Natural Product: NPC552076

Natural Product IDNPC552076
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 [(10~{R},11~{R},13~{R},17~{R})-10,13-dimethyl-3-oxo-17-vinyl-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-11-yl] acetate
IUPAC Name [(10~{R},11~{R},13~{R},17~{R})-10,13-dimethyl-3-oxo-17-vinyl-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-11-yl] acetate
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000258] Steroids and steroid derivatives
        • [CHEMONTID:0003569] Pregnane steroids
          • [CHEMONTID:0001468] Gluco/mineralocorticoids, progestogins 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 QCQFIWFIKNLLNQ-BZNQHLJXSA-N
Standard InCHI InChI=1S/C23H32O3/c1-5-15-7-9-19-18-8-6-16-12-17(25)10-11-22(16,3)21(18)20(26-14(2)24)13-23(15,19)4/h5,12,15,18-21H,1,6-11,13H2,2-4H3/t15-,18?,19?,20+,21?,22-,23+/m0/s1
SMILES C=C[C@H]1CCC2C3CCC4=CC(=O)CC[C@]4(C)C3[C@H](OC(C)=O)C[C@@]21C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   356.24 Volume:   387.963
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Van der Waals volume.
Dense:   0.918 LogP:   3.418
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.184
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.024
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The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   23.0
TPSA:   43.37
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Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   0.0 Rings:   4.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.524 GASA:   1.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.426 Fsp3:   0.739
MCE-18:   70.2
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MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.677 Fluc inhibitor:   0.004
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.004
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.002
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.461 Promiscuous compounds:   0.452

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.521 MDCK Permeability:   -4.78
Pgp-inhibitor:   0.949 Pgp-substrate:   0.007
PAMPA:   0.012
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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%):   0.141 30% Bioavailability (F30%):   0.201
50% Bioavailability (F50%):   0.595

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.992 MRP1:   0.856
Plasma Protein Binding (PPB):   97.701% Volume Distribution (VD):   -0.284
Fu: 2.393%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.767
OATP1B3 inhibitor:   0.662 BCRP inhibitor:   0.284
BSEP inhibitor:   0.885

ADMET: Metabolism

CYP1A2-inhibitor:   0.002 CYP1A2-substrate:   0.104
CYP2C19-inhibitor:   0.997 CYP2C19-substrate:   0.01
CYP2C9-inhibitor:   0.929 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.563 CYP2D6-substrate:   0.002
CYP3A4-inhibitor:   0.012 CYP3A4-substrate:   0.052
CYP2B6-substrate:   0.999 CYP2C8-inhibitor:   0.999
HLM stability:   0.986
?
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):  9.557 Half-life (T1/2):  0.687

ADMET: Toxicity

hERG Blockers:  0.107 hERG Blockers (10um):  0.543
Human Hepatotoxicity (H-HT):  0.525 Drug-induced Liver Injury (DILI):  0.539
AMES Toxicity:  0.476 Rat Oral Acute Toxicity:  0.528
Maximum Recommended Daily Dose:  0.863 Skin Sensitization:  0.799
Carcinogencity:  0.805 Eye Corrosion:  0.043
Eye Irritation:  0.407 Respiratory Toxicity:  0.759
Drug-induced Neurotoxicity:  0.803 Ototoxicity:  0.302
Hematotoxicity:  0.349 Drug-induced Nephrotoxicity:  0.169
Genotoxicity:  0.801 RPMI-8226 Immunitoxicity:  0.059
A549 Cytotoxicity:  0.321 Hek293 Cytotoxicity:  0.55
BCF:   0.94
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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:   3.756
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.479
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.854
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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
NPO42391 Eunicella cavolini Species Eunicellidae Eukaryota n.a. n.a. n.a. Database[COCONUT]

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 NPC552076 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
0.5263 Remote Similarity NPC307176
0.5263 Remote Similarity NPC321874
0.5254 Remote Similarity NPC282593
0.5246 Remote Similarity NPC323765
0.5167 Remote Similarity NPC35734
0.5167 Remote Similarity NPC159577
0.5167 Remote Similarity NPC115023
0.5167 Remote Similarity NPC602429
0.5082 Remote Similarity NPC149203

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC552076 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
0.5263 Remote Similarity NPD4747 Phase 4
0.5079 Remote Similarity NPD5737 Phase 4

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