Natural Product: NPC298851

Natural Product IDNPC298851
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Methyl (1S,4As,5As,6R,10Ar)-1-Methyl-2'-Oxospiro[1,4A,5,5A,7,8,10,10A-Octahydropyrano[3,4-F]Indolizine-6,3'-1H-Indole]-4-Carboxylate
IUPAC Name methyl (1S,4aS,5aS,6R,10aR)-1-methyl-2'-oxospiro[1,4a,5,5a,7,8,10,10a-octahydropyrano[3,4-f]indolizine-6,3'-1H-indole]-4-carboxylate
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2135897
PubChem CID 94160
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 JMIAZDVHNCCPDM-DAFCLMLCSA-N
Standard InCHI InChI=1S/C21H24N2O4/c1-12-14-10-23-8-7-21(16-5-3-4-6-17(16)22-20(21)25)18(23)9-13(14)15(11-27-12)19(24)26-2/h3-6,11-14,18H,7-10H2,1-2H3,(H,22,25)/t12-,13-,14+,18-,21+/m0/s1
SMILES COC(=O)C1=CO[C@H]([C@@H]2[C@@H]1C[C@@H]1N(C2)CC[C@@]21C(=Nc1c2cccc1)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   368.17 Volume:   370.326
?
Van der Waals volume.
Dense:   0.994 LogP:   1.051
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.365
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.744
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   26.0
TPSA:   71.36
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   1.0 Rings:   5.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.772 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.959 Fsp3:   0.524
MCE-18:   127.75
?
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:   0.273 Fluc inhibitor:   0.002
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.308
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.088
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.002 Promiscuous compounds:   0.035

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.89 MDCK Permeability:   -4.855
Pgp-inhibitor:   0.001 Pgp-substrate:   0.886
PAMPA:   0.011
?
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%):   0.548 30% Bioavailability (F30%):   0.76
50% Bioavailability (F50%):   0.96

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.995 MRP1:   0.999
Plasma Protein Binding (PPB):   59.48% Volume Distribution (VD):   0.119
Fu: 42.239%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.099
OATP1B3 inhibitor:   0.006 BCRP inhibitor:   0.004
BSEP inhibitor:   0.779

ADMET: Metabolism

CYP1A2-inhibitor:   0.999 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.961 CYP2C19-substrate:   0.001
CYP2C9-inhibitor:   0.024 CYP2C9-substrate:   0.048
CYP2D6-inhibitor:   0.019 CYP2D6-substrate:   0.006
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   0.01
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.021
HLM stability:   0.203
?
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):  5.817 Half-life (T1/2):  2.045

