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Chemical Structure| 14970-87-7 Chemical Structure| 14970-87-7

Structure of 14970-87-7

Chemical Structure| 14970-87-7

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Product Citations

Product Citations      Show More

Andrews, Emily R ;

Abstract: Metal chelators developed from peptides boast favorable attributes such as low toxicity, ease of synthesis, and high tunabilty to the target metal ion. It is for these reasons that peptides are used for metal sensing and sequestration in the body and environment. Herein, two unique sets of metal targeting peptides are discussed: (1) bifunctional Szeto-Schiller and Kelley peptide probes to signal the presence of and remove labile iron (Fe2+ and Fe3+) in the mitochondria, to mitigate the progression of Ferroptosis and (2) Pb2+ targeting peptides designed to exist in aqueous environments for the removal of toxic lead ions from waterways. These peptides were synthesized manually via solid phase peptide synthesis (SPPS) and determination of impurities and success of synthesis was carried out using analytical high-performance liquid chromatography (HPLC). Aspects of these peptides and their syntheses were explored, with special attention given to membrane lipophilicity, degree of epimerization due to synthetic protocols and protecting groups, and simulated metal complexation structures using computational modeling software. It was determined through these studies that the reagents used for peptide synthesis are heavily residue-dependent, and both the iron and lead (II) targeting peptides have shown promising metal chelation at early stages. Recommendations for further methods for analysis and determination of the lipophilicities of the iron probes are discussed, as well as additional computational studies and paths for sequence optimization for the lead (II) peptides.

Purchased from AmBeed: ; ; ; ; ; ;

Kumpati, Greeshma P ; Ronayne, Conor T ; Johnson, Joseph L ; Gardner, Zachary S ; Singh, Anuj K ; Iyer, Ananth , et al.

Abstract: Glutathione transferase (GSTP1 and GSTM2) are tractable targets for anticancer drug development. In this work, a series of 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol (NBDHEX) based analogues were designed, synthesized, and evaluated both theoretically and experimentally as GSTP1 and GSTM2 inhibitors. Among the synthesized compounds, 3h showed selective inhibition toward GSTP1 while 5b showed selective inhibition of GSTM2. Compounds 5b and 5c exhibited stronger potency while compound 3h showed slightly lower potency against the tested cancer cells than its parent molecule NBDHEX. Comprehensive biological studies were conducted on the effect of 3h, 5b and 5c towards breast cancer MDA-MB-231 and pancreatic MiaPaCa-2 cell lines revealed that 3h, 5b and 5c could activate JNK pathway and induce cell apoptosis. Furthermore in vivo experiments using NSG mice demonstrated that 5b significantly reduced tumor growth when administered in combination with gemcitabine, effectively overcoming gemcitabine resistance in the MiaPaCa-2 cell model through targeted inhibition of GSTM2. These findings suggests that, 5b could become a promising candidate for further development as a potential antitumor agent in cancer therapy.

Keywords: anticancer agents ; oxidative stress ; GSTP1 ; GSTM2 ; JNK ; gemcitabine resistance

Purchased from AmBeed: ; ; ;

Alternative Products

Product Details of [ 14970-87-7 ]

CAS No. :14970-87-7
Formula : C6H14O2S2
M.W : 182.30
SMILES Code : SCCOCCOCCS
MDL No. :MFCD00015873
InChI Key :HCZMHWVFVZAHCR-UHFFFAOYSA-N
Pubchem ID :84733

Safety of [ 14970-87-7 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H301-H332-H410
Precautionary Statements:P261-P264-P270-P271-P273-P301+P310+P330-P304+P340+P312-P391-P405-P501
Class:6.1
UN#:2810
Packing Group:

Computational Chemistry of [ 14970-87-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 0
Fraction Csp3 1.0
Num. rotatable bonds 7
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 48.98
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

96.06 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

2.43
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

0.51
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

0.88
Log Po/w (MLOGP)?

MLOGP: Topological method implemented from
Moriguchi I. et al. 1992 Chem. Pharm. Bull.
Moriguchi I. et al. 1994 Chem. Pharm. Bull.
Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.

