Ro 90-7501

[Description]:

Ro 90-7501 is an amyloid β42 (Aβ42) fibril assembly inhibitor that reduces Aβ42-induced cytotoxicity (EC50 of 2 μM). Ro 90-7501 inhibits ATM phosphorylation and DNA repair. RO 90-7501 selectively enhances toll-like receptor 3 (TLR3) and RIG-I-like receptor (RLR) ligand-induced IFN-β gene expression and antiviral response[2]. Ro 90-7501 also inhibits protein phosphatase 5 (PP5) in a TPR-dependent manner[3]. Ro 90-7501 has significant radiosensitizing effects on cervical cancer cells[4].

[Related Catalog]:

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> Cell Cycle/DNA Damage >> ATM/ATR

Signaling Pathways >> Metabolic Enzyme/Protease >> Phosphatase

Signaling Pathways >> PI3K/Akt/mTOR >> ATM/ATR

Research Areas >> Neurological Disease

[Target]

Amyloid β42

ATM

Protein phosphatase 5

Apoptosis

[In Vitro]

Ro 90-7501 significantly enhances radiosensitivity compared with control HeLa and ME-180 cells. Ro 90-7501 significantly increases apoptosis and impaired cell cycle after irradiation. Ro 90-7501 suppresses the phosphorylation of ATM and its downstream proteins, such as H2AX, Chk1, and Chk2, after irradiation[1]. RO 90-7501, itself affects neither IFN-β nor NFκB promoter activity, but significantly enhances poly I:C-induced IFN-β promoter activation and inhibits the activation of NFκB in a dose-dependent manner. Treatment of cells with RO 90-7501 significantly enhances the antiviral activity of poly I:C[2].

[In Vivo]

Ro 90-7501 (5 μg/g; intraperitoneal injection; daily; for 21 days; female BALB/c nude mice) treatment significantly delays tumor growth and significantly decreases tumor volume[1]. Animal Model: Female BALB/c nude mice (8-week-old) with HeLa cells under irradiation[1] Dosage: 5 μg/g Administration: Intraperitoneal injection; daily; for 21 days Result: Tumor growth was significantly delayed in the combination group. Tumor volume was also significantly decreased in the irradiation group.

[References]

[1]. Tamari K, et al. Ro 90-7501 Is a Novel Radiosensitizer for Cervical Cancer Cells that Inhibits ATM Phosphorylation. Anticancer Res. 2019 Sep;39(9):4805-4810.

[2]. Guo F, et al. RO 90-7501 enhances TLR3 and RLR agonist induced antiviral response. PLoS One. 2012;7(10):e42583.

[3]. Hong TJ, et al. Ro 90-7501 inhibits PP5 through a novel, TPR-dependent mechanism. Biochem Biophys Res Commun. 2017 Jan 8;482(2):215-220.

[4]. Bohrmann B, et al. Self-assembly of beta-amyloid 42 is retarded by small molecular ligands at the stage of structural intermediates. J Struct Biol. 2000 Jun;130(2-3):232-46.

[ Density]:
1.443g/cm3

[ Boiling Point ]:
751.035ºC at 760 mmHg

[ Molecular Formula ]:
C₂₀H₁₆N₆

[ Molecular Weight ]:
340.38100

[ Flash Point ]:
449.122ºC

[ Exact Mass ]:
340.14400

[ PSA ]:
109.40000

[ LogP ]:
5.10000

[ Vapour Pressure ]:
0mmHg at 25°C

[ Index of Refraction ]:
1.842

Click to get detail MSDS

[ Symbol ]:

GHS07

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H315-H319-H335

[ Precautionary Statements ]:
P261-P305 + P351 + P338

[ Personal Protective Equipment ]:
dust mask type N95 (US);Eyeshields;Gloves

[ Hazard Codes ]:
Xi

[ Risk Phrases ]:
36/37/38

[ Safety Phrases ]:
26-36/37

[ RIDADR ]:
NONH for all modes of transport

Self-assembly of beta-amyloid 42 is retarded by small molecular ligands at the stage of structural intermediates.

J. Struct. Biol. 130 , 232-246, (2000)

Assemblyof the amyloid-beta peptide (Abeta) into fibrils and its deposition in distinct brain areas is considered responsible for the pathogenesis of Alzheimer's disease (AD). Thus, inhibition of fibr...

Protein aggregation and neurodegenerative disease.

Nat. Med. 10 Suppl , S10-S17 , (2004)

Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS) and prion diseases are increasingly being realized...

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