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| Ref Type | Journal Article | ||||||||||||
| PMID | (32350132) | ||||||||||||
| Authors | Banks E, Grondine M, Bhavsar D, Barry E, Kettle JG, Reddy VP, Brown C, Wang H, Mettetal JT, Collins T, Adeyemi O, Overman R, Lawson D, Harmer AR, Reimer C, Drew L, Packer MJ, Cosulich S, Jones RD, Shao W, Wilson D, Guichard S, Fawell S, Anjum R | ||||||||||||
| Title | Discovery and pharmacological characterization of AZD3229, a potent KIT/PDGFRα inhibitor for treatment of gastrointestinal stromal tumors. | ||||||||||||
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| Abstract Text | Gastrointestinal stromal tumor (GIST) is the most common human sarcoma driven by mutations in KIT or platelet-derived growth factor α (PDGFRα). Although first-line treatment, imatinib, has revolutionized GIST treatment, drug resistance due to acquisition of secondary KIT/PDGFRα mutations develops in a majority of patients. Second- and third-line treatments, sunitinib and regorafenib, lack activity against a plethora of mutations in KIT/PDGFRα in GIST, with median time to disease progression of 4 to 6 months and inhibition of vascular endothelial growth factor receptor 2 (VEGFR2) causing high-grade hypertension. Patients with GIST have an unmet need for a well-tolerated drug that robustly inhibits a range of KIT/PDGFRα mutations. Here, we report the discovery and pharmacological characterization of AZD3229, a potent and selective small-molecule inhibitor of KIT and PDGFRα designed to inhibit a broad range of primary and imatinib-resistant secondary mutations seen in GIST. In engineered and GIST-derived cell lines, AZD3229 is 15 to 60 times more potent than imatinib in inhibiting KIT primary mutations and has low nanomolar activity against a wide spectrum of secondary mutations. AZD3229 causes durable inhibition of KIT signaling in patient-derived xenograft (PDX) models of GIST, leading to tumor regressions at doses that showed no changes in arterial blood pressure (BP) in rat telemetry studies. AZD3229 has a superior potency and selectivity profile to standard of care (SoC) agents-imatinib, sunitinib, and regorafenib, as well as investigational agents, avapritinib (BLU-285) and ripretinib (DCC-2618). AZD3229 has the potential to be a best-in-class inhibitor for clinically relevant KIT/PDGFRα mutations in GIST. | ||||||||||||
| Molecular Profile | Treatment Approach |
|---|---|
| No data available in table | |
| Gene Name | Source | Synonyms | Protein Domains | Gene Description | Gene Role |
|---|---|---|---|---|---|
| No data available in table | |||||
| Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
|---|---|---|---|---|
| AZD3229 | AZD-3229|AZD 3229 | KIT Inhibitor 57 PDGFR-alpha Inhibitor 10 | AZD3229 is an inhibitor of Kit and Pdgfra that may have anti-tumor activity against KIT/PDGFRA-driven tumors and may also be effective against acquired resistance mutations seen with other Kit/Pdgfra inhibitors (PMID: 32350132, PMID: 32220888). |
| Gene | Variant | Impact | Protein Effect | Variant Description | Associated with drug Resistance |
|---|---|---|---|---|---|
| No data available in table | |||||
| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| KIT K642E KIT N822K | gastrointestinal stromal tumor | sensitive | Regorafenib | Preclinical - Pdx | Actionable | In a preclinical study, Stivarga (regorafenib) suppressed tumor growth in a patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT K642E and KIT N822K, but was less potent in comparison to treatment with AZD3229 (PMID: 32350132). | 32350132 |
| KIT K642E KIT N822K | gastrointestinal stromal tumor | sensitive | AZD3229 | Preclinical - Pdx | Actionable | In a preclinical study, AZD3229 inhibited Kit signaling and tumor growth in a patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT K642E and KIT N822K (PMID: 32350132). | 32350132 |
| KIT W557_K558del KIT V654A | gastrointestinal stromal tumor | sensitive | Sunitinib | Preclinical - Pdx | Actionable | In a preclinical study, Sutent (sunitinib) inhibited tumor growth in a patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT W557_K558del and KIT V654A, which was established from a patient who did not respond to Gleevec (imatinib) treatment (PMID: 32350132). | 32350132 |
