Natural Product: NPC117780

Natural Product IDNPC117780
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Meso-Monomethyldihydroguaiaretic Acid
IUPAC Name 4-[(2R,3S)-4-(3,4-dimethoxyphenyl)-2,3-dimethylbutyl]-2-methoxyphenol
Synonyms Meso-Monomethyldihydroguaiaretic Acid
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL551810
PubChem CID 11725068
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0001392] Lignans, neolignans and related compounds
      • [CHEMONTID:0001969] Dibenzylbutane lignans

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 NNYAKQAKXHZMKI-CABCVRRESA-N
Standard InCHI InChI=1S/C21H28O4/c1-14(10-16-6-8-18(22)20(12-16)24-4)15(2)11-17-7-9-19(23-3)21(13-17)25-5/h6-9,12-15,22H,10-11H2,1-5H3/t14-,15+/m1/s1
SMILES C[C@H](Cc1ccc(c(c1)OC)O)[C@@H](C)Cc1ccc(c(c1)OC)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   344.2 Volume:   374.001
?
Van der Waals volume.
Dense:   0.92 LogP:   2.875
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.882
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.655
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The logarithm of aqueous solubility value.
Rotatable Bonds:   8.0 Rigid Bonds:   12.0
TPSA:   47.92
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   1.0 Rings:   2.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.767 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.768 Fsp3:   0.429
MCE-18:   28.0
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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:   0.351 Fluc inhibitor:   0.205
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.014
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.135
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.605 Promiscuous compounds:   0.24

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.075 MDCK Permeability:   -4.716
Pgp-inhibitor:   0.265 Pgp-substrate:   0.142
PAMPA:   0.007
?
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):   0.001
20% Bioavailability (F20%):   0.359 30% Bioavailability (F30%):   0.972
50% Bioavailability (F50%):   0.997

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.364
Plasma Protein Binding (PPB):   90.197% Volume Distribution (VD):   -0.106
Fu: 9.525%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.928
OATP1B3 inhibitor:   0.968 BCRP inhibitor:   0.805
BSEP inhibitor:   0.992

ADMET: Metabolism

CYP1A2-inhibitor:   0.702 CYP1A2-substrate:   0.838
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.834 CYP2C9-substrate:   1.0
CYP2D6-inhibitor:   0.324 CYP2D6-substrate:   0.993
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.141 CYP2C8-inhibitor:   1.0
HLM stability:   0.999
?
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):  8.162 Half-life (T1/2):  1.201

ADMET: Toxicity

hERG Blockers:  0.405 hERG Blockers (10um):  0.855
Human Hepatotoxicity (H-HT):  0.53 Drug-induced Liver Injury (DILI):  0.276
AMES Toxicity:  0.264 Rat Oral Acute Toxicity:  0.12
Maximum Recommended Daily Dose:  0.07 Skin Sensitization:  0.884
Carcinogencity:  0.245 Eye Corrosion:  0.961
Eye Irritation:  0.998 Respiratory Toxicity:  0.093
Drug-induced Neurotoxicity:  0.304 Ototoxicity:  0.506
Hematotoxicity:  0.386 Drug-induced Nephrotoxicity:  0.595
Genotoxicity:  0.004 RPMI-8226 Immunitoxicity:  0.182
A549 Cytotoxicity:  0.314 Hek293 Cytotoxicity:  0.357
BCF:   2.053
?
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:   4.413
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.741
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.042
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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
NPO7850 Schisandra propinqua Species Schisandraceae Eukaryota n.a. stem n.a. DOI[10.1002/cjoc.20010190319]
NPO7850 Schisandra propinqua Species Schisandraceae Eukaryota n.a. stem n.a. DOI[10.1016/j.tet.2008.10.079]
NPO7850 Schisandra propinqua Species Schisandraceae Eukaryota n.a. stem n.a. PMID[11395273]
NPO7850 Schisandra propinqua Species Schisandraceae Eukaryota n.a. stem n.a. PMID[18536373]
NPO7850 Schisandra propinqua Species Schisandraceae Eukaryota aerial parts Erlang Mountain area of Sichuan Province, China 2007-SEP PMID[19413342]
NPO7850 Schisandra propinqua Species Schisandraceae Eukaryota n.a. n.a. n.a. PMID[20681569]
NPO7850 Schisandra propinqua Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7374 Seseli montanum Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7850 Schisandra propinqua Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7374 Seseli montanum Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7850 Schisandra propinqua Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11167 Prunus ssiori Species Rosaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9834 Veronica austriaca Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6903 Lecanora straminea Species Lecanoraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7128 Cynthia savignyi n.a. 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
NPT189 Cell line Vero Chlorocebus aethiops IC50 = 47.75 ug.mL-1 PMID[28844400]
NPT1452 Cell line C8166 Homo sapiens CC50 = 17200.0 nM PMID[19413342]
NPT88 Organism Mycobacterium tuberculosis Mycobacterium tuberculosis MIC = 50.0 ug.mL-1 PMID[28844400]
NPT88 Organism Mycobacterium tuberculosis Mycobacterium tuberculosis -logMIC = 3.94 n.a. PMID[28844400]
NPT24 Organism Human immunodeficiency virus 1 Human immunodeficiency virus 1 EC50 = 2900.0 nM PMID[19413342]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 25.0 ug.mL-1 PMID[28844400]
NPT17 Organism Staphylococcus epidermidis Staphylococcus epidermidis MIC > 50.0 ug.mL-1 PMID[28844400]
NPT1531 Organism Enterococcus faecium Enterococcus faecium MIC > 50.0 ug.mL-1 PMID[28844400]
NPT1477 Organism Staphylococcus haemolyticus Staphylococcus haemolyticus MIC > 50.0 ug.mL-1 PMID[28844400]
NPT2 Others Unspecified n.a. Ratio CC50/EC50 = 5.8 n.a. PMID[19413342]

