Natural Product: NPC583033

Natural Product IDNPC583033
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~{R})-2-hydroxy-1-(1~{H}-indol-3-yl)-5-methyl-hexan-3-one
IUPAC Name (2~{R})-2-hydroxy-1-(1~{H}-indol-3-yl)-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 AYJJYONYYXAVTL-OAHLLOKOSA-N
Standard InCHI InChI=1S/C15H19NO2/c1-10(2)7-14(17)15(18)8-11-9-16-13-6-4-3-5-12(11)13/h3-6,9-10,15-16,18H,7-8H2,1-2H3/t15-/m1/s1
SMILES CC(C)CC(=O)[C@H](O)CC1=CNC2=CC=CC=C12

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   245.14 Volume:   266.278
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Van der Waals volume.
Dense:   0.921 LogP:   2.86
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.549
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.203
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The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   11.0
TPSA:   53.09
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Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   2.0 Rings:   2.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.851 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.751 Fsp3:   0.4
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:   Rejected GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.299 Fluc inhibitor:   0.003
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.056
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.348
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.174 Promiscuous compounds:   0.365

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.677 MDCK Permeability:   -4.485
Pgp-inhibitor:   0.005 Pgp-substrate:   0.687
PAMPA:   0.281
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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):   0.0
20% Bioavailability (F20%):   0.001 30% Bioavailability (F30%):   0.022
50% Bioavailability (F50%):   0.763

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.327 MRP1:   0.154
Plasma Protein Binding (PPB):   66.231% Volume Distribution (VD):   -0.161
Fu: 34.496%
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The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.149
OATP1B3 inhibitor:   0.573 BCRP inhibitor:   0.052
BSEP inhibitor:   0.677

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.003 CYP2C19-substrate:   0.36
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.009
CYP2D6-inhibitor:   0.005 CYP2D6-substrate:   0.982
CYP3A4-inhibitor:   0.074 CYP3A4-substrate:   0.745
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.97
HLM stability:   0.999
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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):  9.729 Half-life (T1/2):  0.906

ADMET: Toxicity

hERG Blockers:  0.138 hERG Blockers (10um):  0.481
Human Hepatotoxicity (H-HT):  0.496 Drug-induced Liver Injury (DILI):  0.257
AMES Toxicity:  0.718 Rat Oral Acute Toxicity:  0.54
Maximum Recommended Daily Dose:  0.697 Skin Sensitization:  0.78
Carcinogencity:  0.536 Eye Corrosion:  0.093
Eye Irritation:  0.872 Respiratory Toxicity:  0.773
Drug-induced Neurotoxicity:  0.774 Ototoxicity:  0.617
Hematotoxicity:  0.353 Drug-induced Nephrotoxicity:  0.677
Genotoxicity:  0.649 RPMI-8226 Immunitoxicity:  0.065
A549 Cytotoxicity:  0.203 Hek293 Cytotoxicity:  0.258
BCF:   0.808
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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:   3.289
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.685
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.167
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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
NPO49260 Bacillus sp. B-60 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 NPC583033 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
0.7755 Intermediate Similarity NPC480551
0.7647 Intermediate Similarity NPC480550
0.5614 Remote Similarity NPC200214
0.5614 Remote Similarity NPC469358
0.56 Remote Similarity NPC230869
0.5517 Remote Similarity NPC480549
0.5417 Remote Similarity NPC601214
0.54 Remote Similarity NPC96102
0.5323 Remote Similarity NPC605381
0.5294 Remote Similarity NPC279081
0.5273 Remote Similarity NPC267343
0.5246 Remote Similarity NPC480548
0.5192 Remote Similarity NPC29886
0.5192 Remote Similarity NPC72435
0.5185 Remote Similarity NPC310665
0.5179 Remote Similarity NPC315555
0.5179 Remote Similarity NPC600736
0.5172 Remote Similarity NPC609424
0.5156 Remote Similarity NPC603162
0.5094 Remote Similarity NPC154339
0.5091 Remote Similarity NPC603879
0.5085 Remote Similarity NPC608269
0.5079 Remote Similarity NPC606619
0.5079 Remote Similarity NPC610347

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC583033 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
0.5472 Remote Similarity NPD786 Pre-clinical
0.54 Remote Similarity NPD198 Clinical (unspecified phase)

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