| KIT W557_K558del KIT V654A | gastrointestinal stromal tumor | sensitive | AZD3229 | Preclinical - Pdx | Actionable | In a preclinical study, AZD3229 inhibited Kit signaling and tumor growth in a patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT W557_K558del and KIT V654A, which was established from a patient who did not respond to Gleevec (imatinib) treatment (PMID: 32350132). | 32350132 |
| KIT W557_K558del KIT Y823D | gastrointestinal stromal tumor | sensitive | AZD3229 | Preclinical - Pdx | Actionable | In a preclinical study, AZD3229 inhibited Kit signaling and tumor growth in a patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT W557_K558del and KIT Y823D (PMID: 32350132). | 32350132 |
| KIT W557_K558del KIT Y823D | gastrointestinal stromal tumor | sensitive | Regorafenib | Preclinical - Pdx | Actionable | In a preclinical study, Stivarga (regorafenib) inhibited tumor growth in a patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT W557_K558del and KIT Y823D (PMID: 32350132). | 32350132 |
| KIT V560_Y578del KIT V654A | gastrointestinal stromal tumor | resistant | Imatinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Gleevec (imatinib) failed to decrease cell viability and KIT signaling in a gastrointestinal stromal tumor cell line harboring KIT V560_Y578del and KIT V654A in culture, and did suppress tumor growth in cell line xenograft models (PMID: 32350132). | 32350132 |
| KIT V560_Y578del KIT V654A | gastrointestinal stromal tumor | predicted - resistant | Ripretinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Qinlock (ripretinib) resulted in slight decreases in cell viability and KIT signaling in a gastrointestinal stromal tumor cell line harboring KIT V560_Y578del and KIT V654A in culture, but failed to suppress tumor growth in cell line xenograft models (PMID: 32350132). | 32350132 |
| KIT V560_Y578del KIT V654A | gastrointestinal stromal tumor | sensitive | Sunitinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Sutent (sunitinib) inhibited growth of a gastrointestinal stromal tumor cell line harboring KIT V560_Y578del and KIT V654A in culture, and inhibited tumor growth in cell line xenograft models (PMID: 32350132). | 32350132 |
| KIT V560_Y578del KIT V654A | gastrointestinal stromal tumor | resistant | Avapritinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Ayvakit (avapritinib) failed to decrease cell viability and KIT signaling in a gastrointestinal stromal tumor cell line harboring KIT V560_Y578del and KIT V654A in culture, and did suppress tumor growth in cell line xenograft models (PMID: 32350132). | 32350132 |
| KIT V560_Y578del KIT V654A | gastrointestinal stromal tumor | sensitive | AZD3229 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, AZD3229 suppressed Kit signaling and cell growth in culture, and inhibited tumor growth in a cell line xenograft model of gastrointestinal stromal tumor harboring KIT V560_Y578del and KIT V654A (PMID: 32350132). | 32350132 |
| KIT W557_K558del KIT D816H | Advanced Solid Tumor | sensitive | AZD3229 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, AZD3229 inhibited growth of cells in culture and tumor growth in a cell line xenograft model of transformed cells expressing KIT W557_K558del and KIT D816H (PMID: 32350132). | 32350132 |
| KIT W557_K558del KIT V654A | Advanced Solid Tumor | sensitive | AZD3229 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del and KIT V654A demonstrated sensitivity to treatment with AZD3229 in both culture and cell line xenograft models, resulting in reduced cell viability, decreased KIT signaling, and tumor regression (PMID: 32350132). | 32350132 |
| KIT W557_K558del KIT V654A | Advanced Solid Tumor | resistant | Avapritinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Ayvakit (avapritinib) failed to inhibit cell growth or KIT signaling in culture and did not suppress tumor growth in cell line xenograft models of transformed cells expressing KIT W557_K558del and KIT V654A (PMID: 32350132). | 32350132 |
