Ro5-3335

Ro5-3335
Identifiers
	IUPAC name 7-chloro-5-(1H-pyrrol-2-yl)-1,3-dihydro-1,4-benzodiazepin-2-one;
CAS Number	30195-30-3;
PubChem CID	64983;
ChemSpider	58508;
UNII	DLH4T68L7I;
ChEBI	CHEBI:131785;
ChEMBL	ChEMBL91609;
CompTox Dashboard (EPA)	DTXSID20184270 ;
Chemical and physical data
Formula	C13H10ClN3O
Molar mass	259.69 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES C1C(=O)NC2=C(C=C(C=C2)Cl)C(=N1)C3=CC=CN3;
	InChI InChI=1S/C13H10ClN3O/c14-8-3-4-10-9(6-8)13(11-2-1-5-15-11)16-7-12(18)17-10/h1-6,15H,7H2,(H,17,18); Key:XWNMORIHKRROGW-UHFFFAOYSA-N;

Ro5-3335 is an experimental drug from the benzodiazepine family which acts as a selective inhibitor of the protein Runt-related transcription factor 1 (RUNX1). Inhibition of this protein is useful in numerous medical applications, and Ro5-3335 has beneficial effects against diverse conditions including HIV infection, leukemia and some other forms of cancer, recovery following heart attack, acute kidney injury, and some types of retinopathy.^[1]^[2]^[3]^[4]^[5]^[6]^[7]^[8]^[9]

References

^ Cunningham L, Finckbeiner S, Hyde RK, Southall N, Marugan J, Yedavalli VR, et al. (September 2012). "Identification of benzodiazepine Ro5-3335 as an inhibitor of CBF leukemia through quantitative high throughput screen against RUNX1-CBFβ interaction". Proceedings of the National Academy of Sciences of the United States of America. 109 (36): 14592–14597. Bibcode:2012PNAS..10914592C. doi:10.1073/pnas.1200037109. PMC 3437880. PMID 22912405.
^ Klase Z, Yedavalli VS, Houzet L, Perkins M, Maldarelli F, Brenchley J, et al. (March 2014). "Activation of HIV-1 from latent infection via synergy of RUNX1 inhibitor Ro5-3335 and SAHA". PLOS Pathogens. 10 (3): e1003997. doi:10.1371/journal.ppat.1003997. PMC 3961356. PMID 24651404.
^ Delgado-Tirado S, Amarnani D, Zhao G, Rossin EJ, Eliott D, Miller JB, et al. (November 2020). "Topical delivery of a small molecule RUNX1 transcription factor inhibitor for the treatment of proliferative vitreoretinopathy". Scientific Reports. 10 (1): 20554. doi:10.1038/s41598-020-77254-0. PMC 7705016. PMID 33257736.
^ Zhang D, Liang C, Li P, Yang L, Hao Z, Kong L, et al. (August 2021). "Runt-related transcription factor 1 (Runx1) aggravates pathological cardiac hypertrophy by promoting p53 expression". Journal of Cellular and Molecular Medicine. 25 (16): 7867–7877. doi:10.1111/jcmm.16704. PMC 8358850. PMID 34190420.
^ Jeong EM, Pereira M, So EY, Wu KQ, Del Tatto M, Wen S, et al. (December 2022). "Targeting RUNX1 as a novel treatment modality for pulmonary arterial hypertension". Cardiovascular Research. 118 (16): 3211–3224. doi:10.1093/cvr/cvac001. PMC 9799056. PMID 35018410.
^ Martin TP, MacDonald EA, Bradley A, Watson H, Saxena P, Rog-Zielinska EA, et al. (December 2023). "Ribonucleicacid interference or small molecule inhibition of Runx1 in the border zone prevents cardiac contractile dysfunction following myocardial infarction". Cardiovascular Research. 119 (16): 2663–2671. doi:10.1093/cvr/cvad107. PMC 10730241. PMID 37433039.
^ Chen H, Wang S, Zhang X, Hua X, Liu M, Wang Y, et al. (June 2024). "Pharmacological inhibition of RUNX1 reduces infarct size after acute myocardial infarction in rats and underlying mechanism revealed by proteomics implicates repressed cathepsin levels". Functional & Integrative Genomics. 24 (3): 113. doi:10.1007/s10142-024-01391-2. PMC 11166773. PMID 38862712.
^ Kobayashi Y, Ando K, Imaizumi Y, Sakamoto H, Kitanosono H, Taguchi M, et al. (December 2024). "RUNX1 expression is regulated by a super-enhancer and is a therapeutic target in adult T-cell leukemia/lymphoma". Leukemia & Lymphoma. 65 (14): 2116–2128. doi:10.1080/10428194.2024.2393258. PMID 39219309.
^ Fontecha-Barriuso M, Villar-Gomez N, Guerrero-Mauvecin J, Martinez-Moreno JM, Carrasco S, Martin-Sanchez D, et al. (December 2024). "Runt-related transcription factor 1 (RUNX1) is a mediator of acute kidney injury". The Journal of Pathology. 264 (4): 396–410. doi:10.1002/path.6355. PMID 39472111.

