Natural Product: NPC118522

Natural Product IDNPC118522
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 L-Norepinephrine
IUPAC Name 4-[(1S)-2-amino-1-hydroxyethyl]benzene-1,2-diol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL18824
PubChem CID 5814
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0000134] Phenols
        • [CHEMONTID:0001286] Benzenediols
          • [CHEMONTID:0000135] Catechols

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 SFLSHLFXELFNJZ-MRVPVSSYSA-N
Standard InCHI InChI=1S/C8H11NO3/c9-4-8(12)5-1-2-6(10)7(11)3-5/h1-3,8,10-12H,4,9H2/t8-/m1/s1
SMILES NC[C@H](c1ccc(c(c1)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   169.07 Volume:   167.826
?
Van der Waals volume.
Dense:   1.007 LogP:   -1.664
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   -0.794
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -0.628
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   6.0
TPSA:   86.71
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   5.0 Rings:   1.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.472 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.676 Fsp3:   0.25
MCE-18:   14.0
?
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:   1 PAINS Alert:   1
Colloidal aggregators:   0.663 Fluc inhibitor:   0.004
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.029
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.002
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.18 Promiscuous compounds:   0.924

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.929 MDCK Permeability:   -5.248
Pgp-inhibitor:   0.0 Pgp-substrate:   0.041
PAMPA:   0.997
?
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%):   0.913 30% Bioavailability (F30%):   0.85
50% Bioavailability (F50%):   0.996

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.225
Plasma Protein Binding (PPB):   28.904% Volume Distribution (VD):   0.011
Fu: 65.236%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.435
OATP1B3 inhibitor:   0.972 BCRP inhibitor:   0.004
BSEP inhibitor:   0.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.001 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.313 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.001
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.15
HLM stability:   0.0
?
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):  16.065 Half-life (T1/2):  2.285

ADMET: Toxicity

hERG Blockers:  0.159 hERG Blockers (10um):  0.581
Human Hepatotoxicity (H-HT):  0.442 Drug-induced Liver Injury (DILI):  0.019
AMES Toxicity:  0.601 Rat Oral Acute Toxicity:  0.285
Maximum Recommended Daily Dose:  0.883 Skin Sensitization:  0.965
Carcinogencity:  0.531 Eye Corrosion:  0.766
Eye Irritation:  0.951 Respiratory Toxicity:  0.659
Drug-induced Neurotoxicity:  0.26 Ototoxicity:  0.695
Hematotoxicity:  0.06 Drug-induced Nephrotoxicity:  0.081
Genotoxicity:  0.538 RPMI-8226 Immunitoxicity:  0.02
A549 Cytotoxicity:  0.425 Hek293 Cytotoxicity:  0.08
BCF:   0.79
?
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:   2.877
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   3.983
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.634
?
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
NPO4640 Portulaca oleracea Species Portulacaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/j.carres.2012.01.012]
NPO4640 Portulaca oleracea Species Portulacaceae Eukaryota n.a. n.a. n.a. PMID[26562741]
NPO4640 Portulaca oleracea Species Portulacaceae Eukaryota n.a. n.a. n.a. PMID[29517238]
NPO4640 Portulaca oleracea Species Portulacaceae Eukaryota n.a. n.a. n.a. PMID[31625751]
NPO4640 Portulaca oleracea Species Portulacaceae Eukaryota n.a. Along the Valencian coast, Spain 2020-Jun&Jul PMID[35161358]
NPO4640 Portulaca oleracea Species Portulacaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4640 Portulaca oleracea Species Portulacaceae Eukaryota Herb n.a. n.a. Database[FooDB]
NPO4640 Portulaca oleracea Species Portulacaceae Eukaryota Plant n.a. n.a. Database[FooDB]
NPO4640 Portulaca oleracea Species Portulacaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO4640 Portulaca oleracea Species Portulacaceae Eukaryota n.a. n.a. Database[FooDB]
NPO4640 Portulaca oleracea Species Portulacaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO4640 Portulaca oleracea Species Portulacaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO4640 Portulaca oleracea Species Portulacaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO4640 Portulaca oleracea Species Portulacaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]

