Delving into the Latest Updates on Gemcitabine elaidate with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Gemcitabine 5'-elaidic acid ester, Gemcitabine elaidate (USAN/INN)

+ [2]

Target-

Action

inhibitors

Mechanism

DNA synthesis inhibitors

Therapeutic Areas

NeoplasmsDigestive System DisordersEndocrinology and Metabolic Disease+ [1]

Active Indication-

Inactive Indication

AdenomaAdvanced Malignant Solid NeoplasmAdvanced Pancreatic Adenocarcinoma+ [3]

Originator Organization

Clavis Pharma

Active Organization-

Inactive Organization

Clavis Pharma

Clovis Oncology, Inc.Aqualis

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC27H43F2N3O5

InChIKeyHESSNRGIEVBPRB-QDDPNBLJSA-N

CAS Registry210829-30-4

The purpose of the first part of the study is to evaluate the safety, tolerability, and pharmacokinetics of ascending doses of gemcitabine elaidate in combination with cisplatin given to patients with advanced solid tumors, and to select a dose for further evaluation in the second part of the study.
The purpose of the second part of the study is to determine the safety, tolerability, and exploratory clinical activity of gemcitabine elaidate in combination with cisplatin given to patients with Stage IIIb/IV non-small-cell lung cancer (NSCLC).

Start Date01 Jul 2012

Sponsor / Collaborator

Clovis Oncology, Inc.

NL-OMON34352

/ CompletedNot Applicable

A phase I, open-label, two-stage, randomized, crossover, comparative pharmacokinetic and safety study of two formulations of CO-1.01 for injection in patients with advanced solid tumors. - Phase I PK study of CO-1.01 in patients with advanced solid tumors.

Start Date04 Apr 2011

Sponsor / Collaborator

Clovis Oncology, Inc.

NCT01233375

/ CompletedPhase 2

A Phase II, Open-Label, Multicenter Study to Evaluate the Antitumor Efficacy of CO-1.01 for Infusion as Second-Line Therapy for Gemcitabine- Refractory Patients With Stage IV Pancreatic Adenocarcinoma and No Tumor hENT1 Expression

The purpose of this study is to determine whether CO-1.01 is safe and effective for treating metastatic pancreatic cancer that did not respond to gemcitabine.

Start Date01 Apr 2011

Sponsor / Collaborator

Clovis Oncology, Inc.

100 Clinical Results associated with Gemcitabine elaidate

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100 Translational Medicine associated with Gemcitabine elaidate

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100 Patents (Medical) associated with Gemcitabine elaidate

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34

Literatures (Medical) associated with Gemcitabine elaidate

02 Aug 2024·Nucleosides, Nucleotides & Nucleic Acids

Effects of nucleoside analogues, lipophilic prodrugs and elaidic acids on core signaling pathways in cancer cells

Article

Author: Frańczak, Marika A. ; Peters, Godefridus J. ; van der Sande, Claudine ; Giovannetti, Elisa

OBJECTIVESNucleoside analogs such as gemcitabine (GEM; dFdC) and cytarabine (Ara-C) require nucleoside transporters to enter cells, and deficiency in equilibrative nucleoside transporter 1 (ENT1) can lead to resistance to these drugs. To facilitate transport-independent uptake, prodrugs with a fatty acid chain attached to the 5'-position of the ribose group of gemcitabine or cytarabine were developed (CP-4126 and CP-4055, respectively). As antimetabolites can activate cellular survival pathways, we investigated whether the prodrugs or their side-chains had similar or decreased effects.METHODSTwo cell lines A549 (non-small cell lung cancer) and WiDr (colon cancer cells) were exposed for 2-24hr to IC₅₀ concentrations of GEM, Ara-C, CP-4126, CP4055 and elaidic acid (EA) concentrations corresponding to the CP-4126 and CP-4055 IC₅₀. Cells were harvested and analyzed for proteins in cell survival pathways (p-AKT/AKT, p-ERK/ERK, p-P38/P38, GSK-3β/pGSK-3β) by using Western Blotting.RESULTSAll drugs and their derivatives showed time- and cell-line-dependent effects. In A549 cells, GEM, CP-4126 and EA-4126 decreased the p-AKT/AKT ratio at 2 and 24 hr. For the p-ERK/ERK ratio, GEM, EA-4126, Ara-C, CP-4045 and EA-4055 exposure led to an increase after 6 hr in A549 cells. Interestingly, Ara-C, CP-4055 and EA-4055 decreased p-ERK/ERK ratio in WiDr cells after 4 hr. In A549 cells, the p-GSK-3β/GSK-3β ratio decreased after exposure to Ara-C and CP-4055 but in WiDr cells increased after 24 hr. In A549 cells treatment with Ara-C, CP-4055 and EA-4126 decreased the p-P38/P38 after 6 hr.CONCLUSIONSThe findings suggest that both parent drugs, prodrugs, and the EA chain influence cell survival and signaling pathways.

29 Mar 2024·Cell death discovery

Gemcitabine elaidate and ONC201 combination therapy for inhibiting pancreatic cancer in a KRAS mutated syngeneic mouse model.