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[1] Cunningham L, Finckbeiner S, Hyde RK, Southall N, Marugan J, Yedavalli VR, et al. (September 2012). "Identification of benzodiazepine Ro5-3335 as an inhibitor of CBF leukemia through quantitative high throughput screen against RUNX1-CBFβ interaction". Proceedings of the National Academy of Sciences of the United States of America. 109 (36): 14592–14597. Bibcode:2012PNAS..10914592C. doi:10.1073/pnas.1200037109. PMC 3437880. PMID 22912405.

[2] Klase Z, Yedavalli VS, Houzet L, Perkins M, Maldarelli F, Brenchley J, et al. (March 2014). "Activation of HIV-1 from latent infection via synergy of RUNX1 inhibitor Ro5-3335 and SAHA". PLOS Pathogens. 10 (3): e1003997. doi:10.1371/journal.ppat.1003997. PMC 3961356. PMID 24651404.

[3] Delgado-Tirado S, Amarnani D, Zhao G, Rossin EJ, Eliott D, Miller JB, et al. (November 2020). "Topical delivery of a small molecule RUNX1 transcription factor inhibitor for the treatment of proliferative vitreoretinopathy". Scientific Reports. 10 (1): 20554. doi:10.1038/s41598-020-77254-0. PMC 7705016. PMID 33257736.

[4] Zhang D, Liang C, Li P, Yang L, Hao Z, Kong L, et al. (August 2021). "Runt-related transcription factor 1 (Runx1) aggravates pathological cardiac hypertrophy by promoting p53 expression". Journal of Cellular and Molecular Medicine. 25 (16): 7867–7877. doi:10.1111/jcmm.16704. PMC 8358850. PMID 34190420.

[5] Jeong EM, Pereira M, So EY, Wu KQ, Del Tatto M, Wen S, et al. (December 2022). "Targeting RUNX1 as a novel treatment modality for pulmonary arterial hypertension". Cardiovascular Research. 118 (16): 3211–3224. doi:10.1093/cvr/cvac001. PMC 9799056. PMID 35018410.

[6] Martin TP, MacDonald EA, Bradley A, Watson H, Saxena P, Rog-Zielinska EA, et al. (December 2023). "Ribonucleicacid interference or small molecule inhibition of Runx1 in the border zone prevents cardiac contractile dysfunction following myocardial infarction". Cardiovascular Research. 119 (16): 2663–2671. doi:10.1093/cvr/cvad107. PMC 10730241. PMID 37433039.

[7] Chen H, Wang S, Zhang X, Hua X, Liu M, Wang Y, et al. (June 2024). "Pharmacological inhibition of RUNX1 reduces infarct size after acute myocardial infarction in rats and underlying mechanism revealed by proteomics implicates repressed cathepsin levels". Functional & Integrative Genomics. 24 (3): 113. doi:10.1007/s10142-024-01391-2. PMC 11166773. PMID 38862712.

[8] Kobayashi Y, Ando K, Imaizumi Y, Sakamoto H, Kitanosono H, Taguchi M, et al. (December 2024). "RUNX1 expression is regulated by a super-enhancer and is a therapeutic target in adult T-cell leukemia/lymphoma". Leukemia & Lymphoma. 65 (14): 2116–2128. doi:10.1080/10428194.2024.2393258. PMID 39219309.

[9] Fontecha-Barriuso M, Villar-Gomez N, Guerrero-Mauvecin J, Martinez-Moreno JM, Carrasco S, Martin-Sanchez D, et al. (December 2024). "Runt-related transcription factor 1 (RUNX1) is a mediator of acute kidney injury". The Journal of Pathology. 264 (4): 396–410. doi:10.1002/path.6355. PMID 39472111.

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