Natural Product: NPC490988

Natural Product IDNPC490988
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Scoulerine
IUPAC Name 3,10-dimethoxy-6,8,13,13a-tetrahydro-5H-isoquinolino[2,1-b]isoquinoline-2,9-diol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 22955
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000279] Alkaloids and derivatives
      • [CHEMONTID:0001909] Protoberberine alkaloids and derivatives

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 KNWVMRVOBAFFMH-UHFFFAOYSA-N
Standard InCHI InChI=1S/C19H21NO4/c1-23-17-4-3-11-7-15-13-9-16(21)18(24-2)8-12(13)5-6-20(15)10-14(11)19(17)22/h3-4,8-9,15,21-22H,5-7,10H2,1-2H3
SMILES COC1=C(C2=C(CC3C4=CC(=C(C=C4CCN3C2)OC)O)C=C1)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   327.15 Volume:   333.293
?
Van der Waals volume.
Dense:   0.982 LogP:   1.2
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.361
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.179
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   21.0
TPSA:   62.16
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   4.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.888 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.994 Fsp3:   0.368
MCE-18:   74.462
?
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:   1
Colloidal aggregators:   0.339 Fluc inhibitor:   0.327
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.479
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.408
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.002 Promiscuous compounds:   0.08

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.947 MDCK Permeability:   -4.716
Pgp-inhibitor:   0.229 Pgp-substrate:   0.165
PAMPA:   0.006
?
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):   0.058
20% Bioavailability (F20%):   0.184 30% Bioavailability (F30%):   0.24
50% Bioavailability (F50%):   0.966

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.304 MRP1:   0.949
Plasma Protein Binding (PPB):   82.498% Volume Distribution (VD):   -0.327
Fu: 15.799%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.961
OATP1B3 inhibitor:   0.991 BCRP inhibitor:   0.735
BSEP inhibitor:   0.79

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.74
CYP2C19-inhibitor:   0.999 CYP2C19-substrate:   0.002
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   1.0
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.024
CYP3A4-inhibitor:   0.95 CYP3A4-substrate:   0.964
CYP2B6-substrate:   0.891 CYP2C8-inhibitor:   0.954
HLM stability:   0.974
?
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):  4.338 Half-life (T1/2):  2.493

ADMET: Toxicity

hERG Blockers:  0.311 hERG Blockers (10um):  0.629
Human Hepatotoxicity (H-HT):  0.461 Drug-induced Liver Injury (DILI):  0.042
AMES Toxicity:  0.665 Rat Oral Acute Toxicity:  0.555
Maximum Recommended Daily Dose:  0.735 Skin Sensitization:  0.868
Carcinogencity:  0.764 Eye Corrosion:  0.001
Eye Irritation:  0.349 Respiratory Toxicity:  0.97
Drug-induced Neurotoxicity:  0.316 Ototoxicity:  0.648
Hematotoxicity:  0.13 Drug-induced Nephrotoxicity:  0.11
Genotoxicity:  0.331 RPMI-8226 Immunitoxicity:  0.077
A549 Cytotoxicity:  0.323 Hek293 Cytotoxicity:  0.552
BCF:   1.215
?
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:   3.816
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.019
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.429
?
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
NPO41563 transgenic Escherichia coli + Saccharomyces cerevisiae strains Strain n.a. n.a. n.a. n.a. n.a. PMID[18492807]

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 NPC490988 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
1.0 High Similarity NPC249797
1.0 High Similarity NPC193949
0.8036 Intermediate Similarity NPC276588
0.8036 Intermediate Similarity NPC127674
0.8036 Intermediate Similarity NPC278799
0.7377 Intermediate Similarity NPC276944
0.7377 Intermediate Similarity NPC238530
0.7167 Intermediate Similarity NPC295691
0.7167 Intermediate Similarity NPC207757
0.7167 Intermediate Similarity NPC54379
0.7143 Intermediate Similarity NPC88249
0.6833 Remote Similarity NPC189266
0.6833 Remote Similarity NPC2413
0.6833 Remote Similarity NPC110416
0.6515 Remote Similarity NPC232514
0.6349 Remote Similarity NPC204828
0.6349 Remote Similarity NPC5238
0.6271 Remote Similarity NPC220858
0.6032 Remote Similarity NPC469817
0.6032 Remote Similarity NPC172765
0.5968 Remote Similarity NPC151895
0.5806 Remote Similarity NPC147390
0.5806 Remote Similarity NPC428
0.5469 Remote Similarity NPC321505
0.5469 Remote Similarity NPC179825
0.5385 Remote Similarity NPC39701
0.5385 Remote Similarity NPC184026
0.5294 Remote Similarity NPC264850
0.5156 Remote Similarity NPC210437
0.5156 Remote Similarity NPC16107
0.5156 Remote Similarity NPC106295
0.5147 Remote Similarity NPC312025
0.5085 Remote Similarity NPC192768
0.5077 Remote Similarity NPC51957

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC490988 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
0.5156 Remote Similarity NPD4584 Phase 2

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