Lificiguat binds to the β subunit ofsoluble guanylyl cyclase(sGC) withK_dof 0.6-1.1 μM in the presence of CO.

Kd: 0.6-1.1 μM (sGC, in the presence of CO)^[1]

Soluble guanylate cyclase (sGC) is a heterodimeric heme protein and the primary NO receptor. Lificiguat (YC-1) binds near or directly to the heme-containing domain of the beta subunit. In the absence of CO, Lificiguat (YC-1) binds with K_d=9-21 μM, depending on construct. In the presence of CO, these values decrease to 0.6-1.1 μM. Lificiguat (YC-1) greatly enhanced CO binding to heterodimeric sGC, as expected (K_d=1 μM). Lificiguat (YC-1) stimulates sGC two- to four-fold in the absence of NO but acts synergistically with CO or NO to achieve several hundred fold activation. Binding of Lificiguat(YC-1) can also overcome inhibitory phosphorylation of sGC^[1]. Lificiguat (YC-1) is a soluble guanylyl cyclase (sGC) activator. HCC cell lines HepG2, BEL-7402 and HCCLM3 are incubated for 72 h with Sorafenib and/or Lificiguat (YC-1). Sorafenib or Lificiguat (YC-1) alone inhibits HCC cell proliferation in a dose-dependent manner. Moreover, combination of Sorafenib and Lificiguat (YC-1) significantly suppresses proliferation of HCC cells in a dose-dependent manner. In addition, at the ED₅₀doses for both Sorafenib and Lificiguat (YC-1), combination index values (CI)=0.93 in HepG2, 0.95 in BEL-7402 and 0.72 in HCCLM3 respectively, suggesting that Sorafenib and Lificiguat (YC-1) synergistically inhibit proliferation of HCC cells^[2].

Lificiguat (YC-1) (30 or 60 mg/kg, i.p.) inhibits MDA-MB-468 tumor growth in a dose-dependent manner. The effect of the prodrug formulation of Lificiguat (YC-1), YC-1-S, in MDA-MB-468 tumor-bearing mice is also investigated. In vivo pharmacokinetic analysis reveal that YC-1-S is quickly converted into its active form. Mice are administered 20, 40 or 80 mg/kg YC-1-S p.o. YC-1-S also displays dose-dependent inhibition of MDA-MB468 tumor growth. Both Lificiguat (YC-1) and YC-1-S dose-dependently reduce tumor weight. Moreover, the mean body weight of mice is not affected by Lificiguat (YC-1) or YC-1-S compare with vehicle-treated groups^[3]. Lificiguat (YC-1) is a potent NO-GC activator reported to improve rodent learning behavior when examined with the Morris water maze (MWM) and avoidance tests. Lificiguat (YC-1) enhances long-term potentiation (LTP) in hippocampal Schafer collateral-CA1 synapse via the NO-cGMP-PKG-dependent pathway and potentiated LTP induction in the amygdala, increases the activation of ERK, and potentiated the expression of brain-derived neurotrophic factor (BDNF) cAMP response element-binding protein (CREB) in response to fear memory test^[4].

304.34

Solid

C₁₉H₁₆N₂O₂

170632-47-0

利非西呱

Room temperature in continental US; may vary elsewhere.

DMSO : ≥ 100 mg/mL(328.58 mM)

*"≥" means soluble, but saturation unknown.

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂： 10% DMSO    40%PEG300   5%Tween-80   45% saline

  Solubility: ≥ 2.5 mg/mL (8.21 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (8.21 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH2O 中，得到澄清透明的生理盐水溶液
• 2.

  请依序添加每种溶剂： 10% DMSO    90% (20%SBE-β-CDin saline)

  Solubility: 2.5 mg/mL (8.21 mM); Suspended solution; Need ultrasonic

  此方案可获得 2.5 mg/mL (8.21 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。

  将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
• 3.

  请依序添加每种溶剂： 10% DMSO    90%corn oil

  Solubility: ≥ 2.5 mg/mL (8.21 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (8.21 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。