LATS-IN-2

LATS-IN-2 is an efficiently acting LATS ( large tumor suppressor kinase) inhibitor. LATS-IN-2 shows potent inhibitory activity against LATS1 with an IC₅₀ value of 1.3 nM. LATS-IN-2 suppresses the phosphorylation of YAP by inhibiting LATS kinase activity. LATS-IN-2 increases the thickness of the epidermis in mice. LATS-IN-2 can be used for the study of ocular diseases such as limbal stem cell deficiency and corneal endothelial dysfunction ^[1].

In Vivo, LATS-IN-2 (Compound 133) (0.2-2 mg/mL, topical application, twice daily, 2 days) significantly up-regulates the expression of YAP target gene Cyr61 in a dose-dependent manner in the skin around the wound edge of mice with full-thickness excisional wounds^[1].

In Vitro, LATS-IN-2 (Compound 133) (9 μM, 1 h) dramatically reduces the phosphorylation level of YAP (Ser127) in human HaCaT keratinocytes^[1]. LATS-IN-2 (1-20 μM, 12-16 days) promotes 100- to 2200-fold expansion of seeded LSCs, and maintains p63alpha-positive cells in the expanded population^[1]. LATS-IN-2 (0.5-25 μM, 1-2 weeks) induces strong proliferation of human CECs^[1].

References:
[1]. BEHNKE, Dirk, et al. 6-6 FUSED BICYCLIC HETEROARYL COMPOUNDS AND THEIR USE AS LATS INHIBITORS. WO 2018/198077 A2. World Intellectual Property Organization (WIPO). 01 November 2018.