TIP48/49-IN-1

TIP48/49-IN-1 is an orally active, specific RUVBL1/2 (TIP48/49) ATPase inhibitor with an IC₅₀ of 59 nM against purified RUVBL1/2. TIP48/49-IN-1 inhibits the DNA replication process, leading to S-phase arrest. TIP48/49-IN-1 induces apoptosis. TIP48/49-IN-1 can be used for the research of non-small cell lung cancer (NSCLC) cells^[1]. In Vitro:TIP48/49-IN-1 (Compound B) (100 nM; 3 days) depletes the PIKK family proteins ATM, ATR and DNA-PKCS in H₂009 NSCLC cells^[1].
TIP48/49-IN-1 (100 nM; 24 h) alters the transcriptome of H2009 and H596 non-small cell lung cancer (NSCLC) cells, and significantly downregulates DNA replication-related genes^[1].
TIP48/49-IN-1 (100 nM; 12 h) enhances the binding of PAQosome components to RUVBL1 and impairs PAQosome maturation/dissociation in H₂009 non-small cell lung cancer cells^[1].
TIP48/49-IN-1 (100 nM; 48 h) induces S-phase arrest and subsequent apoptosis in sensitive non-small cell lung cancer (NSCLC) cell lines, including H2009^[1].
TIP48/49-IN-1 (100 nM; 24 h) delays S-phase progression in synchronized H2009 non-small cell lung cancer cells^[1].
TIP48/49-IN-1 (100 nM; 12-72 h) initially reduces the levels of ssDNA and chromatin-bound RPA2 in H2009 non-small cell lung cancer cells, and subsequently induces replication catastrophe at 48 h, accompanied by high levels of ssDNA and RPA hyperloading^[1].
TIP48/49-IN-1 (100 nM; 6-12 h) accelerates the replication fork speed of H2009 non-small cell lung cancer (NSCLC) cells at 6 h post-treatment^[1].
TIP48/49-IN-1 (100 nM; 12 h) increases POLE abundance at active replication forks in H2009 non-small cell lung cancer cells and reduces core histone abundance^[1].
TIP48/49-IN-1 (25-50 nM; 3 days) radiosensitizes 8 NSCLC cell lines, but exerts no such effect on normal bronchial epithelial cells HBEC3KT or HBEC30KT^[1].
TIP48/49-IN-1 (25 nM; 3 days) slows the DSB repair kinetics in H2009 non-small cell lung cancer cells, but exerts no such effect on HBEC3KT normal bronchial epithelial cells^[1].
TIP48/49-IN-1 (150 nM; 3 days) inhibits ionizing radiation damage repair in organoids derived from 5 patients with primary non-small cell lung cancer^[1]. In Vivo:TIP48/49-IN-1 (Compound B) (175 mg/kg/day; p.o.; twice daily on treatment days; schedule: 4 days on, 9 days off, 3 days on, 7 days off, 3 days on) significantly inhibits H₂009 NSCLC xenograft growth in female NOD.CB17-PrkdcSCID/J mice by depleting RUVBL1/2-dependent PIKK-family proteins^[1].
TIP48/49-IN-1 (175 mg/kg/day; p.o.; twice daily on treatment days; schedule: 4 days on, 9 days off, 3 days on, 7 days off, 3 days on) inhibits H596 NSCLC xenograft growth in female NOD.CB17-PrkdcSCID/J mice by depleting RUVBL1/2-dependent PIKK-family proteins, with modest efficacy relative to H2009 tumors^[1].
TIP48/49-IN-1 (125 mg/kg/day; p.o.; twice daily on treatment days; schedule: 4 days of treatment with 9 A.M. and 5 P.M. doses, plus 2 Gy IR at 12 P.M. on treatment days, with an additional 2 Gy IR on the fifth day) potentiates the antitumor efficacy of ionizing radiation in H1299 NSCLC xenografts without causing obvious toxicity in female nude mice^[1].