Natural Product: NPC553095

Natural Product IDNPC553095
Common Name
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The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 2'-Methylsattazolin
IUPAC Name 1-(1~{H}-indol-3-yl)-2-methoxy-5-methyl-hexan-3-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic 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 IOCIZGGXXCGMCP-UHFFFAOYSA-N
Standard InCHI InChI=1S/C16H21NO2/c1-11(2)8-15(18)16(19-3)9-12-10-17-14-7-5-4-6-13(12)14/h4-7,10-11,16-17H,8-9H2,1-3H3
SMILES COC(CC1=CNC2=CC=CC=C12)C(=O)CC(C)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   259.16 Volume:   283.574
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Van der Waals volume.
Dense:   0.914 LogP:   3.113
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.087
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.437
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The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   11.0
TPSA:   42.09
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Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   1.0 Rings:   2.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.864 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.785 Fsp3:   0.438
MCE-18:   24.0
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MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.175 Fluc inhibitor:   0.002
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.066
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.422
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.144 Promiscuous compounds:   0.232

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.772 MDCK Permeability:   -4.615
Pgp-inhibitor:   0.04 Pgp-substrate:   0.083
PAMPA:   0.378
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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):   0.002
20% Bioavailability (F20%):   0.004 30% Bioavailability (F30%):   0.029
50% Bioavailability (F50%):   0.794

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.952 MRP1:   0.406
Plasma Protein Binding (PPB):   88.73% Volume Distribution (VD):   0.041
Fu: 12.653%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.532
OATP1B3 inhibitor:   0.9 BCRP inhibitor:   0.024
BSEP inhibitor:   0.832

ADMET: Metabolism

CYP1A2-inhibitor:   0.118 CYP1A2-substrate:   0.989
CYP2C19-inhibitor:   0.994 CYP2C19-substrate:   0.389
CYP2C9-inhibitor:   0.061 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.005 CYP2D6-substrate:   0.916
CYP3A4-inhibitor:   0.821 CYP3A4-substrate:   0.839
CYP2B6-substrate:   0.559 CYP2C8-inhibitor:   0.995
HLM stability:   0.998
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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):  8.594 Half-life (T1/2):  0.411

ADMET: Toxicity

hERG Blockers:  0.154 hERG Blockers (10um):  0.535
Human Hepatotoxicity (H-HT):  0.575 Drug-induced Liver Injury (DILI):  0.248
AMES Toxicity:  0.524 Rat Oral Acute Toxicity:  0.397
Maximum Recommended Daily Dose:  0.425 Skin Sensitization:  0.553
Carcinogencity:  0.554 Eye Corrosion:  0.152
Eye Irritation:  0.908 Respiratory Toxicity:  0.644
Drug-induced Neurotoxicity:  0.754 Ototoxicity:  0.425
Hematotoxicity:  0.433 Drug-induced Nephrotoxicity:  0.422
Genotoxicity:  0.263 RPMI-8226 Immunitoxicity:  0.047
A549 Cytotoxicity:  0.1 Hek293 Cytotoxicity:  0.164
BCF:   0.766
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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:   3.359
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.746
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.278
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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
NPO58480 Bacillus sp. SNA-60-367 Genus Bacillaceae Bacteria n.a. n.a. n.a. Database[COCONUT]

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 NPC553095 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
0.6852 Remote Similarity NPC480549
0.6786 Remote Similarity NPC480548
0.5926 Remote Similarity NPC600736
0.5789 Remote Similarity NPC200214
0.5781 Remote Similarity NPC228835
0.5738 Remote Similarity NPC49954
0.5738 Remote Similarity NPC11126
0.566 Remote Similarity NPC310665
0.5636 Remote Similarity NPC59269
0.5439 Remote Similarity NPC480551
0.5424 Remote Similarity NPC282231
0.5424 Remote Similarity NPC480550
0.5385 Remote Similarity NPC29886
0.5306 Remote Similarity NPC601214
0.5263 Remote Similarity NPC605329
0.5254 Remote Similarity NPC608269
0.5238 Remote Similarity NPC605381
0.5224 Remote Similarity NPC17059
0.5192 Remote Similarity NPC279081
0.5152 Remote Similarity NPC470499
0.5152 Remote Similarity NPC606272
0.5088 Remote Similarity NPC55772
0.5085 Remote Similarity NPC609424
0.5079 Remote Similarity NPC248454
0.5077 Remote Similarity NPC603162

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC553095 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
0.5143 Remote Similarity NPD4184 Phase 2
0.5091 Remote Similarity NPD786 Pre-clinical

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