Delving into the Latest Updates on Motesanib Diphosphate with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Motesanib, Motesanib diphosphate (USAN), Motesanib phosphate (JAN)

+ [1]

Target

PDGFR x RET x VEGFR1 x VEGFR2 x VEGFR3 x c-Kit

Mechanism

PDGFR antagonists(Platelet-derived growth factor receptor antagonists), RET inhibitors(Tyrosine-protein kinase receptor RET inhibitors), VEGFR1 antagonists(Vascular endothelial growth factor receptor 1 antagonists)

+ [3]

Therapeutic Areas

NeoplasmsRespiratory DiseasesDigestive System Disorders+ [3]

Active Indication-

Inactive Indication

Advanced cancerAdvanced Lung Non-Small Cell CarcinomaAdvanced Malignant Solid Neoplasm+ [12]

Originator Organization

Amgen, Inc.

Active Organization-

Inactive Organization

Amgen, Inc.

Takeda Pharmaceutical Co., Ltd.

Drug Highest PhaseDiscontinuedPhase 3

First Approval Date-

Regulation-

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Structure

Molecular FormulaC22H23N5O

InChIKeyRAHBGWKEPAQNFF-UHFFFAOYSA-N

CAS Registry453562-69-1

View All Structures (2)

In 2008 there were more than 40,000 deaths caused by metastatic breast cancer in the United States. The development of new treatment strategies is essential to improve outcome for patients with metastatic breast cancer
There is significant preclinical and clinical evidence indicating that creating new blood vessels (neoangiogenesis) to provide nutrients to solid tumors, including breast cancer, provides the necessary conditions to allow tumor growth. Vascular endothelial growth factor (VEGF) is one of the important molecules regulating new blood vessel formations and subsequent invasion and metastases. As a result, agents that inhibit VEGF are of substantial interest for the treatment of advanced diseases.
This study will further the body of research of motesanib which has been shown in preclinical pharmacology and clinical pharmacology studies to be a potent, orally bioavailable multi-kinase inhibitor with anti-angiogenic and anti-tumor activity achieved by selectively targeting all known VEGF, platelet-derived growth factor (PDGF), and Kit receptors.

Start Date01 Dec 2013

Sponsor / Collaborator

Sidney Kimmel Cancer Center at Thomas Jefferson University

[+2]

NCT02629848 / TerminatedPhase 3

A Global Phase 3, Randomized, Placebo Controlled, Double-Blind Trial of AMG 706 in Combination With Paclitaxel and Carboplatin for Advanced Non-Squamous Non-Small Cell Lung Cancer (Asian Phase 3 Study)

This study will evaluate progression free survival (PFS), overall survival (OS), objective response rate (ORR), duration of response, and safety of motesanib (AMG706) in combination with paclitaxel and carboplatin compared to placebo in combination with paclitaxel and carboplatin.

Start Date01 Jul 2012

Sponsor / Collaborator

Takeda Pharmaceutical Co., Ltd.

NCT01386866 / CompletedPhase 1

An Open-label, Single Dose Study of the Mass Balance and Metabolic Disposition of Orally Administered [14C]-Labelled AMG 706 (Motesanib) Followed by Extended Treatment With Motesanib in Patients With Advanced Solid Tumors

In order for a tumour to grow and spread to other parts of the body, it needs to have a blood supply. Certain proteins in the body, called cytokines or growth factors, have been shown to cause the growth of new blood vessels that supply tumours and therefore help the tumour to grow and spread. Motesanib (AMG 706) prevents these proteins from working, and may help to prevent the growth of tumours.
In the first part of this study, we will look at the way your body absorbs this drug into your blood, how your body changes and breaks down the drug, and then how the drug leaves your body in your urine and faeces.
In order to provide potential treatment benefit for the subjects who participated in the first part of the study, the second part of the study will allow subjects to continue on motesanib (AMG 706) treatment. The estimated length of this part of the study is unknown, and dependent on how subjects respond to motesanib (AMG 706).

Start Date01 May 2009

Sponsor / Collaborator

Amgen, Inc.

100 Clinical Results associated with Motesanib Diphosphate

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100 Translational Medicine associated with Motesanib Diphosphate

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100 Patents (Medical) associated with Motesanib Diphosphate

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108

Literatures (Medical) associated with Motesanib Diphosphate

18 Sep 2024·Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico

Construction and clinical significance of prognostic risk markers based on cancer driver genes in lung adenocarcinoma.

