Sandbox Reserved 425: Difference between revisions
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The brand name for ponatinib is Iclusig. Iclusig received an accelerated approval grant through the Food and Drug Administration. It was mainly prescribed to patients suffering from Chronic Myeloid Leukemia or Acute Lymphoblastic Leukemia who did not make any progress with the first and second generation TKIs. However, the clinical trials data displayed a spike in adverse effects. These consequences include heart failure, stroke, coronary artery disease, loss of blood flow to body parts leading to amputation amongst other narrowing of blood vessels<ref>FDA Drug Safety Communication: FDA investigating leukemia drug Iclusig (ponatinib) after increased reports of serious blood clots in arteries and veins; Drug Safety and Availability; United States Food and Drug Administration (2013). Web. [http://www.fda.gov/Drugs/DrugSafety/ucm370945.htm]</ref>. | The brand name for ponatinib is Iclusig. Iclusig received an accelerated approval grant through the Food and Drug Administration. It was mainly prescribed to patients suffering from Chronic Myeloid Leukemia or Acute Lymphoblastic Leukemia who did not make any progress with the first and second generation TKIs. However, the clinical trials data displayed a spike in adverse effects. These consequences include heart failure, stroke, coronary artery disease, loss of blood flow to body parts leading to amputation amongst other narrowing of blood vessels<ref>FDA Drug Safety Communication: FDA investigating leukemia drug Iclusig (ponatinib) after increased reports of serious blood clots in arteries and veins; Drug Safety and Availability; United States Food and Drug Administration (2013). Web. [http://www.fda.gov/Drugs/DrugSafety/ucm370945.htm]</ref>. | ||
FGFR-4 is abundantly present in human prostate cancer observed in vitro and in mouse model simulations<ref name="nine">PMID: 22573348</ref>. A <scene name='48/483882/Variant/ | FGFR-4 is abundantly present in human prostate cancer observed in vitro and in mouse model simulations<ref name="nine">PMID: 22573348</ref>. A <scene name='48/483882/Variant/9'>variant</scene> of FGFR-4 with Arg388 replacing Gly388 is implicated with increased human prostate cancer. This variation causes increased receptor stability and activation<ref name="ten">PMID:18670643</ref>. A study revealed that the <scene name='48/483882/Inhibition/1'>inhibition</scene> of FGFR-4 signaling completely curtailed prostate cancer cell lines that were responsible for tumor growth<ref name="nine">PMID: 22573348</ref>. Due to the significant results of diminished cell growth in treated tumors, targeting fibroblast growth factor signaling appears to provide a promising step towards combating aggressive prostate cancer. | ||
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==Quiz Question 1== | ==Quiz Question 1== | ||
Ponatinib is unique in it's ability to bind to the mutated BCR-ABL because of it's preference to shift to the DFG-out conformation. In theory, if a competitive inhibitor was created by nature to prevent Ponatinib from binding to BCR-ABL to further its drug resistance, what specific structural characteristics would the inhibitor need to | Ponatinib is unique in it's ability to bind to the mutated BCR-ABL because of it's preference to shift to the DFG-out conformation. In theory, if a competitive inhibitor was created by nature to prevent Ponatinib from binding to BCR-ABL to further its drug resistance, what specific structural characteristics would the inhibitor need to possess? Consider the unique binding methods of Ponatinib and the <scene name='48/483882/Active_sitezoom/1'>DFG-out</scene> conformation. | ||
a. Small, fully conjugated aromatic system with no electronegative substituents, to prevent unwanted hydrogen bonding. | a. Small, fully conjugated aromatic system with no electronegative substituents, to prevent unwanted hydrogen bonding. | ||