CHEK1 checkpoint kinase 1
ENSG00000149554 · protein coding · Open Targets profile
Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest and activation of DNA repair in response to the presence of DNA damage or unreplicated DNA (PubMed:11535615, PubMed:12399544, PubMed:12446774, PubMed:14559997, PubMed:14988723, PubMed:15311285, PubMed:15650047, PubMed:15665856, PubMed:32357935). May also negatively regulate cell cycle progression during unperturbed cell cycles (PubMed:11535615, PubMed:12399544, PubMed:12446774, PubMed:14559997, PubMed:14988723, PubMed:15311285, PubMed:15650047, PubMed:15665856). This regulation is achieved by a number of mechanisms that together help to preserve the integrity of the genome (PubMed:11535615, PubMed:12399544, PubMed:12446774, PubMed:14559997, PubMed:14988723, PubMed:15311285, PubMed:15650047, PubMed:15665856). Recognizes the substrate consensus sequence [R-X-X- S/T] (PubMed:11535615, PubMed:12399544, PubMed:12446774, PubMed:14559997, PubMed:14988723, PubMed:15311285, PubMed:15650047, PubMed:15665856). Binds to and phosphorylates CDC25A, CDC25B and CDC25C (PubMed:12676583, PubMed:12676925, PubMed:12759351, PubMed:14559997, PubMed:14681206, PubMed:19734889, PubMed:9278511). Phosphorylation of CDC25A at 'Ser-178' and 'Thr-507' and phosphorylation of CDC25C at 'Ser-216' creates binding sites for 14-3-3 proteins which inhibit CDC25A and CDC25C (PubMed:9278511). Phosphorylation of CDC25A at 'Ser- 76', 'Ser-124', 'Ser-178', 'Ser-279' and 'Ser-293' promotes proteolysis of CDC25A (PubMed:12676583, PubMed:12676925, PubMed:12759351, PubMed:14681206, PubMed:19734889, PubMed:9278511). Phosphorylation of CDC25A at 'Ser-76' primes the protein for subsequent phosphorylation at 'Ser-79', 'Ser-82' and 'Ser-88' by NEK11, which is required for polyubiquitination and degradation of CDCD25A (PubMed:19734889, PubMed:20090422, PubMed:9278511). Inhibition of CDC25 leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression (PubMed:9278511). Also phosphorylates NEK6 (PubMed:18728393). Binds to and phosphorylates RAD51 at 'Thr-309', which promotes the release of RAD51 from BRCA2 and enhances the association of RAD51 with chromatin, thereby promoting DNA repair by homologous recombination (PubMed:15665856). Phosphorylates multiple sites within the C-terminus of TP53, which promotes activation of TP53 by acetylation and promotes cell cycle arrest and suppression of cellular proliferation (PubMed:10673501, PubMed:15659650, PubMed:16511572). Also promotes repair of DNA cross-links through phosphorylation of FANCE (PubMed:17296736). Binds to and phosphorylates TLK1 at 'Ser-743', which prevents the TLK1-dependent phosphorylation of the chromatin assembly factor ASF1A (PubMed:12660173, PubMed:12955071). This may enhance chromatin assembly both in the presence or absence of DNA damage (PubMed:12660173, PubMed:12955071). May also play a role in replication fork maintenance through regulation of PCNA (PubMed:18451105). May regulate the transcription of genes that regulate cell-cycle progression through the phosphorylation of histones (By similarity). Phosphorylates histone H3.1 (to form H3T11ph), which leads to epigenetic inhibition of a subset of genes (By similarity). May also phosphorylate RB1 to promote its interaction with the E2F family of transcription factors and subsequent cell cycle arrest (PubMed:17380128). Phosphorylates SPRTN, promoting SPRTN recruitment to chromatin (PubMed:31316063). Reduces replication stress and activates the G2/M checkpoint, by phosphorylating and inactivating PABIR1/FAM122A and promoting the serine/threonine-protein phosphatase 2A-mediated dephosphorylation and stabilization of WEE1 levels and activity (PubMed:33108758). {ECO:0000250|UniProtKB:O35280, ECO:0000269|PubMed:10673501, ECO:0000269|PubMed:11535615, ECO:0000269|PubMed:12399544, ECO:0000269|PubMed:12446774, ECO:0000269|PubMed:12660173, ECO:0000269|PubMed:12676583, ECO:0000269|PubMed:12676925, ECO:0000269|PubMed:12759351, ECO:0000269|PubMed:12955071, ECO:0000269|PubMed:14559997, ECO:0000269|PubMed:14681206, ECO:0000269|PubMed:14988723, ECO:0000269|PubMed:15311285, ECO:0000269|PubMed:15650047, ECO:0000269|PubMed:15659650, ECO:0000269|PubMed:15665856, ECO:0000269|PubMed:16511572, ECO:0000269|PubMed:17296736, ECO:0000269|PubMed:17380128, ECO:0000269|PubMed:18451105, ECO:0000269|PubMed:18728393, ECO:0000269|PubMed:19734889, ECO:0000269|PubMed:20090422, ECO:0000269|PubMed:31316063, ECO:0000269|PubMed:32357935, ECO:0000269|PubMed:33108758, ECO:0000269|PubMed:9278511}.
