LY-3214996

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

LY-3214996 是一种新型强效、选择性、口服活性 ERK1/2 抑制剂，在生化检测中对两种酶的 IC50 均为 5 nM。

LY-3214996 is a novel potent, selective, orally active ERK1/2 inhibitor with IC50 of 5 nM for both enzymes in biochemical assays; potently inhibits cellular phospho-RSK1 in BRAF and RAS mutant cancer cell lines; demonstrates inhibition of cell proliferation, general sensitivitity against tumor cells with MAPK pathway alterations including BRAF, NRAS or KRAS mutation; significantly inhibits tumor growth in vivo and is well tolerated in BRAF or NRAS mutant melanoma, BRAF or KRAS mutant colorectal, lung and pancreatic cancer xenografts or PDX models.Blood Cancer Phase 1 Clinical(In Vitro):Temuterkib is a highly selective inhibitor of ERK1 and ERK2, with IC50 of 5 nM for both enzymes in biochemical assays. Temuterkib potently inhibits cellular phospho-RSK1 in BRAF and RAS mutant cancer cell lines. In an unbiased tumor cell panel sensitivity profiling for inhibition of cell proliferation, tumor cells with MAPK pathway alterations including BRAF, NRAS or KRAS mutation are generally sensitivity to Temuterkib. (In Vivo):In tumor xenograft models, Temuterkib inhibits PD biomarker phospho-p90RSK1 in tumors and the PD effects are correlated with compound exposures and anti-tumor activities. Temuterkib shows either similar or superior anti-tumor activity as compared to other published ERK inhibitors in BRAF or RAS mutant cell lines and xenograft models. Oral administration of single-agent Temuterkib significantly inhibits tumor growth in vivo and is well tolerated in BRAF or NRAS mutant melanoma, BRAF or KRAS mutant colorectal, lung and pancreatic cancer xenografts or PDX models. Therefore, Temuterkib can be tailored for treatment of cancers with MAPK pathway alteration. In addition, Temuterkib has anti-tumor activity in a PLX4032-resistant A375 melanoma xenograft model due to MAPK reactivation, may have potential for treatment of melanoma patients who have failed BRAF therapies. More importantly, Temuterkib can be combined with investigational and approved agents in preclinical models, particularly KRAS mutant models. Combination treatment of Temuterkib and CDK4/6 inhibitor abemaciclib is well tolerated and results in potent tumor growth inhibition or regression in multiple in vivo cancer models, including KRAS mutant colorectal and non-small cell lung cancers.

Temuterkib is a highly selective inhibitor of ERK1 and ERK2, with IC50 of 5 nM for both enzymes in biochemical assays. Temuterkib potently inhibits cellular phospho-RSK1 in BRAF and RAS mutant cancer cell lines. In an unbiased tumor cell panel sensitivity profiling for inhibition of cell proliferation, tumor cells with MAPK pathway alterations including BRAF, NRAS or KRAS mutation are generally sensitivity to Temuterkib.

In tumor xenograft models, Temuterkib inhibits PD biomarker phospho-p90RSK1 in tumors and the PD effects are correlated with compound exposures and anti-tumor activities. Temuterkib shows either similar or superior anti-tumor activity as compared to other published ERK inhibitors in BRAF or RAS mutant cell lines and xenograft models. Oral administration of single-agent Temuterkib significantly inhibits tumor growth in vivo and is well tolerated in BRAF or NRAS mutant melanoma, BRAF or KRAS mutant colorectal, lung and pancreatic cancer xenografts or PDX models. Therefore, Temuterkib can be tailored for treatment of cancers with MAPK pathway alteration. In addition, Temuterkib has anti-tumor activity in a PLX4032-resistant A375 melanoma xenograft model due to MAPK reactivation, may have potential for treatment of melanoma patients who have failed BRAF therapies. More importantly, Temuterkib can be combined with investigational and approved agents in preclinical models, particularly KRAS mutant models. Combination treatment of Temuterkib and CDK4/6 inhibitor abemaciclib is well tolerated and results in potent tumor growth inhibition or regression in multiple in vivo cancer models, including KRAS mutant colorectal and non-small cell lung cancers.

LY 3214996 | LY3214996

MAPK/ERK Signaling

ERK

ERK1|ERK2

Cancer

Blood cancer

1951483-29-6

453.56

C22H27N7O2S

>98% (HPLC)

DMSO: 12 mg/mL (26.5 mM); Water: <1 mg/mL （ < 1 mg/ml refers to the product slightly soluble or insoluble )

CC(N(CCN1CCOCC1)C2=O)(C)C3=C2C=C(S3)C4=CC=NC(NC5=CC=NN5C)=N4

4H-Thieno[2,3-c]pyrrol-4-one,5,6-dihydro-6,6-dimethyl-2-[2-[(1-methyl-1H-pyrazol-5-yl)amino]-4-pyrimidinyl]-5-[2-(4-morpholinyl)ethyl]-

(-20℃)

With Ice Pack

≥ 2 years