E 6201

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

E 6201 (E6201) 是一种有效的、选择性的 MEK1 和 MEKK1 双重抑制剂。

E 6201 (E6201) is a potent, selective, dual MEK1 and MEKK1 inhibitor, inhibits LPS-induced TNFα transcription with IC50 of 50 nM; does not suppress β-actin transcription at 3 uM and only slightly at 10 uM; inhibits MEK1-induced ERK2 phosphorylation with IC50 of 5.2 nM, MKK4-induced JNK phosphorylation with IC50 of 91 nM, and MKK6-induced p38α MAPK phosphorylation with IC50 of 19 nM; also inhibited MEKK1-induced phosphorylation of MEK1, MKK4, and MKK6 with IC50 of 31, 522, and 65 nM, respectively, has no effect on other MAPK family enzymes such as ERK2, JNKs, and p38 MAPK at 10 uM; inhibits TNFα, IL-1β, IL-6, and IL-8 production from LPS-stimulated human PBMCs.Blood Cancer Phase 2 Clinical.

E6201 is an inhibitor of MEKK1 and MEK families but not the MAPK family. E6201 inhibits MEKK1- induced phosphorylation of MEK1, MKK4, and MKK6 with IC50 values of 31, 522, and 65 nM, respectively. E6201 has no effect on other MAPK family enzymes such as ERK2, JNKs, and p38 MAPK at 10 μM.E6201 inhibits LPS-induced TNF transcription with an IC50 value of 50±14 nM, but does not suppress β-actin transcription at 3 μM and only slightly at 10 μM.E6201 inhibits the receptor tyrosine kinases VEGFR2, PDGFR, hepatocyte growth factor receptor, and EGFR with IC50 values of 350, 860, 1100, and 5400 nM, respectively, as well as the nonreceptor tyrosine kinase Syk with an IC50 value of 460 nM. E6201 does not inhibit ZAP-70 or IKK at 10 μM or PKC activity at 100 μM.E6201 inhibits IL-2 production 48 h after stimulation with the T-cell mitogen PHA-P, with an IC50 value of 18 nM.E6201 inhibits the proliferation of EGF-stimulated human keratinocytes with an IC50 value of 160 nM.E6201 suppresses IL-8 production in human keratinocytes 24 h after stimulation with IL-1α or TNFα, with IC50 values of 60 and 30 nM, respectively.E6201 inhibits TNFα, IL-1, IL-6, and IL-8 production from human PBMCs with IC50 values of 20, 16, 52, and 53 nM, respectively. E6201 (0.08-20.0 μM) significantly inhibited triple-negative breast cancer (TNBC) cell proliferation and anchorage-independent colony formation in a dose-dependent manner.E6201 (1 μM) inhibits expression of phospho-ERK and induces G1 phase cell cycle arrest, and apoptosis in TNBC. Cell Viability Assay Cell Line:Human TNBC cell lines BT20, HCC70, MDA-MB-231, HCC1806, HCC1937, SUM149 and SUM159 Concentration:0.00, 0.08, 0.16, 0.31, 0.63, 1.25, 2.50, 5.00, 10.0, 20.0 μM Incubation Time:5 days Result:Inhibited TNBC cell proliferation and anchorage-independent colony formation in a dose-dependent manner.Western Blot Analysis Cell Line:Human TNBC cell lines BT20, HCC70, MDA-MB-231, HCC1806, HCC1937, SUM149 and SUM159 Concentration:1 μM Incubation Time:0, 1, 24 hours Result:pERK expression level showed a rapid (apparent by 1 hour) and sustained (still apparent at 24 hours) decrease in the tested TNBC cell lines following treatment.

E6201 (30 mg/kg; administered via tail vein injection three times per week) inhibits TNBC xenograft tumor growth. E6201 strongly inhibits pERK and Ki-67 expression in xenograft tumor tissues. Animal Model:Female Nod.Scid gamma mice (age 4 to 6 weeks old) bearing MDA-MB-231-LM2 xenograft tumors Dosage:30 mg/kg Administration:Administered via tail vein injection three times per week for 17 days Result:Compared with mice treated with vehicle control, the E6201-treated mice showed 60% tumor growth suppression.

E6201

MAPK/ERK Signaling

MEK

MEK

Cancer

Blood cancer

603987-35-5

389.44

C21H27NO6

>98% (HPLC)

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O=C(C1=C(O)C=C(NCC)C=C1/C=C/C[C@H](O)[C@@H]2O)O[C@@H](C)[C@H](C)/C=C\C2=O

(3S,4R,5Z,8S,9S,11E)-14-(ethylamino)-8,9,16-trihydroxy-3,4-dimethyl-3,4,9,10-tetrahydro-1H-benzo[c][1]oxacyclotetradecine-1,7(8H)-dione

(-20℃)

With Ice Pack

≥ 2 years