Natural Product: NPC138534

Natural Product IDNPC138534
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Stemofoline
IUPAC Name n.a.
Synonyms Stemofoline
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2304257
PubChem CID 44448167
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0004603] Organic oxygen compounds
      • [CHEMONTID:0000323] Organooxygen compounds
        • [CHEMONTID:0000011] Carbohydrates and carbohydrate conjugates
          • [CHEMONTID:0003305] Aminosaccharides
            • [CHEMONTID:0000282] Aminoglycosides

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 DTVYAHOULQCSMS-JQANZLKUSA-N
Standard InCHI InChI=1S/C22H29NO5/c1-5-6-8-21-14-7-9-23(21)13-10-15(21)27-22(14)16(13)11(2)18(28-22)19-17(25-4)12(3)20(24)26-19/h11,13-16H,5-10H2,1-4H3/b19-18-/t11-,13-,14?,15+,16+,21-,22+/m0/s1
SMILES CCCC[C@]12C3CCN2[C@H]2C[C@H]1O[C@@]13[C@@H]2[C@H](C)/C(=C/2C(=C(C)C(=O)O2)OC)/O1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   387.2 Volume:   384.768
?
Van der Waals volume.
Dense:   1.006 LogP:   3.485
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.264
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.947
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   25.0
TPSA:   57.23
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   0.0 Rings:   6.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.691 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   6.906 Fsp3:   0.773
MCE-18:   122.949
?
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:   0.254 Fluc inhibitor:   0.004
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.036
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.132
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.006 Promiscuous compounds:   0.028

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.602 MDCK Permeability:   -4.677
Pgp-inhibitor:   0.189 Pgp-substrate:   0.434
PAMPA:   0.04
?
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):   0.008
20% Bioavailability (F20%):   0.353 30% Bioavailability (F30%):   0.289
50% Bioavailability (F50%):   0.603

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.852 MRP1:   0.862
Plasma Protein Binding (PPB):   93.906% Volume Distribution (VD):   0.231
Fu: 5.807%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.952
OATP1B3 inhibitor:   0.955 BCRP inhibitor:   0.026
BSEP inhibitor:   0.87

ADMET: Metabolism

CYP1A2-inhibitor:   0.265 CYP1A2-substrate:   0.784
CYP2C19-inhibitor:   0.016 CYP2C19-substrate:   0.979
CYP2C9-inhibitor:   0.028 CYP2C9-substrate:   0.471
CYP2D6-inhibitor:   0.011 CYP2D6-substrate:   0.199
CYP3A4-inhibitor:   0.581 CYP3A4-substrate:   0.997
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.982
HLM stability:   0.721
?
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):  9.012 Half-life (T1/2):  1.141

