Natural Product: NPC133011

Natural Product IDNPC133011
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Erysovine
IUPAC Name (2R,13bS)-2,11-dimethoxy-2,6,8,9-tetrahydro-1H-indolo[7a,1-a]isoquinolin-12-ol
Synonyms Erysovine
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL517778
PubChem CID 5317203
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000279] Alkaloids and derivatives
      • [CHEMONTID:0001782] Erythrina alkaloids
        • [CHEMONTID:0002780] Erythrinanes

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 IHPMURIXWRKEKD-KSSFIOAISA-N
Standard InCHI InChI=1S/C18H21NO3/c1-21-14-4-3-13-6-8-19-7-5-12-9-17(22-2)16(20)10-15(12)18(13,19)11-14/h3-4,6,9-10,14,20H,5,7-8,11H2,1-2H3/t14-,18-/m0/s1
SMILES CO[C@H]1C=CC2=CCN3CCc4cc(c(cc4[C@]23C1)O)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   299.15 Volume:   309.844
?
Van der Waals volume.
Dense:   0.965 LogP:   1.341
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.552
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.258
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   20.0
TPSA:   41.93
?
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:   0.91 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.543 Fsp3:   0.444
MCE-18:   98.154
?
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:   0
Colloidal aggregators:   0.382 Fluc inhibitor:   0.056
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.165
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.288
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.012 Promiscuous compounds:   0.084

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.032 MDCK Permeability:   -4.717
Pgp-inhibitor:   0.0 Pgp-substrate:   1.0
PAMPA:   0.008
?
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%):   0.739 30% Bioavailability (F30%):   0.912
50% Bioavailability (F50%):   0.996

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.94 MRP1:   0.968
Plasma Protein Binding (PPB):   84.117% Volume Distribution (VD):   -0.07
Fu: 15.916%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.262
OATP1B3 inhibitor:   0.017 BCRP inhibitor:   0.116
BSEP inhibitor:   0.657

ADMET: Metabolism

CYP1A2-inhibitor:   0.999 CYP1A2-substrate:   0.896
CYP2C19-inhibitor:   0.976 CYP2C19-substrate:   0.187
CYP2C9-inhibitor:   0.966 CYP2C9-substrate:   0.924
CYP2D6-inhibitor:   0.944 CYP2D6-substrate:   0.397
CYP3A4-inhibitor:   0.747 CYP3A4-substrate:   0.993
CYP2B6-substrate:   0.253 CYP2C8-inhibitor:   0.997
HLM stability:   0.992
?
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):  9.923 Half-life (T1/2):  2.102

ADMET: Toxicity

hERG Blockers:  0.289 hERG Blockers (10um):  0.441
Human Hepatotoxicity (H-HT):  0.663 Drug-induced Liver Injury (DILI):  0.158
AMES Toxicity:  0.616 Rat Oral Acute Toxicity:  0.77
Maximum Recommended Daily Dose:  0.851 Skin Sensitization:  0.794
Carcinogencity:  0.667 Eye Corrosion:  0.009
Eye Irritation:  0.562 Respiratory Toxicity:  0.889
Drug-induced Neurotoxicity:  0.694 Ototoxicity:  0.346
Hematotoxicity:  0.229 Drug-induced Nephrotoxicity:  0.499
Genotoxicity:  0.785 RPMI-8226 Immunitoxicity:  0.136
A549 Cytotoxicity:  0.343 Hek293 Cytotoxicity:  0.313
BCF:   1.052
?
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:   3.606
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.892
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.224
?
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
NPO14905 Erythrina variegata Species Fabaceae Eukaryota n.a. root n.a. PMID[10869220]
NPO20031 Erythrina velutina Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[19026536]
NPO8301 Erythrina suberosa Species Fabaceae Eukaryota n.a. seed n.a. PMID[5348524]
NPO20031 Erythrina velutina Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14905 Erythrina variegata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3174 Sulfolobus shibatae Species Sulfolobaceae Archaea n.a. n.a. n.a. Database[COCONUT]
NPO28361 Erythrina salviiflora Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8301 Erythrina suberosa Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8301 Erythrina suberosa Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO13279 Berberis zycium Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO14905 Erythrina variegata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO17657 Erythrina arborescens Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO7457 Erythrina berteroana Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO14905 Erythrina variegata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8301 Erythrina suberosa Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO16399 Erythrina folkersii Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO17657 Erythrina arborescens Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7457 Erythrina berteroana Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28361 Erythrina salviiflora Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO13279 Berberis zycium Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8301 Erythrina suberosa Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO14905 Erythrina variegata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO13279 Berberis zycium Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO17657 Erythrina arborescens Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO29998 Erythrina salvllflora Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO30554 Erythrina folkersll Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO28361 Erythrina salviiflora Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3174 Sulfolobus shibatae Species Sulfolobaceae Archaea n.a. n.a. n.a. Database[UNPD]
NPO7457 Erythrina berteroana Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14905 Erythrina variegata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17657 Erythrina arborescens Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8301 Erythrina suberosa Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20031 Erythrina velutina Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24842 Bulla gouldiana Species Bullidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16399 Erythrina folkersii Species Fabaceae 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
NPT15 Cell line Jurkat Homo sapiens IC50 = 24.0 ug.mL-1 PMID[19026536]
NPT15 Cell line Jurkat Homo sapiens IC50 = 14.2 ug.mL-1 PMID[19026536]
NPT171 Cell line MRC5 Homo sapiens IC50 > 64000.0 nM PMID[35461019]
NPT6 Organism Plasmodium falciparum Plasmodium falciparum IC50 = 4100.0 nM PMID[35461019]

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 NPC133011 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
0.8983 High Similarity NPC82285
0.7541 Intermediate Similarity NPC130926
0.6818 Remote Similarity NPC148898
0.6 Remote Similarity NPC49353
0.5493 Remote Similarity NPC59028
0.5286 Remote Similarity NPC274026

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC133011 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
NPD

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