LC-MB12

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

LC-MB12 是一种具有口服活性靶向降解 FGFR2 的 PROTAC 化合物，DC50 为 11.8 nM。LC-MB12 包含 BGJ398 (FGFR2 抑制剂), PROTAC linker 和 CRBN。LC-MB12 抑制胃癌细胞 FGFR2 信号，具有抗肿瘤活性。

LC-MB12 is an orally active PROTAC compound targets FGFR2degradation with a DC50 of 11.8 nM. LC-MB12 contains BGJ398 (a FGFR2 inhibitor), PROTAC linker and CRBN.LC-MB12 inhibits FGFR2 signaling in gastric cancer cells and has anti-tumor activity.

Cell Viability Assay Cell Line:KATO III, SNU-16, NCI-H716 Concentration:0.5 nM, 1.5 nM, 4.3 nM, 13 nM, 41 nM, 123 nM, 370 nM, 1111 nM, 3333 nM, 10000 nM Incubation Time:72 h Result:Inhibited cell growth with IC50s value of 29.1 nM (KATO III); 3.7 nM (SNU-16); 3.2 nM (NCI-H716).Cell Cycle Analysis Cell Line:KATO III Concentration:29.1 nM Incubation Time:72 h Result:Induced G0/G1 cycle arrest.ImmunofluorescenceCell Line:KATO IIIConcentration:100 nM Incubation Time:3 h, 6 h Result:Promoted FGFR2 was relocated from the cell membrane to intracellular vesicles after treated for 3 or 6 h. Induced receptor internalization and re-localization to the perinuclear section after 6 h treatment.Western Blot Analysis Cell Line:KATO III, NCI-H1581 Concentration: 0.5 nM, 1.5 nM, 4.3 nM, 13 nM, 41 nM, 123 nM, 370 nM, 1111 nM, 3333 nM, 10000 nM Incubation Time:6 h Result:Degraded FGFR2 with a DC50 of 11.8 nM and D max of ~80% after 6 h of treatment.Showed time-dependent effect on degradation,with a detectable reduction in FGFR2 levels after 3 h of treatment and ~90% degradation after 12 h.Degraded of FGFR2 in KATO by 77%, and in NCI-H1581 by 43% after 100 nM treatment for 6 h.

Animal Model:SNU-16 xenografted in BALB/c-nu mice.Dosage:20 mg/kg/day Administration:oral administration (p.o.) 15 days Result:Achieved 63.1% tumor growth inhibition innocuously. Inhibited FGFR phosphorylation and total FGFR2 protein and decreased phosphorylation levels of downstream pPLCγ and ERK1/2.

——

Others

Other Targets

PROTACs | FGFR

——

——

2828438-38-4

899.78

C43H44Cl2N10O8

>98% (HPLC)

In Vitro:?DMSO 中的溶解度 : 130 mg/mL (144.48 mM; 超声助溶 (<60°C)

O=C(NC=1C(Cl)=C(OC)C=C(OC)C1Cl)N(C=2N=CN=C(C2)NC3=CC=C(C=C3)N4CCN(C(=O)C5CCN(C6=CC=C7C(=O)N(C(=O)C7=C6)C8C(=O)NC(=O)CC8)CC5)CC4)C

——

(-20℃)

With Ice Pack

≥ 2 years