Ocadusertib

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Ocadusertib

CAS 2382811-41-6

MF C25H25N5O4 MW 459.5 g/mol

5-benzyl-N-[(3S)-7-(3-hydroxy-3-methylbut-1-ynyl)-5-methyl-4-oxo-2,3-dihydro-1,5-benzoxazepin-3-yl]-1H-1,2,4-triazole-3-carboxamide

5-benzyl-N-[(3S)-7-(3-hydroxy-3-methylbut-1-yn-1-yl)-5-methyl-4-oxo-2,3,4,5-tetrahydro-1,5-benzoxazepin-3-yl]-1H-1,2,4-triazole-3-carboxamide
serine/threonine kinase inhibitor, LY3871801, R552, LY 3871801, R 552, S53J4A7ME4

OriginatorRigel Pharmaceuticals
DeveloperEli Lilly and Company; Rigel Pharmaceuticals
ClassAnti-inflammatories; Antirheumatics; Small molecules
Mechanism of ActionRIPK1 protein inhibitors
Phase IIRheumatoid arthritis
No development reportedUnspecified
28 Mar 2025No recent reports of development identified for phase-I development in Unspecified(In volunteers) in Singapore (PO, Suspension)
14 Nov 2024Pharmacodynamics data from preclinical trials in Rheumatoid arthritis presented at the ACR Convergence 2024 (ACR-2024)
14 Nov 2024Safety and pharmacokinetics data from a phase I trial in Rheumatoid arthritis presented at the ACR Convergence 2024 (ACR-2024)

Ocadusertib (LY3871801/R552) is an oral, potent, and selective small-molecule RIPK1 inhibitor developed by Rigel Pharmaceuticals and Eli Lilly for autoimmune and inflammatory diseases. It is currently in Phase 2 clinical trials for treating moderate-to-severe rheumatoid arthritis. ACR Meeting Abstracts +4

Key Aspects of Ocadusertib:

Mechanism of Action: It inhibits receptor-interacting serine/threonine-protein kinase 1 (RIPK1), which blocks necroptotic (cell death) responses and, consequently, reduces inflammation.
Target Indications: Primarily focused on rheumatoid arthritis, it has also been investigated for psoriasis and general inflammatory joint conditions.
Development Status: As of late 2025, it is in Phase 2 clinical trials (NCT05848258), with previous trials evaluating its safety, tolerability, and pharmacokinetics in healthy volunteers.
Characteristics: It is designed to be a selective inhibitor, showing no significant inhibition in a broad panel of other kinases. ACR Meeting Abstracts +3

Ocadusertib is a small molecule drug. The usage of the INN stem ‘-sertib’ in the name indicates that Ocadusertib is a serine/threonine kinase inhibitor. Ocadusertib is under investigation in clinical trial NCT05848258 (An Adaptive Phase 2a/2b Study of LY3871801 in Adult Participants With Rheumatoid Arthritis). Ocadusertib has a monoisotopic molecular weight of 459.19 Da.

An Adaptive Phase 2a/2b Study of LY3871801 in Adult Participants With Rheumatoid ArthritisCTID: NCT05848258Phase: Phase 2Status: RecruitingDate: 2025-12-09
A Study of LY3871801 in Healthy Asian and Non-Asian ParticipantsCTID: NCT05960851Phase: Phase 1Status: CompletedDate: 2024-01-10
A Drug Interaction Study of LY3871801 in Healthy ParticipantsCTID: NCT05602675Phase: Phase 1Status: CompletedDate: 2023-04-18
A Study of LY3871801 in Healthy ParticipantsCTID: NCT05222399Phase: Phase 1Status: CompletedDate: 2022-03-18

SYN

US10815206, Compound I-69

PAT

US12065447, Compound ZB-R-76

PAT

WO 2014/125444

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2014125444&_cid=P20-MM02QM-54301-1

PAT

I-30: (S)-5-benzyl-N-(7-(3-hydroxy-3-methylbut-1-yn-1-yl)-5-methyl-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]oxazepin-3-yl)-1H-1,2,4-triazole-3-carboxamide;

(S)-5-benzyl-N-(5-methyl-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]oxazepin-3-yl)-4H-1,2,4-triazole-3-carboxamide (WO 2014/125444), having a structure as illustrated below, was used as a comparative compound and was examined using a similar protocol as described by WO 2014/125444. This comparison

compound exhibited 93% inhibition at a dose of 30 mg/kg according to WO 2014/125444; however, in the inventors hands, the compound inhibited only 70% at 30 mg/kg. In comparison, compound I-30 of the present disclosure achieved greater than 85% inhibition at a dose of just 5 mg/kg using the similar assay protocol described above.

PAT