ADMET: Toxicity

hERG Blockers:  0.113 hERG Blockers (10um):  0.5
Human Hepatotoxicity (H-HT):  0.737 Drug-induced Liver Injury (DILI):  0.545
AMES Toxicity:  0.619 Rat Oral Acute Toxicity:  0.651
Maximum Recommended Daily Dose:  0.695 Skin Sensitization:  0.995
Carcinogencity:  0.621 Eye Corrosion:  0.056
Eye Irritation:  0.554 Respiratory Toxicity:  0.314
Drug-induced Neurotoxicity:  0.376 Ototoxicity:  0.453
Hematotoxicity:  0.365 Drug-induced Nephrotoxicity:  0.56
Genotoxicity:  0.667 RPMI-8226 Immunitoxicity:  0.117
A549 Cytotoxicity:  0.143 Hek293 Cytotoxicity:  0.49
BCF:   1.769
?
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:   4.495
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.877
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.506
?
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
NPO1235 Stemona curtisii Species Stemonaceae Eukaryota n.a. n.a. n.a. PMID[15104502]
NPO20479 Stemona burkillii Species Stemonaceae Eukaryota Stems n.a. n.a. PMID[15497953]
NPO28230 Stemona japonica Species Stemonaceae Eukaryota stems and leaves n.a. n.a. PMID[18163592]
NPO221 Stemona aphylla Species Stemonaceae Eukaryota Roots; Stems n.a. n.a. PMID[19374387]
NPO221 Stemona aphylla Species Stemonaceae Eukaryota Stems n.a. n.a. PMID[20415428]
NPO1235 Stemona curtisii Species Stemonaceae Eukaryota n.a. n.a. n.a. PMID[21049906]
NPO1235 Stemona curtisii Species Stemonaceae Eukaryota n.a. root n.a. PMID[21049906]
NPO27067 Stemona cochinchinensis Species Stemonaceae Eukaryota n.a. root n.a. PMID[21049906]
NPO221 Stemona aphylla Species Stemonaceae Eukaryota n.a. root n.a. PMID[21126060]
NPO221 Stemona aphylla Species Stemonaceae Eukaryota Roots Lampang Province, Thailand 2009-APR PMID[21126060]
NPO1235 Stemona curtisii Species Stemonaceae Eukaryota n.a. rhizome n.a. PMID[21902195]
NPO221 Stemona aphylla Species Stemonaceae Eukaryota n.a. n.a. n.a. PMID[21902195]
NPO1235 Stemona curtisii Species Stemonaceae Eukaryota n.a. n.a. n.a. PMID[21902195]
NPO1235 Stemona curtisii Species Stemonaceae Eukaryota n.a. tuberous root n.a. PMID[21902195]
NPO1235 Stemona curtisii Species Stemonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20479 Stemona burkillii Species Stemonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO221 Stemona aphylla Species Stemonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28230 Stemona japonica Species Stemonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27067 Stemona cochinchinensis Species Stemonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27067 Stemona cochinchinensis Species Stemonaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28230 Stemona japonica Species Stemonaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO1235 Stemona curtisii Species Stemonaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28230 Stemona japonica Species Stemonaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO27067 Stemona cochinchinensis Species Stemonaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO1235 Stemona curtisii Species Stemonaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28230 Stemona japonica Species Stemonaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO28230 Stemona japonica Species Stemonaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO1235 Stemona curtisii Species Stemonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27067 Stemona cochinchinensis Species Stemonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO221 Stemona aphylla Species Stemonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20479 Stemona burkillii Species Stemonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28230 Stemona japonica Species Stemonaceae 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
NPT204 Individual protein Acetylcholinesterase Homo sapiens MIC = 10.0 ng PMID[21126060]
NPT4586 Individual protein Nicotinic acetylcholine receptor alpha1 subunit Heliothis virescens EC50 = 50.0 nM PMID[18163592]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT487 Organism Cladosporium cladosporioides Cladosporium cladosporioides EC50 > 219.0 ppm PMID[15497953]

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
- Artemia LC50 > 33.0 ppm PMID[15497953]
- Spodoptera littoralis LC50 = 2.04 ppm PMID[12381121]
- Spodoptera littoralis LC50 = 1.46 ppm PMID[12381121]
- Spodoptera littoralis LC50 = 0.59 microg/dm2 PMID[12381121]

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 NPC138534 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 NPC486937
0.8636 High Similarity NPC486942
0.8636 High Similarity NPC486943
0.8333 Intermediate Similarity NPC486932
0.8333 Intermediate Similarity NPC486948
0.7812 Intermediate Similarity NPC477986
0.7794 Intermediate Similarity NPC323168
0.7794 Intermediate Similarity NPC486935
0.7794 Intermediate Similarity NPC486934
0.7794 Intermediate Similarity NPC111162
0.7794 Intermediate Similarity NPC293550
0.7353 Intermediate Similarity NPC486938
0.7286 Intermediate Similarity NPC486933
0.7286 Intermediate Similarity NPC486928
0.7143 Intermediate Similarity NPC329401
0.7143 Intermediate Similarity NPC477987
0.7042 Intermediate Similarity NPC486931
0.7042 Intermediate Similarity NPC486941
0.6849 Remote Similarity NPC486939
0.6849 Remote Similarity NPC486936
0.6849 Remote Similarity NPC486949
0.6849 Remote Similarity NPC486952
0.6849 Remote Similarity NPC486945
0.6849 Remote Similarity NPC486946
0.6849 Remote Similarity NPC486940
0.6757 Remote Similarity NPC486930
0.6667 Remote Similarity NPC486944
0.6667 Remote Similarity NPC486929
0.6667 Remote Similarity NPC486947
0.6061 Remote Similarity NPC486950
0.5921 Remote Similarity NPC486951
0.5921 Remote Similarity NPC471086
0.5125 Remote Similarity NPC326386

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC138534 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
NPD

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