Tesevatinib Explained

Tesevatinib (KD019, XL647) is an experimental drug proposed for use in kidney cancer and polycystic kidney disease. The drug was first developed by Exelixis, Inc.^[1] and was later acquired by Kadmon Corporation. Tesevatinib binds to and inhibits several tyrosine receptor kinases that play major roles in tumor cell proliferation and tumor vascularization, including epidermal growth factor receptor (EGFR; ERBB1), epidermal growth factor receptor 2 (HER2; ERBB2), vascular endothelial growth factor receptor (VEGFR), and ephrin B4 (EphB4).^[2]

The drug activity was initially studied in non-small cell lung cancer.^[3] In a 2007 pre-clinical study with xenograft tumors of an erlotinib-resistant cell line tesevatinib substantially inhibited the growth of these tumors.^[4] In polycystic kidney disease, a histological study of the drug effects and toxicity in rats and mice was published in July 2017.^[5]

As of March 2019 the drug was in Phase II clinical trials for the treatment of polycystic kidney disease in adults and children.

Notes and References

1. Gendreau SB, Ventura R, Keast P, Laird AD, Yakes FM, Zhang W, Bentzien F, Cancilla B, Lutman J, Chu F, Jackman L, Shi Y, Yu P, Wang J, Aftab DT, Jaeger CT, Meyer SM, De Costa A, Engell K, Chen J, Martini JF, Joly AH . 6 . Inhibition of the T790M gatekeeper mutant of the epidermal growth factor receptor by EXEL-7647 . Clinical Cancer Research . 13 . 12 . 3713–23 . June 2007 . 17575237 . 10.1158/1078-0432.CCR-06-2590 . 30 October 2017 . free .
2. Web site: Substance Name: Tesevatinib [USAN:INN] ]. US National Library of Medicine. 30 October 2017.
3. Carrizosa DR, Mileham KF, Haggstrom DE . New targets and new mechanisms in lung cancer . Oncology . Williston Park, N.Y. . 27 . 5 . 396–404 . May 2013 . 25184262 .
4. Gendreau SB, Ventura R, Keast P, Laird AD, Yakes FM, Zhang W, Bentzien F, Cancilla B, Lutman J, Chu F, Jackman L, Shi Y, Yu P, Wang J, Aftab DT, Jaeger CT, Meyer SM, De Costa A, Engell K, Chen J, Martini JF, Joly AH . 6 . Inhibition of the T790M gatekeeper mutant of the epidermal growth factor receptor by EXEL-7647 . Clinical Cancer Research . 13 . 12 . 3713–23 . June 2007 . 17575237 . 10.1158/1078-0432.CCR-06-2590 . free .
5. Sweeney WE, Frost P, Avner ED . Tesevatinib ameliorates progression of polycystic kidney disease in rodent models of autosomal recessive polycystic kidney disease . World Journal of Nephrology . 6 . 4 . 188–200 . July 2017 . 28729967 . 5500456 . 10.5527/wjn.v6.i4.188 . free .