2. Cell Cycle/DNA Damage Immunology/Inflammation Apoptosis NF-κB
  3. NEKs NOD-like Receptor (NLR) Caspase Apoptosis Pyroptosis NF-κB
  4. Ofirnoflastum

Ofirnoflastum  (Synonyms: Ofirnoflast; HT-6184)

Cat. No.: HY-159520 Purity: 99.93%
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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.

For research use only. We do not sell to patients.

Ofirnoflastum

Ofirnoflastum Chemical Structure

CAS No. : 2731294-23-6

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Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO
ready for reconstitution
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Based on 1 publication(s) in Google Scholar

Ofirnoflastum Related Antibodies

Top Publications Citing Use of Products

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NEK1 NEK2 NEK4 NEK6 NEK7

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NLRP3 NLRP1 NOD1 NOD2

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Caspase 1 Caspase 2 Caspase 3 Caspase 4 Caspase 5 Caspase 6 Caspase 7 Caspase 8 Caspase 9 Caspase 10 Caspase 12 Caspase Caspase 11 Caspase-13

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NF-κB NF-κB1/p50 RelA/p65 RelB c-Rel

  • Biological Activity

  • Purity & Documentation

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  • Customer Review

Description

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[1][2][3][4][5].

IC50 & Target[3][4]

NEK7

46 nM (IC50)

Caspase 8

 

Caspase-1

 

NLRP3

 

In Vitro

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.

Ofirnoflastum Related Antibodies

Immunofluorescence[3]

Cell Line: THP-1-ASC-GFP cells
Concentration: 0.01-10 μM
Incubation Time: 3 h LPS priming; 2 h pre-incubation; 1 h nigericin stimulation
Result: Dose-dependently reduced ASC-GFP speck formation, with an IC50 of 0.194 μM.

ELISA Assay[3]

Cell Line: Human iPSC-derived microglial cells
Concentration: 1 μM
Incubation Time: 5 h LPS priming (final hour with compound); 45 min ATP stimulation
Result: Strongly inhibited ATP-induced IL-1β secretion, with levels reduced to near baseline.
Parmacokinetics
Species Dose Route C0 T1/2 AUClast AUCinf CL Vdss Cmax Tmax F
Mice[3] 0.5 mg/kg i.v. 634.3 ng/mL 1.31 h 530.3 ng·h/mL 537.3 ng·h/mL 15.7 mL/min/kg 1.25 L/kg / / /
Mice[3] 10 mg/kg p.o. / 2.7 h 14280.3 ng·h/mL 16324.8 ng·h/mL / / 2684.1 ng/mL 2 h 134.7 %
In Vivo

Ofirnoflastum (1-5 mg/kg; p.o.; twice daily; day 0 through day 7) reduces disease activity, histopathological damage, and inflammatory cytokine levels in a mouse model of DSS (HY-116282C)-induced colitis, with maximal efficacy achieved at the lowest tested dose[3].
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.

Animal Model: C57BL/6 (female, 11-12 weeks old, 20-25 g, DSS-induced colitis)[3]
Dosage: 1 mg/kg; 2 mg/kg; 5 mg/kg
Administration: p.o.; twice daily; day 0 through day 7
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.
Molecular Weight

501.44

Formula

C23H19F4N7O2
CAS No.
Appearance

Solid

Color

White to off-white

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
Shipping

Room temperature in continental US; may vary elsewhere.
Storage
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 6 months
-20°C 1 month
Solvent & Solubility
In Vitro: 

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.

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 1.9943 mL 9.9713 mL 19.9426 mL
5 mM 0.3989 mL 1.9943 mL 3.9885 mL
View the 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.

  • Molarity Calculator

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Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

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Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

Concentration (start)

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In Vivo:

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.

  • Protocol 1

    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.
  • Protocol 2

    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.
In Vivo Dissolution Calculator
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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Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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).
Calculation results:
Working solution concentration: mg/mL
Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
 If the continuous dosing period exceeds half a month, please choose this protocol carefully.
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.
Purity & Documentation
References

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
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Ofirnoflastum Related Classifications

Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

Ofirnoflastum2731294-23-6Ofirnoflast HT-6184HT6184HT 6184HT-6184NEKsNOD-like Receptor (NLR)CaspaseApoptosisPyroptosisNF-κBNIMA–related KinasesNIMA (never in mitosis gene a)-related Expressed KinasesNuclear factor-κBNuclear factor-kappaBASC specksNLRP3NEK7myelodysplastic syndromesNLRP3 inflammasomeTNFIL-1βcaspase-1caspase-8Inhibitorinhibitorinhibit

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