| KIT A502_Y503dup | Advanced Solid Tumor | sensitive | Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Stivarga (regorafenib) treatment resulted in decreased viability of transformed cells expressing KIT A502_Y503dup in culture, but was less potent compared to treatment with AZD3229 (PMID: 32350132). | 32350132 |
| KIT A502_Y503dup | Advanced Solid Tumor | sensitive | AZD3229 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT A502_Y503dup demonstrated sensitivity to AZD3229 in culture, resulting in reduced cell viability and inhibition of KIT signaling (PMID: 32350132). | 32350132 |
| KIT A502_Y503dup | Advanced Solid Tumor | sensitive | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Ayvakit (avapritinib) treatment resulted in decreased cell viability and reduced KIT signaling in transformed cells expressing KIT A502_Y503dup in culture, but was less potent compared to treatment with AZD3229 (PMID: 32350132). | 32350132 |
| KIT A502_Y503dup | Advanced Solid Tumor | sensitive | Ripretinib | Preclinical - Cell culture | Actionable | In a preclinical study, Qinlock (ripretinib) treatment resulted in decreased cell viability and reduced KIT signaling in transformed cells expressing KIT A502_Y503dup in culture, but was less potent compared to treatment with AZD3229 (PMID: 32350132). | 32350132 |
| KIT A502_Y503dup KIT D816H | Advanced Solid Tumor | resistant | Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT A502_Y503dup and KIT D816H demonstrated resistance to Stivarga (regorafenib) in culture (PMID: 32350132). | 32350132 |
| KIT A502_Y503dup KIT D816H | Advanced Solid Tumor | sensitive | AZD3229 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT A502_Y503dup and KIT D816H demonstrated sensitivity to AZD3229 in culture, resulting in reduced cell viability (PMID: 32350132). | 32350132 |
| KIT A502_Y503dup KIT D816H | Advanced Solid Tumor | resistant | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT A502_Y503dup and KIT D816H demonstrated resistance to Gleevec (imatinib) in culture (PMID: 32350132). | 32350132 |
| KIT A502_Y503dup KIT D816H | Advanced Solid Tumor | resistant | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT A502_Y503dup and KIT D816H demonstrated resistance to Sutent (sunitinib) in culture (PMID: 32350132). | 32350132 |
| KIT A502_Y503dup KIT D816H | Advanced Solid Tumor | sensitive | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT A502_Y503dup and KIT D816H demonstrated increased sensitivity to treatment with Ayvakit (avapritinib) compared to cells expressing KIT A502_Y503dup alone in culture (PMID: 32350132). | 32350132 |
| KIT A502_Y503dup KIT D816H | Advanced Solid Tumor | decreased response | Ripretinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT A502_Y503dup and KIT D816H demonstrated a decreased response to treatment with Qinlock (ripretinib) compared to cells expressing KIT A502_Y503dup alone in culture (PMID: 32350132). | 32350132 |
| KIT A502_Y503dup KIT V654A | Advanced Solid Tumor | sensitive | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT A502_Y503dup and KIT V654A demonstrated sensitivity to Sutent (sunitinib) in culture, resulting in reduced cell viability (PMID: 32350132). | 32350132 |
| KIT A502_Y503dup KIT V654A | Advanced Solid Tumor | decreased response | Ripretinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT A502_Y503dup and KIT V654A demonstrated a decreased response to treatment with Qinlock (ripretinib) compared to cells expressing KIT A502_Y503dup alone in culture (PMID: 32350132). | 32350132 |
| KIT A502_Y503dup KIT V654A | Advanced Solid Tumor | resistant | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT A502_Y503dup and KIT V654A demonstrated resistance to Ayvakit (avapritinib) in culture (PMID: 32350132). | 32350132 |
| KIT A502_Y503dup KIT V654A | Advanced Solid Tumor | resistant | Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT A502_Y503dup and KIT V654A demonstrated resistance to Stivarga (regorafenib) in culture (PMID: 32350132). | 32350132 |
| KIT A502_Y503dup KIT V654A | Advanced Solid Tumor | resistant | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT A502_Y503dup and KIT V654A demonstrated resistance to Gleevec (imatinib) in culture (PMID: 32350132). | 32350132 |
