Natural Product: NPC274184

Natural Product IDNPC274184
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 HDTRYLNUVZCQOY-NCFXGAEVSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 10783457
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0004603] Organic oxygen compounds
      • [CHEMONTID:0000323] Organooxygen compounds
        • [CHEMONTID:0000011] Carbohydrates and carbohydrate conjugates
          • [CHEMONTID:0002105] Glycosyl compounds
            • [CHEMONTID:0002207] O-glycosyl compounds

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 HDTRYLNUVZCQOY-NCFXGAEVSA-N
Standard InCHI InChI=1S/C12H22O11/c13-1-3-5(15)7(17)9(19)11(21-3)23-12-10(20)8(18)6(16)4(2-14)22-12/h3-20H,1-2H2/t3-,4-,5-,6-,7+,8+,9-,10-,11+,12+/m1/s1
SMILES C([C@@H]1[C@H]([C@@H]([C@H]([C@@H](O1)O[C@H]1[C@@H]([C@H]([C@@H]([C@@H](CO)O1)O)O)O)O)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   342.12 Volume:   295.688
?
Van der Waals volume.
Dense:   1.157 LogP:   -2.714
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   -1.983
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -0.043
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   12.0
TPSA:   189.53
?
Topological Polar Surface Area.
 H-Bond Acceptor:   11.0
H-Bond Donor:   8.0 Rings:   2.0
Heavy Atoms:   11.0

MedChem Properties

QED Drug-Likeness Score:   0.243 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.106 Fsp3:   1.0
MCE-18:   45.333
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Accepted
Pfizer Rule:   Rejected GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.252 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.034
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.0
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.546 Promiscuous compounds:   0.026

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.964 MDCK Permeability:   -4.923
Pgp-inhibitor:   0.0 Pgp-substrate:   0.659
PAMPA:   0.998
?
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):   0.998
20% Bioavailability (F20%):   0.267 30% Bioavailability (F30%):   0.997
50% Bioavailability (F50%):   0.904

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.544 MRP1:   0.01
Plasma Protein Binding (PPB):   27.641% Volume Distribution (VD):   -0.539
Fu: 76.161%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.04
BSEP inhibitor:   0.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.062
HLM stability:   0.001
?
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):  0.886 Half-life (T1/2):  2.822

ADMET: Toxicity

hERG Blockers:  0.003 hERG Blockers (10um):  0.043
Human Hepatotoxicity (H-HT):  0.534 Drug-induced Liver Injury (DILI):  0.701
AMES Toxicity:  0.903 Rat Oral Acute Toxicity:  0.006
Maximum Recommended Daily Dose:  0.001 Skin Sensitization:  0.999
Carcinogencity:  0.091 Eye Corrosion:  0.0
Eye Irritation:  0.365 Respiratory Toxicity:  0.002
Drug-induced Neurotoxicity:  0.003 Ototoxicity:  0.975
Hematotoxicity:  0.333 Drug-induced Nephrotoxicity:  0.83
Genotoxicity:  0.052 RPMI-8226 Immunitoxicity:  0.101
A549 Cytotoxicity:  0.173 Hek293 Cytotoxicity:  0.047
BCF:   0.105
?
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:   1.308
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   2.475
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   1.84
?
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
NPO24269 Comatula rotalaria Species Comatulidae Eukaryota n.a. n.a. n.a. PMID[27063022]
NPO24269 Comatula rotalaria Species Comatulidae Eukaryota n.a. n.a. n.a. PMID[32478519]
NPO24269 Comatula rotalaria Species Comatulidae 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 NPC274184 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 NPC107914
1.0 High Similarity NPC242073
0.7692 Intermediate Similarity NPC42503
0.7692 Intermediate Similarity NPC282143
0.7692 Intermediate Similarity NPC299781
0.7692 Intermediate Similarity NPC157193
0.7692 Intermediate Similarity NPC608193
0.7407 Intermediate Similarity NPC23134
0.6897 Remote Similarity NPC124963
0.6667 Remote Similarity NPC326533
0.6562 Remote Similarity NPC31496
0.6452 Remote Similarity NPC317501
0.6452 Remote Similarity NPC605930
0.625 Remote Similarity NPC143326
0.5882 Remote Similarity NPC233726
0.5714 Remote Similarity NPC130683
0.5676 Remote Similarity NPC13143
0.5676 Remote Similarity NPC132938
0.5676 Remote Similarity NPC294813
0.5556 Remote Similarity NPC155457
0.5556 Remote Similarity NPC268243
0.5526 Remote Similarity NPC32148
0.5526 Remote Similarity NPC152384
0.5405 Remote Similarity NPC246558
0.5405 Remote Similarity NPC323361
0.5405 Remote Similarity NPC67660
0.5405 Remote Similarity NPC145112
0.5405 Remote Similarity NPC165198
0.5405 Remote Similarity NPC209753
0.5405 Remote Similarity NPC58629
0.5366 Remote Similarity NPC472174
0.5263 Remote Similarity NPC290179
0.5263 Remote Similarity NPC603514
0.5263 Remote Similarity NPC606861
0.5263 Remote Similarity NPC607126
0.525 Remote Similarity NPC601741
0.5238 Remote Similarity NPC277570
0.5128 Remote Similarity NPC83248
0.5122 Remote Similarity NPC165119

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC274184 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
0.6429 Remote Similarity NPD8994 Approved
0.625 Remote Similarity NPD905 Phase 4
0.5882 Remote Similarity NPD904 Phase 3
0.5714 Remote Similarity NPD887 Approved
0.5714 Remote Similarity NPD895 Phase 4
0.5405 Remote Similarity NPD888 Phase 3
0.5405 Remote Similarity NPD889 Approved
0.5405 Remote Similarity NPD890 Clinical (unspecified phase)
0.5405 Remote Similarity NPD891 Phase 3
0.5405 Remote Similarity NPD892 Phase 3
0.5405 Remote Similarity NPD893 Approved
0.5405 Remote Similarity NPD894 Phase 4

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