Natural Product: NPC480318

Natural Product IDNPC480318
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 ZTTWHZHBPDYSQB-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 95438
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

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 ZTTWHZHBPDYSQB-UHFFFAOYSA-N
Standard InCHI InChI=1S/C12H14N2O2/c1-12(13,11(15)16)6-8-7-14-10-5-3-2-4-9(8)10/h2-5,7,14H,6,13H2,1H3,(H,15,16)
SMILES CC(Cc1c[nH]c2ccccc12)(C(=O)O)N

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   218.11 Volume:   225.387
?
Van der Waals volume.
Dense:   0.968 LogP:   -0.804
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.11
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -0.853
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   11.0
TPSA:   79.11
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   4.0 Rings:   2.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.73 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.619 Fsp3:   0.25
MCE-18:   26.0
?
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:   0.04 Fluc inhibitor:   0.001
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.166
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.284
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.021 Promiscuous compounds:   0.264

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.213 MDCK Permeability:   -4.601
Pgp-inhibitor:   0.0 Pgp-substrate:   0.365
PAMPA:   0.954
?
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%):   0.002 30% Bioavailability (F30%):   0.017
50% Bioavailability (F50%):   0.992

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.059 MRP1:   0.677
Plasma Protein Binding (PPB):   54.516% Volume Distribution (VD):   0.013
Fu: 49.058%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.993
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.0
BSEP inhibitor:   0.007

ADMET: Metabolism

CYP1A2-inhibitor:   0.002 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.001 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.34 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.424 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.107 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.0
HLM stability:   0.019
?
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):  1.51 Half-life (T1/2):  1.977

ADMET: Toxicity

hERG Blockers:  0.057 hERG Blockers (10um):  0.092
Human Hepatotoxicity (H-HT):  0.66 Drug-induced Liver Injury (DILI):  0.118
AMES Toxicity:  0.306 Rat Oral Acute Toxicity:  0.486
Maximum Recommended Daily Dose:  0.604 Skin Sensitization:  0.041
Carcinogencity:  0.291 Eye Corrosion:  0.007
Eye Irritation:  0.529 Respiratory Toxicity:  0.761
Drug-induced Neurotoxicity:  0.584 Ototoxicity:  0.751
Hematotoxicity:  0.431 Drug-induced Nephrotoxicity:  0.451
Genotoxicity:  0.802 RPMI-8226 Immunitoxicity:  0.017
A549 Cytotoxicity:  0.003 Hek293 Cytotoxicity:  0.022
BCF:   0.215
?
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:   2.872
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.021
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.306
?
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
NPO10538 Aspergillus fumigatus Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[17616609]
NPO10538 Aspergillus fumigatus Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[17929896]
NPO10538 Aspergillus fumigatus Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[19113967]
NPO10538 Aspergillus fumigatus Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[19159274]
NPO10538 Aspergillus fumigatus Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[19256529]
NPO10538 Aspergillus fumigatus Species Aspergillaceae Eukaryota n.a. isolated from sediment collected using a hand held deep water sampling device at >33 m depth in Vanuatu 2003 PMID[20303767]
NPO10538 Aspergillus fumigatus Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[21667925]
NPO10538 Aspergillus fumigatus Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[21954885]
NPO10538 Aspergillus fumigatus Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[22106303]
NPO10538 Aspergillus fumigatus Species Aspergillaceae Eukaryota stem bark of Melia azedarach n.a. n.a. PMID[22409377]
NPO10538 Aspergillus fumigatus Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[23557488]
NPO10538 Aspergillus fumigatus Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[23563483]
NPO10538 Aspergillus fumigatus Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[7622436]
NPO10538 Aspergillus fumigatus Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10538 Aspergillus fumigatus Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO10538 Aspergillus fumigatus Species Aspergillaceae 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
NPT2960 Individual protein Brevianamide F prenyltransferase Aspergillus fumigatus Activity <= 2.3 % PMID[19113967]
NPT2960 Individual protein Brevianamide F prenyltransferase Aspergillus fumigatus Activity = 1.0 % PMID[19113967]
NPT1078 Individual protein Indoleamine 2,3-dioxygenase Homo sapiens Activity = 0.0 % PMID[25815143]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT2 Others Unspecified n.a. Activity = 25.0 % PMID[19113967]
NPT2 Others Unspecified n.a. Activity = 24.5 % PMID[19113967]

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 NPC480318 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
0.7292 Intermediate Similarity NPC149155
0.7292 Intermediate Similarity NPC203468
0.7292 Intermediate Similarity NPC110500
0.6538 Remote Similarity NPC480316
0.6531 Remote Similarity NPC78020
0.64 Remote Similarity NPC315555
0.64 Remote Similarity NPC55772
0.6346 Remote Similarity NPC248041
0.6316 Remote Similarity NPC602969
0.6275 Remote Similarity NPC605329
0.6111 Remote Similarity NPC267885
0.6087 Remote Similarity NPC96102
0.6 Remote Similarity NPC606272
0.5926 Remote Similarity NPC480317
0.5893 Remote Similarity NPC283219
0.5778 Remote Similarity NPC601214
0.5625 Remote Similarity NPC279081
0.56 Remote Similarity NPC111275
0.5574 Remote Similarity NPC321708
0.551 Remote Similarity NPC29886
0.549 Remote Similarity NPC310665
0.54 Remote Similarity NPC84911
0.537 Remote Similarity NPC190296
0.5357 Remote Similarity NPC608269
0.5306 Remote Similarity NPC230869
0.5294 Remote Similarity NPC73767
0.5273 Remote Similarity NPC14113
0.5273 Remote Similarity NPC145885
0.5273 Remote Similarity NPC84827
0.5192 Remote Similarity NPC605863
0.5185 Remote Similarity NPC59269
0.5179 Remote Similarity NPC609424
0.5172 Remote Similarity NPC602670
0.5161 Remote Similarity NPC605102
0.5088 Remote Similarity NPC471957

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC480318 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 NPD749 Clinical (unspecified phase)
0.7292 Intermediate Similarity NPD482 Phase 4
0.6087 Remote Similarity NPD198 Clinical (unspecified phase)
0.58 Remote Similarity NPD786 Pre-clinical
0.5397 Remote Similarity NPD2094 Phase 2
0.5397 Remote Similarity NPD2095 Phase 2
0.5312 Remote Similarity NPD2092 Phase 2
0.5231 Remote Similarity NPD2096 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