生物活性

• 描述ML213 is a selective activator of Kv7.2 and Kv7.4 channels, enhances Kv7.2 and Kv7.4 channels with EC50s of 230 and 510 nM, respectively. ML213 causes a concentration-dependent shift in the V1/2 for KCNQ2 activation with an EC50 of 340 ± 70 nM and a maximal shift of 37.4 mV^[3]. ML213 (100 nM-30 µM) increases maximal conductance to a peak at 212% ± 27% of control, with an EC50 of 0.8 ± 0.3 µM. ML213 (10 µM) reduces the deactivation rates of Kv7.4 currents by 4.6-fold in the voltage range from -130 mV to - 90 mV. ML213 is a potent and effective activator of homomeric Kv7.5 channels overexpressed in A7r5 cells. ML213 increases maximal conductance of Kv7.5 channels with an EC50 of 0.7 ± 0.2 µM. ML213 (10 µM) also reduces deactivation rates of Kv7.5 currents by 5.9-fold on average. ML213 produces similar effects on heteromeric Kv7.4/7.5 channels: 204% ± 11% maximal increase in conductance with an EC50 of 1.1 ± 0.6 µM and a 34.2 ± 3.3 mV maximal negative shift of the activation curve, with an EC50 of 3.8 ± 1.2 µM^[4]. ML213 causes a vasorelaxation in different precontracted rat blood vessels. ML213 (10 μM) also hyperpolarizes mesenteric artery smooth muscle cells^[5].
• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT02326272	Psoriasis Pla... more >>que Psoriasis Collapse <<	Phase 3	Completed	-	-
  NCT01769911	Adult Nasal Type Extranodal NK... more >>/T-cell Lymphoma AIDS-related Diffuse Large Cell Lymphoma AIDS-related Diffuse Mixed Cell Lymphoma AIDS-related Diffuse Small Cleaved Cell Lymphoma AIDS-related Immunoblastic Large Cell Lymphoma AIDS-related Lymphoblastic Lymphoma AIDS-related Peripheral/Systemic Lymphoma AIDS-related Small Noncleaved Cell Lymphoma Anaplastic Large Cell Lymphoma Angioimmunoblastic T-cell Lymphoma Cutaneous B-cell Non-Hodgkin Lymphoma Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue Hepatosplenic T-cell Lymphoma HIV-associated Hodgkin Lymphoma Intraocular Lymphoma Nodal Marginal Zone B-cell Lymphoma Noncutaneous Extranodal Lymphoma Peripheral T-cell Lymphoma Recurrent Adult Burkitt Lymphoma Recurrent Adult Diffuse Large Cell Lymphoma Recurrent Adult Diffuse Mixed Cell Lymphoma Recurrent Adult Diffuse Small Cleaved Cell Lymphoma Recurrent Adult Grade III Lymphomatoid Granulomatosis Recurrent Adult Hodgkin Lymphoma Recurrent Adult Immunoblastic Large Cell Lymphoma Recurrent Adult Lymphoblastic Lymphoma Recurrent Adult T-cell Leukemia/Lymphoma Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma Recurrent Grade 1 Follicular Lymphoma Recurrent Grade 2 Follicular Lymphoma Recurrent Grade 3 Follicular Lymphoma Recurrent Mantle Cell Lymphoma Recurrent Marginal Zone Lymphoma Recurrent Mycosis Fungoides/Sezary Syndrome Recurrent Small Lymphocytic Lymphoma Refractory Hairy Cell Leukemia Small Intestine Lymphoma Splenic Marginal Zone Lymphoma Stage I AIDS-related Lymphoma Stage II AIDS-related Lymphoma Stage III AIDS-related Lymphoma Stage IV AIDS-related Lymphoma T-cell Large Granular Lymphocyte Leukemia Testicular Lymphoma Waldenström Macroglobulinemia Collapse <<	Not Applicable	Withdrawn	-	United States, Washington ... more >> Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Seattle, Washington, United States, 98109 Collapse <<
  NCT01521923	Rheumatoid Arthritis	Phase 3	Completed	-	-

• 更多
• 参考文献

• [1] Jepps TA, Bentzen BH, et al. Vasorelaxant effects of novel Kv 7.4 channel enhancers ML213 and NS15370. Br J Pharmacol. 2014 Oct;171(19):4413-24.

  [2] Yu H, Wu M, et al. Discovery, Synthesis, and Structure Activity Relationship of a Series of N-Aryl- bicyclo[2.2.1] heptane-2-carboxamides: Characterization of ML213 as a Novel KCNQ2 and KCNQ4 Potassium Channel Opener. ACS Chem Neurosci. 2011 Oct 19;2(10):572-577.

  [3] Yu H, Wu M, Townsend SD, et al. Discovery, Synthesis, and Structure Activity Relationship of a Series of N-Aryl- bicyclo[2.2.1]heptane-2-carboxamides: Characterization of ML213 as a Novel KCNQ2 and KCNQ4 Potassium Channel Opener. ACS Chem Neurosci. 2011;2(10):572-577

  [4] Brueggemann LI, Haick JM, Cribbs LL, Byron KL. Differential activation of vascular smooth muscle Kv7.4, Kv7.5, and Kv7.4/7.5 channels by ML213 and ICA-069673. Mol Pharmacol. 2014;86(3):330-341

  [5] Jepps TA, Bentzen BH, Stott JB, et al. Vasorelaxant effects of novel Kv 7.4 channel enhancers ML213 and NS15370. Br J Pharmacol. 2014;171(19):4413-4424

• 更多

• Collapse