Synonyms: (Rac)-RP-6306
Compound class:
Synthetic organic
Comment: Lunresertib (RP-6306) is the first lead candidate in the class of protein kinase, membrane associated tyrosine/threonine 1 (PKMYT1) inhibitors to be advanced for clinical evaluation [3]. It is orally bioavailable and selective for PKMYT1, and it is active in appropriate preclinical xenograft models of solid tumours [1]. PKMYT1 is a negative regulator of CDK1 [2], and its inhibition induces activation of CDK1 selectively in CCNE1-overexpressing cells; CCNE1 being a chromosome 19q12 locus that is amplified in multiple tumour types and which is a marker of poor prognosis and/or insensitivity to cytotoxic oncotherapies. As a monotherapy lunresertib induces synthetic lethality in combination with CCNE1 amplification (or alongside inactivating mutations in FBXW7 and PPP2R1A).
Structure note: the INN record for lunresertib does not specify the (S) stereo specification that is declared in the original disclosure of RP-6306's chemical structure [3]. We depict the racaemic mixture with no defined stereo centers. |
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No information available. |
Summary of Clinical Use |
RP-6306 has been advanced to early phase clinical evaluations to determine efficacy against genetically selected advanced solid tumours. It is being tested as a monotherapy and in combination with standard chemotherapies (FOLFIRI, gemcitabine), or with the investigational ATR inhibitor camonsertib. |
Clinical Trials | |||||
Clinical Trial ID | Title | Type | Source | Comment | References |
NCT05147350 | Study of RP-6306 With FOLFIRI in Advanced Solid Tumors | Phase 1 Interventional | Repare Therapeutics | ||
NCT04855656 | Study of RP-6306 Alone or in Combination With RP-3500 in Patients With Advanced Solid Tumors | Phase 1 Interventional | Repare Therapeutics | ||
NCT05147272 | Study of RP-6306 With Gemcitabine in Advanced Solid Tumors | Phase 1 Interventional | Repare Therapeutics | ||
NCT05605509 | RP-6306 in Patients With Advanced Cancer | Phase 2 Interventional | Canadian Cancer Trials Group |