Natural Product: NPC88097

Natural Product IDNPC88097
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Desbromoarborescidine A
IUPAC Name (12bS)-1,2,3,4,6,7,12,12b-octahydroindolo[2,3-a]quinolizine
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL93136
PubChem CID 11276206
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000211] Indoles and derivatives
        • [CHEMONTID:0001213] Pyridoindoles
          • [CHEMONTID:0001914] Beta carbolines

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 OURDZMSSMGUMKR-AWEZNQCLSA-N
Standard InCHI InChI=1S/C15H18N2/c1-2-6-13-11(5-1)12-8-10-17-9-4-3-7-14(17)15(12)16-13/h1-2,5-6,14,16H,3-4,7-10H2/t14-/m0/s1
SMILES C1CC[C@@H]2N(C1)CCc1c2[nH]c2c1cccc2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   226.15 Volume:   245.218
?
Van der Waals volume.
Dense:   0.922 LogP:   2.609
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.491
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.15
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The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   20.0
TPSA:   19.03
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   1.0 Rings:   4.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.73 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.594 Fsp3:   0.467
MCE-18:   65.455
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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:   0.153 Fluc inhibitor:   0.306
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.737
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.434
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.003 Promiscuous compounds:   0.709

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.738 MDCK Permeability:   -4.788
Pgp-inhibitor:   0.016 Pgp-substrate:   0.706
PAMPA:   0.018
?
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%):   0.289 30% Bioavailability (F30%):   0.724
50% Bioavailability (F50%):   0.924

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.949 MRP1:   0.976
Plasma Protein Binding (PPB):   86.716% Volume Distribution (VD):   0.562
Fu: 13.924%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.301
OATP1B3 inhibitor:   0.335 BCRP inhibitor:   0.847
BSEP inhibitor:   0.982

ADMET: Metabolism

CYP1A2-inhibitor:   0.998 CYP1A2-substrate:   0.001
CYP2C19-inhibitor:   0.989 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.999
CYP2D6-inhibitor:   0.952 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.0
HLM stability:   0.001
?
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):  11.055 Half-life (T1/2):  1.66

ADMET: Toxicity

hERG Blockers:  0.715 hERG Blockers (10um):  0.693
Human Hepatotoxicity (H-HT):  0.511 Drug-induced Liver Injury (DILI):  0.092
AMES Toxicity:  0.53 Rat Oral Acute Toxicity:  0.863
Maximum Recommended Daily Dose:  0.972 Skin Sensitization:  0.704
Carcinogencity:  0.58 Eye Corrosion:  0.003
Eye Irritation:  0.554 Respiratory Toxicity:  0.981
Drug-induced Neurotoxicity:  0.869 Ototoxicity:  0.147
Hematotoxicity:  0.066 Drug-induced Nephrotoxicity:  0.433
Genotoxicity:  0.737 RPMI-8226 Immunitoxicity:  0.037
A549 Cytotoxicity:  0.174 Hek293 Cytotoxicity:  0.439
BCF:   1.926
?
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:   3.826
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.046
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.573
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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
NPO11351 Stephania japonica Species Menispermaceae Eukaryota Aerial parts n.a. n.a. PMID[20426456]
NPO11351 Stephania japonica Species Menispermaceae Eukaryota n.a. n.a. n.a. PMID[9392886]
NPO11351 Stephania japonica Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13535 Caloporus dichrous n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO11351 Stephania japonica Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO11351 Stephania japonica Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO11351 Stephania japonica Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO13535 Caloporus dichrous n.a. n.a. n.a. n.a. n.a. n.a. Database[Title]
NPO13649 Dipterocarpus gracilis Species Dipterocarpaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26835 Cetraria tenuifolia Species Parmeliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11351 Stephania japonica Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13535 Caloporus dichrous n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO7930 Julocroton subpannosus n.a. n.a. n.a. 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
NPT1779 Individual protein Serotonin 2b (5-HT2b) receptor Rattus norvegicus -Log KB = 6.66 n.a. PMID[8709108]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT171 Cell line MRC5 Homo sapiens IC50 = 82500.0 nM PMID[19419803]
NPT196 Cell line AGS Homo sapiens IC50 = 50400.0 nM PMID[19419803]
NPT1505 Cell line J82 Homo sapiens IC50 = 90200.0 nM PMID[19419803]
NPT1506 Cell line SK-MES-1 Homo sapiens IC50 = 65100.0 nM PMID[19419803]
NPT116 Cell line HL-60 Homo sapiens IC50 > 100000.0 nM PMID[19419803]
NPT91 Cell line KB Homo sapiens Activity = 100.0 % PMID[19419803]

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 NPC88097 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
0.7018 Intermediate Similarity NPC608552
0.6 Remote Similarity NPC185200
0.5846 Remote Similarity NPC21174
0.5758 Remote Similarity NPC229173
0.5606 Remote Similarity NPC271797
0.5588 Remote Similarity NPC474897
0.5588 Remote Similarity NPC165441
0.527 Remote Similarity NPC483467
0.5263 Remote Similarity NPC198988
0.5135 Remote Similarity NPC486452
0.5135 Remote Similarity NPC74591
0.5067 Remote Similarity NPC486449
0.5067 Remote Similarity NPC63199
0.5067 Remote Similarity NPC313985
0.5067 Remote Similarity NPC249150
0.5067 Remote Similarity NPC111602
0.5067 Remote Similarity NPC102338
0.5067 Remote Similarity NPC486443
0.5067 Remote Similarity NPC486446
0.5067 Remote Similarity NPC196251
0.5067 Remote Similarity NPC273374
0.5067 Remote Similarity NPC33619

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC88097 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
0.5067 Remote Similarity NPD4601 Phase 4

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