Natural Product: NPC14113

Natural Product IDNPC14113
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Hypaphorine
IUPAC Name (2R)-3-(1H-indol-3-yl)-2-(trimethylazaniumyl)propanoate
Synonyms Hypaphorine
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL503867
PubChem CID 160488
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000264] Organic acids and derivatives
      • [CHEMONTID:0000265] Carboxylic acids and derivatives
        • [CHEMONTID:0000013] Amino acids, peptides, and analogues
          • [CHEMONTID:0000347] Amino acids and derivatives
            • [CHEMONTID:0000060] Alpha amino acids and derivatives
              • [CHEMONTID:0002404] Alpha amino acids
                • [CHEMONTID:0004145] D-alpha-amino acids

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 AOHCBEAZXHZMOR-CYBMUJFWSA-N
Standard InCHI InChI=1S/C14H18N2O2/c1-16(2,3)13(14(17)18)8-10-9-15-12-7-5-4-6-11(10)12/h4-7,9,13,15H,8H2,1-3H3/t13-/m1/s1
SMILES [O-]C(=O)[C@H]([N+](C)(C)C)Cc1c[nH]c2c1cccc2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   246.14 Volume:   259.979
?
Van der Waals volume.
Dense:   0.947 LogP:   0.383
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.153
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.986
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   11.0
TPSA:   55.92
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   1.0 Rings:   2.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.8 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.382 Fsp3:   0.357
MCE-18:   28.0
?
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:   0.1 Fluc inhibitor:   0.003
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.073
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.001
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.188 Promiscuous compounds:   0.43

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.124 MDCK Permeability:   -4.828
Pgp-inhibitor:   0.172 Pgp-substrate:   0.004
PAMPA:   0.09
?
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):   0.179
20% Bioavailability (F20%):   0.412 30% Bioavailability (F30%):   0.934
50% Bioavailability (F50%):   0.986

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.214
Plasma Protein Binding (PPB):   47.248% Volume Distribution (VD):   0.124
Fu: 49.631%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.004
BSEP inhibitor:   0.859

ADMET: Metabolism

CYP1A2-inhibitor:   0.034 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.994 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.065 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.572 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.0
HLM stability:   0.057
?
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):  2.197 Half-life (T1/2):  1.653

ADMET: Toxicity

hERG Blockers:  0.064 hERG Blockers (10um):  0.08
Human Hepatotoxicity (H-HT):  0.82 Drug-induced Liver Injury (DILI):  0.04
AMES Toxicity:  0.117 Rat Oral Acute Toxicity:  0.613
Maximum Recommended Daily Dose:  0.914 Skin Sensitization:  0.859
Carcinogencity:  0.193 Eye Corrosion:  0.196
Eye Irritation:  0.879 Respiratory Toxicity:  0.904
Drug-induced Neurotoxicity:  0.892 Ototoxicity:  0.663
Hematotoxicity:  0.689 Drug-induced Nephrotoxicity:  0.446
Genotoxicity:  0.998 RPMI-8226 Immunitoxicity:  0.019
A549 Cytotoxicity:  0.008 Hek293 Cytotoxicity:  0.047
BCF:   1.708
?
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:   4.005
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.708
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.943
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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
NPO29417 Fallopia multiflora Species Polygonaceae Eukaryota n.a. root n.a. PMID[16564530]
NPO20031 Erythrina velutina Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[19026536]
NPO29417 Fallopia multiflora Species Polygonaceae Eukaryota Roots n.a. n.a. PMID[29359942]
NPO29417 Fallopia multiflora Species Polygonaceae Eukaryota Roots n.a. n.a. PMID[31944695]
NPO29417 Fallopia multiflora Species Polygonaceae Eukaryota Roots; Tubers n.a. n.a. PMID[7714535]
NPO29417 Fallopia multiflora Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20031 Erythrina velutina Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6792 Hedysarum polybotrys Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29417 Fallopia multiflora Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO29417 Fallopia multiflora Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO6792 Hedysarum polybotrys Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO20031 Erythrina velutina Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6792 Hedysarum polybotrys Species Fabaceae 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
NPT15 Cell line Jurkat Homo sapiens IC50 > 50.0 ug.mL-1 PMID[19026536]
NPT15 Cell line Jurkat Homo sapiens Inhibition = 5.8 % PMID[19026536]
NPT15 Cell line Jurkat Homo sapiens Inhibition = 20.0 % PMID[19026536]

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT32 Organism Mus musculus Mus musculus Activity = 33.0 % PMID[18571406]
NPT32 Organism Mus musculus Mus musculus Activity = 32.0 % PMID[18571406]
NPT32 Organism Mus musculus Mus musculus Activity = 16.0 % PMID[18571406]





 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 NPC14113 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 NPC145885
1.0 High Similarity NPC84827
0.6136 Remote Similarity NPC601214
0.58 Remote Similarity NPC605863
0.5625 Remote Similarity NPC279081
0.5577 Remote Similarity NPC78020
0.5472 Remote Similarity NPC315555
0.5472 Remote Similarity NPC55772
0.5455 Remote Similarity NPC248041
0.5417 Remote Similarity NPC96102
0.54 Remote Similarity NPC84911
0.537 Remote Similarity NPC149155
0.537 Remote Similarity NPC203468
0.537 Remote Similarity NPC110500
0.537 Remote Similarity NPC605329
0.5306 Remote Similarity NPC230869
0.5273 Remote Similarity NPC480318
0.52 Remote Similarity NPC29886
0.5192 Remote Similarity NPC310665
0.5185 Remote Similarity NPC59269
0.5088 Remote Similarity NPC480317
0.5088 Remote Similarity NPC480316

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC14113 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
0.5417 Remote Similarity NPD198 Clinical (unspecified phase)
0.537 Remote Similarity NPD482 Phase 4
0.5273 Remote Similarity NPD749 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