| KIT A502_Y503dup KIT V654A | Advanced Solid Tumor | sensitive | AZD3229 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT A502_Y503dup and KIT V654A demonstrated sensitivity to AZD3229 in culture, resulting in reduced cell viability (PMID: 32350132). | 32350132 |
| KIT V560_Y578del | gastrointestinal stromal tumor | sensitive | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Gleevec (imatinib) inhibited cell growth and KIT signaling in a gastrointestinal stromal tumor cell line harboring KIT V560_Y578del in culture, but was less potent compared to AZD3229 (PMID: 32350132). | 32350132 |
| KIT V560_Y578del | gastrointestinal stromal tumor | resistant | Ripretinib | Preclinical - Cell culture | Actionable | In a preclinical study, Qinlock (ripretinib) inhibited cell growth and KIT signaling in a gastrointestinal stromal tumor cell line harboring KIT V560_Y578del in culture, but was less potent compared to AZD3229 (PMID: 32350132). | 32350132 |
| KIT V560_Y578del | gastrointestinal stromal tumor | sensitive | Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Stivarga (regorafenib) inhibited growth of a gastrointestinal stromal tumor cell line harboring KIT V560_Y578del in culture, but was less potent compared to AZD3229 (PMID: 32350132). | 32350132 |
| KIT V560_Y578del | gastrointestinal stromal tumor | sensitive | AZD3229 | Preclinical - Cell culture | Actionable | In a preclinical study, AZD3229 inhibited cell growth and KIT signaling in a gastrointestinal stromal tumor cell line harboring KIT V560_Y578del in culture (PMID: 32350132). | 32350132 |
| KIT V560_Y578del | gastrointestinal stromal tumor | sensitive | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Ayvakit (avapritinib) inhibited cell growth and KIT signaling in a gastrointestinal stromal tumor cell line harboring KIT V560_Y578del in culture, but was less potent compared to AZD3229 (PMID: 32350132). | 32350132 |
| KIT V560_Y578del KIT V654A | gastrointestinal stromal tumor | resistant | Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, a gastrointestinal stromal tumor cell line harboring KIT V560_Y578del and KIT V654A demonstrated resistance to Stivarga (regorafenib) in culture (PMID: 32350132). | 32350132 |
| KIT V560D | Advanced Solid Tumor | sensitive | Ripretinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V560D demonstrated sensitivity to Qinlock (ripretinib) in culture, resulting in reduced cell viability (PMID: 32350132). | 32350132 |
| KIT V560D | Advanced Solid Tumor | sensitive | AZD3229 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V560D demonstrated sensitivity to AZD3229 in culture, resulting in reduced cell viability (PMID: 32350132). | 32350132 |
| KIT V560D | Advanced Solid Tumor | sensitive | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Ayvakit (avapritinib) treatment resulted in decreased cell viability in transformed cells expressing KIT V560D in culture, but was less potent compared to treatment with AZD3229 (PMID: 32350132). | 32350132 |
| KIT V560D KIT D816H | Advanced Solid Tumor | resistant | Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V560D and KIT D816H demonstrated resistance to Stivarga (regorafenib) in culture (PMID: 32350132). | 32350132 |
| KIT V560D KIT D816H | Advanced Solid Tumor | decreased response | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V560D and KIT D816H demonstrated a decreased response to treatment with Ayvakit (avapritinib) compared to cells expressing KIT V560D alone in culture (PMID: 32350132). | 32350132 |
| KIT V560D KIT D816H | Advanced Solid Tumor | resistant | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V560D and KIT D816H demonstrated resistance to Gleevec (imatinib) in culture (PMID: 32350132). | 32350132 |
| KIT V560D KIT D816H | Advanced Solid Tumor | sensitive | AZD3229 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V560D and KIT D816H demonstrated sensitivity to AZD3229 in culture, resulting in reduced cell viability (PMID: 32350132). | 32350132 |
| KIT V560D KIT D816H | Advanced Solid Tumor | resistant | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V560D and KIT D816H demonstrated resistance to Sutent (sunitinib) in culture (PMID: 32350132). | 32350132 |
