Natural Product: NPC572505

Natural Product IDNPC572505
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (1~{S})-7-methoxy-1-[(4-methoxyphenyl)methyl]-2-methyl-3,4-dihydro-1~{H}-isoquinolin-6-ol
IUPAC Name (1~{S})-7-methoxy-1-[(4-methoxyphenyl)methyl]-2-methyl-3,4-dihydro-1~{H}-isoquinolin-6-ol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic 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 OUFXWKJGMNDBNH-KRWDZBQOSA-N
Standard InCHI InChI=1S/C19H23NO3/c1-20-9-8-14-11-18(21)19(23-3)12-16(14)17(20)10-13-4-6-15(22-2)7-5-13/h4-7,11-12,17,21H,8-10H2,1-3H3/t17-/m0/s1
SMILES COC1=CC=C(C[C@H]2C3=CC(OC)=C(O)C=C3CCN2C)C=C1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   313.17 Volume:   333.059
?
Van der Waals volume.
Dense:   0.94 LogP:   2.549
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.537
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.21
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   17.0
TPSA:   41.93
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.941 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.6 Fsp3:   0.368
MCE-18:   54.923
?
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:   0.304 Fluc inhibitor:   0.112
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.488
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.497
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.008 Promiscuous compounds:   0.213

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.811 MDCK Permeability:   -4.675
Pgp-inhibitor:   0.747 Pgp-substrate:   0.071
PAMPA:   0.028
?
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):   0.048
20% Bioavailability (F20%):   0.808 30% Bioavailability (F30%):   0.509
50% Bioavailability (F50%):   0.971

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.264 MRP1:   0.77
Plasma Protein Binding (PPB):   49.847% Volume Distribution (VD):   0.063
Fu: 47.905%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.989
OATP1B3 inhibitor:   0.971 BCRP inhibitor:   0.704
BSEP inhibitor:   0.967

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.051
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.001
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   0.983
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.672
CYP3A4-inhibitor:   0.988 CYP3A4-substrate:   0.002
CYP2B6-substrate:   0.992 CYP2C8-inhibitor:   0.47
HLM stability:   0.986
?
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):  10.161 Half-life (T1/2):  1.91

ADMET: Toxicity

hERG Blockers:  0.462 hERG Blockers (10um):  0.619
Human Hepatotoxicity (H-HT):  0.688 Drug-induced Liver Injury (DILI):  0.184
AMES Toxicity:  0.648 Rat Oral Acute Toxicity:  0.286
Maximum Recommended Daily Dose:  0.797 Skin Sensitization:  0.576
Carcinogencity:  0.508 Eye Corrosion:  0.011
Eye Irritation:  0.816 Respiratory Toxicity:  0.672
Drug-induced Neurotoxicity:  0.843 Ototoxicity:  0.501
Hematotoxicity:  0.162 Drug-induced Nephrotoxicity:  0.343
Genotoxicity:  0.349 RPMI-8226 Immunitoxicity:  0.07
A549 Cytotoxicity:  0.124 Hek293 Cytotoxicity:  0.502
BCF:   1.312
?
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:   3.787
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.15
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.354
?
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
NPO19389 Roemeria refracta Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19389 Roemeria refracta Species Papaveraceae 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

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 NPC572505 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
0.8077 Intermediate Similarity NPC191376
0.7593 Intermediate Similarity NPC135538
0.7593 Intermediate Similarity NPC24233
0.7407 Intermediate Similarity NPC147390
0.7407 Intermediate Similarity NPC428
0.7255 Intermediate Similarity NPC314682
0.6964 Remote Similarity NPC321505
0.6964 Remote Similarity NPC179825
0.6909 Remote Similarity NPC609731
0.6515 Remote Similarity NPC603603
0.6429 Remote Similarity NPC185838
0.6418 Remote Similarity NPC240841
0.6308 Remote Similarity NPC256012
0.6308 Remote Similarity NPC610965
0.6182 Remote Similarity NPC213206
0.6182 Remote Similarity NPC188163
0.6182 Remote Similarity NPC328750
0.6094 Remote Similarity NPC317272
0.6094 Remote Similarity NPC268503
0.6081 Remote Similarity NPC601489
0.6081 Remote Similarity NPC604804
0.597 Remote Similarity NPC480592
0.5833 Remote Similarity NPC600872
0.5714 Remote Similarity NPC610959
0.5667 Remote Similarity NPC103379
0.5616 Remote Similarity NPC286119
0.5616 Remote Similarity NPC600054
0.5616 Remote Similarity NPC601504
0.5593 Remote Similarity NPC220858
0.5574 Remote Similarity NPC151895
0.5556 Remote Similarity NPC104196
0.5556 Remote Similarity NPC247639
0.5556 Remote Similarity NPC25084
0.55 Remote Similarity NPC473589
0.5469 Remote Similarity NPC204828
0.5469 Remote Similarity NPC5238
0.5405 Remote Similarity NPC311973
0.5405 Remote Similarity NPC239824
0.5397 Remote Similarity NPC172765
0.5333 Remote Similarity NPC254441
0.527 Remote Similarity NPC609914
0.5263 Remote Similarity NPC484289
0.519 Remote Similarity NPC605743
0.5179 Remote Similarity NPC192768
0.5135 Remote Similarity NPC290582
0.5135 Remote Similarity NPC217748
0.5135 Remote Similarity NPC182052
0.5135 Remote Similarity NPC271013
0.5135 Remote Similarity NPC42663
0.5135 Remote Similarity NPC15414
0.5132 Remote Similarity NPC601503
0.5067 Remote Similarity NPC279228
0.5067 Remote Similarity NPC608819

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC572505 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
0.6182 Remote Similarity NPD4664 Clinical (unspecified phase)
0.5714 Remote Similarity NPD4010 Discontinued

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