Objective: To develop a novel multi-target small molecule agent for the treatment of hypertension with potential renal protection. Design and method: Part I (preclinical): MT-1207 was tested in the in vitro and in vivo preclinical models to evaluate mechanisms of action, hypertension efficacy, and renal protection. The in vitro activity of MT-1207 was evaluated in enzyme and radioligand binding assays. In vivo Spontaneously Hypertensive Rats (SHR) and two-kidney two-clip (2K2C) rat models were used to evaluate antihypertensive effects and renal protection of MT-1207. Preclinical safety evaluation of MT-1207 was conducted in rats and dogs following ICH guidelines. Part II (clinical): MT-1207 in clinical phases I and II were completed based on the clinical protocols. Phase Ia was a single center, randomized, double-blind, placebo-controlled, dose escalation study to evaluate safety, tolerability, pharmacokinetic of single oral dose of MT-1207 in healthy adult subjects. Phase Ia doses were 5, 10, 20, 40, 60, 90 mg. Similarly, Phase Ib study was conducted in patients with hypertension at 10 and 20 mg (BID) for 10 days. Clinical phase II was a multi-center, randomized, double-blind, placebo- and active-controlled, multiple-dose study to evaluate safety and pharmacodynamics of MT-1207 in patients with hypertension for 8 weeks. Results: Preclinical (part I): MT-1207 showed potent selective inhibitions of Adrenergic 1alpha and Serotonin (5-HT2A) receptors with IC50 < 1 nM. The efficacy of antihypertension of MT-1207 in SHR model was evident with a well-defined dose-response relationship at 2.5, 5, and 10 mpk. In 2K2C rat model, both blood pressure and serum uric acid decreased post-dose at 4-week and 9-week, indicating antihypertensive effects and potential kidney protection, respectively. Clinical (part II): in Phase I, healthy volunteers had good tolerability at 40 mg and below. Rapid blood pressure decreases were observed 1-2 hr post dose in patients with 10 and 20 mg doses. Results from Phase II (10 and 20 mg (BID)) with placebo and active drug (amlodipine) study will be presented including summary of adverse effects (AE) and efficacy data. Conclusions: Clinical data (phases I and II) demonstrated antihypertensive effects of MT-1207 with mild adverse effects.