Ofirnoflastum
Based on 1 Customer Validation
Ofirnoflastum (Ofirnoflast) is an orally active first-in-class allosteric NEK7 inhibitor with an IC50 of 46 nM. Ofirnoflastum binds an allosteric site adjacent to NEK7’s ATP-binding pocket, induces conformational shifts, disrupts NEK7-NLRP3 binding, blocks NLRP3 inflammasome assembly, spares NEK7’s physiological functions, and suppresses caspase-1, caspase-8, NF-κB, and TNF activity. Ofirnoflastum reduces pro-inflammatory cytokine production, suppresses ASC specks, IL-1β release, pyroptotic cell death, and leukemic burden, induces apoptosis and erythroid differentiation, restores hematopoiesis, and improves outcomes in colitis models. Ofirnoflastum can be used for the research of myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia.
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- Pureté: 99.93%
- CAS No.: 2731294-23-6
- Formule: C23H19F4N7O2
- Masse moléculaire:501.44
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Stockage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Activité biologique
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Chemical Information
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Solvant et solubilité
- Pureté et documentation
- Références
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Help & FAQs
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Activité biologique
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NEK7 46 nM (IC50) |
Caspase 8 |
Caspase-1 |
NLRP3 |
Ofirnoflast (range of concentrations; 30 min pre-incubation, 3 h LPS (HY-D1056) priming, 3 h Nigericin (HY-100381) stimulation) inhibits nigericin-induced IL-1β secretion in PMA-differentiated THP-1 macrophages with an IC50 of 198 nM[3].
Ofirnoflast (range of concentrations; 30 min pre-incubation, 3 h LPS priming, 3 h Nigericin stimulation) prevents nigericin-induced pyroptotic cell death in PMA-differentiated THP-1 macrophages with an EC50 of 378 nM[3].
Ofirnoflast (0.01-10 μM; 3 h LPS priming, 2 h pre-incubation, 1 h nigericin stimulation) inhibits nigericin-induced ASC speck formation in THP-1-ASC-GFP cells with an IC50 of 0.194 μM[3].
Ofirnoflast (range of concentrations; 5 h LPS priming, final hour with compound, 30 min nigericin stimulation) inhibits nigericin-induced IL-1β secretion in human iPSC-derived microglia with an IC50 of 44 nM[3].
Ofirnoflast (1 μM; 5 h LPS priming, final hour with compound, 45 min ATP stimulation) potently inhibits ATP-induced IL-1β secretion in human iPSC-derived microglia[3].
Ofirnoflastum potently inhibits proinflammatory cytokine secretion, Caspase-1 and Caspase-8 activity, and reverses erythroid differentiation block in LPS-activated inflammatory monocytes, Tet2-mutant monocytes, CMML patient-derived cells, myeloid leukemia cell lines, and MDS patient-derived cells[4].
Ofirnoflastum's anti-inflammatory effects in myeloid leukemia cells are dependent on NEK7 expression[4].
Ofirnoflastum's anti-leukemic activity in Tet2-mutant cells and primary MDS/CMML patient-derived cells is mediated through suppression of chronic inflammation driven by the IL-1β/IL1R1 axis[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:THP-1-ASC-GFP cells
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Concentration:0.01-10 μM
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Incubation Time:3 h LPS priming; 2 h pre-incubation; 1 h nigericin stimulation
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Result:Dose-dependently reduced ASC-GFP speck formation, with an IC50 of 0.194 μM.
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Cell Line:Human iPSC-derived microglial cells
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Concentration:1 μM
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Incubation Time:5 h LPS priming (final hour with compound); 45 min ATP stimulation
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Result:Strongly inhibited ATP-induced IL-1β secretion, with levels reduced to near baseline.
Ofirnoflastum reduces MDS/AML leukemic burden by ~3-fold in patient-derived xenograft mice via suppression of inflammatory/proliferative pathways and induction of apoptosis and erythroid differentiation[4].
Ofirnoflastum reduces CMML leukemic burden by ~3-fold in patient-derived xenograft mice via suppression of inflammatory/proliferative pathways and induction of apoptosis and erythroid differentiation[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6 (female, 11-12 weeks old, 20-25 g, DSS-induced colitis)[3]
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Dosage:1 mg/kg; 2 mg/kg; 5 mg/kg
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Administration:p.o.; twice daily; day 0 through day 7
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Result:Reduced clinical Disease Activity Index (DAI) scores and histopathological damage, including epithelial degeneration, crypt injury, and immune cell infiltration.
Achieved plasma and colon concentrations exceeding in vitro EC50 values and significantly suppressed inflammasome-dependent cytokines (IL-1β, IL-18) and broader inflammatory markers (IL-6, TNF-α, IFN-γ, CXCL1, MIP1a) in both colon homogenates and plasma.
Did not yield additional benefit at the highest dose (5 mg/kg) and was associated with a slight increase in DAI and histopathology scores.
Chemical Information
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CAS No. 2731294-23-6
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Appearance Solid
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Masse moléculaire 501.44
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Formule C23H19F4N7O2
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Color White to off-white
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SMILES
O=C(NC1=C(F)C=C(C2=CN(C3CC3)C4=C2C(N)=NC=N4)C=C1)NC5=NOC(C6(C(F)(F)F)CC6)=C5
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Synonyms
Ofirnoflast; HT-6184
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvant et solubilité
DMSO : ≥ 100 mg/mL (199.43 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
* "≥" means soluble, but saturation unknown.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (4.99 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (4.99 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Pureté et documentation
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Fiche technique (286 KB)
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SDS (254 KB)
- English - EN (254 KB)
- Français - FR (254 KB)
- Deutsch - DE (254 KB)
- Norwegian - NO (254 KB)
- Español - ES (254 KB)
- Swedish - SV (254 KB)
- Italian - IT (254 KB)
- Korean - KR (254 KB)
- Portuguese - PT (254 KB)
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Instruction de manipulation (2659 KB)
Références
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 1.9943 mL | 9.9713 mL | 19.9426 mL | 49.8564 mL |
| 5 mM | 0.3989 mL | 1.9943 mL | 3.9885 mL | 9.9713 mL | |
| 10 mM | 0.1994 mL | 0.9971 mL | 1.9943 mL | 4.9856 mL | |
| 15 mM | 0.1330 mL | 0.6648 mL | 1.3295 mL | 3.3238 mL | |
| 20 mM | 0.0997 mL | 0.4986 mL | 0.9971 mL | 2.4928 mL | |
| 25 mM | 0.0798 mL | 0.3989 mL | 0.7977 mL | 1.9943 mL | |
| 30 mM | 0.0665 mL | 0.3324 mL | 0.6648 mL | 1.6619 mL | |
| 40 mM | 0.0499 mL | 0.2493 mL | 0.4986 mL | 1.2464 mL | |
| 50 mM | 0.0399 mL | 0.1994 mL | 0.3989 mL | 0.9971 mL | |
| 60 mM | 0.0332 mL | 0.1662 mL | 0.3324 mL | 0.8309 mL | |
| 80 mM | 0.0249 mL | 0.1246 mL | 0.2493 mL | 0.6232 mL | |
| 100 mM | 0.0199 mL | 0.0997 mL | 0.1994 mL | 0.4986 mL |
Ofirnoflastum Related Classifications
HY-159520 Related Classifications
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