| KIT V560D KIT D816H | Advanced Solid Tumor | sensitive | Ripretinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V560D and KIT D816H demonstrated sensitivity to Qinlock (ripretinib) in culture, resulting in reduced cell viability (PMID: 32350132). | 32350132 |
| KIT V560D KIT D820A | Advanced Solid Tumor | sensitive | Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Stivarga (regorafenib) treatment resulted in decreased viability of transformed cells expressing KIT V560D and KIT D820A in culture, but was less effective compared to other treatments (PMID: 32350132). | 32350132 |
| KIT V560D KIT D820A | Advanced Solid Tumor | decreased response | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V560D and KIT D820A demonstrated a decreased response to treatment with Ayvakit (avapritinib) compared to cells expressing KIT V560D alone in culture (PMID: 32350132). | 32350132 |
| KIT V560D KIT D820A | Advanced Solid Tumor | sensitive | Ripretinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V560D and KIT D820A demonstrated sensitivity to Qinlock (ripretinib) in culture, resulting in reduced cell viability (PMID: 32350132). | 32350132 |
| KIT V560D KIT D820A | Advanced Solid Tumor | resistant | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V560D and KIT D820A demonstrated resistance to Gleevec (imatinib) in culture (PMID: 32350132). | 32350132 |
| KIT V560D KIT D820A | Advanced Solid Tumor | sensitive | AZD3229 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V560D and KIT D820A demonstrated sensitivity to AZD3229 in culture, resulting in reduced cell viability (PMID: 32350132). | 32350132 |
| KIT V560D KIT D820A | Advanced Solid Tumor | resistant | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V560D and KIT D820A demonstrated resistance to Sutent (sunitinib) in culture (PMID: 32350132). | 32350132 |
| KIT V560D KIT V654A | Advanced Solid Tumor | sensitive | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V560D and KIT V654A demonstrated sensitivity to Sutent (sunitinib) in culture, resulting in reduced cell viability (PMID: 32350132). | 32350132 |
| KIT V560D KIT V654A | Advanced Solid Tumor | resistant | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V560D and KIT V654A demonstrated resistance to Gleevec (imatinib) in culture (PMID: 32350132). | 32350132 |
| KIT V560D KIT V654A | Advanced Solid Tumor | sensitive | AZD3229 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V560D and KIT V654A demonstrated sensitivity to AZD3229 in culture, resulting in reduced cell viability (PMID: 32350132). | 32350132 |
| KIT V560D KIT V654A | Advanced Solid Tumor | decreased response | Ripretinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V560D and KIT V654A demonstrated a decreased response to treatment with Qinlock (ripretinib) compared to cells expressing KIT V560D alone in culture (PMID: 32350132). | 32350132 |
| KIT V560D KIT V654A | Advanced Solid Tumor | resistant | Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT V560D and KIT V654A demonstrated resistance to treatment with Stivarga (regorafenib) in culture (PMID: 32350132). | 32350132 |
| KIT W557_K558del | Advanced Solid Tumor | sensitive | Ripretinib | Preclinical - Cell culture | Actionable | In a preclinical study, Qinlock (ripretinib) treatment resulted in decreased viability of transformed cells expressing KIT W557_K558del in culture, but was less potent compared to treatment with AZD3229 (PMID: 32350132). | 32350132 |
| KIT W557_K558del | Advanced Solid Tumor | sensitive | AZD3229 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del demonstrated sensitivity to AZD3229 in culture, resulting in reduced cell viability (PMID: 32350132). | 32350132 |
| KIT W557_K558del | Advanced Solid Tumor | sensitive | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Ayvakit (avapritinib) treatment resulted in decreased viability of transformed cells expressing KIT W557_K558del in culture, but was less potent compared to treatment with AZD3229 (PMID: 32350132). | 32350132 |
| KIT W557_K558del KIT A829P | Advanced Solid Tumor | resistant | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del and KIT A829P demonstrated resistance to Sutent (sunitinib) in culture (PMID: 32350132). | 32350132 |
