Natural Product: NPC274550

Natural Product IDNPC274550
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Hadacidin
IUPAC Name 2-[formyl(hydroxy)amino]acetic acid
Synonyms Hadacidin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL331373
PubChem CID 12717
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:0002965] N-formyl-alpha amino acids and derivatives
                • [CHEMONTID:0002964] N-formyl-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 URJHVPKUWOUENU-UHFFFAOYSA-N
Standard InCHI InChI=1S/C3H5NO4/c5-2-4(8)1-3(6)7/h2,8H,1H2,(H,6,7)
SMILES C(C(=O)O)N(C=O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   119.02 Volume:   101.329
?
Van der Waals volume.
Dense:   1.175 LogP:   -0.701
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   -0.48
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   0.204
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   2.0
TPSA:   77.84
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   0.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.281 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.961 Fsp3:   0.333
MCE-18:   0.0
?
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:   0.0 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.066
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.0
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.916 Promiscuous compounds:   0.137

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.397 MDCK Permeability:   -4.52
Pgp-inhibitor:   0.0 Pgp-substrate:   0.037
PAMPA:   0.998
?
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):   0.526
20% Bioavailability (F20%):   0.303 30% Bioavailability (F30%):   0.346
50% Bioavailability (F50%):   0.334

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.048 MRP1:   0.923
Plasma Protein Binding (PPB):   11.007% Volume Distribution (VD):   -0.474
Fu: 87.803%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.088
OATP1B3 inhibitor:   0.686 BCRP inhibitor:   0.003
BSEP inhibitor:   0.004

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.965 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.001 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.01 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.001
HLM stability:   0.008
?
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):  2.416 Half-life (T1/2):  1.988

ADMET: Toxicity

hERG Blockers:  0.007 hERG Blockers (10um):  0.014
Human Hepatotoxicity (H-HT):  0.527 Drug-induced Liver Injury (DILI):  0.781
AMES Toxicity:  0.574 Rat Oral Acute Toxicity:  0.238
Maximum Recommended Daily Dose:  0.04 Skin Sensitization:  0.919
Carcinogencity:  0.436 Eye Corrosion:  0.651
Eye Irritation:  0.962 Respiratory Toxicity:  0.37
Drug-induced Neurotoxicity:  0.141 Ototoxicity:  0.511
Hematotoxicity:  0.674 Drug-induced Nephrotoxicity:  0.898
Genotoxicity:  0.997 RPMI-8226 Immunitoxicity:  0.031
A549 Cytotoxicity:  0.001 Hek293 Cytotoxicity:  0.019
BCF:   0.224
?
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:   2.359
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   3.385
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   2.864
?
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
NPO11443 Bistorta amplexicaulis Species Polygonaceae Eukaryota n.a. n.a. n.a. PMID[39741627]
NPO11443 Bistorta amplexicaulis Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[Article]
NPO14471 Streptomyces luridus Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO12507 Bixa orellana Species Bixaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18450 Oxytropis campestris Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6109 Lonchocarpus subglaucescens Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14986 Haplophyton crooksii Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15629 Byssochlamys nivea Species Thermoascaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13357 Vancouveria hexandra Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10103 Senecio iodanthus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14068 Viburnum prunifolium Species Adoxaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15947 Penicillium glabrum Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12507 Bixa orellana Species Bixaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO14068 Viburnum prunifolium Species Adoxaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO21233 Pteris linearis Species Pteridaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12507 Bixa orellana Species Bixaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18450 Oxytropis campestris Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14068 Viburnum prunifolium Species Adoxaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14068 Viburnum prunifolium Species Adoxaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO21402 Vespula vulgaris Species Vespidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10938 Psychotria prunifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12032 Oxylobus adscendens n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO15947 Penicillium glabrum Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14986 Haplophyton crooksii Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11443 Bistorta amplexicaulis Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9544 Eria angustifolia Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14068 Viburnum prunifolium Species Adoxaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO390 Tectocoris diophthalmus Species Scutelleridae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10103 Senecio iodanthus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15629 Byssochlamys nivea Species Thermoascaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14365 Eysenhardtia subcoriacea Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21233 Pteris linearis Species Pteridaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8822 Alphonsea ventricosa Species Annonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9299.2 Hordeum vulgare subsp. vulgare Subspecies Poaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12507 Bixa orellana Species Bixaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5236 Polygonatum biflorum Species Asparagaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13357 Vancouveria hexandra Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4434 Bignonia hyacinthina Species Bignoniaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6109 Lonchocarpus subglaucescens Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18450 Oxytropis campestris Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10234 [brevibacterium] flavum Species Corynebacteriaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO14471 Streptomyces luridus Species Streptomycetaceae Bacteria 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
NPT5640 Individual protein Adenylosuccinate synthetase 2 Homo sapiens IC50 = 3500.0 nM PMID[15214773]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT2 Others Unspecified n.a. Inhibition = 80.0 % PMID[21129960]

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 NPC274550 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 NPC250870
0.6316 Remote Similarity NPC490959
0.6316 Remote Similarity NPC191084
0.55 Remote Similarity NPC320704
0.5238 Remote Similarity NPC249126
0.5217 Remote Similarity NPC327542

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC274550 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
NPD

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