Each band is a group of drugs. It runs from the kind of drug on the left to the furthest stage that drug has reached in any disease on the right. Thicker bands mean more drugs.
Approved bands are highlighted. Withdrawn means the drug was pulled from the market or from development. A combined phase counts as the later one (Phase 1/2 is shown as Phase 2). Hover a band for the drug names. Source: Open Targets Platform, fetched live.
Each row is a cancer, strongest overall evidence first. The two dots show how strong the inherited (germline) and tumour-mutation (somatic) evidence is; the line between them is the gap.
Scores run from 0 (no evidence) to 1 (strongest). A missing dot at 0 means Open Targets holds no evidence of that kind. Source: Open Targets Platform, fetched live.
Tractability
- Small molecule
- Advanced Clinical, Structure with Ligand, High-Quality Ligand, High-Quality Pocket, Druggable Family
- PROTAC
- Literature, UniProt Ubiquitination, Database Ubiquitination, Small Molecule Binder
gnomAD loss of function constraint: o/e 0.5318800210952759 (upper bound 0.7144200205802917). Low values mean loss of function is poorly tolerated, a safety flag for inhibition.
Who runs trials of these drugs
Principal investigators and study chairs on 6 registry trials, updated in the last three years, of the most advanced drugs against CHEK1 (rabusertib, prexasertib, SCH-900776, UCN-01), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Christine ChungMoffitt Cancer Center · 1 of 1 trials Phase 2+
- Emily SlotkinMemorial Sloan Kettering Cancer Center · 1 of 1 trials Phase 2+
- Isabelle Ray-CoquardCentre Leon Berard · 1 of 1 trials Phase 2+
- Joyce A O'ShaughnessyBaylor Scott and White University Medical Center · 1 of 1 trials Phase 2+
- Panagiotis KonstantinopoulosDana-Farber Cancer Institute (DFCI) · 1 of 1 trials Phase 2+
- Cynthia J WetmoreCOG Phase I Consortium · 0 of 1 trials Phase 2+
- Giles W. RobinsonSt. Jude Children's Research Hospital · 0 of 1 trials Phase 2+
Registry trials of rabusertib, prexasertib, SCH-900776, UCN-01 updated in the last three years, counted by the country group of their listed sites. A trial with sites in several groups counts in each; 5 of 6 have all sites in one country.
Site counts are not patients per country, and trials registered only outside ClinicalTrials.gov are not covered. Where sites are is a fact about the record, not a judgement of its quality. Europe is the EU and EEA, the UK and Switzerland. Source: ClinicalTrials.gov, fetched live.
12 trials of drugs against CHEK1 were stopped early; 3 give no reason
Terminated, withdrawn and suspended interventional trials of rabusertib, prexasertib, SCH-900776, UCN-01, PF-00477736, RG-7602, RG-7741, XL-844, AZD-7762, newest update first, live from ClinicalTrials.gov. Each reason is quoted exactly as the registry gives it; we do not sort reasons into safety, efficacy or business. Dates are the last registry update. Showing the 12 most recent of 12.
- terminated · 2022-09-10 · National Cancer Institute (NCI) · matched by the registry's drug synonyms“Eli Lilly prematurely terminated the study.”
- terminated · 2019-06-12 · Dana-Farber Cancer Institute · Prexasertib“Sponsor Decision”
- terminated · 2018-08-27 · Merck Sharp & Dohme LLC · matched by the registry's drug synonymsNo reason given
- terminated · 2017-05-15 · National Cancer Institute (NCI) · UCN-01 (7-hydroxystaurosporine)“IND was withdrawn by CTEP due to low accrual and cost of maintaining the IND.”
