Objective: To analyze the clinical characteristics and diagnosis of multisystemic smooth muscle dysfunction syndrome(MSMDS). Method: Clinical data of a case diagnosed as MSMDS and hospitalized in our hospital in July 2016 was retrospectively analyzed. Literature search was performed at databases of PubMed, Wanfang, China National Knowledge Infrastructure and VIP with the key words "multisystemic smooth muscle dysfunction syndrome" "ACTA2" . The literature retrieval was confined from January 1980 to November 2016.The characteristics of MSMDS were summarized through review of literature. Result: A girl aged 1.6 years had recurrent cough and wheeze for more than 1 year, complicated with congenital fixed dilated pupils, patent ductus arteriosus, pulmonary hypertension, chronic lung disease, and cerebrovascular abnormalities. We had done gene analysis for the patient and found ACTA2 c. 536C>T(p.R179H) heterozygous mutations, but her parents were normal. Totally 11 reports were retrieved from foreign language literature and no report from Chinese literature could be found; the retrieved articles reported a total of 25 cases of multiple system smooth muscle dysfunction syndrome. The minimum age was 11 months, 17 cases were female, 8 were male. The clinical common characteristic is congenital fixed dilated pupils, patent ductus arteriosus, cerebrovascular disease, pulmonary hypertension, chronic lung disease, and so on. Conclusion Genetic testing for ACTA2 gene mutations should be considered in infants presenting with congenital fixed dilated pupils and patent ductus arteriosus.

Angiogenesis is an essential process in tumor growth, invasion and metastasis. VEGF receptor 2 (VEGFR2) inhibitors targeting tumor angiogenic pathway have been widely used in the clinical cancer treatment. However, most of currently used VEGFR2 kinase inhibitors are multi-target inhibitors which might result in target-associated side effects and therefore limited clinical toleration. Highly selective VEGFR inhibitors are still highly demanded from both basic research and clinical application point of view. Here we report the discovery and characterization of a novel VEGFR2 inhibitor (CHMFL-VEGFR2-002), which exhibited high selectivity among structurally closed kinases including PDGFRs, FGFRs, CSF1R, etc. CHMFL-VEGFR2-002 displayed potent inhibitory activity against VEGFR2 kinase in the biochemical assay (IC = 66 nmol/L) and VEGFR2 autophosphorylation in cells (ECs ∼100 nmol/L) as well as potent anti-proliferation effect against VEGFR2 transformed BaF3 cells (GI = 150 nmol/L). In addition, CHMFL-VEGFR2-002 also displayed good anti-angiogenesis efficacy and exhibited good PK (pharmacokinetics) profile with bioavailability over 49% and anti-angiogenesis efficacy in both zebrafish and mouse models without apparent toxicity. These results suggest that CHMFL-VEGFR2-002 might be a useful research tool for dissecting new functions of VEGFR2 kinase as well as a potential anti-angiogenetic agent for the cancer therapy.