Natural Product: NPC576658

Natural Product IDNPC576658
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Cinnamolaurine
IUPAC Name 4-[[(5~{R})-6-methyl-7,8-dihydro-5~{H}-[1,3]dioxolo[4,5-g]isoquinolin-5-yl]methyl]phenol
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 VTOOEPLHEDZMBL-MRXNPFEDSA-N
Standard InCHI InChI=1S/C18H19NO3/c1-19-7-6-13-9-17-18(22-11-21-17)10-15(13)16(19)8-12-2-4-14(20)5-3-12/h2-5,9-10,16,20H,6-8,11H2,1H3/t16-/m1/s1
SMILES CN1CCC2=CC3=C(C=C2[C@H]1CC1=CC=C(O)C=C1)OCO3

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   297.14 Volume:   307.207
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Van der Waals volume.
Dense:   0.967 LogP:   2.561
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.439
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.328
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The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   21.0
TPSA:   41.93
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Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   1.0 Rings:   4.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.925 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.768 Fsp3:   0.333
MCE-18:   66.667
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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:   0.516 Fluc inhibitor:   0.458
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.356
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.276
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.011 Promiscuous compounds:   0.204

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.662 MDCK Permeability:   -4.623
Pgp-inhibitor:   0.318 Pgp-substrate:   0.041
PAMPA:   0.122
?
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%):   0.572 30% Bioavailability (F30%):   0.009
50% Bioavailability (F50%):   0.973

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.974 MRP1:   0.908
Plasma Protein Binding (PPB):   69.631% Volume Distribution (VD):   0.413
Fu: 30.394%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.976
OATP1B3 inhibitor:   0.941 BCRP inhibitor:   0.077
BSEP inhibitor:   0.999

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.476
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.001
CYP2C9-inhibitor:   0.957 CYP2C9-substrate:   1.0
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.99
CYP3A4-inhibitor:   0.396 CYP3A4-substrate:   0.807
CYP2B6-substrate:   0.997 CYP2C8-inhibitor:   0.0
HLM stability:   0.252
?
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):  10.734 Half-life (T1/2):  1.641

ADMET: Toxicity

hERG Blockers:  0.481 hERG Blockers (10um):  0.603
Human Hepatotoxicity (H-HT):  0.738 Drug-induced Liver Injury (DILI):  0.141
AMES Toxicity:  0.622 Rat Oral Acute Toxicity:  0.374
Maximum Recommended Daily Dose:  0.894 Skin Sensitization:  0.663
Carcinogencity:  0.57 Eye Corrosion:  0.01
Eye Irritation:  0.881 Respiratory Toxicity:  0.555
Drug-induced Neurotoxicity:  0.872 Ototoxicity:  0.402
Hematotoxicity:  0.094 Drug-induced Nephrotoxicity:  0.188
Genotoxicity:  0.841 RPMI-8226 Immunitoxicity:  0.051
A549 Cytotoxicity:  0.094 Hek293 Cytotoxicity:  0.71
BCF:   1.545
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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:   3.887
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.531
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.612
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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
NPO15311 Cryptocarya chinensis Species Lauraceae Eukaryota leaves Lai-I, Pingtung County, Taiwan 2005-May PMID[20704331]
NPO48883 Cinnamomum Genus Lauraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15311 Cryptocarya chinensis Species Lauraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15311 Cryptocarya chinensis Species Lauraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO15311 Cryptocarya chinensis Species Lauraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15311 Cryptocarya chinensis Species Lauraceae 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 NPC576658 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
0.8235 Intermediate Similarity NPC185838
0.6667 Remote Similarity NPC191376
0.6552 Remote Similarity NPC321505
0.6552 Remote Similarity NPC179825
0.6182 Remote Similarity NPC314682
0.6 Remote Similarity NPC317272
0.6 Remote Similarity NPC268503
0.6 Remote Similarity NPC135538
0.6 Remote Similarity NPC484289
0.6 Remote Similarity NPC24233
0.5968 Remote Similarity NPC27887
0.5857 Remote Similarity NPC610959
0.5789 Remote Similarity NPC213206
0.5789 Remote Similarity NPC188163
0.5789 Remote Similarity NPC328750
0.5775 Remote Similarity NPC480591
0.5735 Remote Similarity NPC256012
0.5735 Remote Similarity NPC610965
0.5574 Remote Similarity NPC103379
0.5522 Remote Similarity NPC226708
0.5513 Remote Similarity NPC24260
0.5455 Remote Similarity NPC606650
0.5441 Remote Similarity NPC298979
0.5417 Remote Similarity NPC240841
0.5231 Remote Similarity NPC247639
0.5231 Remote Similarity NPC25084
0.5147 Remote Similarity NPC276944
0.5147 Remote Similarity NPC238530
0.5147 Remote Similarity NPC605845
0.5094 Remote Similarity NPC233029
0.5094 Remote Similarity NPC210148
0.5079 Remote Similarity NPC147390
0.5079 Remote Similarity NPC428
0.5068 Remote Similarity NPC603603
0.5067 Remote Similarity NPC73492
0.5067 Remote Similarity NPC299990

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC576658 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
0.5789 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