| Field | Specification |
|---|---|
| Target | |
| CAS no. | |
| Applications | |
| Molecular weight | |
| Molecular formula | C26H19F4N3O3S |
| Purity | |
| SMILES | |
| Form | Solid |
| Storage | |
| Shipping | |
| Catalog no. (Mfr.) | |
| Main SKU |
Compound Overview
RIPK1-IN-17 is an orally active, selective inhibitor of RIPK1 (Kd = 17 nM) with no significant inhibition of RIPK3. It specifically inhibits necroptosis rather than apoptosis by blocking phosphorylation of RIPK1, RIPK3, and MLKL, and it protects mice from hypothermia and death. It can be used to study necroptosis-related diseases such as inflammatory response syndrome (SIRS)[1]. It is supplied as a white to off-white solid (C26H19F4N3O3S, MW 529.51) at 97.09% purity.
Physical & Chemical Properties
| CAS Number | 3033385-59-7 |
|---|---|
| Molecular Formula | C26H19F4N3O3S |
| Molecular Weight | 529.51 g/mol |
| Purity | 97.09% |
| Appearance | Solid |
| Color | White to off-white |
| SMILES | O=C(CC1=CC=CC(OC(F)(F)F)=C1)NC2=C(C=CC(C3=CC=C4N=C(SC4=C3)NC(C5CC5)=O)=C2)F |
| Target | RIPK1 |
| Signaling Pathway | Apoptosis; MAPK/ERK Pathway |
| Storage | Powder: -20°C, 3 years; 4°C, 2 years. In solvent: -80°C, 6 months; -20°C, 1 month. |
| Shipping | Room temperature in continental US; may vary elsewhere. |
Biological Activity
Activity & Target
|
RIPK1 17 nM (Kd) |
Literature Cited
Sources cited in this description and in the In Vitro & In Vivo Data tab. Peer-reviewed publications that used this product are listed under References.
Safety
For Research Use Only. Not for use in diagnostic or therapeutic procedures, and not for human or veterinary use. Handle in accordance with the Safety Data Sheet and your institution's chemical hygiene plan.
In Vitro
RIPK1-IN-17, built by joining two moieties directly through a biphenyl-type linker, is markedly more active against necroptosis in HT-29 cells (EC50 = 0.017 μM) and shows no significant cytotoxicity at the concentrations tested (CC50 > 10 μM)[1]. RIPK1-IN-17 shows significantly enhanced inhibitory activity toward RIPK1 (Kd = 17 nM) and no apparent activity toward RIPK3 at 5000 nM[1]. In HT-29 cells, RIPK1-IN-17 (0.015-0.5 μM) protects against necroptosis induced by TNF-α, Cycloheximide, and Z-VAD-FMK (TCZ) in a dose-dependent manner[1]. In murine L929 cells, RIPK1-IN-17 (0.015-0.5 μM) protects against necroptosis induced by Z-VAD-FMK at a lower concentration[1]. RIPK1-IN-17 (0.1-1 μM) gives no protection against apoptosis induced by Cycloheximide or Smac mimetic in HT-29 cells, even at concentrations up to 1 μM[1]. In HT-29 cells, RIPK1-IN-17 (1 nM-1 μM, 0-6 h) completely inhibits RIPK1 phosphorylation at 1 μM over 6 hours, and at doses of 1 to 1000 nM for 6 hours it dose-dependently inhibits phosphorylation of RIPK1, RIPK3, and MLKL[1].
Western Blot Analysis[1]
| Cell Line | HT-29 cells |
|---|---|
| Concentration | 1 μM |
| Incubation Time | 0 h, 2 h, 4 h, 6 h |
| Result | Completely inhibited RIPK1 phosphorylation and subsequently reduced downstream phosphorylation of RIPK3 and MLKL. |
Western Blot Analysis[1]
| Cell Line | HT-29 cells |
|---|---|
| Concentration | 1 nM, 10 nM, 100 nM, 1000 nM |
| Incubation Time | 6 h |
| Result | Dose-dependently inhibited TSZ-induced phosphorylation of RIPK1, RIPK3, and MLKL. |
In Vivo
In mice, a single oral gavage of RIPK1-IN-17 (1.25-5 mg/kg, oral gavage, once) effectively protects against TNFα-induced SIRS, shown by prevention of hypothermia, improved survival, and lower levels of the key proinflammatory cytokines IL-6 and IL-1β[1]. In mice, RIPK1-IN-17 (100 mg/kg, 200 mg/kg, oral gavage, once) is well tolerated and safe at doses far above its effective therapeutic dose, with no acute toxic reactions or organ damage[1].
| Animal Model | Male C57BL/6 J mice aged 6-8 weeks injected mTNFα[1]. |
|---|---|
| Dosage | 1.25 mg/kg, 2.5 mg/kg, 5 mg/kg |
| Administration | Oral gavage, once, two hours before injection of mTNFα |
| Result | The survival rates of the SIRS mice were indicated as 70, 80, and 100%. Significantly shielded the SIRS mice from hypothermia and death at the dosages of 1.25, 2.5, or 5 mg/kg. Significantly reduced the levels of IL-6 and IL-1β in different tissues. Dose-relatedly decreased the levels of IL-6 in the heart, liver, spleen, lung, kidney, intestine, and brain. Led to a significant decrease in IL-1β levels in the spleen, lung, and intestine, which are the main organs affected in SIRS models. Significantly decreased serum levels of IL-1β (three doses) and IL-6 (high dose). |
| Animal Model | Male C57BL/6 J mice aged 6-8 weeks[1]. |
|---|---|
| Dosage | 100 mg/kg, 200 mg/kg |
| Administration | Oral gavage, once |
| Result | No deaths or weight loss were observed after intragastric administration of the doses. Exhibited normal behavior throughout the 2-week study period. Hematoxylin-Eosin (HE) staining assays revealed no significant pathological damage to the six vital organs (heart, liver, spleen, lung, kidney, and brain). |
Data provided by the manufacturer. Numbered citations refer to the Literature Cited list in the product description.
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