Natural Product: NPC201692

Natural Product IDNPC201692
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Cytochalasin F
IUPAC Name n.a.
Synonyms Cytochalasin F
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL452486
PubChem CID 44558997
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000279] Alkaloids and derivatives
      • [CHEMONTID:0001821] Cytochalasans
        • [CHEMONTID:0002852] Cytochalasins

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 CXWYFIYZAZBQGQ-IDLUQWPUSA-N
Standard InCHI InChI=1S/C29H37NO5/c1-18-9-7-13-21(31)15-16-24(32)34-29-22(14-8-10-18)26-28(3,35-26)19(2)25(29)23(30-27(29)33)17-20-11-5-4-6-12-20/h4-6,8,11-12,14-16,18-19,21-23,25-26,31H,7,9-10,13,17H2,1-3H3,(H,30,33)/b14-8+,16-15+/t18-,19+,21+,22+,23+,25+,26+,28-,29-/m1/s1
SMILES C[C@@H]1CCC[C@@H](/C=C/C(=O)O[C@]23[C@@H](/C=C/C1)[C@H]1[C@@](C)([C@@H](C)[C@H]2[C@H](Cc2ccccc2)N=C3O)O1)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   479.27 Volume:   503.85
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Van der Waals volume.
Dense:   0.951 LogP:   3.616
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.189
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.855
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The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   32.0
TPSA:   91.65
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Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   2.0 Rings:   5.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.368 GASA:   1.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   6.017 Fsp3:   0.586
MCE-18:   141.522
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.885 Fluc inhibitor:   0.03
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.042
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.022
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.014 Promiscuous compounds:   0.402

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.382 MDCK Permeability:   -4.895
Pgp-inhibitor:   0.901 Pgp-substrate:   0.951
PAMPA:   0.518
?
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%):   0.696 30% Bioavailability (F30%):   0.978
50% Bioavailability (F50%):   0.99

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.204
Plasma Protein Binding (PPB):   96.892% Volume Distribution (VD):   -0.291
Fu: 3.074%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   0.948 BCRP inhibitor:   0.022
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.081
CYP2C19-inhibitor:   0.005 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.055
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.018
CYP3A4-inhibitor:   0.036 CYP3A4-substrate:   0.004
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.996
HLM stability:   0.886
?
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):  9.252 Half-life (T1/2):  1.322

ADMET: Toxicity

hERG Blockers:  0.0 hERG Blockers (10um):  0.0
Human Hepatotoxicity (H-HT):  1.0 Drug-induced Liver Injury (DILI):  1.0
AMES Toxicity:  0.93 Rat Oral Acute Toxicity:  0.027
Maximum Recommended Daily Dose:  0.436 Skin Sensitization:  1.0
Carcinogencity:  0.84 Eye Corrosion:  0.0
Eye Irritation:  0.997 Respiratory Toxicity:  0.975
Drug-induced Neurotoxicity:  0.03 Ototoxicity:  0.924
Hematotoxicity:  0.176 Drug-induced Nephrotoxicity:  1.0
Genotoxicity:  1.0 RPMI-8226 Immunitoxicity:  0.045
A549 Cytotoxicity:  0.002 Hek293 Cytotoxicity:  0.416
BCF:   0.991
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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:   3.789
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.352
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.764
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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
NPO32658 geniculosporium sp. Species Xylariaceae Eukaryota n.a. isolated from the marine red alga Polysiphonia n.a. PMID[15787444]
NPO32658 geniculosporium sp. Species Xylariaceae Eukaryota n.a. n.a. n.a. PMID[9917307]

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
NPT1234 Organism Chlorella fusca Chlorella fusca IZ = 1.0 mm PMID[15974618]
NPT1234 Organism Chlorella fusca Chlorella fusca Activity = 94.1 % PMID[15974618]

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 NPC201692 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 NPC308429
0.8052 Intermediate Similarity NPC173934
0.7875 Intermediate Similarity NPC487727
0.716 Intermediate Similarity NPC485195
0.7143 Intermediate Similarity NPC488408
0.7143 Intermediate Similarity NPC31171
0.686 Remote Similarity NPC111586
0.6222 Remote Similarity NPC156348
0.6207 Remote Similarity NPC485197
0.593 Remote Similarity NPC88411
0.5843 Remote Similarity NPC485196
0.5435 Remote Similarity NPC4108
0.5275 Remote Similarity NPC15506
0.5217 Remote Similarity NPC479975

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC201692 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
0.7143 Intermediate Similarity NPD7274 Clinical (unspecified phase)

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