Natural Product: NPC143956

Natural Product IDNPC143956
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 CLWOXNLVWMXBRD-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 5319196
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 CLWOXNLVWMXBRD-UHFFFAOYSA-N
Standard InCHI InChI=1S/C19H23NO3/c1-20(2)9-8-14-11-19(23-3)18(22)12-16(14)17(20)10-13-4-6-15(21)7-5-13/h4-7,11-12,17H,8-10H2,1-3H3,(H-,21,22)
SMILES C[N+]1(C)CCc2cc(c(cc2C1Cc1ccc(cc1)O)[O-])OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   313.17 Volume:   333.059
?
Van der Waals volume.
Dense:   0.94 LogP:   -0.117
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.145
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.58
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   17.0
TPSA:   52.52
?
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:   0.885 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.631 Fsp3:   0.368
MCE-18:   61.385
?
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:   0.74 Fluc inhibitor:   0.001
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.146
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.055
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.029 Promiscuous compounds:   0.111

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.415 MDCK Permeability:   -4.809
Pgp-inhibitor:   0.001 Pgp-substrate:   0.999
PAMPA:   0.669
?
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):   0.752
20% Bioavailability (F20%):   1.0 30% Bioavailability (F30%):   1.0
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.442
Plasma Protein Binding (PPB):   31.774% Volume Distribution (VD):   -0.236
Fu: 61.4%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.757
OATP1B3 inhibitor:   0.546 BCRP inhibitor:   0.074
BSEP inhibitor:   0.1

ADMET: Metabolism

CYP1A2-inhibitor:   0.997 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.47 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.004
CYP3A4-inhibitor:   0.003 CYP3A4-substrate:   0.274
CYP2B6-substrate:   0.442 CYP2C8-inhibitor:   0.0
HLM stability:   0.666
?
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):  3.17 Half-life (T1/2):  2.97

ADMET: Toxicity

hERG Blockers:  0.249 hERG Blockers (10um):  0.44
Human Hepatotoxicity (H-HT):  0.257 Drug-induced Liver Injury (DILI):  0.0
AMES Toxicity:  0.081 Rat Oral Acute Toxicity:  0.721
Maximum Recommended Daily Dose:  0.988 Skin Sensitization:  0.856
Carcinogencity:  0.459 Eye Corrosion:  0.063
Eye Irritation:  0.974 Respiratory Toxicity:  0.995
Drug-induced Neurotoxicity:  0.912 Ototoxicity:  0.125
Hematotoxicity:  0.016 Drug-induced Nephrotoxicity:  0.027
Genotoxicity:  0.98 RPMI-8226 Immunitoxicity:  0.019
A549 Cytotoxicity:  0.0 Hek293 Cytotoxicity:  0.461
BCF:   1.829
?
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:   4.474
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.867
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.202
?
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
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota n.a. n.a. n.a. PMID[1659613]
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota stem bark n.a. n.a. PMID[17918910]
NPO11791 Magnolia obovata Species Magnoliaceae Eukaryota n.a. stem n.a. PMID[18175990]
NPO29110 Litsea cubeba Species Lauraceae Eukaryota n.a. aerial part n.a. PMID[18991207]
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota Stems; Barks n.a. n.a. PMID[19086868]
NPO29110 Litsea cubeba Species Lauraceae Eukaryota essential oil Tibet n.a. PMID[20944522]
NPO11791 Magnolia obovata Species Magnoliaceae Eukaryota n.a. n.a. n.a. PMID[21625478]
NPO25197 Magnolia sprengeri Species Magnoliaceae Eukaryota n.a. n.a. n.a. PMID[22080044]
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota n.a. bark n.a. PMID[23823874]
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota n.a. n.a. n.a. PMID[28485933]
NPO29110 Litsea cubeba Species Lauraceae Eukaryota Twigs n.a. n.a. PMID[28541690]
NPO29110 Litsea cubeba Species Lauraceae Eukaryota n.a. n.a. n.a. PMID[36552598]
NPO29110 Litsea cubeba Species Lauraceae Eukaryota n.a. n.a. n.a. PMID[37746728]
NPO29110 Litsea cubeba Species Lauraceae Eukaryota n.a. n.a. n.a. PMID[39013008]
NPO29110 Litsea cubeba Species Lauraceae Eukaryota n.a. n.a. n.a. PMID[39395223]
NPO29110 Litsea cubeba Species Lauraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25197 Magnolia sprengeri Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11791 Magnolia obovata Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26419 Magnolia rostrata Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21685 Magnolia coco Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26419 Magnolia rostrata Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO25197 Magnolia sprengeri Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO21685 Magnolia coco Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO11791 Magnolia obovata Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO29110 Litsea cubeba Species Lauraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO21685 Magnolia coco Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15826 Cortex magnoliae officinalis n.a. n.a. n.a. n.a. n.a. n.a. Database[TCMID]
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO29110 Litsea cubeba Species Lauraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO25197 Magnolia sprengeri Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO23867 Magnoliae officinalis praeparata n.a. n.a. n.a. n.a. n.a. n.a. Database[TCMID]
NPO11791 Magnolia obovata Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO26419 Magnolia rostrata Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21685 Magnolia coco Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO11791 Magnolia obovata Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO29110 Litsea cubeba Species Lauraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO25197 Magnolia sprengeri Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO11791 Magnolia obovata Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO29110 Litsea cubeba Species Lauraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21685 Magnolia coco Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11791 Magnolia obovata Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26419 Magnolia rostrata Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25197 Magnolia sprengeri Species Magnoliaceae 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 NPC143956 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
0.7037 Intermediate Similarity NPC484288
0.614 Remote Similarity NPC606321
0.5965 Remote Similarity NPC476151
0.5849 Remote Similarity NPC484286
0.5574 Remote Similarity NPC600791
0.5333 Remote Similarity NPC216252

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC143956 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
0.5143 Remote Similarity NPD8252 Phase 4
0.507 Remote Similarity NPD8251 Approved

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