312756-74-4

Basic information

• Product Name: 4-BroMo-N-(4-broMophenyl)-3-[[(phenylMethyl)aMino]sulfonyl]benzaMide
• Synonyms: 4-BroMo-N-(4-broMophenyl)-3-[[(phenylMethyl)aMino]sulfonyl]benzaMide;RAD51-stimulatory compound 1;RS-1;RAD51-Stimulatory Compound-1, RS-1
• CAS NO: 312756-74-4
• Molecular Formula: C₂₀H₁₆Br₂N₂O₃S
• Molecular Weight: 524.22564
• Product Categories: Amines, Aromatics, Pharmaceuticals, Intermediates & Fine Chemicals;API
• Mol File: 312756-74-4.mol
• Article Data: 1

Chemical Properties

• Appearance: off-white to light tan/
• Storage Temp.: room temp
• Solubility: DMSO: ≥10mg/mL
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months.
• CAS DataBase Reference: 4-BroMo-N-(4-broMophenyl)-3-[[(phenylMethyl)aMino]sulfonyl]benzaMide(CAS DataBase Reference)
• NIST Chemistry Reference: 4-BroMo-N-(4-broMophenyl)-3-[[(phenylMethyl)aMino]sulfonyl]benzaMide(312756-74-4)
• EPA Substance Registry System: 4-BroMo-N-(4-broMophenyl)-3-[[(phenylMethyl)aMino]sulfonyl]benzaMide(312756-74-4)

Safety Data

• Hazard Codes: Xi
• Statements: 36
• Safety Statements: 26
• WGK Germany: 3
• Hazardous Substances Data: 312756-74-4(Hazardous Substances Data)

Usage

Description

4-Bromo-N-(4-bromophenyl)-3-[[(phenylmethyl)amino]sulfonyl]benzamide, also known as RS-1, is a cell-permeable sulfonamido-benzamide-based allosteric regulator that activates the human homologous recombination protein RAD51. It stimulates DNA binding and recombinase activities of hRAD51 by locking hRAD51 in an active conformation without affecting its active site ATP hydrolysis. RS-1 enhances hRAD51 filament formation on ssDNA with or without the cofactor NTP and promotes resistance of primary human neonatal dermal fibroblasts to Cisplatin-induced death in a dose-dependent manner.

Uses

Used in Genome Editing Applications:
RS-1 is used as a potent enhancer of CRISPR-mediated genome editing, increasing homology directed repair 3to 6-fold. It significantly increases both Cas9 & TALEN-mediated knock-in efficiencies, making it a valuable tool for researchers working on genome editing techniques.
Used in DNA Repair Research:
RS-1 is used as an activator of DNA repair protein RAD51, stimulating homologous strand assimilation activity at least 5to 11-fold, and enhancing homologous recombination activity of hRAD51. This makes it a useful compound for studying the mechanisms of DNA repair and developing potential therapeutic strategies for DNA repair-related diseases.
Used in Cancer Research:
RS-1 has been shown to promote resistance of primary human neonatal dermal fibroblasts to Cisplatin-induced death in a dose-dependent manner. This property makes it a potential candidate for use in cancer research, particularly in the development of therapies that enhance the effectiveness of chemotherapy drugs.
Used in Pharmaceutical Development:
Due to its ability to stimulate the activity of the DNA repair protein RAD51 and enhance CRISPR genome editing efficiency, RS-1 can be used in the development of new pharmaceuticals targeting DNA repair mechanisms and improving genome editing techniques for various therapeutic applications.

Biological Activity

RS-1 is a RAD51-stimulatory compound, which increases the DNA binding activity of RAD51. It is an HDR(homology-directed repair) enhancer that enhances Cas9- and TALEN-mediated knock-in efficiency in rabbit embryos both in vitro and in vivo.

Biochem/physiol Actions

RS-1 is a sulfonamido-benzamide compound.

in vitro

RS-1 stimulates the binding of hRAD51 to ssDNA. Low-micromolar concentrations of this small molecule enhance DNA binding and result in longer protein–DNA complex lengths. In addition, RS-1 stabilizes the active form of hRAD51 filaments and this is reflected in an enhanced strand assimilation activity[1]. RS-1 enhances Cas9- and TALEN-mediated knock-in efficiency in rabbit embryos both in vitro and in vivo.

References

1) Jayathilaka et al. (2008), A chemical compound that stimulates the human homologous recombination protein RAD51; Proc. Natl. Acad. Sci. USA 105 15848 2) Mason et al. (2014), The RAD51-stimulatory compound RS-1 can exploit the RAD51 overexpression that exists in cancer cells and tumors; Cancer Res. 74 3546 3) Pinder et al. (2015), Nuclear domain ‘knock-in’ screen for the evaluation and identification of small molecule enhancers of CRISPR-based genome editing; Nucleic Acids Res. 43 9379 4) Song et al. (2016), RS-1 enhances CRISPR/Cas9- and TALEN-mediated knock-in efficiency; Nat. Commun. 7 10548

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Relevant articles and documents

METHODS OF TREATING CANCER USING RAD51SMALL MOLECULE STIMULATORS

Methods of killing or inhibiting the growth cancer cells and tumors and of treating cancer by administering compounds that stimulate the activity of RAD51. Cells overexpressing RAD51 or with other imbalances in homologous recombination machinery are parti