EphB4 antagonists(Ephrin type-B receptor 4 antagonists), PDGFRβ inhibitors(Platelet-derived growth factor receptor beta inhibitors), VEGFR2 antagonists(Vascular endothelial growth factor receptor 2 antagonists)

Therapeutic Areas

NeoplasmsUrogenital Diseases

Active Indication

Urologic Neoplasms

Inactive Indication

Advanced Malignant Solid NeoplasmColonic CancerOvarian Cancer+ [1]

Originator Organization

Gilead Sciences, Inc.

Active Organization

Vanthys Pharmaceutical Development (P) Ltd.

University of Utah

Huntsman Cancer Institute

Inactive Organization

Jubilant Innovation Pte Ltd.

Gilead Sciences, Inc.Jubilant Innovation (USA), Inc.

Drug Highest PhasePhase 1

First Approval Date-

Regulation-

Clinical Trials associated with JI-101

NCT01149434 / TerminatedPhase 1/2IIT

Drug- Drug Interaction Study of JI-101 & Everolimus in Advanced Solid Tumors, Expansion Pharmacodynamic Study of JI-101 in Advanced Low Grade Endocrine Tumors, Ovarian Cancers or K-RAS Mutant Colon Cancers

The study consists of two parts: Drug Interaction (Pharmacokinetic) Phase and Pharmacodynamic Phase
The primary study objective for the Drug Interaction Study is to determine the pharmacokinetic interactions between RAD001 and JI-101.
The primary study objective for the Pharmacodynamic Study is progression-free survival at 2 moths, evaluated separately in each of the three cohorts.
These will include a determination of tumor response using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria and an assessment of ephrinB4 expression in blood samples.
Secondary objectives are to determine safety and tolerability of JI-101. The investigational products are everolimus (42-O-(2-hydroxyethyl) rapamycin) and JI-101 (1-[1-(2-amino-pyridin-4-ylmethyl)-1H-indol-4-yl]-3-(5-bromo-2 methoxy-phenyl)-urea)
Eligible patients meeting all study entry criteria will be enrolled in the study. For the Drug Interaction study, patients with solid tumors will receive a single dose (10 mg) of Everolimus by mouth on Day 1 and Day 8 and JI-101 capsules (200 mg) by mouth on Day 8 and Day 15. For the Pharmacodynamic Study, all patients will receive JI-101 capsules by mouth (200 mg BID) for 28 day treatment cycles.

Start Date01 Sep 2010

Sponsor / Collaborator

University of Utah

[+1]

NCT00842335 / CompletedPhase 1/2

A Multicenter, Phase 1/2, Open-Label, Dose-Escalation Study of JI-101, an Oral Angiogenesis Inhibitor, in Patients With Advanced Solid Tumors

The purpose of this study, the first clinical trial of JI-101, is to determine the maximum tolerated dose of JI-101 when given orally to patients with solid tumors. Safety, tolerability, pharmacokinetics, pharmacodynamics, and the effects of the drug on tumor metabolism will also be studied. JI-101 is an inhibitor of new blood vessel growth that may provide benefit to patients with solid tumors that have failed standard therapeutic regimens.

Start Date01 Feb 2009

Sponsor / Collaborator

Jubilant Innovation Pte Ltd.

100 Clinical Results associated with JI-101

100 Translational Medicine associated with JI-101

100 Patents (Medical) associated with JI-101

Literatures (Medical) associated with JI-101

01 Dec 2015·Investigational New DrugsQ3 · MEDICINE

A pilot study of JI-101, an inhibitor of VEGFR-2, PDGFR-β, and EphB4 receptors, in combination with everolimus and as a single agent in an ovarian cancer expansion cohort

Q3 · MEDICINE

Article

Author: Boucher, Kenneth ; Agarwal, Neeraj ; Wade, Mark L ; Patel, Jesal ; Luebke, Aaron ; Sharma, Sunil ; Werner, Theresa L

JI-101 is an oral multi-kinase inhibitor that targets vascular endothelial growth factor receptor type 2 (VEGFR-2), platelet derived growth factor receptor β (PDGFR-β), and ephrin type-B receptor 4 (EphB4). None of the currently approved angiogenesis inhibitors have been reported to inhibit EphB4, and therefore, JI-101 has a novel mechanism of action. We conducted a pilot trial to assess the pharmacokinetics (PK), tolerability, and efficacy of JI-101 in combination with everolimus in advanced cancers, and pharmacodynamics (PD), tolerability, and efficacy of JI-101 in ovarian cancer. This was the first clinical study assessing anti-tumor activity of JI-101 in a combinatorial regimen. In the PK cohort, four patients received single agent 10 mg everolimus on day 1, 10 mg everolimus and 200 mg JI-101 combination on day 8, and single agent 200 mg JI-101 on day 15. In the PD cohort, eleven patients received single agent JI-101 at 200 mg twice daily for 28 day treatment cycles. JI-101 was well tolerated as a single agent and in combination with everolimus. No serious adverse events were observed. Common adverse events were hypertension, nausea, and abdominal pain. JI-101 increased exposure of everolimus by approximately 22%, suggestive of drug-drug interaction. The majority of patients had stable disease at their first set of restaging scans (two months), although no patients demonstrated a response to the drug per RECIST criteria. The novel mechanism of action of JI-101 is promising in ovarian cancer treatment and further prospective studies of this agent may be pursued in a less refractory patient population or in combination with cytotoxic chemotherapy.

01 Jan 2012·Arzneimittelforschung

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

Article

Author: Giri, S. ; Mohd, Z. ; Srinivas, N. ; Gurav, S. ; Gilibili, R. ; 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 Deals associated with JI-101

External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB12744

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Urologic Neoplasms	Phase 1	US	University of Utah	20 May 2011
Urologic Neoplasms	Phase 1	IN	Vanthys Pharmaceutical Development (P) Ltd.	20 May 2011
Urologic Neoplasms	Phase 1	US	Huntsman Cancer Institute	20 May 2011
Colonic Cancer	Preclinical	US	Jubilant Innovation Pte Ltd.	01 Sep 2010
Ovarian Cancer	Preclinical	US	Jubilant Innovation Pte Ltd.	01 Sep 2010
RAS mutant Colorectal Cancer	Preclinical	US	Jubilant Innovation Pte Ltd.	01 Sep 2010
Advanced Malignant Solid Neoplasm	Preclinical	US	Jubilant Innovation Pte Ltd.	01 Feb 2009
Neoplasms	Discovery	-	Gilead Sciences, Inc.	-
Neoplasms	Discovery	-	Jubilant Innovation (USA), Inc.	-

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01149434 (CTgov)	Phase 1/2	Ovarian Cancer \| RAS mutant Colorectal Cancer \| Colonic Cancer \| Advanced Malignant Solid Neoplasm	19	JI-101+Everolimus (Pharmacokinetic Arm)	wufbeorcmh(pamnhtlwsm) = gerbcoujnw atiaunjagm (cwrfjckcde, hrceqqwyya - rdziqscqps) View more	-	25 Sep 2014
NCT01149434 (CTgov)	Phase 1/2		19	JI-101 (Pharmacodynamic Arm)	aocrckabxm(blbqqswofx) = pqnyhkopgc cvnhexxujx (cvovojntfp, ajmjsbctqp - znmtbsenas) View more	-	25 Sep 2014
NCT00842335 (CTgov)	Phase 1/2	Advanced Malignant Solid Neoplasm	18	JI-101	okboedxbqb(gypyraiygr) = mnzdltylru dlnuxmthma (lbelxiwzze, effuvzqrsk - nfhbmbpctu) View more	-	24 Jun 2013

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