AZD5438-PROTAC: A selective CDK2 degrader that protects against cisplatin- and noise-induced hearing loss

by Santanu Hati*, Marisa Zallocchi*, Robert Hazlitt, Yuju Li, Sarath Vijayakumar, Jaeki Min, Zoran Rankovic, Sándor Lovas, Jian Zuo

*Equal contribution

Cyclin-dependent kinase 2 (CDK2) is a potential therapeutic target for the treatment of hearing loss and cancer. Previously, we identified AZD5438 and AT7519-7 as potent inhibitors of CDK2, however, they also targeted additional kinases,…

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Characterization of quinoxaline derivatives for protection against iatrogenically induced hearing loss

by Marisa Zallocchi, Santanu Hati, Zhenhang Xu, William Hausman, Huizhan Liu, David Z He, Jian Zuo

Hair cell loss is the leading cause of hearing and balance disorders in humans. It can be caused by many factors, including noise, aging, and therapeutic agents. Previous studies have shown the therapeutic potential of quinoxaline against drug-induced ototoxicity. Here, we screened a library of 68 quinoxaline derivatives for protection against aminoglycoside-induced damage…

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BRAF inhibition protects against hearing loss in mice

by Matthew A. Ingersoll, Emma A. Malloy, Lauryn E. Caster, Eva M. Holland, Zhenhang Xu, Marisa Zallocchi, Duane Currier, Huizhan Liu, David Z.Z. He, Jaeki Min, Taosheng Chen, Jian Zuo, Tal Teitz*

Hearing loss caused by noise, aging, antibiotics, and chemotherapy affects 10% of the world population, yet there are no Food and Drug Administration (FDA)-approved drugs to prevent it. Here, we screened 162 small-molecule …

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Supplementary Materials for BRAF inhibition protects against hearing loss in mice

by Matthew A. Ingersoll, Emma A. Malloy, Lauryn E. Caster, Eva M. Holland, Zhenhang Xu, Marisa Zallocchi, Duane Currier, Huizhan Liu, David Z.Z. He, Jaeki Min, Taosheng Chen, Jian Zuo, Tal Teitz*

Figures S1 – S8 and Table S1

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Aggressive Childhood Neuroblastomas do not express caspase-8

by Dr Tal Teitz and Dr Vincent Kidd

Neuroblastomas that overexpress N-Myc due to amplification of the MYCN oncogene are aggressive tumors that become very resistant to treatment by chemotherapy and irradiation. to identify tumor suppressor genes in this …

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Development of Second-Generation CDK2 Inhibitors for the Prevention of Cisplatin-Induced Hearing Loss

by Robert A. Hazlitt  Tal Teitz, Justine D. Bonga , Jie Fang , Shiyong Diao, Luigi Iconaru, Lei Yang , Asli N. Goktug , Duane G. Currier, Taosheng Chen, Zoran Rankovic, Jaeki Min, and Jian Zuo

There are currently no FDA-approved therapies to prevent the hearing loss associated with the usage of cisplatin in chemotherapeutic regimens. We recently demonstrated that the pharmacologic inhibition with kenpaullone…

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CDK2 inhibitors as candidate therapeutics for cisplatin- and noise-induced hearing loss

by Tal Teitz, Jie Fang, Asli N. Goktug,  Justine D. Bonga, Shiyong Diao, Robert A. Hazlitt, Luigi Iconaru, Marie Morfouace, Duane Currier, Yinmei Zhou, Robyn A. Umans, Michael R. Taylor, Cheng Cheng, Jaeki Min, Burgess Freeman,, Junmin Peng, Martine F. Roussel, Richard Kriwacki,R. Kiplin Guy,Taosheng Chen, and Jian Zuo

Hearing loss caused by aging, noise, cisplatin toxicity, or other insults affects 360 million people worldwide, but there are no Food and Drug Administration–approved drugs to prevent or treat it. We screened 4,385…

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