MAP4K

MAP4Ks (Mitogen-activated protein kinase kinase kinase kinases) belong to the mammalian Ste20-like family of serine/threonine kinases. MAP4K family members, including Hematopoietic progenitor kinase 1 (HPK1/MAP4K1), Germinal centre kinase (GCK/MAP4K2), Germinal centre kinase-like kinase (GLK/MAP4K3), HPK/GCK-like kinase (HGK/MAP4K4), Misshapen-like kinase 1 (MINK1/MAP4K6) and TRAF2 and NCK interacting kinase (TNIK/MAP4K7), as potent LATS1/2-activating kinases.

Overexpression or deletion of MAP4Ks affects the phosphorylation and activity of Large tumor suppressor 1/2 (LATS1/2, homologues of Wts) and Yes-associated protein (YAP) /transcriptional co-activator with PDZ-binding motif (TAZ). By acting in a LATS-dependent, but Mammalian Ste20-like kinases 1/2 (MST1/2, homologues of Hpo)-independent manner, MAP4Ks restrict the activity of YAP/TAZ by promoting their phosphorylation and inhibiting target gene expression. MAP4Ks are components of the Hippo pathway by directly phosphorylating and activating the LATS1/2 kinases.MAP4K2/4/6 and MST1/2 both belong to the STE20-like kinase family, and their kinase domains are highly homologous to one another. MAP4K4 acts through LATS to inhibit YAP and cell proliferation.

Products for MAP4K

Cat.No. 产品名称 Information
GC69240 HPK1-IN-32 HPK1-IN-32 是一种有效的选择性 HPK1 抑制剂，IC50 为 65 nM。HPK1-IN-32 可用于 HPK1 相关疾病的研究。
GC69239 ZYF0033 ZYF0033 (HPK1-IN-22, compound ZYF0033) 是一种造血祖细胞激酶 1 (HPK1) 抑制剂，基于 MBP 蛋白的磷酸化抑制作用的 IC50 小于 10 nM。ZYF0033 降低 SLP76 (丝氨酸 376) 的磷酸化。ZYF0033 促进抗癌免疫反应。ZYF0033 抑制 4T-1 同基因小鼠模型中的肿瘤生长并导致 DC、NK 细胞和 CD107a+CD8+ T 细胞的肿瘤内浸润增加，但导致 T 细胞、PD-1+CD8+ T 细胞、TIM-3+CD8+ T 细胞和 LAG3+CD8+ T 细胞的浸润减少。
GC69238 HPK1-IN-19 KIF18A-IN-1 是一种造血祖细胞激酶 1 HPK1 的抑制剂，详细信息请参考专利文献 WO2018102366A1 中的化合物 I-47。
GC25289 CompK CompK (compound K), a potent and selective hematopoietic progenitor kinase 1 (HPK1 or MAP4K1) small molecule inhibitor, significantly improves human T-cell functions, with enhanced T-cell receptor avidity to recognize tumor-associated antigens and tumor cytolytic activity by CD8+ T cells.
GC65298 DMX-5804 DMX-5804 is a potent, orally active and selective inhibitor of Mitogen-activated protein kinase kinase kinase kinase-4 (MAP4K4) with IC50 of 3 nM for human MAP4K4. DMX-5804 is more potent on human MAP4K4 with pIC50 of 8.55 than MINK1/MAP4K6 and TNIK/MAP4K7 with pIC50 of 8.18 and 7.96, respectively.
GC63569 HPK1-IN-4 HPK1-IN-4 (comp 22) 是 HPK1 (MAPK41) 的抑制剂 (IC50 = 0.061 nM)，用于免疫治疗的研究。
GC63317 HPK1-IN-8 HPK1-IN-8 是一种变构、非活性构象选择性全长 HPK1 抑制剂。
GC63059 MAP4K4-IN-3 MAP4K4-IN-3 is a potent and selective Mitogen-activated protein kinase 4 (MAP4K4) inhibitor with an IC50 of 14.9 nM in kinase assay, an IC50 of 470 nM in cell assay.
GC63006 HPK1-IN-7 HPK1-IN-7 是一种有效的口服活性 HPK1 (造血祖细胞激酶1, MAP4K1) 抑制剂(IC50=2.6 nM)，具有优良的家族和激酶组选择性。HPK1-IN-7 对 IRAK4 (59 nM) 和 GLK (140 nM) 具有选择性。HPK1-IN-7 联合抗 PD1 对 MC38 同基因肿瘤模型显示出强大的疗效。
GC62514 HPK1-IN-3 HPK1-IN-3 是一种有效的选择性 ATP 竞争性造血祖细胞激酶 1 (HPK1; MAP4K1) 抑制剂，IC50 为 0.25 nM。HPK1-IN-3 具有 IL-2 细胞效力，在人外周血单核细胞 (PBMC) 中的 EC50 为 108 nM。
GC50295 TL4-12 TL4 12 是一种有效的选择性 GCK（生发中心激酶）抑制剂。
GC50252 PF 06260933 dihydrochloride MAP4K4 (HGK) inhibitor; also inhibits MINK and TNIK
GC34208 GNE 220 Hydrochloride GNE220(Hydrochloride)是一种有效的选择性MAP4K4抑制剂，其IC50值为7nM。
GC33123 GNE 220 GNE-220是一种有效的选择性MAP4K4抑制剂，IC50为7nM。
GC31675 PF-06260933 A MAP4K4 inhibitor
GC19260 NCB-0846 A TNIK inhibitor
GC18257 GNE-495 An orally bioavailable, potent, and selective MAP4K4 inhibitor
GC13514 NG25 An inhibitor of MAP4K2 and TAK1
GC12151 B-Raf inhibitor B-Raf inhibitor 是一种有效的双重 TGFβ-activated kinase 1 (TAK1) 和 mitogen-activated protein kinase kinase kinase 2 (MAP4K2) 抑制剂，IC50 分别为 41.1 nM 和 18.2 nM。