Natural Product: NPC263709

Natural Product IDNPC263709
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Corynoxine
IUPAC Name methyl (E)-2-[(3S,6'S,7'S,8'aS)-6'-ethyl-2-oxospiro[1H-indole-3,1'-3,5,6,7,8,8a-hexahydro-2H-indolizine]-7'-yl]-3-methoxyprop-2-enoate
Synonyms Corynoxine
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1909424
PubChem CID 10475115
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000251] Indolizidines

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 DAXYUDFNWXHGBE-NRAMRBJXSA-N
Standard InCHI InChI=1S/C22H28N2O4/c1-4-14-12-24-10-9-22(17-7-5-6-8-18(17)23-21(22)26)19(24)11-15(14)16(13-27-2)20(25)28-3/h5-8,13-15,19H,4,9-12H2,1-3H3,(H,23,26)/b16-13+/t14-,15+,19+,22+/m1/s1
SMILES CO/C=C([C@H]1C[C@@H]2N(C[C@H]1CC)CC[C@]12C(=Nc2c1cccc2)O)/C(=O)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   384.2 Volume:   396.178
?
Van der Waals volume.
Dense:   0.97 LogP:   2.445
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.305
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.617
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   22.0
TPSA:   71.36
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   1.0 Rings:   4.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.49 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.897 Fsp3:   0.545
MCE-18:   107.294
?
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:   0.287 Fluc inhibitor:   0.003
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.085
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.432
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.002 Promiscuous compounds:   0.082

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.795 MDCK Permeability:   -4.558
Pgp-inhibitor:   0.04 Pgp-substrate:   0.876
PAMPA:   0.002
?
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%):   0.016 30% Bioavailability (F30%):   0.032
50% Bioavailability (F50%):   0.48

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.996 MRP1:   0.955
Plasma Protein Binding (PPB):   82.878% Volume Distribution (VD):   0.306
Fu: 14.692%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.032
OATP1B3 inhibitor:   0.002 BCRP inhibitor:   0.003
BSEP inhibitor:   0.808

ADMET: Metabolism

CYP1A2-inhibitor:   0.971 CYP1A2-substrate:   0.002
CYP2C19-inhibitor:   0.946 CYP2C19-substrate:   0.018
CYP2C9-inhibitor:   0.029 CYP2C9-substrate:   0.759
CYP2D6-inhibitor:   0.77 CYP2D6-substrate:   0.024
CYP3A4-inhibitor:   0.986 CYP3A4-substrate:   0.035
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.016
HLM stability:   0.168
?
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):  3.186 Half-life (T1/2):  1.253

