Natural Product: NPC486946

Natural Product IDNPC486946
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 MQEIXFVVCYDTDK-MPSLRERJSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 46889843
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 MQEIXFVVCYDTDK-MPSLRERJSA-N
Standard InCHI InChI=1S/C21H25NO6/c1-10-15-12-9-14-20(6-4-8-23)13(5-7-22(12)20)21(15,27-14)28-17(10)18-16(25-3)11(2)19(24)26-18/h4,6,10,12-15,23H,5,7-9H2,1-3H3/b6-4+,18-17-/t10-,12?,13?,14?,15?,20?,21-/m1/s1
SMILES C[C@@H]1C2C3CC4C5(/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:   387.17 Volume:   373.626
?
Van der Waals volume.
Dense:   1.036 LogP:   0.817
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.121
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.948
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   26.0
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:   0.58 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   7.136 Fsp3:   0.667
MCE-18:   125.0
?
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:   0.125 Fluc inhibitor:   0.001
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.06
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.215
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.031 Promiscuous compounds:   0.274

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.688 MDCK Permeability:   -4.939
Pgp-inhibitor:   0.023 Pgp-substrate:   0.024
PAMPA:   0.057
?
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):   0.033
20% Bioavailability (F20%):   0.611 30% Bioavailability (F30%):   0.904
50% Bioavailability (F50%):   0.851

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.511 MRP1:   0.436
Plasma Protein Binding (PPB):   64.951% Volume Distribution (VD):   -0.032
Fu: 35.318%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.939
OATP1B3 inhibitor:   0.97 BCRP inhibitor:   0.001
BSEP inhibitor:   0.938

ADMET: Metabolism

CYP1A2-inhibitor:   0.086 CYP1A2-substrate:   0.007
CYP2C19-inhibitor:   0.041 CYP2C19-substrate:   0.845
CYP2C9-inhibitor:   0.913 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.006 CYP2D6-substrate:   0.026
CYP3A4-inhibitor:   0.024 CYP3A4-substrate:   0.064
CYP2B6-substrate:   0.001 CYP2C8-inhibitor:   0.689
HLM stability:   0.231
?
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):  6.583 Half-life (T1/2):  1.427

ADMET: Toxicity

hERG Blockers:  0.074 hERG Blockers (10um):  0.27
Human Hepatotoxicity (H-HT):  0.879 Drug-induced Liver Injury (DILI):  0.661
AMES Toxicity:  0.461 Rat Oral Acute Toxicity:  0.46
Maximum Recommended Daily Dose:  0.601 Skin Sensitization:  0.858
Carcinogencity:  0.478 Eye Corrosion:  0.0
Eye Irritation:  0.02 Respiratory Toxicity:  0.239
Drug-induced Neurotoxicity:  0.296 Ototoxicity:  0.873
Hematotoxicity:  0.191 Drug-induced Nephrotoxicity:  0.275
Genotoxicity:  0.958 RPMI-8226 Immunitoxicity:  0.092
A549 Cytotoxicity:  0.05 Hek293 Cytotoxicity:  0.376
BCF:   0.832
?
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:   3.75
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.564
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.781
?
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 = 0.129 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 NPC486946 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
0.9254 High Similarity NPC486930
0.9118 High Similarity NPC486929
0.8571 High Similarity NPC486944
0.8551 High Similarity NPC486949
0.8551 High Similarity NPC486952
0.8382 Intermediate Similarity NPC329401
0.8382 Intermediate Similarity NPC477987
0.7808 Intermediate Similarity NPC486947
0.7571 Intermediate Similarity NPC486938
0.7246 Intermediate Similarity NPC477986
0.7067 Intermediate Similarity NPC486936
0.7067 Intermediate Similarity NPC486943
0.7067 Intermediate Similarity NPC486945
0.7027 Intermediate Similarity NPC486932
0.7027 Intermediate Similarity NPC323168
0.7027 Intermediate Similarity NPC486935
0.7027 Intermediate Similarity NPC486934
0.7027 Intermediate Similarity NPC486948
0.7027 Intermediate Similarity NPC486931
0.7027 Intermediate Similarity NPC111162
0.7027 Intermediate Similarity NPC486933
0.7027 Intermediate Similarity NPC486941
0.7027 Intermediate Similarity NPC486928
0.7027 Intermediate Similarity NPC293550
0.6849 Remote Similarity NPC138534
0.6849 Remote Similarity NPC486937
0.6623 Remote Similarity NPC486939
0.6623 Remote Similarity NPC486940
0.641 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 NPC486946 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