C188-9

C188-9 (TTI-101) is an orally administered, highly selective STAT3 SH2 domain inhibitor with a Kd value of 4.7 nM. C188-9 induces apoptosis in AML cell lines and primary samples while inhibiting colony formation in primary AML cells. C188-9 is suitable for studies on tumors, inflammation, and immune evasion.

STAT3:4-7 μM

Methods: Primary cardiac fibroblasts (CFs) isolated from adult male C57BL/6 mouse hearts were pretreated with C188-9 (10 μM) for 12 h, followed by stimulation with TGF-β1 (10 ng/mL) for 24 h. qRT-PCR was used to detect mRNA levels of fibrosis marker genes: Col1a1, Col1a2, Col3a1, and α-SMA.
Results: TGF-β1 significantly upregulated fibrosis gene and protein expression and increased p-STAT3. [1]
Methods: Mouse C2C12 myotubes (differentiated for 4 days) were pretreated with C188-9 (10 μM) for 1 hour, then co-incubated with 5% (v/v) heat-inactivated plasma from third-degree burn mice for 48 hours. Western blot analysis detected MyHC, p-STAT3, STAT3, Atrogin-1, and MuRF1 protein levels.
Results: C188-9 pretreatment significantly reversed burn plasma-induced myotube atrophy, restored myotube diameter and MyHC levels, and inhibited STAT3 activation and ubiquitin ligase expression.[3]

Methods: Ten-week-old male C57BL/6 mice underwent cardiac injury and fibrosis induction via continuous subcutaneous infusion of ISO (20 mg/kg/day) using an osmotic pump, concurrently receiving intraperitoneal injections of C188-9 (50 mg/kg/day) once daily for 21 consecutive days.
Results: C188-9 treatment significantly improved ISO-induced cardiac dysfunction, reduced cardiac weight index and injury markers, and markedly suppressed the increase in STAT3 phosphorylation in ISO-damaged cardiac tissue. [1]
Methods: Adult male SD rats were subjected to acute ocular hypertension (AOH) by maintaining intraocular pressure at 110 mmHg for 1 hour via anterior chamber perfusion with saline. Three hours prior to AOH, C188-9 (10 mM) was vitreally injected at 5 μL/eye. Immediately after AOH, C188-9 (1 μg/μL) was vitreally injected at 5 μL/eye. Animals were sacrificed 3 days post-AOH for RGC counting.
Results: C188-9 pretreatment significantly reversed the protective effect of LIF, resulting in significantly lower RGC density compared to the LIF+PBS group. [2]
Methods: Male C57BL/6 mice (12–16 weeks old) received second- or third-degree thermal burns covering 20% of the body surface area on the dorsal region. Intraperitoneal injections of C188-9 (50 mg/kg/day) commenced 1 hour post-burn and were administered every 24 hours for 3 days. Relevant parameters were assessed 3 days post-burn.
Results: C188-9 significantly ameliorated burn-induced weight loss, muscle atrophy, and grip strength decline while inhibiting STAT3 phosphorylation and Atrogin-1/MuRF1 upregulation. [3]

DMSO: 262.5 mg/mL (556.71 mM), Sonication is recommended.

10% DMSO+40% PEG300+5% Tween 80+45% Saline: 6 mg/mL (12.72 mM), Solution.