Delving into the Latest Updates on Vanthys Pharmaceutical Development (P) Ltd. with Synapse

概览

疾病领域	数量

肿瘤	1

排名前五的药物类型	数量

小分子化药	1

排名前五的靶点	数量

EphB4 x PDGFRβ x VEGFR2	1

关联

1

项与 Vanthys Pharmaceutical Development (P) Ltd. 相关的药物

JI-101

靶点

EphB4 x PDGFRβ x VEGFR2

作用机制

EphB4拮抗剂 [+2]

在研机构

Vanthys Pharmaceutical Development (P) Ltd. [+2]

原研机构

Gilead Sciences, Inc.

在研适应症

泌尿系统肿瘤

非在研适应症

晚期恶性实体瘤 [+3]

最高研发阶段临床1期

首次获批国家/地区-

首次获批日期-

100 项与 Vanthys Pharmaceutical Development (P) Ltd. 相关的临床结果

登录后查看更多信息

0 项与 Vanthys Pharmaceutical Development (P) Ltd. 相关的专利（医药）

登录后查看更多信息

7

项与 Vanthys Pharmaceutical Development (P) Ltd. 相关的文献（医药）

2012-05-20·Journal of Clinical Oncology

A pharmacodynamic study of JI-101, an orally active inhibitor of VEGF-2, PDGF-β, and EphB4 receptors, in patients with refractory/recurrent ovarian cancer.

作者: Werner, Theresa Louise ; Caligiuri, Philip ; Sharma, Sunil ; Wade, Mark ; Abhyankar, Dhiraj J. ; Srinivas, Nuggehally R ; Luebke, Aaron Lynn ; Heilbrun, Marta Elise

e13548 Background: JI-101 is an oral multi-kinase inhibitor, which targets VEGFR-2, PDGF-β, and EphB4. By targeting multiple angiogenesis signaling pathways, JI-101 has the potential advantage of inhibiting all vital stages of tumor angiogenesis, reducing tumor resistance, and enhancing anti-tumor efficacy. None of the currently approved angiogenesis inhibitors have any appreciable inhibition of EphB4, and therefore, this represents a novel mechanism of action. JI-101 has preclinical activity in various tumor models and has been well tolerated in phase 1 trials. Methods: Eleven women with refractory/recurrent ovarian cancer were enrolled with a median age of 54 yrs (range 52-76). All patients had adequate organ function and ECOG performance status ≤ 2. Each patient received single agent JI-101 at 200mg BID for 28 day treatment cycles. Toxicity and response were evaluated at two month intervals. Results: Eight of 11 patients were evaluable for response (3 were unevaluable due to inability to complete two cycles). A median of 3 cycles (range 2-6) was given. No grade 4 adverse events (AEs) were seen. The most common grade 2/3 hematological AEs were grade 2 anemia (1) and lymphopenia (1). The most common grade 2/3 non-hematological AEs were grade 3 hypertension (7), grade 3 bowel obstruction (2), grade 3 transaminitis (2), and abdominal pain (2). Six patients had stable disease (SD) at two months and two had progressive disease. Best response was SD at four months. Two-month progression free survival was 71% (90% CI 52-99%). Conclusions: JI-101 is well tolerated in refractory/recurrent ovarian cancer patients with the majority of patients with stable disease at two months. The most common toxicity was hypertension, which was easily controlled with anti-hypertensives. The novel mechanism of action of JI-101 is promising in ovarian cancer treatment and further prospective studies of this agent could be pursued in a less refractory patient population.

2012-04-01·Arzneimittelforschung

The Observed Correlation between in vivo Clinical Pharmacokinetic Parameters and in vitro Potency of VEGFR-2 Inhibitors

Article

作者: Bhatnagar, U. ; Sahu, M. ; Srinivas, N. ; Benjamin, B. ; Abhyankar, D.

Literature data on the clinical pharmacokinetics of various VEGFR-2 inhibitors along with in vitro potency data were correlated and a linear relationship was established in spite of limited data set. In this work, a model set comprised of axitinib, recentin, sunitinib, pazopanib, and sorafenib were used. The in vitro potencies of the model set compounds were correlated with the published unbound plasma concentrations (Cmax, Cavg, Ctrough). The established linear regression (r2>0.90) equation was used to predict Cmax, Cavg, Ctrough of the 'prediction set' (motesanib, telatinib, CP547632, vatalanib, vandetanib) using in vitro potency and unbound protein free fraction. Cavg and Ctrough of prediction set were closely matched (0.2-1.8 fold of reported), demonstrating the usefulness of such predictions for tracking the target related modulation and/or efficacy signals within the clinically optimized population average. In case of Cmax where correlation was least anticipated, the predicted values were within 0.1-1.1 fold of those reported. Such predictions of appropriate parameters would provide rough estimates of whether or not therapeutically relevant dose(s) have been administered when clinical investigations of novel agents of this class are being performed. Therefore, it may aid in increasing clinical doses to a desired level if safety of the compound does not compromise such dose increases. In conclusion, the proposed model may prospectively guide the dosing strategies and would greatly aid the development of novel compounds in this class.

2012-01-01·Arzneimittelforschung

Pharmacokinetics, Tissue Distribution and Identification of Putative Metabolites of JI-101 – A Novel Triple Kinase Inhibitor in Rats

Article

作者: Giri, S. ; Mohd, Z. ; Srinivas, N. ; Gilibili, R. ; Gurav, S. ; Mullangi, R. ; Jeniffer, S. ; Govindarajan, R.

JI-101, chemically 1-[1-(2-amino-pyridin-4-ylmethyl)-1H-indol-4-yl]-3-(5-bromo-2-methoxy-phenyl)-urea hydrochloride, is a novel orally active kinase inhibitor, which has shown potent in vitro and in vivo anticancer activity against a variety of cancer cell lines and xenografts. It is currently entering Phase II clinical development for the treatment of solid tumors. The aim of the study is to assess the metabolic stability of JI-101 in various pre-clinical and human liver microsomes, to identify the major CYPs (cytochrome β450) involved in the metabolism of JI-101 and identification of putative metabolites. We have also studied the pharmacokinetics, tissue distribution and excretion of JI-101 in Sprague Dawley rats. JI-101 was found to be stable in various liver microsomes tested. JI-101 is highly permeable and not a substrate for P-gp (permeability glycoprotein). JI-101 excreted through bile along with its mono- and di-hydroxy metabolites. Following oral administration, JI-101 was rapidly absorbed, reaching Cmax within 2 h. The t½ of JI-101 with intravenous and oral route was found to be 1.75 ± 0.79 and 2.66 ± 0.13 h, respectively. The Cl and Vd by intravenous route for JI-101 were found to be 13.0 ± 2.62 mL/min/kg and 2.11 ± 1.42 L/kg, respectively. The tissue distribution of JI-101 was extensive with rapid and preferred uptake into lung tissue. Overall, the oral bioavailability of JI-101 is 55% and the primary route of elimination for JI-101 is feces.

100 项与 Vanthys Pharmaceutical Development (P) Ltd. 相关的药物交易

登录后查看更多信息

100 项与 Vanthys Pharmaceutical Development (P) Ltd. 相关的转化医学

登录后查看更多信息