Natural Product: NPC321505

Natural Product IDNPC321505
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Methyl Coclaurine
IUPAC Name 1-[(4-hydroxyphenyl)methyl]-6-methoxy-2-methyl-3,4-dihydro-1H-isoquinolin-7-ol
Synonyms DL-N-methylcoclaurine
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL453292
PubChem CID 2752274
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0002566] Isoquinolines and derivatives
        • [CHEMONTID:0000054] Benzylisoquinolines

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 BOKVLBSSPUTWLV-UHFFFAOYSA-N
Standard InCHI InChI=1S/C18H21NO3/c1-19-8-7-13-10-18(22-2)17(21)11-15(13)16(19)9-12-3-5-14(20)6-4-12/h3-6,10-11,16,20-21H,7-9H2,1-2H3
SMILES CN1CCC2=CC(=C(C=C2C1CC3=CC=C(C=C3)O)O)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   299.15 Volume:   315.764
?
Van der Waals volume.
Dense:   0.947 LogP:   1.924
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.924
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.544
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The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   17.0
TPSA:   52.93
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.915 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.705 Fsp3:   0.333
MCE-18:   55.25
?
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:   0.464 Fluc inhibitor:   0.08
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.356
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.455
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.009 Promiscuous compounds:   0.086

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.774 MDCK Permeability:   -4.761
Pgp-inhibitor:   0.114 Pgp-substrate:   0.061
PAMPA:   0.06
?
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%):   0.445 30% Bioavailability (F30%):   0.221
50% Bioavailability (F50%):   0.991

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.317 MRP1:   0.921
Plasma Protein Binding (PPB):   49.035% Volume Distribution (VD):   0.017
Fu: 49.354%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.993
OATP1B3 inhibitor:   0.996 BCRP inhibitor:   0.231
BSEP inhibitor:   0.962

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.002
CYP2C19-inhibitor:   0.999 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.848 CYP2C9-substrate:   0.997
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.02
CYP3A4-inhibitor:   0.18 CYP3A4-substrate:   0.036
CYP2B6-substrate:   0.407 CYP2C8-inhibitor:   0.019
HLM stability:   0.361
?
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):  7.615 Half-life (T1/2):  2.286

ADMET: Toxicity

hERG Blockers:  0.335 hERG Blockers (10um):  0.734
Human Hepatotoxicity (H-HT):  0.39 Drug-induced Liver Injury (DILI):  0.012
AMES Toxicity:  0.51 Rat Oral Acute Toxicity:  0.324
Maximum Recommended Daily Dose:  0.817 Skin Sensitization:  0.661
Carcinogencity:  0.564 Eye Corrosion:  0.0
Eye Irritation:  0.568 Respiratory Toxicity:  0.816
Drug-induced Neurotoxicity:  0.694 Ototoxicity:  0.523
Hematotoxicity:  0.041 Drug-induced Nephrotoxicity:  0.072
Genotoxicity:  0.621 RPMI-8226 Immunitoxicity:  0.041
A549 Cytotoxicity:  0.285 Hek293 Cytotoxicity:  0.684
BCF:   1.197
?
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:   3.565
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.618
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.009
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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
NPO27912 Cocculus laurifolius Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27912 Cocculus laurifolius Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO27912 Cocculus laurifolius Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO27912 Cocculus laurifolius Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO27912 Cocculus laurifolius Species Menispermaceae 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
NPT968 Protein family Adrenergic receptor alpha-1 Rattus norvegicus Ki = 2344.23 nM PMID[12880313]
NPT72 Individual protein Solute carrier organic anion transporter family member 1B3 Homo sapiens Inhibition = 94.46 % PMID[23571415]
NPT73 Individual protein Solute carrier organic anion transporter family member 1B1 Homo sapiens Inhibition = 96.63 % PMID[23571415]
NPT2685 Protein family Voltage-gated L-type calcium channel Rattus norvegicus Ki = 22908.68 nM PMID[12880313]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT177 Tissue Aorta Rattus norvegicus Activity = 70.8 % PMID[8778245]
NPT177 Tissue Aorta Rattus norvegicus Activity = 149.6 % PMID[8778245]
NPT177 Tissue Aorta Rattus norvegicus Activity = 106.6 % PMID[8778245]
NPT177 Tissue Aorta Rattus norvegicus IC50 = 24547.09 nM PMID[12880313]
NPT177 Tissue Aorta Rattus norvegicus IC50 = 67608.3 nM PMID[12880313]
NPT20967 Cell line Platelet n.a. Activity = 73.6 % PMID[8778245]
NPT20967 Cell line Platelet n.a. Activity = 13.8 % PMID[8778245]
NPT20967 Cell line Platelet n.a. Activity = 24.8 % PMID[8778245]
NPT20967 Cell line Platelet n.a. Activity = 75.7 % PMID[8778245]

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 NPC321505 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 NPC179825
0.8627 High Similarity NPC191376
0.7925 Intermediate Similarity NPC147390
0.7925 Intermediate Similarity NPC428
0.7619 Intermediate Similarity NPC610959
0.7547 Intermediate Similarity NPC185838
0.7273 Intermediate Similarity NPC609914
0.6875 Remote Similarity NPC480592
0.6818 Remote Similarity NPC240841
0.6667 Remote Similarity NPC103379
0.6604 Remote Similarity NPC484289
0.6552 Remote Similarity NPC135538
0.6552 Remote Similarity NPC24233
0.6418 Remote Similarity NPC603603
0.5972 Remote Similarity NPC286119
0.5806 Remote Similarity NPC189266
0.5806 Remote Similarity NPC2413
0.5806 Remote Similarity NPC110416
0.5789 Remote Similarity NPC601489
0.5789 Remote Similarity NPC604804
0.5775 Remote Similarity NPC480591
0.5763 Remote Similarity NPC88249
0.5758 Remote Similarity NPC317272
0.5758 Remote Similarity NPC268503
0.5753 Remote Similarity NPC600872
0.5614 Remote Similarity NPC314682
0.5507 Remote Similarity NPC256012
0.5507 Remote Similarity NPC610965
0.5469 Remote Similarity NPC249797
0.5469 Remote Similarity NPC193949
0.541 Remote Similarity NPC609731
0.5385 Remote Similarity NPC295691
0.5385 Remote Similarity NPC207757
0.5385 Remote Similarity NPC54379
0.5357 Remote Similarity NPC192768
0.5254 Remote Similarity NPC213206
0.5254 Remote Similarity NPC188163
0.5254 Remote Similarity NPC328750
0.5231 Remote Similarity NPC104196
0.5172 Remote Similarity NPC34559
0.5128 Remote Similarity NPC181796
0.5128 Remote Similarity NPC290005
0.5128 Remote Similarity NPC54654
0.5128 Remote Similarity NPC7715
0.5128 Remote Similarity NPC328155
0.5128 Remote Similarity NPC222661
0.5128 Remote Similarity NPC285931
0.5077 Remote Similarity NPC172765
0.5065 Remote Similarity NPC254441

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC321505 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
0.6393 Remote Similarity NPD4010 Discontinued
0.5254 Remote Similarity NPD4664 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