Natural Product: NPC269843

Natural Product IDNPC269843
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Methylcurcumin
IUPAC Name n.a.
Synonyms Methylcurcumin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL494826
PubChem CID NA
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002650] Diarylheptanoids
        • [CHEMONTID:0002651] Linear diarylheptanoids
          • [CHEMONTID:0000356] Curcuminoids

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 MXGYVBOZRLQICP-VUSYVUDMSA-N
Standard InCHI InChI=1S/C22H22O6/c1-26-20-11-7-16(13-22(20)28-3)5-9-18(24)14-17(23)8-4-15-6-10-19(25)21(12-15)27-2/h4-14,23,25H,1-3H3/b8-4+,9-5+,17-14-
SMILES COc1cc(/C=C/C(=O)/C=C(/C=C/c2ccc(c(c2)OC)O)O)ccc1OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   382.14 Volume:   398.332
?
Van der Waals volume.
Dense:   0.959 LogP:   3.057
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.148
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.397
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   8.0 Rigid Bonds:   16.0
TPSA:   85.22
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   2.0 Rings:   2.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.405 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.52 Fsp3:   0.136
MCE-18:   14.0
?
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:   0.987 Fluc inhibitor:   1.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.349
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.803
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.653 Promiscuous compounds:   0.537

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.116 MDCK Permeability:   -4.844
Pgp-inhibitor:   0.948 Pgp-substrate:   0.001
PAMPA:   0.019
?
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):   0.107
20% Bioavailability (F20%):   0.989 30% Bioavailability (F30%):   0.99
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.0
Plasma Protein Binding (PPB):   94.833% Volume Distribution (VD):   -0.555
Fu: 5.952%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.991
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.059 CYP1A2-substrate:   0.083
CYP2C19-inhibitor:   0.015 CYP2C19-substrate:   0.061
CYP2C9-inhibitor:   0.217 CYP2C9-substrate:   0.062
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.554
CYP3A4-inhibitor:   0.701 CYP3A4-substrate:   0.29
CYP2B6-substrate:   0.07 CYP2C8-inhibitor:   1.0
HLM stability:   0.95
?
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):  7.786 Half-life (T1/2):  1.021

ADMET: Toxicity

hERG Blockers:  0.102 hERG Blockers (10um):  0.114
Human Hepatotoxicity (H-HT):  0.643 Drug-induced Liver Injury (DILI):  0.849
AMES Toxicity:  0.424 Rat Oral Acute Toxicity:  0.215
Maximum Recommended Daily Dose:  0.525 Skin Sensitization:  0.88
Carcinogencity:  0.497 Eye Corrosion:  0.025
Eye Irritation:  0.95 Respiratory Toxicity:  0.732
Drug-induced Neurotoxicity:  0.448 Ototoxicity:  0.443
Hematotoxicity:  0.263 Drug-induced Nephrotoxicity:  0.775
Genotoxicity:  0.36 RPMI-8226 Immunitoxicity:  0.136
A549 Cytotoxicity:  0.121 Hek293 Cytotoxicity:  0.251
BCF:   1.138
?
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:   3.83
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.02
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.6
?
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
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. root n.a. PMID[18484537]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. rhizome n.a. PMID[18484537]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota rhizomes n.a. n.a. PMID[19615910]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[29323912]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. rhizome n.a. PMID[731398]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. root n.a. PMID[731398]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO23911 Alpinia officinarum Species Zingiberaceae 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
NPT664 Protein family Histone deacetylase Homo sapiens Activity = 13.0 % PMID[32273215]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT306 Cell line PC-3 Homo sapiens IC50 = 20900.0 nM PMID[19249204]
NPT858 Cell line LNCaP Homo sapiens IC50 = 6800.0 nM PMID[19249204]
NPT83 Cell line MCF7 Homo sapiens IC50 = 15400.0 nM PMID[19249204]
NPT82 Cell line MDA-MB-231 Homo sapiens IC50 = 7200.0 nM PMID[19249204]
NPT858 Cell line LNCaP Homo sapiens IC50 = 47000.0 nM PMID[22672984]
NPT306 Cell line PC-3 Homo sapiens IC50 = 33100.0 nM PMID[22672984]

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 NPC269843 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
0.8776 High Similarity NPC109083
0.8113 Intermediate Similarity NPC189844
0.7959 Intermediate Similarity NPC280001
0.66 Remote Similarity NPC224814
0.6379 Remote Similarity NPC158949
0.6316 Remote Similarity NPC478444
0.6316 Remote Similarity NPC478448
0.6234 Remote Similarity NPC478449
0.6234 Remote Similarity NPC478453
0.6234 Remote Similarity NPC478450
0.6167 Remote Similarity NPC84076
0.6154 Remote Similarity NPC478452
0.6111 Remote Similarity NPC14007
0.6076 Remote Similarity NPC478451
0.5849 Remote Similarity NPC130193
0.5849 Remote Similarity NPC160900
0.5789 Remote Similarity NPC60962
0.5641 Remote Similarity NPC478447
0.5469 Remote Similarity NPC90128
0.5439 Remote Similarity NPC71941
0.5375 Remote Similarity NPC478446
0.5345 Remote Similarity NPC106659
0.5316 Remote Similarity NPC478443
0.5309 Remote Similarity NPC478445
0.5273 Remote Similarity NPC107588
0.5273 Remote Similarity NPC137537
0.5246 Remote Similarity NPC110313
0.5192 Remote Similarity NPC36108
0.5192 Remote Similarity NPC233731
0.5192 Remote Similarity NPC610203
0.5185 Remote Similarity NPC78918
0.5185 Remote Similarity NPC39793
0.5185 Remote Similarity NPC139617
0.5156 Remote Similarity NPC474784

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC269843 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
0.5849 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