| KIT W557_K558del KIT A829P | Advanced Solid Tumor | sensitive | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Ayvakit (avapritinib) treatment resulted in decreased viability of transformed cells expressing KIT W557_K558del and KIT A829P in culture, but was less effective compared to other treatments (PMID: 32350132). | 32350132 |
| KIT W557_K558del KIT A829P | Advanced Solid Tumor | resistant | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del and KIT A829P demonstrated resistance to Gleevec (imatinib) in culture (PMID: 32350132). | 32350132 |
| KIT W557_K558del KIT A829P | Advanced Solid Tumor | conflicting | Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del and KIT A829P were sensitive to treatment with Stivarga (regorafenib), but demonstrated a decreased response compared to cells expressing KIT W557_K558del alone in culture (PMID: 32350132). | 32350132 |
| KIT W557_K558del KIT A829P | Advanced Solid Tumor | sensitive | Ripretinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del and KIT A829P demonstrated sensitivity to Qinlock (ripretinib) in culture, resulting in reduced cell viability (PMID: 32350132). | 32350132 |
| KIT W557_K558del KIT A829P | Advanced Solid Tumor | sensitive | AZD3229 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del and KIT A829P demonstrated sensitivity to AZD3229 in culture, resulting in reduced cell viability (PMID: 32350132). | 32350132 |
| KIT W557_K558del KIT D816H | Advanced Solid Tumor | sensitive | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del and KIT D816H demonstrated sensitivity to Ayvakit (avapritinib) in culture, resulting in reduced cell viability (PMID: 32350132). | 32350132 |
| KIT W557_K558del KIT D816H | Advanced Solid Tumor | sensitive | Ripretinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del and KIT D816H demonstrated sensitivity to Qinlock (ripretinib) in culture, resulting in reduced cell viability (PMID: 32350132). | 32350132 |
| KIT W557_K558del KIT D820A | Advanced Solid Tumor | sensitive | AZD3229 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del and KIT D820A demonstrated sensitivity to AZD3229 in culture, resulting in reduced cell viability (PMID: 32350132). | 32350132 |
| KIT W557_K558del KIT D820A | Advanced Solid Tumor | resistant | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del and KIT D820A demonstrated resistance to Sutent (sunitinib) in culture (PMID: 32350132). | 32350132 |
| KIT W557_K558del KIT D820A | Advanced Solid Tumor | sensitive | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Ayvakit (avapritinib) treatment resulted in decreased viability of transformed cells expressing KIT W557_K558del and KIT D820A in culture, but was less effective compared to other treatments (PMID: 32350132). | 32350132 |
| KIT W557_K558del KIT D820A | Advanced Solid Tumor | sensitive | Ripretinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del and KIT D820A demonstrated sensitivity to Qinlock (ripretinib) in culture, resulting in reduced cell viability (PMID: 32350132). | 32350132 |
| KIT W557_K558del KIT D820A | Advanced Solid Tumor | conflicting | Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del and KIT D820A were sensitive to treatment with Stivarga (regorafenib), demonstrating reduced cell viability in culture (PMID: 32350132). | 32350132 |
| KIT W557_K558del KIT D820A | Advanced Solid Tumor | resistant | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del and KIT D820A demonstrated resistance to Gleevec (imatinib) in culture (PMID: 32350132). | 32350132 |
| KIT W557_K558del KIT N822K | Advanced Solid Tumor | conflicting | Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del and KIT N822K was sensitive to treatment with Stivarga (regorafenib), demonstrating decreased cell viability in culture (PMID: 32350132). | 32350132 |
| KIT W557_K558del KIT N822K | Advanced Solid Tumor | resistant | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del and KIT N822K demonstrated resistance to Sutent (sunitinib) in culture (PMID: 32350132). | 32350132 |
