Natural Product: NPC58785

Natural Product IDNPC58785
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 SBGGUHPMRYOCBS-ZDUSSCGKSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 155514
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 SBGGUHPMRYOCBS-ZDUSSCGKSA-N
Standard InCHI InChI=1S/C19H21NO4/c1-20-5-4-10-7-14(21)19(22)18-12-9-16(24-3)15(23-2)8-11(12)6-13(20)17(10)18/h7-9,13,21-22H,4-6H2,1-3H3/t13-/m0/s1
SMILES CN1CCc2cc(c(c3-c4cc(c(cc4C[C@H]1c23)OC)OC)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   327.15 Volume:   333.293
?
Van der Waals volume.
Dense:   0.982 LogP:   1.607
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.881
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.591
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   20.0
TPSA:   62.16
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   4.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.831 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.068 Fsp3:   0.368
MCE-18:   76.077
?
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:   1
Colloidal aggregators:   0.685 Fluc inhibitor:   0.018
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.669
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.426
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.005 Promiscuous compounds:   0.831

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.117 MDCK Permeability:   -4.805
Pgp-inhibitor:   0.003 Pgp-substrate:   0.616
PAMPA:   0.021
?
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):   0.066
20% Bioavailability (F20%):   0.987 30% Bioavailability (F30%):   0.993
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.391 MRP1:   0.959
Plasma Protein Binding (PPB):   70.403% Volume Distribution (VD):   -0.021
Fu: 32.206%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.938
OATP1B3 inhibitor:   0.939 BCRP inhibitor:   0.796
BSEP inhibitor:   0.327

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.992 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.389 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.987 CYP2D6-substrate:   0.004
CYP3A4-inhibitor:   0.926 CYP3A4-substrate:   0.125
CYP2B6-substrate:   0.157 CYP2C8-inhibitor:   0.247
HLM stability:   0.229
?
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):  14.199 Half-life (T1/2):  2.516

ADMET: Toxicity

hERG Blockers:  0.394 hERG Blockers (10um):  0.684
Human Hepatotoxicity (H-HT):  0.543 Drug-induced Liver Injury (DILI):  0.059
AMES Toxicity:  0.671 Rat Oral Acute Toxicity:  0.716
Maximum Recommended Daily Dose:  0.894 Skin Sensitization:  0.789
Carcinogencity:  0.668 Eye Corrosion:  0.002
Eye Irritation:  0.2 Respiratory Toxicity:  0.941
Drug-induced Neurotoxicity:  0.817 Ototoxicity:  0.386
Hematotoxicity:  0.126 Drug-induced Nephrotoxicity:  0.283
Genotoxicity:  0.796 RPMI-8226 Immunitoxicity:  0.066
A549 Cytotoxicity:  0.341 Hek293 Cytotoxicity:  0.309
BCF:   1.493
?
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:   4.072
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.32
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.702
?
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
NPO2884 Annona squamosa Species Annonaceae Eukaryota seeds n.a. n.a. PMID[11141125]
NPO2884 Annona squamosa Species Annonaceae Eukaryota n.a. n.a. n.a. PMID[12398544]
NPO2884 Annona squamosa Species Annonaceae Eukaryota n.a. n.a. n.a. PMID[18419154]
NPO2884 Annona squamosa Species Annonaceae Eukaryota n.a. n.a. n.a. PMID[19296389]
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]
NPO2884 Annona squamosa Species Annonaceae Eukaryota Barks n.a. n.a. PMID[2348205]
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]
NPO2884 Annona squamosa Species Annonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2884 Annona squamosa Species Annonaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO2884 Annona squamosa Species Annonaceae Eukaryota n.a. n.a. Database[FooDB]
NPO2884 Annona squamosa Species Annonaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO2884 Annona squamosa Species Annonaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO2884 Annona squamosa Species Annonaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
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

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

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 NPC58785 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
0.7333 Intermediate Similarity NPC253043
0.65 Remote Similarity NPC99659
0.65 Remote Similarity NPC325871
0.6364 Remote Similarity NPC199465
0.625 Remote Similarity NPC239775
0.6094 Remote Similarity NPC212794
0.5909 Remote Similarity NPC63997
0.5909 Remote Similarity NPC16805
0.5909 Remote Similarity NPC474931
0.5909 Remote Similarity NPC167546
0.5781 Remote Similarity NPC13504
0.5758 Remote Similarity NPC136508
0.5606 Remote Similarity NPC606254
0.5538 Remote Similarity NPC158376
0.5441 Remote Similarity NPC205421
0.5441 Remote Similarity NPC607722
0.5294 Remote Similarity NPC195075
0.5294 Remote Similarity NPC117188
0.5294 Remote Similarity NPC145832
0.5294 Remote Similarity NPC27410
0.5294 Remote Similarity NPC600388
0.5278 Remote Similarity NPC229166
0.5147 Remote Similarity NPC609009
0.5072 Remote Similarity NPC605949
0.5068 Remote Similarity NPC128560

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC58785 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