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
NPT282 Individual protein MAP kinase ERK2 Homo sapiens Potency = 39810.7 nM PubChem BioAssay data set
NPT151 Individual protein 15-hydroxyprostaglandin dehydrogenase [NAD+] Homo sapiens Potency = 35481.3 nM PubChem BioAssay data set
NPT109 Individual protein Cytochrome P450 3A4 Homo sapiens Potency = 31622.8 nM PubChem BioAssay data set
NPT199 Individual protein DNA polymerase kappa Homo sapiens Potency n.a. 11917.3 nM PubChem BioAssay data set
NPT199 Individual protein DNA polymerase kappa Homo sapiens Potency n.a. 3162.3 nM PubChem BioAssay data set
NPT50 Individual protein Tyrosyl-DNA phosphodiesterase 1 Homo sapiens Potency = 398.1 nM PubChem BioAssay data set
NPT50 Individual protein Tyrosyl-DNA phosphodiesterase 1 Homo sapiens Potency = 17782.8 nM PubChem BioAssay data set
NPT50 Individual protein Tyrosyl-DNA phosphodiesterase 1 Homo sapiens Potency = 44668.4 nM PubChem BioAssay data set
NPT55 Individual protein Putative fructose-1,6-bisphosphate aldolase Giardia intestinalis Potency = 19905.4 nM PubChem BioAssay data set
NPT55 Individual protein Putative fructose-1,6-bisphosphate aldolase Giardia intestinalis Potency = 7062.7 nM PubChem BioAssay data set
NPT58 Individual protein Bloom syndrome protein Homo sapiens Potency = 12589.3 nM PubChem BioAssay data set
NPT533 Protein-protein interaction Runt-related transcription factor 1/Core-binding factor subunit beta Homo sapiens Potency n.a. 2818.4 nM PubChem BioAssay data set
NPT533 Protein-protein interaction Runt-related transcription factor 1/Core-binding factor subunit beta Homo sapiens Potency n.a. 14125.4 nM PubChem BioAssay data set
NPT48 Individual protein Lysine-specific demethylase 4D-like Homo sapiens Potency = 3548.1 nM PubChem BioAssay data set
NPT444 Individual protein Ubiquitin carboxyl-terminal hydrolase 1 Homo sapiens Potency n.a. 112201.8 nM PubChem BioAssay data set
NPT46 Individual protein Thyroid hormone receptor beta-1 Homo sapiens Potency = 50118.7 nM PubChem BioAssay data set
NPT51 Individual protein Microtubule-associated protein tau Homo sapiens Potency = 22387.2 nM PubChem BioAssay data set
NPT51 Individual protein Microtubule-associated protein tau Homo sapiens Potency = 35481.3 nM PubChem BioAssay data set
NPT755 Individual protein Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 Homo sapiens Potency n.a. 79432.8 nM PubChem BioAssay data set
NPT47 Individual protein ATP-dependent DNA helicase Q1 Homo sapiens Potency = 14125.4 nM PubChem BioAssay data set
NPT49 Individual protein DNA-(apurinic or apyrimidinic site) lyase Homo sapiens Potency = 3981.1 nM PubChem BioAssay data set
NPT53 Individual protein 4'-phosphopantetheinyl transferase ffp Bacillus subtilis Potency = 7943.3 nM PubChem BioAssay data set
NPT532 Individual protein Lysine-specific demethylase 4A Homo sapiens Potency n.a. 89125.1 nM PubChem BioAssay data set
NPT49 Individual protein DNA-(apurinic or apyrimidinic site) lyase Homo sapiens Potency n.a. 446.7 nM PubChem BioAssay data set
NPT49 Individual protein DNA-(apurinic or apyrimidinic site) lyase Homo sapiens Potency n.a. 1000.0 nM PubChem BioAssay data set

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT2 Others Unspecified n.a. Potency n.a. 14068.4 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 22387.2 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 14125.4 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 39810.7 nM PubChem BioAssay data set

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 NPC118522 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 NPC115627
1.0 High Similarity NPC169207
0.7333 Intermediate Similarity NPC323775
0.7333 Intermediate Similarity NPC236347
0.6667 Remote Similarity NPC483291
0.6429 Remote Similarity NPC290566
0.6429 Remote Similarity NPC145638
0.5172 Remote Similarity NPC215351
0.5172 Remote Similarity NPC20142
0.5161 Remote Similarity NPC146422

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC118522 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
1.0 High Similarity NPD9384 Phase 4
0.7333 Intermediate Similarity NPD9620 Phase 2
0.7333 Intermediate Similarity NPD9621 Phase 4
0.7059 Intermediate Similarity NPD9381 Approved
0.6667 Remote Similarity NPD601 Phase 4
0.6471 Remote Similarity NPD597 Approved
0.6429 Remote Similarity NPD9380 Phase 2
0.6333 Remote Similarity NPD9622 Phase 4
0.5946 Remote Similarity NPD5314 Phase 2
0.5641 Remote Similarity NPD598 Approved
0.55 Remote Similarity NPD9619 Approved
0.5161 Remote Similarity NPD9379 Phase 4
0.5135 Remote Similarity NPD1136 Phase 4
0.5135 Remote Similarity NPD9570 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