Natural Product: NPC474931

Natural Product IDNPC474931
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Sauveoline
IUPAC Name (6aR)-1,2-dimethoxy-6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline-10,11-diol
Synonyms Sauveoline
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL488204
PubChem CID 44559867
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000279] Alkaloids and derivatives
      • [CHEMONTID:0000381] Aporphines

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 FNHRMNVLZGCBIE-GFCCVEGCSA-N
Standard InCHI InChI=1S/C19H21NO4/c1-20-7-6-11-9-14(23-2)19(24-3)17-15(11)12(20)8-10-4-5-13(21)18(22)16(10)17/h4-5,9,12,21-22H,6-8H2,1-3H3/t12-/m1/s1
SMILES CN1CCC2=CC(=C(C3=C2C1CC4=C3C(=C(C=C4)O)O)OC)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   327.15 Volume:   333.293
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Van der Waals volume.
Dense:   0.982 LogP:   1.81
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.99
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.422
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The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   20.0
TPSA:   62.16
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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:   0.831 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.15 Fsp3:   0.368
MCE-18:   76.077
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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:   1
Colloidal aggregators:   0.645 Fluc inhibitor:   0.019
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.51
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.489
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.004 Promiscuous compounds:   0.453

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.971 MDCK Permeability:   -4.77
Pgp-inhibitor:   0.001 Pgp-substrate:   0.125
PAMPA:   0.565
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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):   0.069
20% Bioavailability (F20%):   0.905 30% Bioavailability (F30%):   0.748
50% Bioavailability (F50%):   0.99

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.281 MRP1:   0.994
Plasma Protein Binding (PPB):   53.769% Volume Distribution (VD):   0.147
Fu: 46.882%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.339
OATP1B3 inhibitor:   0.932 BCRP inhibitor:   0.22
BSEP inhibitor:   0.447

ADMET: Metabolism

CYP1A2-inhibitor:   0.996 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.97 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.102 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.97 CYP2D6-substrate:   0.003
CYP3A4-inhibitor:   0.623 CYP3A4-substrate:   0.025
CYP2B6-substrate:   0.701 CYP2C8-inhibitor:   0.0
HLM stability:   0.111
?
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):  15.753 Half-life (T1/2):  2.528

ADMET: Toxicity

hERG Blockers:  0.441 hERG Blockers (10um):  0.703
Human Hepatotoxicity (H-HT):  0.43 Drug-induced Liver Injury (DILI):  0.009
AMES Toxicity:  0.746 Rat Oral Acute Toxicity:  0.533
Maximum Recommended Daily Dose:  0.784 Skin Sensitization:  0.973
Carcinogencity:  0.722 Eye Corrosion:  0.0
Eye Irritation:  0.127 Respiratory Toxicity:  0.969
Drug-induced Neurotoxicity:  0.435 Ototoxicity:  0.762
Hematotoxicity:  0.094 Drug-induced Nephrotoxicity:  0.075
Genotoxicity:  0.387 RPMI-8226 Immunitoxicity:  0.042
A549 Cytotoxicity:  0.297 Hek293 Cytotoxicity:  0.487
BCF:   1.369
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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:   3.889
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.528
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.651
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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
NPO32838 artabottys maingayi Species n.a. n.a. n.a. n.a. n.a. PMID[8676127]

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
NPT1073 Individual protein Dopamine transporter Rattus norvegicus IC50 > 100000.0 nM PMID[18710917]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT2 Others Unspecified n.a. Ratio IC50 < 0.63 n.a. PMID[22705001]
NPT2 Others Unspecified n.a. Ratio IC50 < 0.005 n.a. PMID[8759172]

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 NPC474931 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
0.7667 Intermediate Similarity NPC205421
0.7667 Intermediate Similarity NPC607722
0.6667 Remote Similarity NPC136508
0.6471 Remote Similarity NPC114364
0.619 Remote Similarity NPC326316
0.619 Remote Similarity NPC158376
0.619 Remote Similarity NPC81733
0.6176 Remote Similarity NPC320223
0.6154 Remote Similarity NPC117188
0.6154 Remote Similarity NPC145832
0.6129 Remote Similarity NPC99659
0.6129 Remote Similarity NPC325871
0.6 Remote Similarity NPC609009
0.5942 Remote Similarity NPC610764
0.5909 Remote Similarity NPC600388
0.5634 Remote Similarity NPC128560
0.5634 Remote Similarity NPC229166
0.5588 Remote Similarity NPC247389
0.5522 Remote Similarity NPC212794
0.5522 Remote Similarity NPC606254
0.5493 Remote Similarity NPC600118
0.5441 Remote Similarity NPC253043
0.5441 Remote Similarity NPC605949
0.5278 Remote Similarity NPC298979
0.5224 Remote Similarity NPC13504
0.5217 Remote Similarity NPC195075
0.5217 Remote Similarity NPC27410
0.5211 Remote Similarity NPC219341
0.5143 Remote Similarity NPC63997
0.5143 Remote Similarity NPC16805
0.5143 Remote Similarity NPC167546
0.5139 Remote Similarity NPC199465
0.5077 Remote Similarity NPC185838

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC474931 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
0.5873 Remote Similarity NPD2421 Phase 4
0.5781 Remote Similarity NPD2420 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