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 NPC117780 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 NPC227217
0.8158 Intermediate Similarity NPC165133
0.8158 Intermediate Similarity NPC242885
0.8158 Intermediate Similarity NPC95614
0.8158 Intermediate Similarity NPC232316
0.8 Intermediate Similarity NPC274356
0.8 Intermediate Similarity NPC101748
0.7727 Intermediate Similarity NPC607444
0.7105 Intermediate Similarity NPC165106
0.7045 Intermediate Similarity NPC56214
0.6739 Remote Similarity NPC127587
0.6731 Remote Similarity NPC487677
0.6731 Remote Similarity NPC487675
0.6667 Remote Similarity NPC487676
0.6429 Remote Similarity NPC477886
0.6415 Remote Similarity NPC300776
0.6415 Remote Similarity NPC176814
0.6415 Remote Similarity NPC4982
0.6415 Remote Similarity NPC606629
0.625 Remote Similarity NPC487679
0.625 Remote Similarity NPC487678
0.625 Remote Similarity NPC156840
0.62 Remote Similarity NPC487680
0.6154 Remote Similarity NPC284464
0.6136 Remote Similarity NPC85488
0.6111 Remote Similarity NPC46880
0.6071 Remote Similarity NPC31751
0.6 Remote Similarity NPC291101
0.6 Remote Similarity NPC487681
0.6 Remote Similarity NPC266197
0.6 Remote Similarity NPC344161
0.5893 Remote Similarity NPC106739
0.5893 Remote Similarity NPC161249
0.5814 Remote Similarity NPC8547
0.5789 Remote Similarity NPC471505
0.5778 Remote Similarity NPC57490
0.5745 Remote Similarity NPC31344
0.5745 Remote Similarity NPC317769
0.5714 Remote Similarity NPC249788
0.5652 Remote Similarity NPC299406
0.5581 Remote Similarity NPC257124
0.5556 Remote Similarity NPC251855
0.5556 Remote Similarity NPC474017
0.549 Remote Similarity NPC603109
0.5484 Remote Similarity NPC478703
0.5484 Remote Similarity NPC478704
0.5455 Remote Similarity NPC221049
0.5455 Remote Similarity NPC140359
0.5435 Remote Similarity NPC470626
0.5435 Remote Similarity NPC603326
0.5424 Remote Similarity NPC64201
0.5417 Remote Similarity NPC203133
0.5357 Remote Similarity NPC194519
0.5333 Remote Similarity NPC471693
0.5333 Remote Similarity NPC76451
0.5333 Remote Similarity NPC282291
0.5333 Remote Similarity NPC193544
0.5333 Remote Similarity NPC166137
0.5333 Remote Similarity NPC169973
0.5294 Remote Similarity NPC5428
0.5294 Remote Similarity NPC232275
0.5283 Remote Similarity NPC68779
0.5283 Remote Similarity NPC108598
0.5263 Remote Similarity NPC106920
0.5263 Remote Similarity NPC15811
0.5217 Remote Similarity NPC255675
0.5192 Remote Similarity NPC11258
0.5192 Remote Similarity NPC21867
0.5192 Remote Similarity NPC45774
0.5192 Remote Similarity NPC74914
0.5111 Remote Similarity NPC80241
0.5111 Remote Similarity NPC301641
0.5111 Remote Similarity NPC485483
0.5106 Remote Similarity NPC603989
0.5102 Remote Similarity NPC177291
0.5102 Remote Similarity NPC127937
0.5091 Remote Similarity NPC275950
0.5091 Remote Similarity NPC228771

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC117780 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
0.7105 Intermediate Similarity NPD5283 Phase 2
0.5581 Remote Similarity NPD228 Phase 0

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