| Identification | Back Directory | [Name]
(E)-3-(2-(thiophen-2-yl)vinyl)-1H-pyrazole | [CAS]
1070881-42-3 | [Synonyms]
Terevalefim
Terevalefim（ANG-3777）
(E)-3-(2-(thiophen-2-yl)vinyl)-1H-pyrazole
1H-Pyrazole, 3-[(1E)-2-(2-thienyl)ethenyl]-
3-[(E)-2-(thiophen-2-yl)ethenyl]-2H-pyrazole
ANG-3777,Terevalefim,injury,acute,inhibit,ANG 3777,AKI,kidney,ANG3777,transplantation,c-Met/HGFR,HGF,Inhibitor | [Molecular Formula]
C9H8N2S | [MOL File]
1070881-42-3.mol | [Molecular Weight]
176.24 |
| Chemical Properties | Back Directory | [Boiling point ]
369.3±11.0 °C(Predicted) | [density ]
1.318±0.06 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO : 100 mg/mL (567.41 mM; Need ultrasonic) | [pka]
14.05±0.10(Predicted) |
| Hazard Information | Back Directory | [Description]
Terevalefim (ANG-3777) is a hepatocyte growth factor (HGF) mimetic that in preclinical and phase 2 studies has demonstrated the ability to activate the c-Met receptor and the pathways associated with that activation, improving renal function in induced-AKI in animals and long-term graft function occurring in renal transplantation recipients with signs of DGF[1-2]. | [Biological Functions]
ANG-3777 (Terevalefim) is an HGF mimetic that in vitro induces the same c-Met cascades and cellular effects as endogenous HGF. In animals, ANG-3777 stimulates tubular repair and regeneration, resulting in improved renal function following ischemia reperfusion injury. In humans, ANG-3777 has been shown to improve renal function up to 1 year after kidney transplantation in patients with signs of delayed graft function[1].
| [in vitro]
In vitro, ANG-3777 reduces apoptosis and increases cell proliferation, migration, morphogenesis, and angiogenesis in injured kidneys. In animal models, ANG-3777 mitigates the effects of renal damage secondary to ischemia reperfusion injury and nephrotoxic chemicals[1]. | [in vivo]
In vivo, Terevalefim results in dimerization and phosphorylation, and thus activation of the c-Met receptor, followed by activation of c-Met signaling cascades. The presence of c-Met is needed for ANG-3777 activity, and ANG-3777 selectively phosphorylates c-Met. Furthermore, c-Met phosphorylation induced by ANG-3777 occurs in a dose- and time-dependent manner with selective phosphorylation of c-Met and its downstream effector of ERK. No phosphorylation of IFGR, Tie2, EGFR, or FGFR occurs[2]. | [References]
[1] Ayad S, et al. Hepatocyte Growth Factor Mimetic ANG-3777 for Cardiac Surgery–Associated Acute Kidney Injury. Kidney International Reports, 2020; 5: 2325–2332.
[2] Vincenti F, et al. Phase 3 trial design of the hepatocyte growth factor mimetic ANG-3777 in renal transplant recipients with delayed graft function. Kidney International Reports, 2021; 6: 296-303. |
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