Natural Product: NPC92327

Natural Product IDNPC92327
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Pregna-1,4,20-Trien-3-One
IUPAC Name (8S,9S,10R,13R,14S,17R)-17-ethenyl-10,13-dimethyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-3-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1689218
PubChem CID 13034987
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 KFTYFBOHSUEIEJ-NWSAAYAGSA-N
Standard InCHI InChI=1S/C21H28O/c1-4-14-6-8-18-17-7-5-15-13-16(22)9-11-21(15,3)19(17)10-12-20(14,18)2/h4,9,11,13-14,17-19H,1,5-8,10,12H2,2-3H3/t14-,17-,18-,19-,20+,21-/m0/s1
SMILES C=C[C@H]1CC[C@H]2[C@@H]3CCC4=CC(=O)C=C[C@]4(C)[C@H]3CC[C@]12C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   296.21 Volume:   335.791
?
Van der Waals volume.
Dense:   0.882 LogP:   4.341
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.649
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.781
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   22.0
TPSA:   17.07
?
Topological Polar Surface Area.
 H-Bond Acceptor:   1.0
H-Bond Donor:   0.0 Rings:   4.0
Heavy Atoms:   1.0

MedChem Properties

QED Drug-Likeness Score:   0.615 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.253 Fsp3:   0.667
MCE-18:   64.457
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.841 Fluc inhibitor:   0.411
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.049
?
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:   0.841 Promiscuous compounds:   0.248

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.771 MDCK Permeability:   -4.612
Pgp-inhibitor:   0.985 Pgp-substrate:   0.001
PAMPA:   0.005
?
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%):   0.09 30% Bioavailability (F30%):   0.366
50% Bioavailability (F50%):   0.792

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.991 MRP1:   0.069
Plasma Protein Binding (PPB):   95.876% Volume Distribution (VD):   0.498
Fu: 4.37%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.995
OATP1B3 inhibitor:   0.996 BCRP inhibitor:   0.747
BSEP inhibitor:   0.998

ADMET: Metabolism

CYP1A2-inhibitor:   0.004 CYP1A2-substrate:   0.42
CYP2C19-inhibitor:   0.699 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.249
CYP2D6-inhibitor:   0.038 CYP2D6-substrate:   0.93
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.921
?
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):  13.139 Half-life (T1/2):  0.926

ADMET: Toxicity

hERG Blockers:  0.219 hERG Blockers (10um):  0.595
Human Hepatotoxicity (H-HT):  0.559 Drug-induced Liver Injury (DILI):  0.322
AMES Toxicity:  0.182 Rat Oral Acute Toxicity:  0.635
Maximum Recommended Daily Dose:  0.971 Skin Sensitization:  0.951
Carcinogencity:  0.954 Eye Corrosion:  0.908
Eye Irritation:  0.999 Respiratory Toxicity:  0.985
Drug-induced Neurotoxicity:  0.468 Ototoxicity:  0.172
Hematotoxicity:  0.24 Drug-induced Nephrotoxicity:  0.177
Genotoxicity:  0.869 RPMI-8226 Immunitoxicity:  0.035
A549 Cytotoxicity:  0.043 Hek293 Cytotoxicity:  0.793
BCF:   2.563
?
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:   4.335
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.36
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.132
?
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
NPO30138 Carijoa Genus Clavulariidae Eukaryota n.a. n.a. n.a. PMID[21235217]

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
NPT172 Organism Proteus mirabilis Proteus mirabilis MIC = 40.0 ug.mL-1 PMID[21235217]
NPT1246 Organism Salmonella Salmonella MIC = 40.0 ug.mL-1 PMID[21235217]
NPT173 Organism Klebsiella pneumoniae Klebsiella pneumoniae MIC = 40.0 ug.mL-1 PMID[21235217]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 40.0 ug.mL-1 PMID[21235217]
NPT19 Organism Escherichia coli Escherichia coli MIC = 40.0 ug.mL-1 PMID[21235217]
NPT175 Organism Enterococcus faecalis Enterococcus faecalis MIC = 40.0 ug.mL-1 PMID[21235217]
NPT314 Organism Bacillus cereus Bacillus cereus MIC = 40.0 ug.mL-1 PMID[21235217]

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 NPC92327 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
0.7551 Intermediate Similarity NPC176107
0.74 Intermediate Similarity NPC105197
0.7115 Intermediate Similarity NPC474463
0.6727 Remote Similarity NPC190211
0.6727 Remote Similarity NPC218301
0.6727 Remote Similarity NPC273199
0.6607 Remote Similarity NPC608739
0.6531 Remote Similarity NPC54123
0.6491 Remote Similarity NPC255309
0.625 Remote Similarity NPC176171
0.6167 Remote Similarity NPC177141
0.6154 Remote Similarity NPC6434
0.5738 Remote Similarity NPC164835
0.5738 Remote Similarity NPC228669
0.5667 Remote Similarity NPC470923
0.5645 Remote Similarity NPC128488
0.5645 Remote Similarity NPC304968
0.5574 Remote Similarity NPC310981
0.5556 Remote Similarity NPC30421
0.5469 Remote Similarity NPC600537
0.5385 Remote Similarity NPC601481
0.5323 Remote Similarity NPC474807
0.5312 Remote Similarity NPC111684
0.5312 Remote Similarity NPC281134
0.5231 Remote Similarity NPC58052
0.5224 Remote Similarity NPC471398
0.5224 Remote Similarity NPC604986
0.5152 Remote Similarity NPC96377

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC92327 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
0.6154 Remote Similarity NPD4195 Phase 4
0.5556 Remote Similarity NPD3573 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