What is IDH1 inhibitor?

Ivosidenib is the first approved oral, targeted, small-molecule inhibitor of the isocitrate dehydrogenase 1 (IDH1) mutation seen in AML. IDH1 mutations have been associated with significantly worse outcomes in disease-free survival, relapse-free survival, and overall survival (NCCN, 2018).

Is Ivosidenib approved for cholangiocarcinoma?

In August, the FDA approved ivosidenib tablets (Tibsovo) for the treatment of IDH1-mutated cholangiocarcinoma, making it the first agent with such an indication. Since its approval, ivosidenib has offered patients with IDH1-mutated cholangiocarcinoma a second- or third-line option where none existed before.

What is IDH1 and IDH2?

Isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) are key metabolic enzymes that convert isocitrate to α-ketoglutarate. IDH1/2 mutations define distinct subsets of cancers, including low-grade gliomas and secondary glioblastomas, chondrosarcomas, intrahepatic cholangiocarcinomas, and hematologic malignancies.

Is Enasidenib FDA approved?

The U.S. Food and Drug Administration (FDA) approved enasidenib, an isocitrate dehydrogenase-2 (IDH2) inhibitor, for adults with relapsed/refractory IDH2-mutated acute myeloid leukemia (AML).

What is IDH2 mutation?

The IDH2 gene mutations involved in CN-AML are called somatic mutations; they are found only in cells that become cancerous and are not inherited. These mutations change single protein building blocks (amino acids) in the isocitrate dehydrogenase 2 enzyme.

Is IDH1 mutation good?

A systematic review reported similar results. Based on the review of current literature IDH1 mutation is an independent factor for longer overall survival (OS) and progression free survival (PFS) in GBM patients when compared to wild-type IDH1. The prognostic significance opens up new avenues for treatment.

Is ivosidenib a chemotherapy drug?

Ivosidenib (Tibsovo) – Chemotherapy Drug Information | Chemocare.

Is Tibsovo FDA approved?

On August 25, 2021, FDA approved ivosidenib (brand name Tibsovo) for adult patients with previously treated, locally advanced or metastatic cholangiocarcinoma with an isocitrate dehydrogenase-1 mutation as detected by an FDA-approved test.

What does IDH1 positive mean?

The determination of the IDH1 mutation status strongly supports the differential diagnosis between an anaplastic glioma and a glioblastoma. Furthermore, the detection of even single IDH1 R132H-positive cells clearly supports the diagnosis of a diffusely infiltrating glioma.

What is IDH1 wild type?

As a reversible dehydrogenase, wild-type IDH1 is a homodimeric enzyme that reversibly catalyzes isocitrate into α-KG accompanied with the generation of NADPH from NADP+ in cytosol, which has been proven to be physiologically crucial in the metabolism of lipids, amino acids, and sugars in cells.

Is Ivosidenib an IDH1 inhibitor?

Ivosidenib, an IDH1 inhibitor, in a patient with recurrent, IDH1-mutant glioblastoma: a case report from a Phase I study NCBI Skip to main content

What do we know about small molecule inhibitors targeting IDH2 and IDH1?

Phase I/II trials have shown evidence of safety, tolerability, and encouraging evidence of efficacy of two small molecule inhibitors targeting IDH2 and IDH1 gene mutations, respectively enasidenib and ivosidenib.

Can IDH inhibitors be used in gliomas?

This has led to the US FDA (MD, USA) approval of enasidenib (AG-221, an IDH2 inhibitor) and ivosidenib (AG-120, an IDH1 inhibitor) for adult patients with AML [20–22]. Ongoing trials are investigating the role of IDH inhibitors in solid tumors, including gliomas.

How effective is Ivosidenib in the treatment of idh1-mutant AML?

Ivosidenib is a targeted, potent, oral inhibitor of the mutant IDH1 protein . Preclinical studies showed that treatment with ivosidenib decreased intracellular 2-HG level in IDH1 -mutant AML cells in vitro [ 30 ], and resulted in >84% 2-HG inhibition in human IDH1 -mutant brain tumors in a xenograft mouse model [ 31 ].