Natural Product: NPC103822

Natural Product IDNPC103822
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Stereonsteroid A
IUPAC Name (3S,5S,8S,9S,10R,13R,14S,17R)-17-ethenyl-10-(hydroxymethyl)-13-methyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-ol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL491368
PubChem CID 11702475
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 VBJNSFFFEBGPIC-YVFDZHEOSA-N
Standard InCHI InChI=1S/C21H34O2/c1-3-14-5-7-18-17-6-4-15-12-16(23)8-11-21(15,13-22)19(17)9-10-20(14,18)2/h3,14-19,22-23H,1,4-13H2,2H3/t14-,15-,16-,17-,18-,19-,20+,21+/m0/s1
SMILES C=C[C@H]1CC[C@@H]2[C@]1(C)CC[C@H]1[C@H]2CC[C@@H]2[C@]1(CO)CC[C@@H](C2)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   318.26 Volume:   352.49
?
Van der Waals volume.
Dense:   0.903 LogP:   4.383
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.884
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.201
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   21.0
TPSA:   40.46
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   2.0 Rings:   4.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.75 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.505 Fsp3:   0.905
MCE-18:   68.4
?
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:   0.473 Fluc inhibitor:   0.037
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.01
?
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:   0.67 Promiscuous compounds:   0.193

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.795 MDCK Permeability:   -4.8
Pgp-inhibitor:   0.318 Pgp-substrate:   0.131
PAMPA:   0.006
?
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%):   0.035 30% Bioavailability (F30%):   0.28
50% Bioavailability (F50%):   0.714

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.895 MRP1:   0.019
Plasma Protein Binding (PPB):   80.518% Volume Distribution (VD):   0.01
Fu: 21.1%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.966
BSEP inhibitor:   0.626

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.007
CYP2C19-inhibitor:   0.386 CYP2C19-substrate:   0.003
CYP2C9-inhibitor:   0.001 CYP2C9-substrate:   0.215
CYP2D6-inhibitor:   0.324 CYP2D6-substrate:   0.503
CYP3A4-inhibitor:   0.833 CYP3A4-substrate:   0.896
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.865
HLM stability:   0.953
?
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):  12.641 Half-life (T1/2):  1.864

ADMET: Toxicity

hERG Blockers:  0.151 hERG Blockers (10um):  0.317
Human Hepatotoxicity (H-HT):  0.495 Drug-induced Liver Injury (DILI):  0.383
AMES Toxicity:  0.204 Rat Oral Acute Toxicity:  0.096
Maximum Recommended Daily Dose:  0.898 Skin Sensitization:  0.974
Carcinogencity:  0.964 Eye Corrosion:  0.698
Eye Irritation:  0.998 Respiratory Toxicity:  0.975
Drug-induced Neurotoxicity:  0.071 Ototoxicity:  0.297
Hematotoxicity:  0.299 Drug-induced Nephrotoxicity:  0.366
Genotoxicity:  0.034 RPMI-8226 Immunitoxicity:  0.023
A549 Cytotoxicity:  0.271 Hek293 Cytotoxicity:  0.779
BCF:   1.821
?
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:   3.668
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.899
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.4
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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
NPO33076 stereonephthya crystalliana Species Nephtheidae Eukaryota n.a. formosan soft coral n.a. PMID[16441077]

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
NPT139 Cell line HT-29 Homo sapiens ED50 = 7.5 ug ml-1 PMID[22771007]
NPT168 Cell line P388 Mus musculus IC50 = 3.5 ug.mL-1 PMID[13678412]

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 NPC103822 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
0.5625 Remote Similarity NPC114891
0.56 Remote Similarity NPC320549
0.56 Remote Similarity NPC156277
0.56 Remote Similarity NPC58057
0.56 Remote Similarity NPC151018
0.5577 Remote Similarity NPC254340
0.549 Remote Similarity NPC71460
0.549 Remote Similarity NPC218585
0.5385 Remote Similarity NPC148174
0.5179 Remote Similarity NPC167702
0.5179 Remote Similarity NPC192456
0.5179 Remote Similarity NPC280026

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC103822 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
0.56 Remote Similarity NPD4808 Phase 2
0.56 Remote Similarity NPD4809 Phase 4
0.5179 Remote Similarity NPD6113 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