LY-3410738

Product Description

An orally available inhibitor of mutant form of the isocitrate dehydrogenase type 1 (IDH1; IDH-1; IDH1 [NADP+] soluble), including the substitution mutation at arginine (R) in position 132, IDH1(R132), with potential antineoplastic activity. Upon oral administration, IDH1 mutant inhibitor LY3410738 specifically and covalently binds to and modifies a single cysteine (Cys269) in the allosteric binding pocket of mutant forms of IDH1, thereby inactivating IDH1. This inhibits the formation of the oncometabolite 2-hydroxyglutarate (2HG) from alpha-ketoglutarate (a-KG). This depletes 2-HG levels, prevents 2HG-mediated signaling and leads to both an induction of cellular differentiation and an inhibition of cellular proliferation in tumor cells expressing mutant forms of IDH1. In addition, LY3410738 has the ability to cross the blood-brain barrier (BBB). IDH1 mutations, including IDH1(R132) mutations, are highly expressed in certain malignancies, including gliomas; they initiate and drive cancer growth by both blocking cell differentiation and catalyzing the formation of 2HG. (Sourced from: https://www.cancer.gov/publications/dictionaries/cancer-drug/def/idh1-mutant-inhibitor-ly3410738)

Mechanisms of Action: IDH Inhibitor

Novel Mechanism: No

Modality: Small Molecule

Route of Administration: Oral

FDA Designation: None *

Approval Status: Not Approved

Approved Countries: None

Approved Indications: None

Known Adverse Events: None

Company: Eli Lilly
Company Location: INDIANAPOLIS IN 46285
Company CEO: David A. Ricks
Additonal Commercial Interests: None