Natural Product: NPC325741

Natural Product IDNPC325741
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 LDRFQSZFVGJGGP-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 277794
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:0004310] Valine and derivatives

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 LDRFQSZFVGJGGP-UHFFFAOYSA-N
Standard InCHI InChI=1S/C5H11NO3/c1-5(2,9)3(6)4(7)8/h3,9H,6H2,1-2H3,(H,7,8)
SMILES CC(C)(C(C(=O)O)N)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   133.07 Volume:   129.767
?
Van der Waals volume.
Dense:   1.025 LogP:   -2.95
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   -1.254
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   0.471
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   1.0
TPSA:   83.55
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   4.0 Rings:   0.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.459 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.162 Fsp3:   0.8
MCE-18:   5.0
?
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:   0.017 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.008
?
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:   0.662 Promiscuous compounds:   0.33

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.479 MDCK Permeability:   -3.409
Pgp-inhibitor:   0.0 Pgp-substrate:   0.285
PAMPA:   0.956
?
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%):   0.0 30% Bioavailability (F30%):   0.0
50% Bioavailability (F50%):   0.009

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.952 MRP1:   0.866
Plasma Protein Binding (PPB):   25.177% Volume Distribution (VD):   -0.424
Fu: 71.133%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.007
OATP1B3 inhibitor:   0.276 BCRP inhibitor:   0.023
BSEP inhibitor:   0.002

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.002
CYP2C19-inhibitor:   0.111 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.056 CYP2C9-substrate:   0.006
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.403
HLM stability:   0.005
?
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):  2.794 Half-life (T1/2):  2.062

ADMET: Toxicity

hERG Blockers:  0.029 hERG Blockers (10um):  0.073
Human Hepatotoxicity (H-HT):  0.322 Drug-induced Liver Injury (DILI):  0.026
AMES Toxicity:  0.584 Rat Oral Acute Toxicity:  0.296
Maximum Recommended Daily Dose:  0.04 Skin Sensitization:  0.703
Carcinogencity:  0.375 Eye Corrosion:  0.375
Eye Irritation:  0.812 Respiratory Toxicity:  0.345
Drug-induced Neurotoxicity:  0.193 Ototoxicity:  0.32
Hematotoxicity:  0.229 Drug-induced Nephrotoxicity:  0.545
Genotoxicity:  0.41 RPMI-8226 Immunitoxicity:  0.034
A549 Cytotoxicity:  0.011 Hek293 Cytotoxicity:  0.028
BCF:   0.169
?
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:   2.426
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   3.707
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   2.921
?
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
NPO19657 Ursus arctos Species Ursidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19657 Ursus arctos Species Ursidae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO19657 Ursus arctos Species Ursidae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO19657 Ursus arctos Species Ursidae 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

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 NPC325741 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
0.7059 Intermediate Similarity NPC116709
0.7059 Intermediate Similarity NPC21290
0.7059 Intermediate Similarity NPC272614
0.7 Intermediate Similarity NPC270805
0.7 Intermediate Similarity NPC93888
0.65 Remote Similarity NPC226265
0.65 Remote Similarity NPC219143
0.65 Remote Similarity NPC254482
0.65 Remote Similarity NPC110533
0.619 Remote Similarity NPC317691
0.6087 Remote Similarity NPC190385
0.6 Remote Similarity NPC63621
0.6 Remote Similarity NPC132307
0.6 Remote Similarity NPC126925
0.6 Remote Similarity NPC326992
0.6 Remote Similarity NPC121517
0.6 Remote Similarity NPC168375
0.6 Remote Similarity NPC600066
0.5909 Remote Similarity NPC43169
0.5909 Remote Similarity NPC327895
0.5909 Remote Similarity NPC112224
0.5652 Remote Similarity NPC49952
0.5652 Remote Similarity NPC136476
0.55 Remote Similarity NPC237525
0.55 Remote Similarity NPC326212
0.5455 Remote Similarity NPC118459
0.5455 Remote Similarity NPC327698
0.5455 Remote Similarity NPC53449
0.5263 Remote Similarity NPC9294
0.5263 Remote Similarity NPC307739
0.5263 Remote Similarity NPC76217
0.5263 Remote Similarity NPC212144
0.5263 Remote Similarity NPC178595
0.5238 Remote Similarity NPC198301
0.5238 Remote Similarity NPC249126
0.5217 Remote Similarity NPC245027
0.5217 Remote Similarity NPC84636
0.5217 Remote Similarity NPC162620
0.5217 Remote Similarity NPC62045
0.5217 Remote Similarity NPC226027
0.5217 Remote Similarity NPC174246
0.5217 Remote Similarity NPC43204

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC325741 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 NPD8801 Phase 4
0.7059 Intermediate Similarity NPD8210 Phase 3
0.7059 Intermediate Similarity NPD8211 Approved
0.7 Intermediate Similarity NPD8624 Phase 2
0.65 Remote Similarity NPD8215 Phase 4
0.65 Remote Similarity NPD8216 Phase 3
0.65 Remote Similarity NPD8217 Phase 3
0.619 Remote Similarity NPD8214 Approved
0.6087 Remote Similarity NPD9023 Clinical (unspecified phase)
0.6 Remote Similarity NPD8798 Phase 2
0.5263 Remote Similarity NPD8202 Phase 4
0.5263 Remote Similarity NPD8205 Phase 4
0.5217 Remote Similarity NPD9017 Phase 2
0.5217 Remote Similarity NPD9018 Phase 3

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