ML216

Research use only, not for human use.

ML216 (CID49852229) is a potent, selective inhibitor of DNA unwinding activity of BLM (Bloom's syndrome protein) with IC50 of 2.98 and 0.97 uM for full length BLM and BLM636-1298, respectively.

ML216 (CID49852229) is a potent, selective inhibitor of DNA unwinding activity of BLM (Bloom's syndrome protein) with IC50 of 2.98 and 0.97 uM for full length BLM and BLM636-1298, respectively; weak inhibits WRN helicase (IC50=12.6 uM) and does not inhibit RecQ1, RecQ5 and UrvD (IC50>50 uM); disrupts BLM’s binding to DNA, rather than being an inhibitor of ATP binding by BLM, the inhibition of ssDNA-dependent ATPase activity with Ki of 1.76 uM, shows cell-based activity and can induce sister chromatid exchanges, enhances the toxicity of aphidicolin, and exerts antiproliferative activity in cells expressing BLM.

ML216 (12.5-50 μM; 24-72 hours; PSNG5 and PSNG13cells) treatment inhibits the proliferation of PSNF5 cells in a concentration-dependent manner, but not of PSNG13 cells.ML216 treatment leads to a statistically significant increase in the frequency of sister chromatid exchanges (SCEs) in PSNF5 cells, but not in PSNG13 cells.ML216 increases the sensitivity of PSNF5 cells to aphidicolin but has no sensitizing effect on isogenic PSNG13 cells devoid of BLM.?ML216 inhibits both the full length WRN (IC50 of 5 μM) and a truncated WRN500-946 (IC50 of 12.6 μM), with the former being 2.5-fold more sensitive to inhibition. BLM is a little more sensitive than WRN to inhibition by ML216 (1.7-fold based on IC50 values). Despite the detectable inhibition of WRN by ML216, this compound appears selective for BLM in human cells. ML216 inhibits proliferation of WRN+ and WRN? cells equally well, and similarly sensitized both cell types to aphidicolin. Cell Proliferation Assay Cell Line:PSNG5 and PSNG13 cells Concentration:12.5 μM or 50 μMIncubation Time:24 hours, 48 hours, 72 hours Result:Inhibited the proliferation of PSNF5 cells, but not of PSNG13 cells, and did so in a concentration-dependent manner.

Although ML216 inhibits unwinding by the sequence-related BLM and WRN helicases similarly in vitro, the apparent dependence on BLM for ML216 to exert its biological effects in human cells suggests BLM specificity for the drug’s mechanism of action in vivo. A co-crystal structure of BLM in complex with inhibitor would be informative. Cellular cues in vivo may induce a specific conformation of WRN that makes it resistant to ML216.

ML 216 | ML-216 | CID49852229

Cell Cycle/DNA Damage

DNA Repair Protein

BLM

Cancer

——

1430213-30-1

383.3235

C15H9F4N5OS

>98% (HPLC)

DMSO: 1.71 mg/mL

O=C(NC1=NN=C(C2=CC=NC=C2)S1)NC3=CC=C(F)C(C(F)(F)F)=C3

Urea, N-[4-fluoro-3-(trifluoromethyl)phenyl]-N'-[5-(4-pyridinyl)-1,3,4-thiadiazol-2-yl]-

(-20℃)

With Ice Pack

≥ 2 years