Natural Product: NPC486929

Natural Product IDNPC486929
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 YLAGUKSDJBZKIZ-PQNLQUHASA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 46889686
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0004603] Organic oxygen compounds
      • [CHEMONTID:0000323] Organooxygen compounds
        • [CHEMONTID:0000011] Carbohydrates and carbohydrate conjugates
          • [CHEMONTID:0003305] Aminosaccharides
            • [CHEMONTID:0000282] Aminoglycosides

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 YLAGUKSDJBZKIZ-PQNLQUHASA-N
Standard InCHI InChI=1S/C25H29NO6/c1-14-19-16-13-18-24(10-7-5-4-6-8-12-27)17(9-11-26(16)24)25(19,31-18)32-21(14)22-20(29-3)15(2)23(28)30-22/h4-8,10,14,16-19,27H,9,11-13H2,1-3H3/b5-4+,8-6+,10-7+,22-21-/t14-,16?,17?,18?,19?,24?,25-/m1/s1
SMILES C[C@@H]1C2C3CC4C5(/C=C/C=C/C=C/CO)C(CCN35)[C@@]2(O4)O/C/1=C1/C(=C(C)C(=O)O1)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   439.2 Volume:   437.537
?
Van der Waals volume.
Dense:   1.004 LogP:   1.467
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.91
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.814
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   28.0
TPSA:   77.46
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   1.0 Rings:   6.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.521 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   7.241 Fsp3:   0.56
MCE-18:   122.949
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.196 Fluc inhibitor:   0.024
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.13
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.328
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.135 Promiscuous compounds:   0.32

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.788 MDCK Permeability:   -4.861
Pgp-inhibitor:   0.011 Pgp-substrate:   0.216
PAMPA:   0.277
?
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):   0.006
20% Bioavailability (F20%):   0.316 30% Bioavailability (F30%):   0.774
50% Bioavailability (F50%):   0.941

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.027 MRP1:   0.455
Plasma Protein Binding (PPB):   76.717% Volume Distribution (VD):   -0.101
Fu: 20.154%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.983
OATP1B3 inhibitor:   0.972 BCRP inhibitor:   0.001
BSEP inhibitor:   0.993

ADMET: Metabolism

CYP1A2-inhibitor:   0.754 CYP1A2-substrate:   0.005
CYP2C19-inhibitor:   0.004 CYP2C19-substrate:   0.171
CYP2C9-inhibitor:   0.012 CYP2C9-substrate:   0.034
CYP2D6-inhibitor:   0.005 CYP2D6-substrate:   0.006
CYP3A4-inhibitor:   0.009 CYP3A4-substrate:   0.496
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.985
HLM stability:   0.107
?
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):  6.729 Half-life (T1/2):  1.183

ADMET: Toxicity

hERG Blockers:  0.089 hERG Blockers (10um):  0.232
Human Hepatotoxicity (H-HT):  0.883 Drug-induced Liver Injury (DILI):  0.472
AMES Toxicity:  0.663 Rat Oral Acute Toxicity:  0.54
Maximum Recommended Daily Dose:  0.838 Skin Sensitization:  0.873
Carcinogencity:  0.527 Eye Corrosion:  0.0
Eye Irritation:  0.008 Respiratory Toxicity:  0.397
Drug-induced Neurotoxicity:  0.209 Ototoxicity:  0.91
Hematotoxicity:  0.164 Drug-induced Nephrotoxicity:  0.282
Genotoxicity:  0.96 RPMI-8226 Immunitoxicity:  0.073
A549 Cytotoxicity:  0.024 Hek293 Cytotoxicity:  0.392
BCF:   1.133
?
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:   4.043
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.631
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.079
?
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
NPO221 Stemona aphylla Species Stemonaceae Eukaryota Roots; Stems n.a. n.a. PMID[19374387]
NPO221 Stemona aphylla Species Stemonaceae Eukaryota Stems n.a. n.a. PMID[20415428]
NPO221 Stemona aphylla Species Stemonaceae Eukaryota n.a. root n.a. PMID[21126060]
NPO221 Stemona aphylla Species Stemonaceae Eukaryota Roots Lampang Province, Thailand 2009-APR PMID[21126060]
NPO221 Stemona aphylla Species Stemonaceae Eukaryota n.a. n.a. n.a. PMID[21902195]
NPO221 Stemona aphylla Species Stemonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO221 Stemona aphylla Species Stemonaceae 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
NPT2 Others Unspecified n.a. MIC = 0.023 nM PMID[20415428]

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 NPC486929 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
0.9848 High Similarity NPC486930
0.9118 High Similarity NPC486946
0.8333 Intermediate Similarity NPC486944
0.831 Intermediate Similarity NPC486949
0.831 Intermediate Similarity NPC486952
0.8143 Intermediate Similarity NPC329401
0.8143 Intermediate Similarity NPC477987
0.76 Intermediate Similarity NPC486947
0.7361 Intermediate Similarity NPC486938
0.7042 Intermediate Similarity NPC477986
0.6883 Remote Similarity NPC486936
0.6883 Remote Similarity NPC486943
0.6883 Remote Similarity NPC486945
0.6842 Remote Similarity NPC486932
0.6842 Remote Similarity NPC323168
0.6842 Remote Similarity NPC486935
0.6842 Remote Similarity NPC486934
0.6842 Remote Similarity NPC486948
0.6842 Remote Similarity NPC486931
0.6842 Remote Similarity NPC111162
0.6842 Remote Similarity NPC486933
0.6842 Remote Similarity NPC486941
0.6842 Remote Similarity NPC486928
0.6842 Remote Similarity NPC293550
0.6667 Remote Similarity NPC138534
0.6667 Remote Similarity NPC486937
0.6456 Remote Similarity NPC486939
0.6456 Remote Similarity NPC486940
0.625 Remote Similarity NPC486942

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC486929 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