ADMET: Toxicity

hERG Blockers:  0.093 hERG Blockers (10um):  0.175
Human Hepatotoxicity (H-HT):  0.986 Drug-induced Liver Injury (DILI):  0.985
AMES Toxicity:  0.898 Rat Oral Acute Toxicity:  0.926
Maximum Recommended Daily Dose:  0.964 Skin Sensitization:  1.0
Carcinogencity:  0.952 Eye Corrosion:  0.0
Eye Irritation:  0.014 Respiratory Toxicity:  0.997
Drug-induced Neurotoxicity:  0.605 Ototoxicity:  0.778
Hematotoxicity:  0.846 Drug-induced Nephrotoxicity:  0.986
Genotoxicity:  0.999 RPMI-8226 Immunitoxicity:  0.15
A549 Cytotoxicity:  0.783 Hek293 Cytotoxicity:  0.776
BCF:   0.69
?
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:   3.507
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.689
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.216
?
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
NPO17943 Amburana cearensis Species Fabaceae Eukaryota n.a. trunk bark n.a. DOI[10.1016/S0031-9422(98)00497-X]
NPO19381 Maxillaria densa Species Orchidaceae Eukaryota n.a. n.a. n.a. PMID[10479332]
NPO14112 Uncaria rhynchophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. PMID[10869194]
NPO14112 Uncaria rhynchophylla Species Rubiaceae Eukaryota leaves n.a. n.a. PMID[18588343]
NPO14112 Uncaria rhynchophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. PMID[19331340]
NPO13989 Uncaria macrophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. PMID[21070010]
NPO13989 Uncaria macrophylla Species Rubiaceae Eukaryota n.a. aerial part n.a. PMID[21070010]
NPO18193 Clivia nobilis Species Amaryllidaceae Eukaryota n.a. n.a. n.a. PMID[21469691]
NPO19381 Maxillaria densa Species Orchidaceae Eukaryota n.a. n.a. n.a. PMID[23234371]
NPO25416 Uncaria cordata Species Rubiaceae Eukaryota n.a. n.a. n.a. PMID[27128898]
NPO22126 Penicillium funiculosum Species Trichocomaceae Eukaryota n.a. n.a. n.a. PMID[27359163]
NPO14112 Uncaria rhynchophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. PMID[27700077]
NPO14112 Uncaria rhynchophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. PMID[28225280]
NPO40904 Pausinystalia yohimbe Species n.a. n.a. Bark n.a. n.a. PMID[30059216]
NPO14112 Uncaria rhynchophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. PMID[31789520]
NPO14112 Uncaria rhynchophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. PMID[31804070]
NPO17943 Amburana cearensis Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[37400005]
NPO19381 Maxillaria densa Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24190 Uncaria sterrophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13989 Uncaria macrophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25416 Uncaria cordata Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14112 Uncaria rhynchophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1603 Monostroma nitidum Species Monostromataceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18193 Clivia nobilis Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14694 Sickingia williamsii n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO18277 Scurrula fusca Species Loranthaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22126 Penicillium funiculosum Species Trichocomaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10315 Cestrum parqui Species Solanaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17943 Amburana cearensis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11476 Lecanora broccha Species Lecanoraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25416 Uncaria cordata Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO13989 Uncaria macrophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO14616 Uncaria kunstleri Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO24190 Uncaria sterrophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO17464 Uncaria sessilifructus Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO14112 Uncaria rhynchophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO10088 Uncaria attenuata Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO13989 Uncaria macrophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO1603 Monostroma nitidum Species Monostromataceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14616 Uncaria kunstleri Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO17464 Uncaria sessilifructus Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO10088 Uncaria attenuata Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24190 Uncaria sterrophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14112 Uncaria rhynchophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO25416 Uncaria cordata Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO13989 Uncaria macrophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO14112 Uncaria rhynchophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO14112 Uncaria rhynchophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO13989 Uncaria macrophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO11476 Lecanora broccha Species Lecanoraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13989 Uncaria macrophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25416 Uncaria cordata Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19160 Klasea quinquefolia Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1603 Monostroma nitidum Species Monostromataceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4468 Cuspidaria pterocarpa Species Bignoniaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9282 Stereocaulon colensoi Species Stereocaulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18193 Clivia nobilis Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO907 Dictyostelium purpureum Species n.a. Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14694 Sickingia williamsii n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO22126 Penicillium funiculosum Species Trichocomaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6849 Lomatia arborescens Species Proteaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10315 Cestrum parqui Species Solanaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11596 Lomatia ilicifolia Species Proteaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10088 Uncaria attenuata Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17464 Uncaria sessilifructus Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18862 Aria pinnatifida Species Rosaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10499 Haplopappus paucidentatus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15198 Leproloma diffusum Species Stereocaulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24190 Uncaria sterrophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8745 Senecio alloeophyllus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17943 Amburana cearensis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19381 Maxillaria densa Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14616 Uncaria kunstleri Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18277 Scurrula fusca Species Loranthaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14112 Uncaria rhynchophylla Species Rubiaceae 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
NPT271 Individual protein Delta opioid receptor Homo sapiens Activity = -3.9 % PMID[33635670]
NPT145 Individual protein Mu opioid receptor Homo sapiens Activity = 97.8 % PMID[33635670]
NPT145 Individual protein Mu opioid receptor Homo sapiens Activity = 80.1 % PMID[33635670]
NPT145 Individual protein Mu opioid receptor Homo sapiens Ki = 16.4 nM PMID[33635670]
NPT271 Individual protein Delta opioid receptor Homo sapiens Activity = 73.8 % PMID[33635670]
NPT272 Individual protein Kappa opioid receptor Homo sapiens Activity = 3.8 % PMID[33635670]
NPT272 Individual protein Kappa opioid receptor Homo sapiens Activity = 75.3 % PMID[33635670]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT116 Cell line HL-60 Homo sapiens IC50 > 40000.0 nM PMID[21070010]
NPT660 Cell line SW480 Homo sapiens IC50 > 40000.0 nM PMID[21070010]
NPT177 Tissue Aorta Rattus norvegicus IC50 > 30.0 ug.mL-1 PMID[21070010]

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT29 Organism Rattus norvegicus Rattus norvegicus ED50 = 6.75 mg.kg-1 PMID[33635670]





 Experimental ADME

Experiment Model Experiment Tissue ADME Type ADME Relation ADME Value ADME Unit Reference
n.a. n.a. Drug recovery > 80.0 % PMID[33620222]
Rattus norvegicus Plasma Drug recovery > 90.0 % PMID[33620222]





 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 NPC263709 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 NPC63210
1.0 High Similarity NPC176006
1.0 High Similarity NPC310403
1.0 High Similarity NPC97380
0.8194 Intermediate Similarity NPC243673
0.8194 Intermediate Similarity NPC148468
0.7733 Intermediate Similarity NPC181138
0.7733 Intermediate Similarity NPC210415
0.7733 Intermediate Similarity NPC298851
0.7733 Intermediate Similarity NPC21752
0.7733 Intermediate Similarity NPC276993
0.7403 Intermediate Similarity NPC117628
0.7179 Intermediate Similarity NPC52059
0.6129 Remote Similarity NPC486459
0.6129 Remote Similarity NPC731
0.5833 Remote Similarity NPC601243
0.5789 Remote Similarity NPC486458
0.5714 Remote Similarity NPC211525
0.5714 Remote Similarity NPC153694

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC263709 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