CID-1067700

CID-1067700 has significant inhibitory activity against the Rab GTPases, in particular Rab2 and Rab7. Its EC₅₀ value for Rab GTPases is in the range of 20–500nM. CID-1067700 inhibits the binding of BODIPY-conjugated nucleotides in a dose-dependent manner, with corresponding EC₅₀ values ​​of 11.22±1.34nM for BODIPY-GTP and 20.96±1.34nM for BODIPY-GDP^[1].

In vitro, treatment with 40μM CID-1067700 for 48h inhibited induction of CSR to IgG, IgA and IgE, hampered NF-κB activation and AID expression in human and mouse B cells^[2]. Treatment with 20-100μM of CID-1067700 for 24 or 72h did not show any significant toxic effects on the viability of Adipose-derived stem cells (ASCs)^[3]. A 10-day treatment with 40μM CID-1067700 induced the differentiation of ASCs into basal KLCs and promoted their differentiation into differentiated KLCs^[3].

In vivo, CID-1067700 (16mg/kg/d; i.p.), administered from day 7 to day 12, did not have a therapeutic effect on tumor progression in Foxn1^nu/nu mice bearing Daudi cell-derived xenografts^[4]. CID-1067700 (16mg/kg/w; i.p.), administered for 10 weeks, prevented disease development in lupus disease and reduced IgG-IC deposition in MRL/Faslpr/lpr mice^[2].

Reference:
[1]Agola JO, Hong L, Surviladze Z, et al. A competitive nucleotide binding inhibitor: in vitro characterization of Rab7 GTPase inhibition. ACS Chem Biol. 2012 Jun 15;7(6):1095-108.
[2] Lam T, Kulp DV, Wang R, et al. Small Molecule Inhibition of Rab7 Impairs B Cell Class Switching and Plasma Cell Survival To Dampen the Autoantibody Response in Murine Lupus. J Immunol. 2016;197(10):3792-3805.
[3] Alghazali R, Tabebi M, Elmasry M, El-Serafi A. Rab7 inhibitor enhances stem cell differentiation into keratinocyte-like cells with anti-inflammatory properties. Front Immunol. 2025;16:1503007.
[4] Fernandez M, Wang R, Wang J, et al. Targeting RAB7 in human B lymphoma by a small molecule inhibitor arrests tumor cell growth. Front Oncol. 2025;15:1616519.

CID-1067700是Rab GTPases的抑制剂，特别是对Rab2和Rab7具有显著的抑制作用。CID-1067700对Rab GTPases的EC₅₀值在20-500nM范围内。CID-1067700以剂量依赖的方式抑制BODIPY联合核苷酸的结合，对BODIPY-GTP的EC₅₀值为11.22±1.34nM，对BODIPY-GDP的EC₅₀值为20.96±1.34nM^[1]。

体外实验中，40μM的CID-1067700处理48小时抑制了人和小鼠B细胞中CSR对IgG、IgA和IgE的诱导，NF-κB的激活以及AID的表达^[2]。20-100μM的CID-1067700处理24或72小时，对脂肪源性干细胞（ASCs）的活性均没有明显的毒性影响^[3]。40μM的CID-1067700处理10天，能诱导ASCs向基底型KLCs分化，并促进其向分化型KLCs分化^[3]。

体内实验中，CID-1067700（16mg/kg/d; i.p.），从第7天持续至第12天给药，对接种了Daudi的Foxn1^nu/nu鼠的肿瘤进展并未产生治疗效果^[4]。CID-1067700（16mg/kg/w; i.p.），连续给药10周，能够阻止狼疮病的发展，并减少MRL/Faslpr/lpr小鼠体内IgG-IC的沉积^[2]。