sb-1518 and Lymphoma

sb-1518 has been researched along with Lymphoma* in 1 studies

Other Studies

1 other study(ies) available for sb-1518 and Lymphoma

Article	Year
Discovery of the macrocycle 11-(2-pyrrolidin-1-yl-ethoxy)-14,19-dioxa-5,7,26-triaza-tetracyclo[19.3.1.1(2,6).1(8,12)]heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene (SB1518), a potent Janus kinase 2/fms-like tyrosine kinase-3 (JAK2/FLT3) inhibitor Journal of medicinal chemistry, 2011, Jul-14, Volume: 54, Issue:13 Discovery of the activating mutation V617F in Janus Kinase 2 (JAK2(V617F)), a tyrosine kinase critically involved in receptor signaling, recently ignited interest in JAK2 inhibitor therapy as a treatment for myelofibrosis (MF). Herein, we describe the design and synthesis of a series of small molecule 4-aryl-2-aminopyrimidine macrocycles and their biological evaluation against the JAK family of kinase enzymes and FLT3. The most promising leads were assessed for their in vitro ADME properties culminating in the discovery of 21c, a potent JAK2 (IC(50) = 23 and 19 nM for JAK2(WT) and JAK2(V617F), respectively) and FLT3 (IC(50) = 22 nM) inhibitor with selectivity against JAK1 and JAK3 (IC(50) = 1280 and 520 nM, respectively). Further profiling of 21c in preclinical species and mouse xenograft and allograft models is described. Compound 21c (SB1518) was selected as a development candidate and progressed into clinical trials where it is currently in phase 2 for MF and lymphoma. Topics: Adenosine Triphosphate; Animals; Antineoplastic Agents; Binding Sites; Bridged-Ring Compounds; Cell Line, Tumor; Dogs; Drug Screening Assays, Antitumor; fms-Like Tyrosine Kinase 3; Humans; In Vitro Techniques; Janus Kinase 2; Lymphoma; Mice; Mice, Nude; Microsomes, Liver; Models, Molecular; Neoplasm Transplantation; Primary Myelofibrosis; Pyrimidines; Rats; Solubility; Transplantation, Heterologous; Transplantation, Homologous	2011

Article

Year

Discovery of the macrocycle 11-(2-pyrrolidin-1-yl-ethoxy)-14,19-dioxa-5,7,26-triaza-tetracyclo[19.3.1.1(2,6).1(8,12)]heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene (SB1518), a potent Janus kinase 2/fms-like tyrosine kinase-3 (JAK2/FLT3) inhibitor

Journal of medicinal chemistry, 2011, Jul-14, Volume: 54, Issue:13

Discovery of the activating mutation V617F in Janus Kinase 2 (JAK2(V617F)), a tyrosine kinase critically involved in receptor signaling, recently ignited interest in JAK2 inhibitor therapy as a treatment for myelofibrosis (MF). Herein, we describe the design and synthesis of a series of small molecule 4-aryl-2-aminopyrimidine macrocycles and their biological evaluation against the JAK family of kinase enzymes and FLT3. The most promising leads were assessed for their in vitro ADME properties culminating in the discovery of 21c, a potent JAK2 (IC(50) = 23 and 19 nM for JAK2(WT) and JAK2(V617F), respectively) and FLT3 (IC(50) = 22 nM) inhibitor with selectivity against JAK1 and JAK3 (IC(50) = 1280 and 520 nM, respectively). Further profiling of 21c in preclinical species and mouse xenograft and allograft models is described. Compound 21c (SB1518) was selected as a development candidate and progressed into clinical trials where it is currently in phase 2 for MF and lymphoma.

Topics: Adenosine Triphosphate; Animals; Antineoplastic Agents; Binding Sites; Bridged-Ring Compounds; Cell Line, Tumor; Dogs; Drug Screening Assays, Antitumor; fms-Like Tyrosine Kinase 3; Humans; In Vitro Techniques; Janus Kinase 2; Lymphoma; Mice; Mice, Nude; Microsomes, Liver; Models, Molecular; Neoplasm Transplantation; Primary Myelofibrosis; Pyrimidines; Rats; Solubility; Transplantation, Heterologous; Transplantation, Homologous

2011