Fsp3:   0.3
MCE-18:   28.0
?
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:   0.402 Fluc inhibitor:   0.942
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.064
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.309
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.503 Promiscuous compounds:   0.261

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.14 MDCK Permeability:   -4.795
Pgp-inhibitor:   0.09 Pgp-substrate:   0.037
PAMPA:   0.134
?
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%):   0.136 30% Bioavailability (F30%):   0.183
50% Bioavailability (F50%):   0.974

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.61
Plasma Protein Binding (PPB):   96.474% Volume Distribution (VD):   0.1
Fu: 2.9%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.996
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.712
BSEP inhibitor:   0.998

ADMET: Metabolism

CYP1A2-inhibitor:   0.015 CYP1A2-substrate:   0.006
CYP2C19-inhibitor:   0.995 CYP2C19-substrate:   0.012
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.653
CYP2D6-inhibitor:   0.978 CYP2D6-substrate:   0.362
CYP3A4-inhibitor:   0.608 CYP3A4-substrate:   0.366
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.996
HLM stability:   0.658
?
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):  8.762 Half-life (T1/2):  1.285

ADMET: Toxicity

hERG Blockers:  0.2 hERG Blockers (10um):  0.642
Human Hepatotoxicity (H-HT):  0.576 Drug-induced Liver Injury (DILI):  0.135
AMES Toxicity:  0.391 Rat Oral Acute Toxicity:  0.211
Maximum Recommended Daily Dose:  0.451 Skin Sensitization:  0.484
Carcinogencity:  0.322 Eye Corrosion:  0.123
Eye Irritation:  0.903 Respiratory Toxicity:  0.553
Drug-induced Neurotoxicity:  0.394 Ototoxicity:  0.574
Hematotoxicity:  0.158 Drug-induced Nephrotoxicity:  0.572
Genotoxicity:  0.065 RPMI-8226 Immunitoxicity:  0.104
A549 Cytotoxicity:  0.144 Hek293 Cytotoxicity:  0.362
BCF:   1.414
?
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:   3.678
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.781
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.777
?
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
NPO20323 Saururus chinensis Species Saururaceae Eukaryota n.a. n.a. n.a. PMID[10924192]
NPO20323 Saururus chinensis Species Saururaceae Eukaryota n.a. n.a. n.a. PMID[11754613]
NPO20323 Saururus chinensis Species Saururaceae Eukaryota n.a. root n.a. PMID[14750033]
NPO20323 Saururus chinensis Species Saururaceae Eukaryota n.a. n.a. n.a. PMID[15482936]
NPO20323 Saururus chinensis Species Saururaceae Eukaryota roots n.a. n.a. PMID[18841903]
NPO20323 Saururus chinensis Species Saururaceae Eukaryota Roots n.a. n.a. PMID[24359277]
NPO20323 Saururus chinensis Species Saururaceae Eukaryota Aerial Parts n.a. n.a. PMID[24387347]
NPO20323 Saururus chinensis Species Saururaceae Eukaryota n.a. n.a. n.a. PMID[31642320]
NPO20323 Saururus chinensis Species Saururaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20323 Saururus chinensis Species Saururaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO20323 Saururus chinensis Species Saururaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO20323 Saururus chinensis Species Saururaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO20323 Saururus chinensis Species Saururaceae 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
NPT3118 Cell line Cell line Homo sapiens IC50 = 3800.0 nM PMID[8277308]
NPT3118 Cell line Cell line Homo sapiens Activity = 6.78 AU/mm PMID[8277308]
NPT3118 Cell line Cell line Homo sapiens Activity = 5.81 AU/mm PMID[8277308]
NPT3118 Cell line Cell line Homo sapiens Activity = 118.3 nmol/mg LDL PMID[8277308]
NPT113 Cell line RAW264.7 Mus musculus IC50 = 21100.0 nM PMID[31642320]
NPT621 Tissue Plasma Homo sapiens IC50 = 2900.0 nM PMID[23398362]

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 NPC191037 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
1.0 High Similarity NPC58607
1.0 High Similarity NPC178284
0.7451 Intermediate Similarity NPC94276
0.7451 Intermediate Similarity NPC109822
0.7451 Intermediate Similarity NPC605984
0.7143 Intermediate Similarity NPC483401
0.7069 Intermediate Similarity NPC147821
0.7069 Intermediate Similarity NPC319625
0.7069 Intermediate Similarity NPC183181
0.7069 Intermediate Similarity NPC41706
0.6981 Remote Similarity NPC273295
0.6981 Remote Similarity NPC222004
0.6981 Remote Similarity NPC602870
0.6949 Remote Similarity NPC476387
0.6949 Remote Similarity NPC237594
0.6949 Remote Similarity NPC119060
0.6452 Remote Similarity NPC77861
0.6071 Remote Similarity NPC470258
0.5915 Remote Similarity NPC107145
0.5833 Remote Similarity NPC203831
0.5714 Remote Similarity NPC267291
0.5667 Remote Similarity NPC9370
0.5667 Remote Similarity NPC287495
0.5645 Remote Similarity NPC7903
0.5645 Remote Similarity NPC160991
0.5616 Remote Similarity NPC473909
0.56 Remote Similarity NPC36108
0.56 Remote Similarity NPC233731
0.56 Remote Similarity NPC610203
0.5571 Remote Similarity NPC304048
0.5484 Remote Similarity NPC114901
0.5484 Remote Similarity NPC48990
0.5484 Remote Similarity NPC601893
0.5467 Remote Similarity NPC470413
0.5385 Remote Similarity NPC249791
0.5312 Remote Similarity NPC291101
0.5312 Remote Similarity NPC111247
0.5312 Remote Similarity NPC266197
0.5312 Remote Similarity NPC292056
0.5303 Remote Similarity NPC118787
0.5179 Remote Similarity NPC218856
0.5179 Remote Similarity NPC210623
0.5179 Remote Similarity NPC226788
0.5102 Remote Similarity NPC310905

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC191037 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