Dordaviprone

Dordaviprone
Clinical data
Trade names	Modeyso
Other names	ONC201, ONC-201
AHFS/Drugs.com	Modeyso
License data	US DailyMed: Dordaviprone;
Routes of; administration	By mouth
Drug class	Protease activator
ATC code	None;
Legal status
Legal status	US: ℞-only;
Identifiers
	IUPAC name 11-benzyl-7-[(2-methylphenyl)methyl]-2,5,7,11-tetrazatricyclo[7.4.0.02,6]trideca-1(9),5-dien-8-one;
CAS Number	1616632-77-9; as HCl: 1638178-82-1;
PubChem CID	73777259;
DrugBank	DB14844; as HCl: DBSALT003291;
ChemSpider	30904994;
UNII	9U35A31JAI; as HCl: 53VG71J90J;
KEGG	D12733; as HCl: D12734;
ChEBI	CHEBI:232328;
ChEMBL	ChEMBL4297310;
Chemical and physical data
Formula	C24H26N4O
Molar mass	386.499 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC1=CC=CC=C1CN2C(=O)C3=C(CCN(C3)CC4=CC=CC=C4)N5C2=NCC5;
	InChI InChI=1S/C24H26N4O/c1-18-7-5-6-10-20(18)16-28-23(29)21-17-26(15-19-8-3-2-4-9-19)13-11-22(21)27-14-12-25-24(27)28/h2-10H,11-17H2,1H3; Key:VLULRUCCHYVXOH-UHFFFAOYSA-N; Key:HKBXPCQCBQFDML-UHFFFAOYSA-N;

Dordaviprone, sold under the brand name Modeyso is an anti-cancer medication used for the treatment of diffuse midline glioma (a type of brain tumor).^[1]^[2] Dordaviprone is a protease activator of the mitochondrial caseinolytic protease P.^[1] It is dopamine receptor D2 antagonist and an allosteric activator of the mitochondrial caseinolytic protease P.^[3]

Dordaviprone was approved for medical use in the United States in August 2025.^[2] It is the first approval of a systemic therapy for H3 K27M-mutant diffuse midline glioma by the US Food and Drug Administration.^[2]

Medical uses

Dordaviprone is indicated for the treatment of people with diffuse midline glioma harboring an H3 K27M mutation with progressive disease following prior therapy.^[1]^[2]

History

Efficacy was evaluated in an integrated efficacy population of 50 participants with recurrent H3 K27M-mutant diffuse midline glioma enrolled across five open-label, non-randomized clinical trials conducted in the US (ONC006 [NCT02525692], ONC013 [NCT03295396], ONC014 [NCT03416530], ONC016 [NCT05392374], and ONC018 [NCT03134131]).^[2] The efficacy population comprised participants who received single-agent dordaviprone for diffuse midline glioma harboring an H3 K27M mutation and had progressive and measurable disease per Response Assessment in Neuro-Oncology-High Grade Glioma (RANO-HGG) criteria.^[2] Participants were also at least 90 days post radiation therapy, had an adequate washout period from prior anticancer therapies, a Karnofsky Performance Status/Lansky Performance Status (KPS/LPS) score ≥ 60, and stable or decreasing corticosteroid use.^[2] Participants with diffuse intrinsic pontine glioma, primary spinal tumors, atypical histologies, or cerebrospinal fluid dissemination were excluded.^[2]

The US Food and Drug Administration granted the application for dordaviprone priority review, orphan drug, rare pediatric disease, and fast track designations.^[2]

Society and culture

Legal status

Dordaviprone was approved for medical use in the United States in August 2025.^[2]^[4]

Names

Dordaviprone is the international nonproprietary name.^[5]

Dordaviprone is sold under the brand name Modeyso.^[2]^[4]

References

^ ^a ^b ^c ^d https://pp.jazzpharma.com/pi/modeyso.en.USPI.pdf
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k "FDA grants accelerated approval to dordaviprone for diffuse midline glioma". U.S. Food and Drug Administration (FDA). 6 August 2025. Retrieved 7 August 2025. This article incorporates text from this source, which is in the public domain.
^ Prabhu VV, Morrow S, Rahman Kawakibi A, Zhou L, Ralff M, Ray J, et al. (December 2020). "ONC201 and imipridones: Anti-cancer compounds with clinical efficacy". Neoplasia. 22 (12). New York, N.Y.: 725–744. doi:10.1016/j.neo.2020.09.005. PMC 7588802. PMID 33142238.
^ ^a ^b "Jazz Pharmaceuticals Announces U.S. FDA Approval of Modeyso (dordaviprone) as the First and Only Treatment for Recurrent H3 K27M-mutant Diffuse Midline Glioma" (Press release). Jazz Pharmaceuticals. 6 August 2025. Retrieved 10 August 2025 – via PR Newswire.
^ World Health Organization (2023). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 89". WHO Drug Information. 37 (1). hdl:10665/366661.

External links

Clinical trial number NCT02525692 for "Oral ONC201 in Adult Recurrent Glioblastoma" at ClinicalTrials.gov
Clinical trial number NCT03295396 for "ONC201 in Adults With Recurrent H3 K27M-mutant Glioma" at ClinicalTrials.gov
Clinical trial number NCT03416530 for "ONC201 in Pediatric H3 K27M Gliomas" at ClinicalTrials.gov
Clinical trial number NCT05392374 for "Expanded Access Use of ONC201 in a Patient With Diffuse Intrinsic Pontine Gliomas" at ClinicalTrials.gov
Clinical trial number NCT03134131 for "Expanded Access to ONC201 for Patients With H3 K27M-mutant and/or Midline High Grade Gliomas" at ClinicalTrials.gov

[Modeyso_FDA_label-1] ttps://pp.jazzpharma.com/pi/modeyso.en.USPI.pdf

[FDA_20250806-2] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k "FDA grants accelerated approval to dordaviprone for diffuse midline glioma". U.S. Food and Drug Administration (FDA). 6 August 2025. Retrieved 7 August 2025. This article incorporates text from this source, which is in the public domain.

[pmid33142238-3] Prabhu VV, Morrow S, Rahman Kawakibi A, Zhou L, Ralff M, Ray J, et al. (December 2020). "ONC201 and imipridones: Anti-cancer compounds with clinical efficacy". Neoplasia. 22 (12). New York, N.Y.: 725–744. doi:10.1016/j.neo.2020.09.005. PMC 7588802. PMID 33142238.

[Jazz_PR-4] "Jazz Pharmaceuticals Announces U.S. FDA Approval of Modeyso (dordaviprone) as the First and Only Treatment for Recurrent H3 K27M-mutant Diffuse Midline Glioma" (Press release). Jazz Pharmaceuticals. 6 August 2025. Retrieved 10 August 2025 – via PR Newswire.

[5] World Health Organization (2023). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 89". WHO Drug Information. 37 (1). hdl:10665/366661.

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