Natural Product: NPC53649

Natural Product IDNPC53649
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Cladosporin
IUPAC Name (3R)-6,8-dihydroxy-3-[[(2R,6S)-6-methyloxan-2-yl]methyl]-3,4-dihydroisochromen-1-one
Synonyms Cladosporin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL448685
PubChem CID 13990016
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0002279] Benzene and substituted derivatives
        • [CHEMONTID:0000176] Benzoic acids and derivatives
          • [CHEMONTID:0001248] Hydroxybenzoic acid 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 WOMKDMUZNBFXKG-ZWKOPEQDSA-N
Standard InCHI InChI=1S/C16H20O5/c1-9-3-2-4-12(20-9)8-13-6-10-5-11(17)7-14(18)15(10)16(19)21-13/h5,7,9,12-13,17-18H,2-4,6,8H2,1H3/t9-,12+,13+/m0/s1
SMILES C[C@H]1CCC[C@H](C[C@H]2Cc3cc(cc(c3C(=O)O2)O)O)O1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   292.13 Volume:   293.028
?
Van der Waals volume.
Dense:   0.997 LogP:   2.077
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.196
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.468
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   18.0
TPSA:   75.99
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.819 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.773 Fsp3:   0.562
MCE-18:   60.52
?
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:   0.278 Fluc inhibitor:   0.072
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.178
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.218
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.253 Promiscuous compounds:   0.534

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.963 MDCK Permeability:   -4.764
Pgp-inhibitor:   0.297 Pgp-substrate:   0.056
PAMPA:   0.062
?
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):   0.002
20% Bioavailability (F20%):   0.057 30% Bioavailability (F30%):   0.86
50% Bioavailability (F50%):   0.976

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.007 MRP1:   0.605
Plasma Protein Binding (PPB):   88.557% Volume Distribution (VD):   0.225
Fu: 11.815%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.992
OATP1B3 inhibitor:   0.995 BCRP inhibitor:   0.795
BSEP inhibitor:   0.842

ADMET: Metabolism

CYP1A2-inhibitor:   0.999 CYP1A2-substrate:   0.221
CYP2C19-inhibitor:   0.759 CYP2C19-substrate:   0.3
CYP2C9-inhibitor:   0.786 CYP2C9-substrate:   0.982
CYP2D6-inhibitor:   0.009 CYP2D6-substrate:   0.998
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.137
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.991
HLM stability:   0.992
?
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):  5.138 Half-life (T1/2):  1.359

ADMET: Toxicity

hERG Blockers:  0.084 hERG Blockers (10um):  0.418
Human Hepatotoxicity (H-HT):  0.468 Drug-induced Liver Injury (DILI):  0.768
AMES Toxicity:  0.913 Rat Oral Acute Toxicity:  0.274
Maximum Recommended Daily Dose:  0.876 Skin Sensitization:  0.999
Carcinogencity:  0.523 Eye Corrosion:  0.231
Eye Irritation:  0.971 Respiratory Toxicity:  0.327
Drug-induced Neurotoxicity:  0.374 Ototoxicity:  0.321
Hematotoxicity:  0.041 Drug-induced Nephrotoxicity:  0.748
Genotoxicity:  0.623 RPMI-8226 Immunitoxicity:  0.131
A549 Cytotoxicity:  0.925 Hek293 Cytotoxicity:  0.561
BCF:   1.253
?
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:   3.922
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.151
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.526
?
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
NPO10055 Stichoneuron caudatum Species Stemonaceae Eukaryota n.a. n.a. n.a. PMID[24606395]
NPO40235 Aspergillus sp. SF-5974 Strain Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[26651366]
NPO40236 Aspergillus sp. SF-5976 Strain Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[26651366]
NPO40236 Aspergillus sp. SF-5976 Strain Aspergillaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4946 Antidesma venosum Species Phyllanthaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1387 Lactarius violascens Species Russulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10055 Stichoneuron caudatum Species Stemonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6417 Lecanora grumosa Species Lecanoraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4946 Antidesma venosum Species Phyllanthaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7499 Mammillaria krameri Species Cactaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11458 Hymenoxys subintegra Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6874 Desmodium floribundum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6189 Rhamnus nipalensis Species Rhamnaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10055 Stichoneuron caudatum Species Stemonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8748 Dacrydium nidulum Species Podocarpaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1387 Lactarius violascens Species Russulaceae 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
NPT3174 Individual protein Lysyl-tRNA synthetase Homo sapiens IC50 > 20000.0 nM PMID[23587422]
NPT3174 Individual protein Lysyl-tRNA synthetase Homo sapiens Delta Tm = 1.3 degrees C PMID[29779382]
NPT3174 Individual protein Lysyl-tRNA synthetase Homo sapiens IC50 = 105000.0 nM PMID[29779382]
NPT3565 Individual protein Lysine--tRNA ligase Plasmodium falciparum (isolate 3D7) Delta Tm = 17.3 degrees C PMID[29779382]
NPT3565 Individual protein Lysine--tRNA ligase Plasmodium falciparum (isolate 3D7) IC50 = 120.0 nM PMID[29779382]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT6 Organism Plasmodium falciparum Plasmodium falciparum EC50 = 45.0 nM PMID[23587422]
NPT6 Organism Plasmodium falciparum Plasmodium falciparum EC50 = 90.0 nM PMID[23587422]
NPT6 Organism Plasmodium falciparum Plasmodium falciparum EC50 = 40.0 nM PMID[29779382]
NPT141 Organism Agrobacterium tumefaciens Agrobacterium tumefaciens Activity = -79.0 % DOI[10.1021/np50107a012]
NPT141 Organism Agrobacterium tumefaciens Agrobacterium tumefaciens Activity = -14.0 % DOI[10.1021/np50107a012]
NPT141 Organism Agrobacterium tumefaciens Agrobacterium tumefaciens Activity = -41.0 % DOI[10.1021/np50107a012]
NPT141 Organism Agrobacterium tumefaciens Agrobacterium tumefaciens Activity = -90.0 % DOI[10.1021/np50107a012]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 24000.0 nM PMID[26651366]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 27000.0 nM PMID[26651366]

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 NPC53649 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
0.7455 Intermediate Similarity NPC764
0.7455 Intermediate Similarity NPC487444
0.74 Intermediate Similarity NPC609111
0.6897 Remote Similarity NPC212484
0.6552 Remote Similarity NPC116462
0.6071 Remote Similarity NPC70380
0.6 Remote Similarity NPC235115
0.5806 Remote Similarity NPC472602
0.5667 Remote Similarity NPC608268
0.5397 Remote Similarity NPC472035
0.5323 Remote Similarity NPC191835
0.5323 Remote Similarity NPC609527
0.5323 Remote Similarity NPC610163
0.5323 Remote Similarity NPC611086
0.5312 Remote Similarity NPC481134
0.5278 Remote Similarity NPC487443
0.5238 Remote Similarity NPC212693
0.5238 Remote Similarity NPC94248
0.5172 Remote Similarity NPC600571
0.5156 Remote Similarity NPC609495
0.5152 Remote Similarity NPC126882
0.5085 Remote Similarity NPC159721
0.5082 Remote Similarity NPC105456
0.5082 Remote Similarity NPC139634

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC53649 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