Mutant IDH1/NAMPT-IN-1
Mutant IDH1/NAMPT-IN-1 (Compound 23h) is a dual inhibitor of mutant isocitrate dehydrogenase 1 (mutant IDH1) (IC50=14.93 nM) and nicotinamide phosphoribosyltransferase (NAMPT) (IC50=12.56 nM). Mutant IDH1/NAMPT-IN-1 can induce apoptosis. Mutant IDH1/NAMPT-IN-1 crosses the blood-brain barrier effectively.
For research use only. We do not sell to patients.
- CAS No.: 3040122-14-0
- Formula: C30H29FN6O4
- Molecular Weight:556.59
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
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- References
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Biological Activity
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IDH1 14.93 nM (IC50) |
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| U-87MG ATCC | IC50 |
0.32 μM
Compound: 23h
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Antiproliferative activity against human U-87 MG cells harboring IDH1 R132H mutant assessed as inhibition of cell growth incubated for 72 hrs by CCK8 assay
Antiproliferative activity against human U-87 MG cells harboring IDH1 R132H mutant assessed as inhibition of cell growth incubated for 72 hrs by CCK8 assay
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[PMID: 38651495] |
| U-87MG ATCC | IC50 |
0.42 μM
Compound: 23h
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Antiproliferative activity against human U-87 MG cells harboring wildtype IDH1 assessed as inhibition of cell growth incubated for 72 hrs by CCK8 assay
Antiproliferative activity against human U-87 MG cells harboring wildtype IDH1 assessed as inhibition of cell growth incubated for 72 hrs by CCK8 assay
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[PMID: 38651495] |
| U-87MG ATCC | IC50 |
0.47 μM
Compound: 23h
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Antiproliferative activity against human U-87 MG cells harboring IDH1 R132H mutant assessed as inhibition of cell growth incubated for 48 hrs by CCK8 assay
Antiproliferative activity against human U-87 MG cells harboring IDH1 R132H mutant assessed as inhibition of cell growth incubated for 48 hrs by CCK8 assay
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[PMID: 38651495] |
| U-87MG ATCC | IC50 |
0.77 μM
Compound: 23h
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Antiproliferative activity against human U-87 MG cells harboring wildtype IDH1 assessed as inhibition of cell growth incubated for 48 hrs by CCK8 assay
Antiproliferative activity against human U-87 MG cells harboring wildtype IDH1 assessed as inhibition of cell growth incubated for 48 hrs by CCK8 assay
|
[PMID: 38651495] |
| U-87MG ATCC | IC50 |
0.89 μM
Compound: 23h
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Antiproliferative activity against human U-87 MG cells harboring IDH1 R132H mutant assessed as inhibition of cell growth incubated for 24 hrs by CCK8 assay
Antiproliferative activity against human U-87 MG cells harboring IDH1 R132H mutant assessed as inhibition of cell growth incubated for 24 hrs by CCK8 assay
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[PMID: 38651495] |
| U-87MG ATCC | IC50 |
1.26 μM
Compound: 23h
|
Antiproliferative activity against human U-87 MG cells harboring wildtype IDH1 assessed as inhibition of cell growth incubated for 24 hrs by CCK8 assay
Antiproliferative activity against human U-87 MG cells harboring wildtype IDH1 assessed as inhibition of cell growth incubated for 24 hrs by CCK8 assay
|
[PMID: 38651495] |
Mutant IDH1/NAMPT-IN-1 (0.5-2 μM; 48 h) is able to dose-dependently reduce 2-HG levels in U87 MG-IDH1R132H cells[1].
Mutant IDH1/NAMPT-IN-1 shows antiproliferative activity against U87 MG IC50=1.26 μM (24 h), 0.77 μM (48 h), 0.42 μM (72 h). Antiproliferative activity against U87 MG-IDH1R132H IC50=0.89 μM (24 h), 0.47 μM (48 h), 0.32 μM (72 h)[1].
Mutant IDH1/NAMPT-IN-1 (0.5 μM; 6 h) improves the thermal stability of NAMPT and IDH1R132H in U87 MG-IDH1R132H cells[1].
Mutant IDH1/NAMPT-IN-1 (0.1-2 μM; 48 h) dose-dependently induces apoptosis in U87 MG-IDH1R132H cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:U87 MG-IDH1R132H
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Concentration:0.1 μM, 0.5 μM, 1 μM, 2 μM
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Incubation Time:48 h
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Result:The apoptosis rate at the concentration of 2 μM was significantly higher than that of the combined group of AG-120 (HY-18767) and FK866 (HY-50876).
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Cell Line:U87 MG-IDH1R132H
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Concentration:0.5 μM
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Incubation Time:6 h
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Result:Reduced the expression levels of IDH1R132H, downstream protein TET2, and NAMPT, as well as the upstream protein NAPRT. Decreased the expression of H3K4me3 and H3K27me3.
Mutant IDH1/NAMPT-IN-1 (i.v.;400 mg/kg; single dose) is safe to administer in ICR mice[1].
Pharmacokinetic Analysis in SD rats[1]
| Route | Dose (mg/kg) | t1/2 (h) | Cmax (ng/mL) | Tmax (h) | AUC0-t (ng·h/mL) | AUC0−∞ (ng·h/mL) | Cl ((L/h)/kg) | F (%) |
| i.v. | 1 | 1.16 ± 0.08 | 4065.66 ± 565.86 | 0.033 | 1933.17 ± 131.71 | 1944.08 ± 132.42 | 0.26 ± 0.02 | / |
| p.o. | 10 | 2.06 ± 0.29 | 866.57 ± 225.07 | 0.75 | 919.04 ± 40.19 | 921.26 ± 40.82 | / | 4.75% |