Article

Author: Mahato, Ram I ; Staller, Dalton W ; Kumar, Virender ; Shrestha, Prakash ; Sethi, Bharti

Approximately 90% of pancreatic cancer (PC) contain KRAS mutations. Mutated KRAS activates the downstream oncogenic PI3K/AKT and MEK signaling pathways and induces drug resistance. However, targeting both pathways with different drugs can also lead to excessive toxicity. ONC201 is a dual PI3K/AKT and MEK pathway inhibitor with an excellent safety profile that targets death receptor 5 (DR5) to induce apoptosis. Gemcitabine (GEM) is a first-line chemotherapy in PC, but it is metabolically unstable and can be stabilized by a prodrug approach. In this study, phospho-Akt, phospho-mTOR, and phospho-ERK protein expressions were evaluated in patient PDAC-tissues (n = 10). We used lipid-gemcitabine (L_GEM) conjugate, which is more stable and enters the cells by passive diffusion. Further, we evaluated the efficacy of L_GEM and ONC201 in PC cells and "KrasLSL-G12D; p53LoxP; Pdx1-CreER (KPC) triple mutant xenograft tumor-bearing mice. PDAC patient tissues showed significantly higher levels of p-AKT (Ser473), p-ERK (T202/T204), and p-mTOR compared to surrounding non-cancerous tissues. ONC201 in combination with L_GEM, showed a superior inhibitory effect on the growth of MIA PaCa-2 cells. In our in-vivo study, we found that ONC201 and L_GEM combination prevented neoplastic proliferation via AKT/ERK blockade to overcome chemoresistance and increased T-cell tumor surveillance. Simultaneous inhibition of the PI3K/AKT and MEK pathways with ONC201 is an attractive approach to potentiate the effect of GEM. Our findings provide insight into rational-directed precision chemo and immunotherapy therapy in PDAC.

25 Jul 2023·ACS nano

Transforming Cancer-Associated Fibroblast Barrier into Drug Depots to Boost Chemo-Immunotherapy in "Shooting Fish in a Barrel" Pattern.

Article

Author: Huang, Xinyan ; Yuan, Shijun ; Liu, Jinhu ; Xia, Zhenxing ; Liang, Shuang ; Fu, Shunli ; Liu, Meichen ; Liu, Shujun ; Liu, Yongjun ; Zhang, Na ; Mu, Weiwei ; Gao, Tong

The cancer-associated fibroblast (CAF) barrier in pancreatic ductal adenocarcinoma (PDAC) greatly restricts clinical outcomes. Major obstacles to PDAC treatment include restricted immune cell infiltration and drug penetration and the immunosuppressive microenvironment. Here, we reported a "shooting fish in a barrel" strategy by preparing a lipid-polymer hybrid drug delivery system (PI/JGC/L-A) that could overcome the CAF barrier by turning it into a "barrel" with antitumor drug depot properties to alleviate the immunosuppressive microenvironment and increase immune cell infiltration. PI/JGC/L-A is composed of a pIL-12-loaded polymeric core (PI) and a JQ1 and gemcitabine elaidate coloaded liposomal shell (JGC/L-A) that has the ability to stimulate exosome secretion. By normalizing the CAF barrier to create a CAF "barrel" with JQ1, stimulating the secretion of gemcitabine-loaded exosomes from the CAF "barrel" to the deep tumor site, and leveraging the CAF "barrel" to secrete IL-12, PI/JGC/L-A realized effective drug delivery to the deep tumor site, activated antitumor immunity at the tumor site, and produced significant antitumor effects. In summary, our strategy of transforming the CAF barrier into antitumor drug depots represents a promising strategy against PDAC and might benefit the treatment of any tumors facing a drug delivery barrier.

100 Deals associated with Gemcitabine elaidate

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External Link

KEGG	Wiki	ATC	Drug Bank
D10222	-	-	DB12564

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Pancreatic adenocarcinoma metastatic	Phase 2	Ukraine	Clovis Oncology, Inc.	01 May 2010
Pancreatic adenocarcinoma metastatic	Phase 2	Russia	Clovis Oncology, Inc.	01 May 2010
Pancreatic adenocarcinoma metastatic	Phase 2	Brazil	Clovis Oncology, Inc.	01 May 2010
Pancreatic adenocarcinoma metastatic	Phase 2	Argentina	Clovis Oncology, Inc.	01 May 2010
Pancreatic adenocarcinoma metastatic	Phase 2	Canada	Clovis Oncology, Inc.	01 May 2010
Adenoma	Phase 2	Norway	Clavis Pharma	01 Apr 2009
Adenoma	Phase 2	Belgium	Clavis Pharma	01 Apr 2009
Advanced Pancreatic Adenocarcinoma	Phase 2	Belgium	Clavis Pharma	01 Apr 2009
Advanced Pancreatic Adenocarcinoma	Phase 2	Norway	Clavis Pharma	01 Apr 2009
Pancreatic Cancer	Phase 2	-	Aqualis	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01124786 (LEAP, CTgov)	Phase 2	Pancreatic adenocarcinoma metastatic	367	CO-1.01 (CO-1.01)	ltzzklubtx(pjcuezhaqt) = wjuqtsrzvt gdhehnhpkn (ndhyaqczrs, xnhtfyltlo - mvhbmqpout) View more	-	17 Apr 2014
				Gemcitabine (Gemcitabine)	ltzzklubtx(pjcuezhaqt) = zwskxhubhk gdhehnhpkn (ndhyaqczrs, erqgmvuzet - lbbgoxktpq) View more
NCT01124786 (LEAP, ASCO2013)	Phase 2	Metastatic Pancreatic Ductal Adenocarcinoma	367	CO-101	(fermifvqnm): HR = 0.994 (95% CI, 0.746 - 1.326)	Negative	20 May 2013
				Gemcitabine
ASCO2010	Phase 2	Pancreatic Cancer	-	CP-4126	tlofekkysn(nfvkyvdfse) = hznlnsqoyp adbrtrusbm (vmcfbdcofv )	-	20 May 2010
				Gemcitabine	tlofekkysn(nfvkyvdfse) = euyxvrjlrp adbrtrusbm (vmcfbdcofv )