0.61
Log Po/w (SILICOS-IT)?

SILICOS-IT: Hybrid fragmental/topological method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

1.59
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.2

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-0.83
Solubility 27.0 mg/ml ; 0.148 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Very soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-2.1
Solubility 1.46 mg/ml ; 0.00799 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble
Log S (SILICOS-IT)?

SILICOS-IT: Fragmental method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-2.01
Solubility 1.78 mg/ml ; 0.00975 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble

Pharmacokinetics

GI absorption?

Gatrointestinal absorption: according to the white of the BOILED-Egg

High
BBB permeant?

BBB permeation: according to the yolk of the BOILED-Egg

No
P-gp substrate?

P-glycoprotein substrate: SVM model built on 1033 molecules (training set)
and tested on 415 molecules (test set)
10-fold CV: ACC=0.72 / AUC=0.77
External: ACC=0.88 / AUC=0.94

No
CYP1A2 inhibitor?

Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.83 / AUC=0.90
External: ACC=0.84 / AUC=0.91

No
CYP2C19 inhibitor?

Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.80 / AUC=0.86
External: ACC=0.80 / AUC=0.87

No
CYP2C9 inhibitor?

Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set)
and tested on 2075 molecules (test set)
10-fold CV: ACC=0.78 / AUC=0.85
External: ACC=0.71 / AUC=0.81

No
CYP2D6 inhibitor?

Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set)
and tested on 1068 molecules (test set)
10-fold CV: ACC=0.79 / AUC=0.85
External: ACC=0.81 / AUC=0.87

No
CYP3A4 inhibitor?

Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set)
and tested on 2579 molecules (test set)
10-fold CV: ACC=0.77 / AUC=0.85
External: ACC=0.78 / AUC=0.86

No
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-7.05 cm/s

Druglikeness

Lipinski?

Lipinski (Pfizer) filter: implemented from
Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev.
MW ≤ 500
MLOGP ≤ 4.15
N or O ≤ 10
NH or OH ≤ 5

0.0
Ghose?

Ghose filter: implemented from
Ghose AK. et al. 1999 J. Comb. Chem.
160 ≤ MW ≤ 480
-0.4 ≤ WLOGP ≤ 5.6
40 ≤ MR ≤ 130
20 ≤ atoms ≤ 70

None
Veber?

Veber (GSK) filter: implemented from
Veber DF. et al. 2002 J. Med. Chem.
Rotatable bonds ≤ 10
TPSA ≤ 140

0.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

0.0
Muegge?

Muegge (Bayer) filter: implemented from
Muegge I. et al. 2001 J. Med. Chem.
200 ≤ MW ≤ 600
-2 ≤ XLOGP ≤ 5
TPSA ≤ 150
Num. rings ≤ 7
Num. carbon > 4
Num. heteroatoms > 1
Num. rotatable bonds ≤ 15
H-bond acc. ≤ 10
H-bond don. ≤ 5

1.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.55

Medicinal Chemistry

PAINS?

Pan Assay Interference Structures: implemented from
Baell JB. & Holloway GA. 2010 J. Med. Chem.

0.0 alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

1.0 alert: heavy_metal
Leadlikeness?

Leadlikeness: implemented from
Teague SJ. 1999 Angew. Chem. Int. Ed.
250 ≤ MW ≤ 350
XLOGP ≤ 3.5
Num. rotatable bonds ≤ 7

No; 1 violation:MW<1.0
Synthetic accessibility?

Synthetic accessibility score: from 1 (very easy) to 10 (very difficult)
based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties,
trained on 12'782'590 molecules and tested on 40 external molecules (r2 = 0.94)

2.44

Application In Synthesis of [ 14970-87-7 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 14970-87-7 ]

[ 14970-87-7 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 14970-87-7 ]
  • [ 63521-92-6 ]
  • [ 591-80-0 ]
  • C11H20O3S2 [ No CAS ]
 

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