Natural Product: NPC521945

Natural Product IDNPC521945
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (5R)-5-[(4-methoxyphenyl)methyl]-6-methyl-7,8-dihydro-5H-[1,3]dioxolo[4,5-g]isoquinoline
IUPAC Name (5~{R})-5-[(4-methoxyphenyl)methyl]-6-methyl-7,8-dihydro-5~{H}-[1,3]dioxolo[4,5-g]isoquinoline
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 HOZOQGVLWPYGIE-QGZVFWFLSA-N
Standard InCHI InChI=1S/C19H21NO3/c1-20-8-7-14-10-18-19(23-12-22-18)11-16(14)17(20)9-13-3-5-15(21-2)6-4-13/h3-6,10-11,17H,7-9,12H2,1-2H3/t17-/m1/s1
SMILES COC1=CC=C(C[C@@H]2C3=CC4=C(C=C3CCN2C)OCO4)C=C1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   311.15 Volume:   324.503
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Van der Waals volume.
Dense:   0.959 LogP:   2.863
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.571
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.947
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The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   21.0
TPSA:   30.93
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Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   0.0 Rings:   4.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.871 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.664 Fsp3:   0.368
MCE-18:   66.154
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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:   0 PAINS Alert:   0
Colloidal aggregators:   0.41 Fluc inhibitor:   0.445
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.39
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.329
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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:   0.547

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.632 MDCK Permeability:   -4.626
Pgp-inhibitor:   0.933 Pgp-substrate:   0.112
PAMPA:   0.003
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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%):   0.424 30% Bioavailability (F30%):   0.007
50% Bioavailability (F50%):   0.55

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.991 MRP1:   0.798
Plasma Protein Binding (PPB):   68.427% Volume Distribution (VD):   0.221
Fu: 29.714%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.564
OATP1B3 inhibitor:   0.282 BCRP inhibitor:   0.162
BSEP inhibitor:   0.999

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.705
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.03
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   0.999
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   0.984 CYP3A4-substrate:   0.99
CYP2B6-substrate:   1.0 CYP2C8-inhibitor:   0.0
HLM stability:   0.667
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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):  8.043 Half-life (T1/2):  1.984

ADMET: Toxicity

hERG Blockers:  0.622 hERG Blockers (10um):  0.613
Human Hepatotoxicity (H-HT):  0.721 Drug-induced Liver Injury (DILI):  0.142
AMES Toxicity:  0.677 Rat Oral Acute Toxicity:  0.703
Maximum Recommended Daily Dose:  0.962 Skin Sensitization:  0.23
Carcinogencity:  0.64 Eye Corrosion:  0.002
Eye Irritation:  0.462 Respiratory Toxicity:  0.909
Drug-induced Neurotoxicity:  0.955 Ototoxicity:  0.253
Hematotoxicity:  0.095 Drug-induced Nephrotoxicity:  0.53
Genotoxicity:  0.935 RPMI-8226 Immunitoxicity:  0.068
A549 Cytotoxicity:  0.11 Hek293 Cytotoxicity:  0.315
BCF:   1.898
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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:   4.043
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.014
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.033
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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
NPO23121 Hedycarya angustifolia Species Monimiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23121 Hedycarya angustifolia Species Monimiaceae 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 NPC521945 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
0.8723 High Similarity NPC314682
0.7451 Intermediate Similarity NPC213206
0.7451 Intermediate Similarity NPC188163
0.7451 Intermediate Similarity NPC328750
0.6897 Remote Similarity NPC27887
0.6727 Remote Similarity NPC185838
0.6667 Remote Similarity NPC135538
0.6667 Remote Similarity NPC24233
0.661 Remote Similarity NPC247639
0.661 Remote Similarity NPC25084
0.6333 Remote Similarity NPC475959
0.6308 Remote Similarity NPC256012
0.6308 Remote Similarity NPC610965
0.6094 Remote Similarity NPC317272
0.6094 Remote Similarity NPC268503
0.6 Remote Similarity NPC73492
0.6 Remote Similarity NPC299990
0.5846 Remote Similarity NPC226708
0.5616 Remote Similarity NPC600054
0.5616 Remote Similarity NPC601504
0.5571 Remote Similarity NPC603603
0.5556 Remote Similarity NPC216459
0.5556 Remote Similarity NPC41178
0.5556 Remote Similarity NPC138487
0.55 Remote Similarity NPC609731
0.5493 Remote Similarity NPC240841
0.5469 Remote Similarity NPC326205
0.5429 Remote Similarity NPC276890
0.541 Remote Similarity NPC147390
0.541 Remote Similarity NPC428
0.5385 Remote Similarity NPC24260
0.5333 Remote Similarity NPC474915
0.5323 Remote Similarity NPC317439
0.5286 Remote Similarity NPC76682
0.5286 Remote Similarity NPC10908
0.5286 Remote Similarity NPC63646
0.5286 Remote Similarity NPC317145
0.5286 Remote Similarity NPC198498
0.5286 Remote Similarity NPC115284
0.5224 Remote Similarity NPC276944
0.5224 Remote Similarity NPC238530
0.52 Remote Similarity NPC112248
0.5192 Remote Similarity NPC233029
0.5192 Remote Similarity NPC210148
0.5161 Remote Similarity NPC191376
0.5156 Remote Similarity NPC31311
0.5156 Remote Similarity NPC234392
0.5152 Remote Similarity NPC247389
0.5147 Remote Similarity NPC14622
0.5147 Remote Similarity NPC70290
0.5147 Remote Similarity NPC215098
0.5147 Remote Similarity NPC124302
0.5147 Remote Similarity NPC73020
0.5132 Remote Similarity NPC601503
0.5079 Remote Similarity NPC321505
0.5079 Remote Similarity NPC179825
0.5075 Remote Similarity NPC606650
0.5072 Remote Similarity NPC46744
0.5068 Remote Similarity NPC12424
0.5068 Remote Similarity NPC129518
0.5068 Remote Similarity NPC251580
0.5063 Remote Similarity NPC601489
0.5063 Remote Similarity NPC604804

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC521945 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
0.7451 Intermediate Similarity NPD4664 Clinical (unspecified phase)
0.5286 Remote Similarity NPD8099 Discontinued
0.5147 Remote Similarity NPD4420 Pre-clinical

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