Article

Author: Li, Jingyan ; Huo, Tingting ; Su, Yazhou ; Wang, Yanan

BACKGROUNDCancer driver genes (CDGs) have been reported as key factors influencing the progression of lung adenocarcinoma (LUAD). However, the role of CDGs in LUAD prognosis has not been fully elucidated.METHODSLUAD transcriptome data and CDG-related data were obtained from public databases and literature. Differentially expressed CDGs (DE-CDGs) greatly associated with LUAD survival (P < 0.05) were identified to establish a prognostic model. In addition, immune analysis of high-risk (HR) and low-risk (LR) groups was conducted by utilizing the CIBERSORT and single sample gene set enrichment analysis (ssGSEA) algorithms to assess immune differences. Subsequently, mutation analysis was conducted using maftools. Finally, candidate drugs were identified using the CellMiner database.RESULTS40 DE-CDGs significantly associated with LUAD survival and 11 DE-CDGs associated with prognosis were identified through screening. Regression analysis revealed that risk score can independently predict LUAD prognosis (P < 0.05). Immune landscape analysis revealed that compared to the HR group, the LR group had higher immune scores and high infiltration of various immune cells such as follicular helper B cells and T cells. Mutation landscape analysis demonstrated that missense mutation was the most common mutation type in both risk groups. Drug prediction analysis revealed strong correlations of fulvestrant, S-63845, sapacitabine, lomustine, BLU-667, SR16157, motesanib, AZD-9496, XK-469, dimethylfasudil, P-529, and imatinib with the model genes, suggesting their potential as candidate drugs targeting the model genes.CONCLUSIONThis study identified 11 effective biomarkers, DE-CDGs, which can predict LUAD prognosis and explored the biological significance of CDGs in LUAD prognosis, immunotherapy, and treatment.

27 Oct 2023·Scientific reports

A novel prognostic N⁷-methylguanosine-related long non-coding RNA signature in clear cell renal cell carcinoma.

Article

Author: Wu, MingSong ; Zheng, Xiang ; Lu, Jing ; Luo, Wang ; Wang, JinJing ; Qian, ShengYan ; Bai, ZhiXun

Clear cell renal cell carcinoma (ccRCC) is regulated by methylation modifications and long noncoding RNAs (lncRNAs). However, knowledge of N⁷-methylguanosine (m⁷G)-related lncRNAs that predict ccRCC prognosis remains insufficient. A prognostic multi-lncRNA signature was created using LASSO regression to examine the differential expression of m7G-related lncRNAs in ccRCC. Furthermore, we performed Kaplan-Meier analysis and area under the curve (AUC) analysis for diagnosis. In all, a model based on five lncRNAs was developed. Principal component analysis (PCA) indicated that the risk model precisely separated the patients into different groups. The IC₅₀ value for drug sensitivity divided patients into two risk groups. High-risk group of patients was more susceptible to A.443654, A.770041, ABT.888, AMG.706, and AZ628. Moreover, a lower tumor mutation burden combined with low-risk scores was associated with a better prognosis of ccRCC. Quantitative real-time polymerase chain reaction (qRT-PCR) exhibited that the expression levels of LINC01507, AC093278.2 were very high in all five ccRCC cell lines, AC084876.1 was upregulated in all ccRCC cell lines except 786-O, and the levels of AL118508.1 and DUXAP8 were upregulated in the Caki-1 cell line. This risk model may be promising for the clinical prediction of prognosis and immunotherapeutic responses in patients with ccRCC.

01 Aug 2023·International ophthalmology

Effect of topical motesanib in experimental corneal neovascularization model.

Review

Author: Tektemur, Ahmet ; Balbaba, Mehmet ; Çelenk, Mukaddes ; Erdağ, Murat ; Yıldırım, Hakan

