Natural Product: NPC191213

Natural Product IDNPC191213
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 VZTUKBKUWSHDFM-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 3462225
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 VZTUKBKUWSHDFM-UHFFFAOYSA-N
Standard InCHI InChI=1S/C17H15NO2/c1-2-4-12-10(3-1)7-13-15-11(5-6-18-13)8-14-17(16(12)15)20-9-19-14/h1-4,8,13,18H,5-7,9H2
SMILES c1ccc2-c3c4c(CCNC4Cc2c1)cc1c3OCO1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   265.11 Volume:   272.564
?
Van der Waals volume.
Dense:   0.973 LogP:   2.56
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.679
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.088
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   24.0
TPSA:   30.49
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   1.0 Rings:   5.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.794 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.103 Fsp3:   0.294
MCE-18:   79.455
?
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:   0.839 Fluc inhibitor:   0.206
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.638
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.309
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.003 Promiscuous compounds:   0.292

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.898 MDCK Permeability:   -4.659
Pgp-inhibitor:   0.195 Pgp-substrate:   0.429
PAMPA:   0.17
?
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):   0.001
20% Bioavailability (F20%):   0.028 30% Bioavailability (F30%):   0.065
50% Bioavailability (F50%):   0.594

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.989 MRP1:   0.947
Plasma Protein Binding (PPB):   77.115% Volume Distribution (VD):   0.84
Fu: 22.145%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.296
OATP1B3 inhibitor:   0.518 BCRP inhibitor:   0.042
BSEP inhibitor:   0.974

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.59
CYP2C19-inhibitor:   0.999 CYP2C19-substrate:   0.012
CYP2C9-inhibitor:   0.984 CYP2C9-substrate:   1.0
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.946
CYP3A4-inhibitor:   0.777 CYP3A4-substrate:   0.93
CYP2B6-substrate:   0.999 CYP2C8-inhibitor:   0.0
HLM stability:   0.686
?
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):  4.756 Half-life (T1/2):  1.187

