WM-1119

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

WM-1119 (WM1119) 是一种高效、选择性的赖氨酸乙酰转移酶 KAT6A 抑制剂，Kd 为 2 nM。

WM-1119 (WM1119) is a highly potent, selective inhibitor of lysine acetyltransferase KAT6A with Kd of 2 nM, shows greate bioavailability and specificity for KAT6A than WM-8014; displays 1,100-fold and 250-fold selectivity over KAT5 and KAT7, respectively; causes cell cycle arrest in G1 and senescence phenotype similar to WM-8014; demonstrates growth inhibition assays in lymphoma cell line EMRK1184 (IC50=0.25 uM, 10-fold potency than WM-8014), increases levels of Cdkn2a and Cdkn2b mRNA and p16INK4a and p19ARF protein, as well as a delayed increase in Cdkn1a mRNA; arrests lymphoma growth in vivo without effect on haematocrit, erythrocytes or platelet numbers.

WM-1119 induces cell cycle exit and cellular senescence without causing DNA damage. WM-1119 is 1,100-fold and 250-fold more active against KAT6A than against KAT5 or KAT7, respectively, and so shows greater specificity for KAT6A than does WM-8014. Treatment of MEFs with WM-1119 results in cell cycle arrest in G1 and a senescence phenotype similar to that seen upon treatment with WM-8014. Notably, the activity of WM-1119 in this cell-based assay is an order of magnitude greater than WM-8014 and WM-1119 is able to induce cell cycle arrest at 1 μM. Treatment with WM-1119 inhibits the proliferation of the EMRK1184 lymphoma cells in vitro, WM-1119 (IC50=0.25 μM) is ninefold more active than WM-8014 (IC50=2.3 μM), as expected on the basis of reduced protein binding.

By day 14, the cohorts that are treated four times per day with WM-1119 have arrested tumour growth, with the exception of one mouse that does not respond. Spleen weights in the WM-1119-treatment group (treated four times per day) are substantially lower than spleen weights in the vehicle-treated group. Treatment with WM-1119 three times per day leads to a significant reduction in tumour burden and spleen weight, but is not as effective as treatment four times per day. WM-1119 is well-tolerated; mice show no generalized ill effects and weight loss is not observed. The proportion and overall number of tumour cells is substantially reduced by WM-1119 treatment (four times per day).

WM1119 | WM 1119

Chromatin/Epigenetic

HAT

KAT6A|KAT5|KAT7

Cancer

——

2055397-28-7

389.377

C18H13F2N3O3S

>98% (HPLC)

DMSO: ≥150 mg/mL (385.23 mM) （ < 1 mg/ml refers to the product slightly soluble or insoluble )

O=C(NNS(=O)(C1=CC=CC=C1F)=O)C2=CC(C3=NC=CC=C3)=CC(F)=C2

Benzoic acid, 3-fluoro-5-(2-pyridinyl)-, 2-[(2-fluorophenyl)sulfonyl]hydrazide

(-20℃)

With Ice Pack

≥ 2 years