ML 228

HIF pathway activator (EC₅₀ values are 1.23 and 1.4 μM for HRE gene reporter assay and HIF-1α nuclear translocation assay respectively); acts via chelation of iron, independently of PHD. Also exhibits > 80% inhibition of the human A₃ receptor, dopamine transporter, μ receptor, hERG and 5-HT_2B receptor, and rat sodium channel site 2, at a concentration of 10 μM.

Suicidal Ideation vs. Suicide Attempts: Clinical and Psychosocial Profile Differences Among Depressed Patients: A Study on Personality Traits, Psychopathological Variables, and Sociodemographic Factors in 228 Patients.[Pubmed:28225508]

J Nerv Ment Dis. 2017 May;205(5):361-371.

This study investigated whether personality traits, psychopathological characteristics, and sociodemographic factors in depressed patients differentiate patients with only suicidal thoughts from those who have attempted suicide. We investigated two groups of patients with an affective disorder: 198 patients with a suicide attempt within the last 3 months (sex ratio male to female, 1:1.3; mean age male to female, 44.8/44.7 years) and 30 patients without a suicide attempt but with suicidal thoughts (sex ratio male to female, 1:2; mean age male to female, 39.4/42.6 years) using a comprehensive measurement (Mini-International Neuropsychiatric Interview, Structured Clinical Interview for DSM-4 Axis II disorders, Hamilton Depression Scale, Beck Depression Inventory, State-Trait Anxiety Inventory, Hamilton Anxiety Scale, Brief Psychiatric Rating Scale, Clinical Global Impression Scale, Beck-Hopelessness Scale, Scale for Suicide Ideation, Impulsivity Rating Scale, Barratt Impulsivity Scale, Inventory for the Assessment of Aggression Factors, State-Trait Anger Expression Inventory, Ways of Coping Checklist). Several differences distinguished the two groups, namely, in personality traits such as anxiety or coping strategies and sociodemographics (e.g., education level). Personality traits, psychopathological characteristics, and sociodemographic factors are useful tools for assessing suicidal risk. Our findings encourage us to suggest that clinicians pay particular attention to sociodemographic variables such as separation/divorce and a lower education level when conducting risk assessments on suicidal patients.

The educational gradient in cardiovascular risk factors: impact of shared family factors in 228,346 Norwegian siblings.[Pubmed:28356092]

BMC Public Health. 2017 Mar 30;17(1):281.

BACKGROUND: Various indicators of childhood socioeconomic position have been related to cardiovascular disease (CVD) risk in adulthood. We investigated the impact of shared family factors on the educational gradient in midlife CVD risk factors by assessing within sibling similarities in the gradient using a discordant sibling design. METHODS: Norwegian health survey data (1980-2003) was linked to educational and generational data. Participants with a full sibling in the health surveys (228,346 individuals in 98,046 sibships) were included. Associations between attained educational level (7-9 years, 10-11 years, 12 years, 13-16 years, or >16 years) and CVD risk factor levels in the study population was compared with the corresponding associations within siblings. RESULTS: Educational gradients in risk factors were attenuated when factors shared by siblings was taken into account: A one category lower educational level was associated with 0.7 (95% confidence interval 0.6 to 0.8) mm Hg higher systolic blood pressure (27% attenuation), 0.4 (0.4 to 0.5) mmHg higher diastolic blood pressure (30%), 1.0 (1.0 to 1.1) more beats per minute higher heart rate (21%), 0.07 (0.06 to 0.07) mmol/l higher serum total cholesterol (32%), 0.2 (0.2 to 0.2) higher smoking level (5 categories) (30%), 0.15 (0.13 to 0.17) kg/m(2) higher BMI (43%), and 0.2 (0.2 to 0.2) cm lower height (52%). Attenuation increased with shorter age-difference between siblings. CONCLUSION: About one third of the educational gradients in modifiable CVD risk factors may be explained by factors that siblings share. This implies that childhood environment is important for the prevention of CVD.

Discovery of a new molecular probe ML228: an activator of the hypoxia inducible factor (HIF) pathway.[Pubmed:22172704]

Bioorg Med Chem Lett. 2012 Jan 1;22(1):76-81.

Hypoxia and ischemia are linked to several serious public health problems that affect most major organ systems. Specific examples include diseases of the cardiovascular, pulmonary, renal, neurologic, and musculoskeletal systems. The most significant pathway for cellular response to hypoxia is the hypoxia inducible factor (HIF) pathway. HIFs are transcription factors responsible for the activation of genes which encode proteins that mediate adaptive responses to reduced oxygen availability. A high-throughput cell-based HIF-mediated gene reporter screen was carried out using the NIH's Molecular Libraries Small Molecule Repository to identify activators of the HIF pathway. This communication describes the subsequent medicinal chemistry optimization of a triazine scaffold that led to the identification of the new molecular probe ML228. A discussion of HIF activation SAR within this chemotype as well as detailed in vitro characterization of the probe molecule is presented here.

ML228 (CID-46742353) is a potent the Hypoxia Inducible Factor (HIF) pathway activator with EC50 of 1 μM. ML228 potently activates HIF in vitro as well as its downstream target VEGF.

ML 228,1357171-62-0,Natural Products,HIF, buy ML 228 , ML 228 supplier , purchase ML 228 , ML 228 cost , ML 228 manufacturer , order ML 228 , high purity ML 228