| KIT W557_K558del KIT N822K | Advanced Solid Tumor | sensitive | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Ayvakit (avapritinib) treatment resulted in decreased viability of transformed cells expressing KIT W557_K558del and KIT N822K in culture, but was less effective compared to other treatments (PMID: 32350132). | 32350132 |
| KIT W557_K558del KIT N822K | Advanced Solid Tumor | sensitive | AZD3229 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del and KIT N822K demonstrated sensitivity to AZD3229 in culture, resulting in reduced cell viability (PMID: 32350132). | 32350132 |
| KIT W557_K558del KIT N822K | Advanced Solid Tumor | resistant | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del and KIT N822K demonstrated resistance to Gleevec (imatinib) in culture (PMID: 32350132). | 32350132 |
| KIT W557_K558del KIT N822K | Advanced Solid Tumor | sensitive | Ripretinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del and KIT N822K demonstrated sensitivity to Qinlock (ripretinib) in culture, resulting in reduced cell viability (PMID: 32350132). | 32350132 |
| KIT W557_K558del KIT T670I | Advanced Solid Tumor | decreased response | Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del and KIT T670I demonstrated a decreased response to treatment with Stivarga (regorafenib) compared to cells expressing KIT W557_K558del alone in culture (PMID: 32350132). | 32350132 |
| KIT W557_K558del KIT T670I | Advanced Solid Tumor | resistant | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del and KIT T670I demonstrated resistance to Ayvakit (avapritinib) in culture (PMID: 32350132). | 32350132 |
| KIT W557_K558del KIT T670I | Advanced Solid Tumor | sensitive | AZD3229 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del and KIT T670I demonstrated sensitivity to AZD3229 in culture, resulting in reduced cell viability (PMID: 32350132). | 32350132 |
| KIT W557_K558del KIT T670I | Advanced Solid Tumor | decreased response | Ripretinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del and KIT T670I demonstrated a decreased response to treatment with Qinlock (ripretinib) compared to cells expressing KIT W557_K558del alone in culture (PMID: 32350132). | 32350132 |
| KIT W557_K558del KIT V654A | Advanced Solid Tumor | resistant | Ripretinib | Preclinical - Cell culture | Actionable | In a preclinical study, Qinlock (ripretinib) failed to reduce cell viability and inhibit KIT signaling in transformed cells expressing KIT W557_K558del and KIT V654A in culture (PMID: 32350132). | 32350132 |
| KIT W557_K558del KIT Y823D | Advanced Solid Tumor | predicted - sensitive | Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del and KIT Y823D demonstrated sensitivity to treatment with Stivarga (regorafenib), but was decreased compared to cells expressing KIT W557_K558del alone in culture (PMID: 32350132). | 32350132 |
| KIT W557_K558del KIT Y823D | Advanced Solid Tumor | decreased response | Ripretinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del and KIT Y823D demonstrated a decreased response to treatment with Qinlock (ripretinib) compared to cells expressing KIT W557_K558del alone in culture (PMID: 32350132). | 32350132 |
| KIT W557_K558del KIT Y823D | Advanced Solid Tumor | decreased response | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del and KIT Y823D demonstrated a decreased response to treatment with Ayvakit (avapritinib) compared to cells expressing KIT W557_K558del alone in culture (PMID: 32350132). | 32350132 |
| KIT W557_K558del KIT Y823D | Advanced Solid Tumor | resistant | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del and KIT Y823D demonstrated resistance to Sutent (sunitinib) in culture (PMID: 32350132). | 32350132 |
| KIT W557_K558del KIT Y823D | Advanced Solid Tumor | sensitive | AZD3229 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del and KIT Y823D demonstrated sensitivity to AZD3229 in culture, resulting in reduced cell viability (PMID: 32350132). | 32350132 |
| KIT W557_K558del KIT Y823D | Advanced Solid Tumor | resistant | Imatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing KIT W557_K558del and KIT Y823D demonstrated resistance to Gleevec (imatinib) in culture (PMID: 32350132). | 32350132 |