Incb18424 targeting jak pathway
INCB18424 Origin:
INCB18424 structure is relatively small for a molecular drug and this JAK2 inhibitor is being increasing used in therapeutic avenues owing to the remarkable success it generated in the preclinical assessments. The inhibition of JAK family members by INCB18424 shows a specificity towards JAK1 and JAK2 inhibition which is evident with much lower and clinically relevant doses needed for them, compared to its dose required for JAK3 inhibition and thus it is more potent against JAK1 and to some extent to JAK2 but not towards JAK3. Incyte is the manufacturer of INCB81424 JAK inhibitor is manufactured by Incyte Company and this Incyte JAK2 inhibitor is marketed under the brand name ‘Ruxolitinib'.
INCB18424 Properties:
INCB18424 price is on a higher side and one has to pay around $100 for a 2 mg vial. As stated above, it is more specific towards JAK1 and 2 as evident from INCB18424 IC50 values of 2.7 nM, 4.5 nM and 332 nM for JAK1, JAK2 and JAK3, respectively. INCB81424 solubility is not there in water but can be achieved in acidic buffers and DMSO. INCB18424 suppliers provide it under the trade name of Ruxolitinib and it can be used for medicinal and laboratory uses.
Myeloproliferative Diseases:
Myeloproliferative diseases are one of the most debilitating diseases because these conditions not only affect the patient's life in most disastrous ways, but also because there is currently no hope for the availability of a proper cure against them. One of the most common examples of this category is Myelofibrosis (MF) which though is a rare but when encountered, a critical blood cancer. It is associated with enlarged spleen, bone marrow failure etc. The symptoms like fatigue and night sweats soon set in and patients have to go for a poor quality of life coupled with considerable weight loss and shortened life expectancy. Polycythemia vera (PCV) and Essential thrombocythemia are other famous examples of Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs). Prognosis for Myelofibrosis is very dismal and it soon develops into fatal acute myelogenous leukemia (AML), for which also there is no treatment available [2]. The highly significant morbidity and mortality rates associated with stem cell transplantation limit these options to younger patients.
JAK Inhibitors against Myeloproliferative Diseases:
JAK2 has been implicated in myeloproliferative diseases. Since INCB18424 targets V617F mutation found in hematologic malignancies, INCB18424 clinical trials were warranted for MPNs treatment after the successful assessment of its safety and efficaciousness was done in MF patients. Another derivative of INCB81424, INCB16562 was also very successful targeting V617F mutation of MF and thrombocytosis in rat models. This successful targeting offered a new hope to >90% of PCV patients and ~60% of essential thrombocytosis (ET) and MF patients carrying this mutation. INCB81424 soon became the first JAK2 inhibitor tried on MF patients and showed promise by reducing spleen size and overall improved survival of patients.
Clinical Studies from Incyte:
The orally administered INCB81424 was used in Incyte phase II studies in advanced cases of PV and essential thrombocythemia (ET). Incyte reported successful in meeting the primary endpoint in a second phase III clinical trial. Another phase III INCB18424 randomized trial in PV is going on.
INCB18424 structure is relatively small for a molecular drug and this JAK2 inhibitor is being increasing used in therapeutic avenues owing to the remarkable success it generated in the preclinical assessments. The inhibition of JAK family members by INCB18424 shows a specificity towards JAK1 and JAK2 inhibition which is evident with much lower and clinically relevant doses needed for them, compared to its dose required for JAK3 inhibition and thus it is more potent against JAK1 and to some extent to JAK2 but not towards JAK3. Incyte is the manufacturer of INCB81424 JAK inhibitor is manufactured by Incyte Company and this Incyte JAK2 inhibitor is marketed under the brand name ‘Ruxolitinib'.
INCB18424 Properties:
INCB18424 price is on a higher side and one has to pay around $100 for a 2 mg vial. As stated above, it is more specific towards JAK1 and 2 as evident from INCB18424 IC50 values of 2.7 nM, 4.5 nM and 332 nM for JAK1, JAK2 and JAK3, respectively. INCB81424 solubility is not there in water but can be achieved in acidic buffers and DMSO. INCB18424 suppliers provide it under the trade name of Ruxolitinib and it can be used for medicinal and laboratory uses.
Myeloproliferative Diseases:
Myeloproliferative diseases are one of the most debilitating diseases because these conditions not only affect the patient's life in most disastrous ways, but also because there is currently no hope for the availability of a proper cure against them. One of the most common examples of this category is Myelofibrosis (MF) which though is a rare but when encountered, a critical blood cancer. It is associated with enlarged spleen, bone marrow failure etc. The symptoms like fatigue and night sweats soon set in and patients have to go for a poor quality of life coupled with considerable weight loss and shortened life expectancy. Polycythemia vera (PCV) and Essential thrombocythemia are other famous examples of Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs). Prognosis for Myelofibrosis is very dismal and it soon develops into fatal acute myelogenous leukemia (AML), for which also there is no treatment available [2]. The highly significant morbidity and mortality rates associated with stem cell transplantation limit these options to younger patients.
JAK Inhibitors against Myeloproliferative Diseases:
JAK2 has been implicated in myeloproliferative diseases. Since INCB18424 targets V617F mutation found in hematologic malignancies, INCB18424 clinical trials were warranted for MPNs treatment after the successful assessment of its safety and efficaciousness was done in MF patients. Another derivative of INCB81424, INCB16562 was also very successful targeting V617F mutation of MF and thrombocytosis in rat models. This successful targeting offered a new hope to >90% of PCV patients and ~60% of essential thrombocytosis (ET) and MF patients carrying this mutation. INCB81424 soon became the first JAK2 inhibitor tried on MF patients and showed promise by reducing spleen size and overall improved survival of patients.
Clinical Studies from Incyte:
The orally administered INCB81424 was used in Incyte phase II studies in advanced cases of PV and essential thrombocythemia (ET). Incyte reported successful in meeting the primary endpoint in a second phase III clinical trial. Another phase III INCB18424 randomized trial in PV is going on.
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