Natural Product: NPC160193

Natural Product IDNPC160193
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 6,7-Dimethoxy-2-Methyl-3,4-Dihydro-1H-Isoquinoline
IUPAC Name 6,7-dimethoxy-2-methyl-3,4-dihydro-1H-isoquinoline
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1196025
PubChem CID 27694
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0002955] Tetrahydroisoquinolines

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 TXPPKWZEHFNZOE-UHFFFAOYSA-N
Standard InCHI InChI=1S/C12H17NO2/c1-13-5-4-9-6-11(14-2)12(15-3)7-10(9)8-13/h6-7H,4-5,8H2,1-3H3
SMILES CN1CCc2cc(c(cc2C1)OC)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   207.13 Volume:   219.663
?
Van der Waals volume.
Dense:   0.943 LogP:   1.001
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.888
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -0.934
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   11.0
TPSA:   21.7
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   0.0 Rings:   2.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.736 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   1.894 Fsp3:   0.5
MCE-18:   25.667
?
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:   0 PAINS Alert:   0
Colloidal aggregators:   0.086 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.616
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.262
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.229 Promiscuous compounds:   0.272

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.484 MDCK Permeability:   -4.718
Pgp-inhibitor:   0.355 Pgp-substrate:   0.731
PAMPA:   0.006
?
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):   0.073
20% Bioavailability (F20%):   0.119 30% Bioavailability (F30%):   0.055
50% Bioavailability (F50%):   0.65

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.469 MRP1:   0.909
Plasma Protein Binding (PPB):   22.761% Volume Distribution (VD):   0.329
Fu: 73.532%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.737
OATP1B3 inhibitor:   0.871 BCRP inhibitor:   0.634
BSEP inhibitor:   0.955

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.87 CYP2C9-substrate:   0.227
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.001
CYP3A4-inhibitor:   0.971 CYP3A4-substrate:   0.02
CYP2B6-substrate:   0.44 CYP2C8-inhibitor:   0.015
HLM stability:   0.185
?
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):  9.818 Half-life (T1/2):  3.674

ADMET: Toxicity

hERG Blockers:  0.428 hERG Blockers (10um):  0.652
Human Hepatotoxicity (H-HT):  0.619 Drug-induced Liver Injury (DILI):  0.159
AMES Toxicity:  0.544 Rat Oral Acute Toxicity:  0.688
Maximum Recommended Daily Dose:  0.577 Skin Sensitization:  0.779
Carcinogencity:  0.711 Eye Corrosion:  0.37
Eye Irritation:  0.653 Respiratory Toxicity:  0.943
Drug-induced Neurotoxicity:  0.845 Ototoxicity:  0.349
Hematotoxicity:  0.502 Drug-induced Nephrotoxicity:  0.478
Genotoxicity:  0.648 RPMI-8226 Immunitoxicity:  0.07
A549 Cytotoxicity:  0.102 Hek293 Cytotoxicity:  0.231
BCF:   0.941
?
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:   3.011
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.17
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.464
?
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
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota n.a. n.a. n.a. PMID[19919095]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota flower buds and leaves Khon Kaen province, Thailand 2010 PMID[23270663]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota Leaves n.a. n.a. PMID[23642481]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota Flowers n.a. n.a. PMID[26462418]
NPO4880 Artemisia ifranensis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota n.a. n.a. Database[FooDB]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota Rhizome n.a. n.a. Database[FooDB]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO4880 Artemisia ifranensis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16366 Citrus cavaleriei Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1652 Arichanna gaschkevitchii Species Geometridae 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
NPT295 Individual protein Serotonin transporter Homo sapiens Ki = 46700.0 nM PMID[24187998]
NPT246 Individual protein Dopamine transporter Homo sapiens Ki > 10000000.0 nM PMID[24187998]
NPT228 Individual protein Norepinephrine transporter Homo sapiens Ki = 128900.0 nM PMID[24187998]
NPT261 Individual protein Monoamine oxidase A Homo sapiens Ki = 27000.0 nM PMID[24187998]
NPT582 Individual protein Monoamine oxidase B Homo sapiens Ki = 29000.0 nM PMID[24187998]
NPT412 Protein complex Neuronal acetylcholine receptor; alpha4/beta2 Rattus norvegicus Ki = 870.0 nM PMID[24187998]
NPT418 Protein complex Neuronal acetylcholine receptor; alpha4/beta4 Rattus norvegicus Ki = 300000.0 nM PMID[24187998]
NPT417 Protein complex Neuronal acetylcholine receptor; alpha3/beta4 Rattus norvegicus Ki = 300000.0 nM PMID[24187998]
NPT964 Protein complex Nicotinic acetylcholine receptor alpha-4/beta-2 Mus musculus IC50 = 12000.0 nM PMID[24187998]
NPT417 Protein complex Neuronal acetylcholine receptor; alpha3/beta4 Rattus norvegicus IC50 = 100000.0 nM PMID[24187998]
NPT410 Individual protein Neuronal acetylcholine receptor protein alpha-7 subunit Homo sapiens IC50 > 100000.0 nM PMID[29384668]
NPT410 Individual protein Neuronal acetylcholine receptor protein alpha-7 subunit Homo sapiens EC50 > 100000.0 nM PMID[29384668]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT28438 Unchecked Unchecked n.a. Activity = 54.47 % PMID[37689215]
NPT28855 Cell line ECa-109 cell line Homo sapiens FC = 7.7 n.a. PMID[36892076]
NPT28855 Cell line ECa-109 cell line Homo sapiens IC50 = 891.2 nM PMID[36892076]
NPT28855 Cell line ECa-109 cell line Homo sapiens Activity = 90.9 % PMID[36892076]
NPT2 Others Unspecified n.a. Ki > 500000.0 nM PMID[24187998]
NPT2 Others Unspecified n.a. Ratio Ki > 300.0 n.a. PMID[24187998]

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 NPC160193 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
0.7632 Intermediate Similarity NPC7018
0.6429 Remote Similarity NPC301050
0.6 Remote Similarity NPC609445
0.5714 Remote Similarity NPC86469
0.5652 Remote Similarity NPC128019
0.5417 Remote Similarity NPC37144
0.5192 Remote Similarity NPC153631
0.5128 Remote Similarity NPC104070
0.5106 Remote Similarity NPC172403

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC160193 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