Natural Product: NPC254421

Natural Product IDNPC254421
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 IRJULQGCGHNQDS-FVBIZVIFSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 5318078
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000258] Steroids and steroid derivatives
        • [CHEMONTID:0001194] Oxosteroids

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 IRJULQGCGHNQDS-FVBIZVIFSA-N
Standard InCHI InChI=1S/C21H27NO2/c1-12-16-5-6-17-15-4-3-13-9-14(23)7-8-20(13,2)19(15)18(24)10-21(16,17)11-22-12/h7-9,11-12,15-19,24H,3-6,10H2,1-2H3/t12?,15?,16?,17?,18?,19?,20-,21?/m0/s1
SMILES CC1C2CCC3C4CCC5=CC(=O)C=C[C@]5(C)C4C(CC23C=N1)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   325.2 Volume:   347.021
?
Van der Waals volume.
Dense:   0.937 LogP:   2.49
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.697
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.09
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   25.0
TPSA:   49.66
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   1.0 Rings:   5.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.742 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   5.461 Fsp3:   0.714
MCE-18:   107.944
?
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:   0.657 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.157
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.187
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.02 Promiscuous compounds:   0.003

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.051 MDCK Permeability:   -4.736
Pgp-inhibitor:   0.393 Pgp-substrate:   0.077
PAMPA:   0.321
?
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):   0.019
20% Bioavailability (F20%):   0.114 30% Bioavailability (F30%):   0.473
50% Bioavailability (F50%):   0.882

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.981 MRP1:   0.952
Plasma Protein Binding (PPB):   91.398% Volume Distribution (VD):   0.386
Fu: 11.729%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.103
OATP1B3 inhibitor:   0.449 BCRP inhibitor:   0.033
BSEP inhibitor:   0.994

ADMET: Metabolism

CYP1A2-inhibitor:   0.031 CYP1A2-substrate:   0.003
CYP2C19-inhibitor:   0.168 CYP2C19-substrate:   0.009
CYP2C9-inhibitor:   0.029 CYP2C9-substrate:   0.004
CYP2D6-inhibitor:   0.002 CYP2D6-substrate:   0.512
CYP3A4-inhibitor:   0.178 CYP3A4-substrate:   0.006
CYP2B6-substrate:   0.151 CYP2C8-inhibitor:   0.932
HLM stability:   0.131
?
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):  9.115 Half-life (T1/2):  2.417

ADMET: Toxicity

hERG Blockers:  0.275 hERG Blockers (10um):  0.699
Human Hepatotoxicity (H-HT):  0.662 Drug-induced Liver Injury (DILI):  0.053
AMES Toxicity:  0.276 Rat Oral Acute Toxicity:  0.875
Maximum Recommended Daily Dose:  0.991 Skin Sensitization:  0.533
Carcinogencity:  0.832 Eye Corrosion:  0.0
Eye Irritation:  0.045 Respiratory Toxicity:  0.951
Drug-induced Neurotoxicity:  0.797 Ototoxicity:  0.887
Hematotoxicity:  0.033 Drug-induced Nephrotoxicity:  0.136
Genotoxicity:  0.942 RPMI-8226 Immunitoxicity:  0.049
A549 Cytotoxicity:  0.007 Hek293 Cytotoxicity:  0.594
BCF:   0.999
?
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:   3.808
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.381
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.594
?
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
NPO30941 Holarrhena antidysenterica Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO765 Holarrhena pubescens Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11658 Alternanthera philoxeroides Species Amaranthaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11658 Alternanthera philoxeroides Species Amaranthaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO30941 Holarrhena antidysenterica Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO765 Holarrhena pubescens Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO765 Holarrhena pubescens Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO11658 Alternanthera philoxeroides Species Amaranthaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO30941 Holarrhena antidysenterica Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO765 Holarrhena pubescens Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO765 Holarrhena pubescens Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11658 Alternanthera philoxeroides Species Amaranthaceae 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

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 NPC254421 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 NPC169375
0.5538 Remote Similarity NPC334061
0.5143 Remote Similarity NPC44063

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC254421 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
0.5625 Remote Similarity NPD6079 Phase 4
0.5538 Remote Similarity NPD4696 Phase 4
0.5455 Remote Similarity NPD5211 Phase 2
0.5143 Remote Similarity NPD5697 Phase 4
0.507 Remote Similarity NPD4632 Approved
0.5068 Remote Similarity NPD6054 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