Therapy Detail
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| Therapy Name | thioureidobutyronitrile |
| Synonyms | |
| Therapy Description |
Kevetrin (thioureidobutyronitrile) leads to stabilization of wild-type Tp53 and degradation of mutant Tp53, resulting in apoptosis and decreased growth of tumors with wild-type and mutant Tp53 (J Clin Oncol 31, 2013 (suppl; abstr TPS2627)). |
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| Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
|---|---|---|---|---|
| thioureidobutyronitrile | Kevetrin|NSC-525990 | p53 Activator 11 | Kevetrin (thioureidobutyronitrile) leads to stabilization of wild-type Tp53 and degradation of mutant Tp53, resulting in apoptosis and decreased growth of tumors with wild-type and mutant Tp53 (J Clin Oncol 31, 2013 (suppl; abstr TPS2627)). |
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| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| TP53 C242fs | acute myeloid leukemia | predicted - sensitive | thioureidobutyronitrile | Preclinical - Cell culture | Actionable | In a preclinical study, Kevetrin (thioureidobutyronitrile) treatment resulted in apoptosis, decreased cell viability, altered cell cycle progression, elevated expression of Tp53 target genes, and increased Tp53 nuclear localization in an acute myeloid leukemia cell line harboring TP53 C242fs in culture (PMID: 32945487). | 32945487 |
| TP53 I255N | acute myeloid leukemia | predicted - sensitive | thioureidobutyronitrile | Preclinical - Patient cell culture | Actionable | In a preclinical study, Kevetrin (thioureidobutyronitrile) treatment resulted in apoptosis of leukemic blast cells and decreased cell viability in patient-derived acute myeloid leukemia cells harboring TP53 I255N in culture (PMID: 32945487). | 32945487 |
| TP53 mutant | ovarian serous carcinoma | sensitive | thioureidobutyronitrile | Preclinical - Cell culture | Actionable | In a preclinical study, Kevetrin (thioureidobutyronitrile) treatment decreased mutant Tp53 level, resulted in apoptosis of ovarian serous carcinoma cells harboring TP53 mutations in culture (Proceedings of the AACR, Vol 58, Apr 2017, abstract # 3221). | detail... |
| TP53 R248Q | acute myeloid leukemia | predicted - sensitive | thioureidobutyronitrile | Preclinical - Cell culture | Actionable | In a preclinical study, Kevetrin (thioureidobutyronitrile) treatment resulted in apoptosis, decreased cell viability, elevated expression of Tp53 target genes, and increased Tp53 nuclear localization in an acute myeloid leukemia cell line harboring TP53 R248Q in culture (PMID: 32945487). | 32945487 |
| TP53 wild-type | endometrioid ovary carcinoma | sensitive | thioureidobutyronitrile | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Kevetrin (thioureidobutyronitrile) treatment increased Tp53 and Cdkn1a protein levels, resulted in growth inhibition of TP53 wild-type endometrioid ovary carcinoma cells in culture and in cell line xenograft models (Proceedings of the AACR, Vol 58, Apr 2017, abstract # 3221). | detail... |
| TP53 del | ovarian clear cell carcinoma | predicted - sensitive | thioureidobutyronitrile | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Kevetrin (thioureidobutyronitrile) treatment resulted in Tp53-independent increase of Cdkn1a expression and apoptosis of ovarian clear cell carcinoma cells harboring TP53 deletion in culture and in cell line xenograft models (Proceedings of the AACR, Vol 58, Apr 2017, abstract # 3221). | detail... |
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| Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
|---|---|---|---|---|---|---|
| NCT01664000 | Phase I | thioureidobutyronitrile | A Safety, Pharmacokinetic and Pharmacodynamic Study of Kevetrin in Patients With Advanced Solid Tumors | Completed | USA | 0 |
| NCT03042702 | Phase II | thioureidobutyronitrile | A Phase 2 Study of Kevetrin in Subjects With Ovarian Cancer | Completed | USA | 0 |
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