Natural Product: NPC556148

Natural Product IDNPC556148
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (1~{S})-1-[(3-hydroxy-4-methoxy-phenyl)methyl]-7-methoxy-2-methyl-3,4-dihydro-1~{H}-isoquinolin-6-ol
IUPAC Name (1~{S})-1-[(3-hydroxy-4-methoxy-phenyl)methyl]-7-methoxy-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 HZRFPHXHCRIHFX-HNNXBMFYSA-N
Standard InCHI InChI=1S/C19H23NO4/c1-20-7-6-13-10-17(22)19(24-3)11-14(13)15(20)8-12-4-5-18(23-2)16(21)9-12/h4-5,9-11,15,21-22H,6-8H2,1-3H3/t15-/m0/s1
SMILES COC1=CC=C(C[C@H]2C3=CC(OC)=C(O)C=C3CCN2C)C=C1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   329.16 Volume:   341.85
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Van der Waals volume.
Dense:   0.963 LogP:   1.793
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.942
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.888
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The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   17.0
TPSA:   62.16
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Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.903 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.807 Fsp3:   0.368
MCE-18:   58.154
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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:   0.388 Fluc inhibitor:   0.015
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.5
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.451
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.005 Promiscuous compounds:   0.219

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.036 MDCK Permeability:   -4.752
Pgp-inhibitor:   0.17 Pgp-substrate:   0.169
PAMPA:   0.101
?
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):   0.039
20% Bioavailability (F20%):   0.921 30% Bioavailability (F30%):   0.822
50% Bioavailability (F50%):   0.992

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.212 MRP1:   0.757
Plasma Protein Binding (PPB):   48.52% Volume Distribution (VD):   -0.154
Fu: 50.343%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.983
OATP1B3 inhibitor:   0.977 BCRP inhibitor:   0.717
BSEP inhibitor:   0.592

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.002
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   0.996
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.049
CYP3A4-inhibitor:   0.982 CYP3A4-substrate:   0.004
CYP2B6-substrate:   0.87 CYP2C8-inhibitor:   0.867
HLM stability:   0.868
?
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):  6.683 Half-life (T1/2):  2.347

ADMET: Toxicity

hERG Blockers:  0.367 hERG Blockers (10um):  0.603
Human Hepatotoxicity (H-HT):  0.747 Drug-induced Liver Injury (DILI):  0.147
AMES Toxicity:  0.607 Rat Oral Acute Toxicity:  0.26
Maximum Recommended Daily Dose:  0.843 Skin Sensitization:  0.783
Carcinogencity:  0.432 Eye Corrosion:  0.003
Eye Irritation:  0.828 Respiratory Toxicity:  0.651
Drug-induced Neurotoxicity:  0.733 Ototoxicity:  0.584
Hematotoxicity:  0.118 Drug-induced Nephrotoxicity:  0.25
Genotoxicity:  0.585 RPMI-8226 Immunitoxicity:  0.075
A549 Cytotoxicity:  0.176 Hek293 Cytotoxicity:  0.577
BCF:   1.218
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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:   3.627
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.921
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.178
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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
NPO25677 Xylopia parviflora Species Annonaceae Eukaryota n.a. root n.a. PMID[15081299]
NPO25677 Xylopia parviflora Species Annonaceae Eukaryota n.a. bark n.a. PMID[15081299]
NPO10227 Erythrina lithosperma Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO42109 Stephania cepharantha Hayata Genus Menispermaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25677 Xylopia parviflora Species Annonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO56398 Polyalthia nitidissima Species Annonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25677 Xylopia parviflora Species Annonaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO10227 Erythrina lithosperma Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO10227 Erythrina lithosperma Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO10227 Erythrina lithosperma Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25677 Xylopia parviflora Species Annonaceae 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 NPC556148 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
0.86 High Similarity NPC147390
0.86 High Similarity NPC428
0.8431 Intermediate Similarity NPC135538
0.8431 Intermediate Similarity NPC24233
0.7885 Intermediate Similarity NPC191376
0.6786 Remote Similarity NPC321505
0.6786 Remote Similarity NPC179825
0.6377 Remote Similarity NPC600872
0.6119 Remote Similarity NPC603603
0.6111 Remote Similarity NPC314682
0.6061 Remote Similarity NPC480592
0.6029 Remote Similarity NPC240841
0.6 Remote Similarity NPC213206
0.6 Remote Similarity NPC188163
0.6 Remote Similarity NPC328750
0.5965 Remote Similarity NPC185838
0.5862 Remote Similarity NPC609731
0.5692 Remote Similarity NPC317272
0.5692 Remote Similarity NPC268503
0.569 Remote Similarity NPC220858
0.5571 Remote Similarity NPC610959
0.557 Remote Similarity NPC473589
0.5556 Remote Similarity NPC204828
0.5556 Remote Similarity NPC5238
0.55 Remote Similarity NPC103379
0.5484 Remote Similarity NPC172765
0.5479 Remote Similarity NPC286119
0.5441 Remote Similarity NPC256012
0.5441 Remote Similarity NPC610965
0.541 Remote Similarity NPC151895
0.5397 Remote Similarity NPC104196
0.5325 Remote Similarity NPC601489
0.5325 Remote Similarity NPC604804
0.5273 Remote Similarity NPC192768
0.527 Remote Similarity NPC311973
0.527 Remote Similarity NPC239824
0.52 Remote Similarity NPC254441
0.5156 Remote Similarity NPC247639
0.5156 Remote Similarity NPC25084
0.5135 Remote Similarity NPC609914
0.5088 Remote Similarity NPC484289
0.5079 Remote Similarity NPC13504
0.5077 Remote Similarity NPC600388

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC556148 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
0.6 Remote Similarity NPD4664 Clinical (unspecified phase)
0.5556 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