THERAPY DOSSIER · th-cc0b94f9246e

R-roscovitine (seliciclib), reconstituted in DMSO

Drug · Pan cyclin-dependent kinase inhibitor targeting CDK1, CDK2, CDK5, CDK7 and CDK9 (INHIBITOR; direct interaction; disease efficacy)

Not approved Suggest a correction

Evidence & regulatory context

Mechanism: Pan cyclin-dependent kinase inhibitor targeting CDK1, CDK2, CDK5, CDK7 and CDK9 (INHIBITOR; direct interaction; disease efficacy)
Target: CHEMBL308 (CDK1); CHEMBL301 (CDK2); CHEMBL4036 (CDK5); CHEMBL3055 (CDK7); CHEMBL3116 (CDK9)
Injury models: Radiation
Reported indication: Not recorded
First approval: Not recorded
Development stage: In trials, not approved
ChEMBL record: CHEMBL14762 ↗
ChEMBL max phase: 2 / 4 (development scale, not regulatory approval)
Synonyms: Seliciclib; Roscovitine; R-roscovitine; CYC-202; AL-39256; NSC-701554
Note: Not recorded

Clinical trials 6

0 linked trials carry an injury-indication flag. These flags support record-level exploration and sit alongside the stringent aggregate counts described in Methods.

NCT03774446 ↗PHASE2recruiting

A Phase 2 Multicenter Study of Seliciclib (R-roscovitine) for Cushing Disease

Cushing Disease

Enrolment: 13 · Results not recorded

NCT02649751 ↗PHASE2terminated

Phase II dose-ranging, double-blind, placebo-controlled study of (R)-roscovitine in adults with cystic fibrosis (ROSCO-CF)

Cystic Fibrosis

Enrolment: 49 · Results not recorded

NCT02160730 ↗PHASE2terminated

Treatment of Pituitary Cushing Disease With a Selective CDK Inhibitor, R-roscovitine

Cushings Disease

Enrolment: 4 · Results not recorded

NCT00372073 ↗PHASE2terminated

A Phase IIb Randomized Study of Oral Seliciclib in Previously Treated Non-Small Cell Lung Cancer

Non-small Cell Lung Cancer

Enrolment: 187 · Results not recorded

NCT01333423 ↗PHASE1withdrawn

Phase I dose expansion of liposomal doxorubicin with seliciclib in metastatic triple negative breast cancer

Breast Cancer

Enrolment: 0 · Results not recorded

NCT00999401 ↗PHASE1completed

A Phase I Study of Oral Sapacitabine and Oral Seliciclib in Patients With Advanced Solid Tumors

Advanced Solid Tumors

Enrolment: 103 · Results not recorded

Preclinical evidence 2

2 studies reported at therapy level; 2 evidence entries itemised.

PMID 23236487 ↗2012Reported benefit

Prevention of radiation-induced salivary gland dysfunction utilizing a CDK inhibitor in a mouse model.

MouseRadiationFVBFemalen = Flow cytometry at least 9 mice per treatment; real-time RT-…Intraperitoneal injection25 mg/kg or 100 mg/kgPretreatment, 2 hours before irradiation

Model: Targeted head and neck irradiation of the salivary glands under ketamine and xylazine anaesthesia with the body shielded by lead, single 5 Gy dose from a cobalt therapeutic irradiator (Theratron-80); a separate arm used fractionated 2 Gy per day for five consecutive days (cumulative 10 Gy)

Roscovitine before irradiation increased G2/M arrest and p21 expression, transiently reduced PCNA positivity and significantly reduced cleaved caspase-3 positive acinar cells at 24 and 48 hours. Stimulated salivary flow was preserved at day 3 with 100 mg/kg and at day 30 with both doses, including…

Extraction: extract · Supplied extraction confidence: 0.92. Machine-extracted fields require source verification.

PMID 32883957 ↗2020Reported benefit

Cdk5-mediated Drp1 phosphorylation drives mitochondrial defects and neuronal apoptosis in radiation-induced optic neuropathy.

MixedRadiationBALB/cMaleIntraperitoneal (in vivo); culture medium (in vitro)In vivo: mdivi-1 3 mg/kg and roscovitine 3.5 mg/kg intraper…First dose 6 h before irradiation; in vitro drug added 2 h before irradiation

Model: Radiation-induced optic neuropathy produced by head-only X-ray irradiation (10 Gy selected after dose finding at 0, 8, 10 and 12 Gy, dose rate 600 rad/min); in vitro 6 Gy X-ray irradiation of R28 cells

Head irradiation increased phospho-Drp1 (Ser616), Fis1 and Cdk5, raised reactive oxygen species, fragmented mitochondria, reduced retinal ganglion cell numbers and outer nuclear layer thickness, and delayed and attenuated visual-evoked potential P1 and P2 waves. Both mdivi-1 and roscovitine suppres…

Extraction: extract · Supplied extraction confidence: 0.85. Machine-extracted fields require source verification.

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