|
Gastrointestinal Stromal Tumors
|
|
0.750 |
GeneticVariation
|
BEFREE |
In addition, it could inhibit imatinib resistant cKIT T670I and V654A mutants <i>in vitro</i> and <i>in vivo</i> GIST preclinical models.
|
31205508 |
2019 |
|
Gastrointestinal Stromal Tumors
|
|
0.750 |
GeneticVariation
|
BEFREE |
Compound 24 displays good antiproliferative effects against c-KIT T670I mutant-driven GIST cell lines (GIST-T1/T670I and GIST-5R) and also exhibits suitable in vivo pharmacokinetic profiles as well as dose-dependent antitumor efficacy.
|
31046271 |
2019 |
|
Gastrointestinal Stromal Tumors
|
|
0.750 |
GeneticVariation
|
BEFREE |
These were PDX models harboring primary and secondary <i>KIT</i> and additional mutations; <i>KIT</i> exon 11 (p.Y570_L576del), <i>KIT</i> exon 17 (p.D816E), and <i>PTEN</i> (p.T321fs) mutations in GIST-RX1 from a patient who was unresponsive to imatinib, sunitinib, and sorafenib, and <i>KIT</i> exon 11 (p.K550_splice) and <i>KIT</i> exon 14 (p.T670I) mutations in GIST-RX2 and <i>KIT</i> exon 9 (p.502_503insYA) and <i>KIT</i> exon 17 (p.D820E) mutations in GIST-RX4 from patients with imatinib and imatinib/sunitinib resistance, respectively.
|
29100343 |
2017 |
|
Gastrointestinal Stromal Tumors
|
|
0.750 |
GeneticVariation
|
BEFREE |
Compound 35 displayed strong antiproliferative effect against GISTs cancer cell lines GIST-T1 (cKIT wt, GI50 = 4 nM) and GIST-5R (cKIT T670I, GI50 = 26 nM).
|
27545040 |
2016 |
|
Gastrointestinal Stromal Tumors
|
|
0.750 |
GeneticVariation
|
CLINVAR |
KRAS and KIT Gatekeeper Mutations Confer Polyclonal Primary Imatinib Resistance in GI Stromal Tumors: Relevance of Concomitant Phosphatidylinositol 3-Kinase/AKT Dysregulation.
|
24687822 |
2015 |
|
Gastrointestinal Stromal Tumors
|
|
0.750 |
GeneticVariation
|
CLINVAR |
Prospective enterprise-level molecular genotyping of a cohort of cancer patients.
|
25157968 |
2014 |
|
Gastrointestinal Stromal Tumors
|
|
0.750 |
GeneticVariation
|
BEFREE |
Herein, by introducing adaptive elements into the inhibitor core structure, we undertake the structure-based development of type II hybrid inhibitors to overcome gatekeeper drug-resistant mutations in cSrc-T338M, as well as clinically relevant tyrosine kinase KIT-T670I and Abl-T315I variants, as essential targets in gastrointestinal stromal tumors (GISTs) and chronic myelogenous leukemia (CML).
|
23773153 |
2013 |
|
Gastrointestinal Stromal Tumors
|
|
0.750 |
GeneticVariation
|
CLINVAR |
Secondary c-Kit mutations confer acquired resistance to RTK inhibitors in c-Kit mutant melanoma cells.
|
23582185 |
2013 |
|
Gastrointestinal Stromal Tumors
|
|
0.750 |
GeneticVariation
|
CLINVAR |
Novel, activating KIT-N822I mutation in familial cutaneous mastocytosis.
|
21689725 |
2011 |
|
Gastrointestinal Stromal Tumors
|
|
0.750 |
GeneticVariation
|
CLINVAR |
Juxtamembrane-type c-kit gene mutation found in aggressive systemic mastocytosis induces imatinib-resistant constitutive KIT activation.
|
17259998 |
2007 |
|
Gastrointestinal Stromal Tumors
|
|
0.750 |
GeneticVariation
|
CLINVAR |
GIST cells carrying KIT -del557-558/T670I or KIT -InsAY502-503/V654A mutations were resistant to imatinib, while PKC412 significantly inhibited autophosporylation of these mutants.
|
15685537 |
2005 |
|
Gastrointestinal Stromal Tumors
|
|
0.750 |
GeneticVariation
|
CLINVAR |
A new mutation in the KIT ATP pocket causes acquired resistance to imatinib in a gastrointestinal stromal tumor patient.
|
15236194 |
2004 |
|
Malignant Neoplasms
|
|
0.010 |
GeneticVariation
|
BEFREE |
Compound 35 displayed strong antiproliferative effect against GISTs cancer cell lines GIST-T1 (cKIT wt, GI50 = 4 nM) and GIST-5R (cKIT T670I, GI50 = 26 nM).
|
27545040 |
2016 |
|
Neoplasms
|
|
0.010 |
GeneticVariation
|
BEFREE |
In the BaF3-TEL-cKIT-T670I isogenic cell inoculated xenograft mouse model, 35 exhibited dose dependent tumor growth suppression efficacy and 100 mg/kg dosage provided 47.7% tumor growth inhibition (TGI) without obvious toxicity.
|
27545040 |
2016 |
|
Primary malignant neoplasm
|
|
0.010 |
GeneticVariation
|
BEFREE |
Compound 35 displayed strong antiproliferative effect against GISTs cancer cell lines GIST-T1 (cKIT wt, GI50 = 4 nM) and GIST-5R (cKIT T670I, GI50 = 26 nM).
|
27545040 |
2016 |
|
Myeloid Leukemia, Chronic
|
|
0.010 |
GeneticVariation
|
BEFREE |
Herein, by introducing adaptive elements into the inhibitor core structure, we undertake the structure-based development of type II hybrid inhibitors to overcome gatekeeper drug-resistant mutations in cSrc-T338M, as well as clinically relevant tyrosine kinase KIT-T670I and Abl-T315I variants, as essential targets in gastrointestinal stromal tumors (GISTs) and chronic myelogenous leukemia (CML).
|
23773153 |
2013 |
|
Gastrointestinal Neoplasms
|
|
0.010 |
GeneticVariation
|
BEFREE |
The KIT/FLT3 inhibitor SU-11248 potently inhibits the imatinib-resistant KIT(V559D/T670I) kinase, consistent with the clinical efficacy of SU-11248 against imatinib-resistant gastrointestinal tumors, and the EGFR inhibitors EKB-569 and CI-1033, but not GW-572016 and ZD-6474, potently inhibit the gefitinib- and erlotinib-resistant EGFR(L858R/T790M) kinase.
|
16046538 |
2005 |