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Chemical Structure| 7787-70-4 Chemical Structure| 7787-70-4

Structure of 7787-70-4

Chemical Structure| 7787-70-4

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Product Citations

Product Citations

Ang, Charles G ; Hyatt, Nadia L ; Le Minh, Giang ; Gupta, Monisha ; Kadam, Manali ; Hogg, Philip J , et al.

Abstract: Disulfide exchange is underexplored as a mechanism influencing HIV-1 entry. Prior studies demonstrated that redox enzyme inhibition can prevent HIV-1 infection but with limited mechanistic explanation. We hypothesize that ligand-driven rearrangement (“conformational activation”) enables enzyme-mediated disulfide exchange in Env residues (“disulfide trigger”) that promotes fusion transformations, enhancing virus entry. We tested soluble CD4 and CD4-binding site entry inhibitors as conformational activators and the ubiquitous redox enzyme thioredoxin-1 (Trx1) as disulfide trigger. We found that combination treatment caused fusion-like Env transformation and pseudovirus lysis, independent of cells. Notably, only compounds associated with gp120 shedding caused lysis when paired with Trx1. In each case, lysis was prevented by adding the fusion inhibitor T20, demonstrating that six-helix bundle formation is required as in virus-cell fusion. In contrast to conformationally activating ligands, neither the ground state stabilizer BMS-806 with Trx1 nor Trx1 alone caused lysis. Order of addition experiments reinforced conformational activation/disulfide trigger as a sequential process, with virus/activator preincubation transiently enhancing lysis and virus/Trx1 preincubation reducing lysis. Lastly, addition of exogenous Trx1 to typical pseudovirus infections exhibited dose-dependent enhancement of infection. Altogether, these data support conformational activation and disulfide triggering as a mechanism that can induce and enhance the fusogenic transformation of Env.

Keywords: HIV-1 ; Env ; thioredoxins ; allosteric disulfides ; virus entry ; entry inhibitors ; thiols ; disulfide exchange

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Alternative Products

Product Details of [ 7787-70-4 ]

CAS No. :7787-70-4
Formula : BrCu
M.W : 143.45
SMILES Code : [Cu+].[Br-]
MDL No. :MFCD00010969
InChI Key :NKNDPYCGAZPOFS-UHFFFAOYSA-M
Pubchem ID :24593

Safety of [ 7787-70-4 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H302-H315-H318-H335-H410
Precautionary Statements:P261-P264-P270-P271-P280-P302+P352-P304+P340-P305+P351+P338-P310-P330-P362+P364-P403+P233-P501
Class:9
UN#:3077
Packing Group:

Computational Chemistry of [ 7787-70-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 2
Num. arom. heavy atoms 0
Fraction Csp3 None
Num. rotatable bonds 0
Num. H-bond acceptors None
Num. H-bond donors None
Molar Refractivity 8.93
TPSA ?

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

0.0 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

None
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

None
Log Po/w (WLOGP)?

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

None
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.

None
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

None
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

None

Water Solubility

Log S (ESOL):?

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

None
Solubility None mg/ml ; None mol/l
Class?

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

None
Log S (Ali)?

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

None
Solubility None mg/ml ; None mol/l
Class?

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

None
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

None
Solubility None mg/ml ; None mol/l
Class?

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

None

Pharmacokinetics

GI absorption?

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

None
BBB permeant?

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

None
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

None
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

None
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

None
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

None
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

None
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

None
Log Kp (skin permeation)?

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

None 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

None
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

None
Egan?

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

None
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

None
Bioavailability Score?

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

None

Medicinal Chemistry

PAINS?

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

None alert
Brenk?

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

None 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
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)

None

Application In Synthesis of [ 7787-70-4 ]

* 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.

  • Upstream synthesis route of [ 7787-70-4 ]
  • Downstream synthetic route of [ 7787-70-4 ]

[ 7787-70-4 ] Synthesis Path-Upstream   1~1

  • 1
  • [ 64628-73-5 ]
  • [ 7787-70-4 ]
  • [ 95668-21-6 ]
References: [1] Patent: US6323155, 2001, B1, .
 

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