- terminated · 2015-08-21 · Exelixis · matched by the registry's drug synonymsNo reason given
- terminated · 2015-03-02 · National Cancer Institute (NCI) · matched by the registry's drug synonyms“Early termination for discouraging results”
- terminated · 2013-07-09 · National Cancer Institute (NCI) · matched by the registry's drug synonymsNo reason given
- withdrawn · 2012-08-28 · Dartmouth-Hitchcock Medical Center · matched by the registry's drug synonyms“Insufficient population of eligible patients.”
- terminated · 2012-04-03 · Pfizer · PF-00477736“See termination reason in detailed description.”
- terminated · 2011-02-11 · AstraZeneca · matched by the registry's drug synonyms“Termination of the study was made after a full review of program data and assessment of the current risk-benefit profile.”
- terminated · 2011-02-07 · AstraZeneca · matched by the registry's drug synonyms“Termination of the study was made after a full review of program data and assessment of the current risk-benefit profile.”
- terminated · 2008-06-04 · Exelixis · matched by the registry's drug synonyms“Study closed due to slow enrollment”
Paediatric incentives and obligations for CHEK1's drugs
For rabusertib, prexasertib, SCH-900776, UCN-01, PF-00477736, RG-7602, RG-7741, XL-844, AZD-7762: what EMA and FDA publish about paediatric plans, orphan status and pediatric approvals, and how many registered studies take children. Each line is a yes, no or not published fact from the record linked under it; none of it is a forecast.
- FDA pediatric target list: yes · CHEK1 is on the list. Membership alone neither requires nor waives a pediatric study.Rule: Target is on FDA's Pediatric Molecular Target List (relevant targets). Source: FDA Pediatric Molecular Target List (Listed as February 2026 on the FDA Pediatric Oncology page; the file served is 9.7.22_the_relevant_molecular_target_list.xlsx, whose Summary of Changes sheet is headed 'SEPTEMBER 2022 UPDATE' (footnote date 2022-09-01)), 2026-11-11
- EU paediatric investigation plan: no · No EMA paediatric investigation plan decision names rabusertib, prexasertib, sch-900776, ucn-01, pf-00477736, rg-7602, rg-7741, xl-844, azd-7762Rule: An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name. Source: EMA data download (dated snapshot), 2026-11-11
- EU orphan designation: no · No EU orphan designation names rabusertib, prexasertib, sch-900776, ucn-01, pf-00477736, rg-7602, rg-7741, xl-844, azd-7762Rule: An EU orphan designation lists the drug as its active substance (exact name) or belongs to a medicine that does; withdrawn and expired designations are listed with their status. Source: EMA data download (dated snapshot), 2026-11-11
- Authorised in the EU: no · EMA lists no centrally authorised medicine of rabusertib, prexasertib, sch-900776, ucn-01, pf-00477736, rg-7602, rg-7741, xl-844, azd-7762Rule: An EMA medicine record lists the drug as its active substance or INN, exact name; national-only authorisations are not in this file. Source: EMA data download (dated snapshot), 2026-11-11
- FDA orphan designation: not published · FDA's orphan designation database turns away automated requests, so this app does not read it; search it by hand at the linkRule: Would be: an FDA orphan designation names the drug. Source: FDA orphan designations search
- FDA pediatric oncology approval: no · FDA's table lists no pediatric approval of rabusertib, prexasertib, sch-900776, ucn-01, pf-00477736, rg-7602, rg-7741, xl-844, azd-7762Rule: FDA's Pediatric Oncology Drug Approvals table names the drug. Source: FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03), 2026-11-11
- Registered studies open to children: yes · 6 interventional studies of rabusertib, prexasertib, sch-900776, ucn-01, pf-00477736, rg-7602, rg-7741, xl-844, azd-7762 include patients under 18; 0 are recruiting, not yet recruiting or activeRule: The registry's age group includes Child (birth to 17 years), which also counts studies that set no minimum age. Source: ClinicalTrials.gov search, 2026-11-11
Rare pediatric disease voucher. FDA, content current as of 29 Apr 2026: “As of February 3, 2026, enactment of the Consolidated Appropriations Act, 2026, the rare pediatric disease PRV program will sunset after September 30, 2029. FDA may not award any PRVs under this program after September 30, 2029.” Voucher sale prices are not shown here; they appear only as company-reported news. FDA: Rare Pediatric Disease Designation and Priority Review Voucher Programs
All 9 drugs and clinical candidates as a table
Each drug, stage and indication links to its Open Targets record, where the trials and approvals behind it are listed. Salt forms (for example a mesylate) are listed as Open Targets records them, as separate entries.