ADMET: Toxicity

hERG Blockers:  0.164 hERG Blockers (10um):  0.187
Human Hepatotoxicity (H-HT):  0.946 Drug-induced Liver Injury (DILI):  0.974
AMES Toxicity:  0.612 Rat Oral Acute Toxicity:  0.716
Maximum Recommended Daily Dose:  0.617 Skin Sensitization:  0.958
Carcinogencity:  0.776 Eye Corrosion:  0.0
Eye Irritation:  0.264 Respiratory Toxicity:  0.924
Drug-induced Neurotoxicity:  0.544 Ototoxicity:  0.715
Hematotoxicity:  0.747 Drug-induced Nephrotoxicity:  0.935
Genotoxicity:  0.985 RPMI-8226 Immunitoxicity:  0.027
A549 Cytotoxicity:  0.029 Hek293 Cytotoxicity:  0.343
BCF:   0.597
?
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:   3.368
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.674
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.144
?
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]
NPO16501 Capsicum annuum Species Solanaceae Eukaryota n.a. fruit n.a. PMID[12932131]
NPO16501 Capsicum annuum Species Solanaceae Eukaryota n.a. n.a. n.a. PMID[20460582]
NPO9390 Uncaria gambir Species Rubiaceae Eukaryota n.a. n.a. n.a. PMID[21192716]
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]
NPO16501 Capsicum annuum Species Solanaceae Eukaryota n.a. fruit n.a. PMID[25172746]
NPO22126 Penicillium funiculosum Species Trichocomaceae Eukaryota n.a. n.a. n.a. PMID[27359163]
NPO53708 Struchium sparganophora Genus Asteraceae Eukaryota n.a. n.a. n.a. PMID[35315297]
NPO17943 Amburana cearensis Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[37400005]
NPO16501 Capsicum annuum Species Solanaceae Eukaryota n.a. n.a. n.a. PMID[8910532]
NPO11476 Lecanora broccha Species Lecanoraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28120 Anisopappus pinnatifidus Species Asteraceae 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]
NPO16419 Rumex chalepensis Species Polygonaceae 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]
NPO9390 Uncaria gambir Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19381 Maxillaria densa Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27397 Drymaria cordata Species Caryophyllaceae 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]
NPO4940 Peyrousea umbellata n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO27221 Prosopis spicigera Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2296 Agaricus arvensis Species Agaricaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18817 Platycarpha glomerata n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO16501 Capsicum annuum Species Solanaceae Eukaryota Resin, Exudate, Sap n.a. n.a. Database[FooDB]
NPO16501 Capsicum annuum Species Solanaceae Eukaryota n.a. n.a. Database[FooDB]
NPO16501 Capsicum annuum Species Solanaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO16501 Capsicum annuum Species Solanaceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO16501 Capsicum annuum Species Solanaceae Eukaryota Pericarp n.a. n.a. Database[FooDB]
NPO16501 Capsicum annuum Species Solanaceae Eukaryota Root n.a. n.a. Database[FooDB]
NPO16501 Capsicum annuum Species Solanaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO16501 Capsicum annuum Species Solanaceae Eukaryota Tissue Culture n.a. n.a. Database[FooDB]
NPO9390 Uncaria gambir Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO16501 Capsicum annuum Species Solanaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO9390 Uncaria gambir 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]
NPO16501 Capsicum annuum Species Solanaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO27397 Drymaria cordata Species Caryophyllaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO16501 Capsicum annuum Species Solanaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO9390 Uncaria gambir Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO16501 Capsicum annuum Species Solanaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO16419 Rumex chalepensis Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO18193 Clivia nobilis Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10315 Cestrum parqui Species Solanaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28001 Zeora sordida n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO27913 Ageratina tomentella Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6849 Lomatia arborescens Species Proteaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22126 Penicillium funiculosum Species Trichocomaceae 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]
NPO27397 Drymaria cordata Species Caryophyllaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO907 Dictyostelium purpureum Species n.a. Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3254 Fusarium caucasicum Species Nectriaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9282 Stereocaulon colensoi Species Stereocaulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4468 Cuspidaria pterocarpa Species Bignoniaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1603 Monostroma nitidum Species Monostromataceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4940 Peyrousea umbellata n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO18817 Platycarpha glomerata n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO28344 Rubus xanthocarpus Species Rosaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19160 Klasea quinquefolia Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9390 Uncaria gambir Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16419 Rumex chalepensis Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19381 Maxillaria densa Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11476 Lecanora broccha Species Lecanoraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17943 Amburana cearensis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8745 Senecio alloeophyllus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19583 Ficus nervosa Species Moraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9061 Euthamia graminifolia 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]
NPO10499 Haplopappus paucidentatus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18277 Scurrula fusca Species Loranthaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18862 Aria pinnatifida Species Rosaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27722 Caralluma stalagmifera Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2296 Agaricus arvensis Species Agaricaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16501 Capsicum annuum Species Solanaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10334 Andropogon polyneuros Species Poaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27221 Prosopis spicigera Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28120 Anisopappus pinnatifidus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11596 Lomatia ilicifolia Species Proteaceae 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
NPO53708 Struchium sparganophora n.a. n.a. 65.73 n.a. n.a. μg/100g PMID[35315297]

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
NPT2484 Cell line GAMG Homo sapiens IC50 = 12300.0 nM PMID[27543880]
NPT2 Others Unspecified n.a. Potency n.a. 354.8 nM PubChem BioAssay data set
NPT30059 Cell line SK-N-BE(2) Homo sapiens IC50 = 20000.0 nM PMID[27543880]

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
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 NPC298851 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 NPC181138
1.0 High Similarity NPC210415
1.0 High Similarity NPC21752
1.0 High Similarity NPC276993
0.7733 Intermediate Similarity NPC63210
0.7733 Intermediate Similarity NPC176006
0.7733 Intermediate Similarity NPC310403
0.7733 Intermediate Similarity NPC97380
0.7733 Intermediate Similarity NPC263709
0.7403 Intermediate Similarity NPC243673
0.7403 Intermediate Similarity NPC148468
0.631 Remote Similarity NPC52059
0.593 Remote Similarity NPC159563
0.593 Remote Similarity NPC293255
0.5773 Remote Similarity NPC486458
0.5773 Remote Similarity NPC486459
0.5773 Remote Similarity NPC731
0.5747 Remote Similarity NPC117628
0.5341 Remote Similarity NPC211525
0.5341 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 NPC298851 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