ADMET: Toxicity

hERG Blockers:  0.54 hERG Blockers (10um):  0.664
Human Hepatotoxicity (H-HT):  0.722 Drug-induced Liver Injury (DILI):  0.301
AMES Toxicity:  0.852 Rat Oral Acute Toxicity:  0.732
Maximum Recommended Daily Dose:  0.864 Skin Sensitization:  0.948
Carcinogencity:  0.49 Eye Corrosion:  0.008
Eye Irritation:  0.296 Respiratory Toxicity:  0.972
Drug-induced Neurotoxicity:  0.888 Ototoxicity:  0.69
Hematotoxicity:  0.165 Drug-induced Nephrotoxicity:  0.705
Genotoxicity:  0.763 RPMI-8226 Immunitoxicity:  0.071
A549 Cytotoxicity:  0.113 Hek293 Cytotoxicity:  0.244
BCF:   1.972
?
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:   4.006
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.514
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.88
?
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
NPO9632 Annona reticulata Species Annonaceae Eukaryota n.a. stem n.a. DOI[10.1021/np50053a043]
NPO2884 Annona squamosa Species Annonaceae Eukaryota seeds n.a. n.a. PMID[11141125]
NPO10210 Artabotrys uncinatus Species Annonaceae Eukaryota n.a. n.a. n.a. PMID[11575948]
NPO2884 Annona squamosa Species Annonaceae Eukaryota n.a. n.a. n.a. PMID[12398544]
NPO18932 Melia azedarach Species Meliaceae Eukaryota n.a. Brazilian n.a. PMID[15387656]
NPO18932 Melia azedarach Species Meliaceae Eukaryota n.a. ripe fruit n.a. PMID[16205005]
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota n.a. n.a. n.a. PMID[1659613]
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota stem bark n.a. n.a. PMID[17918910]
NPO2884 Annona squamosa Species Annonaceae Eukaryota n.a. n.a. n.a. PMID[18419154]
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota Stems; Barks n.a. n.a. PMID[19086868]
NPO2884 Annona squamosa Species Annonaceae Eukaryota n.a. n.a. n.a. PMID[19296389]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota n.a. n.a. n.a. PMID[19919095]
NPO2884 Annona squamosa Species Annonaceae Eukaryota n.a. n.a. n.a. PMID[21910504]
NPO2884 Annona squamosa Species Annonaceae Eukaryota seeds n.a. n.a. PMID[22011319]
NPO2884 Annona squamosa Species Annonaceae Eukaryota n.a. seed n.a. PMID[22011319]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota flower buds and leaves Khon Kaen province, Thailand 2010 PMID[23270663]
NPO2884 Annona squamosa Species Annonaceae Eukaryota Barks n.a. n.a. PMID[2348205]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota Leaves n.a. n.a. PMID[23642481]
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota n.a. bark n.a. PMID[23823874]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota Flowers n.a. n.a. PMID[26462418]
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota n.a. n.a. n.a. PMID[28485933]
NPO18932 Melia azedarach Species Meliaceae Eukaryota Fruits n.a. n.a. PMID[33253570]
NPO18932 Melia azedarach Species Meliaceae Eukaryota n.a. n.a. n.a. PMID[36362399]
NPO18932 Melia azedarach Species Meliaceae Eukaryota Seeds n.a. n.a. PMID[3701342]
NPO9632 Annona reticulata Species Annonaceae Eukaryota n.a. n.a. n.a. PMID[8277309]
NPO2884 Annona squamosa Species Annonaceae Eukaryota n.a. fruit n.a. PMID[8786370]
NPO2884 Annona squamosa Species Annonaceae Eukaryota bark n.a. n.a. PMID[9214729]
NPO18932 Melia azedarach Species Meliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10210 Artabotrys uncinatus Species Annonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9632 Annona reticulata Species Annonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2884 Annona squamosa Species Annonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9632 Annona reticulata Species Annonaceae Eukaryota n.a. n.a. Database[FooDB]
NPO2884 Annona squamosa Species Annonaceae Eukaryota n.a. n.a. Database[FooDB]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota n.a. n.a. Database[FooDB]
NPO9632 Annona reticulata Species Annonaceae Eukaryota n.a. n.a. Database[FooDB]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota Rhizome n.a. n.a. Database[FooDB]
NPO2884 Annona squamosa Species Annonaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO9632 Annona reticulata Species Annonaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO9632 Annona reticulata Species Annonaceae Eukaryota Bark n.a. n.a. Database[FooDB]
NPO10210 Artabotrys uncinatus Species Annonaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO30627 Nodus nelumbinis n.a. n.a. n.a. n.a. n.a. n.a. Database[HerDing]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO7913 Stamen nelumbinis n.a. n.a. n.a. n.a. n.a. n.a. Database[HerDing]
NPO9632 Annona reticulata Species Annonaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO18932 Melia azedarach Species Meliaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO2884 Annona squamosa Species Annonaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO11101 Receptaculum nelumbinis n.a. n.a. n.a. n.a. n.a. n.a. Database[HerDing]
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO2884 Annona squamosa Species Annonaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO17209 Nodus nelumbinis rhizomatis n.a. n.a. n.a. n.a. n.a. n.a. Database[TCMID]
NPO9632 Annona reticulata Species Annonaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18932 Melia azedarach Species Meliaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO10210 Artabotrys uncinatus Species Annonaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO11101 Receptaculum nelumbinis n.a. n.a. n.a. n.a. n.a. n.a. Database[TCMID]
NPO7913 Stamen nelumbinis n.a. n.a. n.a. n.a. n.a. n.a. Database[TCMID]
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO18932 Melia azedarach Species Meliaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO2884 Annona squamosa Species Annonaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO9632 Annona reticulata Species Annonaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO18932 Melia azedarach Species Meliaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18932 Melia azedarach Species Meliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9632 Annona reticulata Species Annonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10210 Artabotrys uncinatus Species Annonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2884 Annona squamosa Species Annonaceae 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
NPO9632 Annona reticulata Raw Bark 120 120 120 mg/100g Database [DUKE]

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
NPT6293 Organism Mycobacterium sp. Mycobacterium sp. MIC = 12.0 ug.mL-1 PMID[28628823]

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 NPC191213 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 NPC189470
0.7818 Intermediate Similarity NPC203784
0.7818 Intermediate Similarity NPC170503
0.7818 Intermediate Similarity NPC126519
0.7213 Intermediate Similarity NPC152212
0.7213 Intermediate Similarity NPC28341
0.7 Intermediate Similarity NPC6152
0.6562 Remote Similarity NPC267408
0.6508 Remote Similarity NPC112575
0.6462 Remote Similarity NPC155442
0.6462 Remote Similarity NPC312918
0.6393 Remote Similarity NPC298008
0.6349 Remote Similarity NPC470879
0.6119 Remote Similarity NPC135772
0.597 Remote Similarity NPC57036
0.597 Remote Similarity NPC600117
0.5781 Remote Similarity NPC81247
0.5781 Remote Similarity NPC35627
0.5781 Remote Similarity NPC299687
0.5781 Remote Similarity NPC476573
0.5584 Remote Similarity NPC475754
0.5538 Remote Similarity NPC148709
0.5455 Remote Similarity NPC302713
0.5217 Remote Similarity NPC481950
0.5075 Remote Similarity NPC69712
0.5075 Remote Similarity NPC220228

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC191213 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