Therapy Detail
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| Therapy Name | SHP099 + Vemurafenib |
| Synonyms | |
| Therapy Description | |
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| Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
|---|---|---|---|---|
| SHP099 | SHP-099|SHP 099 | SHP2 Inhibitor 20 | SHP099 is an allosteric inhibitor of SHP2 that stabilizes SHP2 in its autoinhibited conformation, which reduces downstream signaling and potentially leads to decreased growth of receptor tyrosine kinase-driven tumors (PMID: 27362227, PMID: 31043123). | |
| Vemurafenib | Zelboraf | RO5185426|PLX4032 | RAF Inhibitor (Pan) 28 | Zelboraf (vemurafenib) inhibits BRAF V600E, wild-type BRAF, ARAF, and CRAF (PMID: 20179705), which may result in an inhibition of the MAPK signaling pathway resulting in a reduction of tumor cell proliferation (PMID: 20823850). Zelboraf (vemurafenib) is FDA approved for BRAF V600E-mutant melanoma and for BRAF V600-positive Erdheim-Chester disease (FDA.gov). |
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| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| BRAF V600E | thyroid cancer | sensitive | SHP099 + Vemurafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of Zelboraf (vemurafenib) and SHP099 inhibited proliferation and induced cell cycle arrest in Zelboraf (vemurafenib)-resistant thyroid cancer cell lines harboring BRAF V600E in culture and inhibited tumor growth in a cell line xenograft model (PMID: 37325052). | 37325052 |
| NRAS Q61K | neuroblastoma | sensitive | SHP099 + Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination treatment of SHP099 and Zelboraf (vemurafenib) in neuroblastoma cell lines either expressing or harboring NRAS Q61K resulted in increased sensitivity compared to Zelboraf (vemurafenib) treatment alone in culture, demonstrating a greater decrease in cell viability (PMID: 32586982). | 32586982 |
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| Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
|---|
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