Natural Product: NPC105127

Natural Product IDNPC105127
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 1H-Indol-3-Ylmethanamine
IUPAC Name 1H-indol-3-ylmethanamine
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL6509
PubChem CID 472107
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000211] Indoles and derivatives
        • [CHEMONTID:0002497] Indoles
          • [CHEMONTID:0004196] 3-alkylindoles

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 JXYGLMATGAAIBU-UHFFFAOYSA-N
Standard InCHI InChI=1S/C9H10N2/c10-5-7-6-11-9-4-2-1-3-8(7)9/h1-4,6,11H,5,10H2
SMILES NCc1c[nH]c2c1cccc2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   146.08 Volume:   158.555
?
Van der Waals volume.
Dense:   0.921 LogP:   1.443
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.097
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.005
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The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   10.0
TPSA:   41.81
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   3.0 Rings:   2.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.63 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   1.841 Fsp3:   0.111
MCE-18:   9.0
?
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:   Accepted BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.26 Fluc inhibitor:   0.03
?
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:   0.119
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.073 Promiscuous compounds:   0.624

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.012 MDCK Permeability:   -4.871
Pgp-inhibitor:   0.085 Pgp-substrate:   0.404
PAMPA:   0.314
?
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):   0.075
20% Bioavailability (F20%):   0.039 30% Bioavailability (F30%):   0.296
50% Bioavailability (F50%):   0.304

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.326 MRP1:   0.279
Plasma Protein Binding (PPB):   36.872% Volume Distribution (VD):   0.407
Fu: 57.501%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.802
OATP1B3 inhibitor:   0.925 BCRP inhibitor:   0.344
BSEP inhibitor:   0.647

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.011
CYP2C19-inhibitor:   0.914 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.41 CYP2C9-substrate:   0.873
CYP2D6-inhibitor:   0.963 CYP2D6-substrate:   0.02
CYP3A4-inhibitor:   0.252 CYP3A4-substrate:   0.862
CYP2B6-substrate:   0.804 CYP2C8-inhibitor:   0.2
HLM stability:   0.003
?
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):  8.599 Half-life (T1/2):  1.813

ADMET: Toxicity

hERG Blockers:  0.256 hERG Blockers (10um):  0.514
Human Hepatotoxicity (H-HT):  0.515 Drug-induced Liver Injury (DILI):  0.085
AMES Toxicity:  0.48 Rat Oral Acute Toxicity:  0.678
Maximum Recommended Daily Dose:  0.584 Skin Sensitization:  0.779
Carcinogencity:  0.346 Eye Corrosion:  0.943
Eye Irritation:  0.936 Respiratory Toxicity:  0.881
Drug-induced Neurotoxicity:  0.85 Ototoxicity:  0.352
Hematotoxicity:  0.326 Drug-induced Nephrotoxicity:  0.236
Genotoxicity:  0.222 RPMI-8226 Immunitoxicity:  0.051
A549 Cytotoxicity:  0.041 Hek293 Cytotoxicity:  0.182
BCF:   0.588
?
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:   2.855
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.249
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.474
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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
NPO27821 Pochonia chlamydosporia Species Clavicipitaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/j.tetlet.2008.10.099]
NPO27821 Pochonia chlamydosporia Species Clavicipitaceae Eukaryota Roots n.a. n.a. PMID[20000774]
NPO7578 Trichoderma cornu-damae Species Hypocreaceae Eukaryota n.a. n.a. n.a. PMID[30457333]
NPO27821 Pochonia chlamydosporia Species Clavicipitaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11781 Amauroascus niger Species Onygenaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7578 Trichoderma cornu-damae Species Hypocreaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14032 Gossypium arboreum Species Malvaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27408 Stereospermum kunthianum Species Bignoniaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17621 Ammocharis tinneana Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27408 Stereospermum kunthianum Species Bignoniaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO27408 Stereospermum kunthianum Species Bignoniaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO16238 Lactarius subdulcis Species Russulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27408 Stereospermum kunthianum Species Bignoniaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23289.2 Heracleum sphondylium subsp. sibiricum Subspecies Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17621 Ammocharis tinneana Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18987.1 Lupinus polyphyllus var. humicola Varieties Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28684 Amianthium muscitoxicum Species Melanthiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11781 Amauroascus niger Species Onygenaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7578 Trichoderma cornu-damae Species Hypocreaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14032 Gossypium arboreum Species Malvaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17082 Lolium remotum Species Poaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27821 Pochonia chlamydosporia Species Clavicipitaceae 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
NPT969 Protein family Adrenergic receptor alpha-2 Rattus norvegicus Ki = 14700.0 nM PMID[15013009]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT2 Others Unspecified n.a. Ki = 3440.0 nM PMID[15013009]

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 NPC105127 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
0.6316 Remote Similarity NPC96102
0.6216 Remote Similarity NPC42372
0.6 Remote Similarity NPC261195
0.5946 Remote Similarity NPC216643
0.5946 Remote Similarity NPC288838
0.5946 Remote Similarity NPC601214
0.5789 Remote Similarity NPC53947
0.5789 Remote Similarity NPC102423
0.5789 Remote Similarity NPC300149
0.5789 Remote Similarity NPC230002
0.55 Remote Similarity NPC131718
0.5476 Remote Similarity NPC84911
0.5366 Remote Similarity NPC230869
0.5366 Remote Similarity NPC138370
0.5366 Remote Similarity NPC279081
0.5238 Remote Similarity NPC29886
0.5238 Remote Similarity NPC72435
0.5238 Remote Similarity NPC601179
0.5238 Remote Similarity NPC604154
0.5116 Remote Similarity NPC154339
0.5116 Remote Similarity NPC608908
0.5106 Remote Similarity NPC149155
0.5106 Remote Similarity NPC203468
0.5106 Remote Similarity NPC110500

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC105127 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
0.6316 Remote Similarity NPD198 Clinical (unspecified phase)
0.5581 Remote Similarity NPD786 Pre-clinical
0.5106 Remote Similarity NPD482 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