PURPOSEThis study aimed to compare the efficacy of topical bevacizumab and motesanib in an experimental corneal neovascularization model, and find the most effective motesanib dose.MATERIALS AND METHODSIn experiments, 42 Wistar Albino rats were randomly divided into six groups (n = 7). Corneal cauterization was applied to all groups except the group 1. Group 1 did not receive any treatment. Topical dimethylsulfoxide was applied to sham group three times a day(tid). Topical bevacizumab drops (5 mg/ml) were applied to Group 3 tid. Topical motesanib drops with a dose of 2.5, 5, and 7.5 mg/ml were respectively applied in Groups 4, 5, and 6 tid. On the 8th day, corneal photographs of all rats were taken under general anesthesia, and the percentage of corneal neovascular area was calculated. VEGF-A mRNA, VEGFR-2 mRNA, miRNA-21, miRNA-27a, miRNA-31, miRNA-126, miRNA-184, and miRNA-204 were evaluated by the qRT-PCR method in corneas taken after decapitation.RESULTSThe percentage of corneal neovascularization areas and VEGF-A mRNA expression levels were decreased in all treatment groups compared to group 2 (p < 0.05). VEGFR-2 mRNA levels were found to be statistically significantly decreased in groups 4 and 6 compared to group 2 (p < 0.05). Statistically significant changes were detected in the expression levels of only miRNA-126 among all miRNAs.CONCLUSIONMotesanib with a dose of 7.5 mg/ml statistically significantly suppressed the VEGFR-2 mRNA level compared with other treatment doses and may be more effective than bevacizumab. Further, miRNA-126 can be used as a proangiogenic marker.

100 Deals associated with Motesanib Diphosphate

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External Link

KEGG	Wiki	ATC	Drug Bank
D08947	Motesanib Diphosphate	-	DB05575

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Advanced Lung Non-Small Cell Carcinoma	Phase 3	-	Amgen, Inc.	01 Jul 2007
Thyroid Cancer	Phase 3	HU	Amgen, Inc.	-
Thyroid Cancer	Phase 3	US	Amgen, Inc.	-
Thyroid Cancer	Phase 3	AT	Amgen, Inc.	-
Thyroid Cancer	Phase 3	BE	Amgen, Inc.	-
Thyroid Cancer	Phase 3	IT	Amgen, Inc.	-
Non-squamous non-small cell lung cancer	Preclinical	-	Takeda Pharmaceutical Co., Ltd.	01 Jul 2012
Advanced Lung Non-Small Cell Carcinoma	Preclinical	-	Takeda Pharmaceutical Co., Ltd.	01 Jul 2007
Thyroid Cancer	Preclinical	DK	Amgen, Inc.	-
Thyroid Cancer	Preclinical	SE	Amgen, Inc.	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00427349 (E4206, Pubmed \| Oncologist)	Phase 2	Neuroendocrine Tumors First line	44	AMG 706	vxuakxmgds(ejxhmjemby) = mhvozfeqmd gbrhqyogug (nsutvepvap ) View more	-	01 Sep 2018
NCT00574951 (CTgov)	Phase 2	Recurrent ovarian cancer \| Recurrent Primary Peritoneal Carcinoma \| Platinum-Resistant Primary Peritoneal Carcinoma \| Fallopian Tube Carcinoma	23	motesanib diphosphate	xbvrfiphkv(tezkfgdmuc) = vqsyzkmkfh dvsfqjydqk (eznrllqlaj, sspxsisabw - lilsqvqpgc) View more	-	11 Jan 2018
NCT02629848 (Pubmed) Manual	Phase 3	Non-Small Cell Lung Cancer	401	Paclitaxel+Carboplatin+Motesanib	(nkpuuafnpr) = nglcebauzz iejviiyyru (fdlgamrvqb ) View more	Negative	10 Nov 2017
				Paclitaxel+Carboplatin+Placebo	(nkpuuafnpr) = frgfbbhdba iejviiyyru (fdlgamrvqb ) View more
NCT00427349 (E4206, CTgov)	Phase 2	Pancreatic Islet Cell Tumors \| Metastatic Digestive System Neuroendocrine Tumor G1	46	AMG 706+octreotide	tqwxkkfvjb(azhqesblyn) = ydmchzoqrh hcfxnxjdpu (cpcqkucfdm, hpvpayprpj - dyzdnflqzc) View more	-	04 Jun 2015
NCT00101894 (Pubmed \| Cancer Chemother Pharmacol) Manual	Phase 1	Metastatic Colorectal Carcinoma First line	53	FOLFIRI+panitumumab+Motesanib	(iiccgbcbnv) = a known adverse event of motesanib and other small molecule VEGF inhibitors ojchdxyekh (qordqjenom ) View more	Positive	01 May 2015
				FOLFOX+panitumumab+Motesanib
MONET1 (Pubmed \| J Thorac Oncol)	Phase 3	Squamous non-small cell lung cancer First line	-	Motesanib 125 mg	(hbqzacmeqf) = lzfloxhyuw coyhgzrmzh (ecblkubjnn )	Negative	01 Aug 2014
				Placebo	(hbqzacmeqf) = hmucmereml coyhgzrmzh (ecblkubjnn )
NCT00094835 (CTgov)	Phase 1/2	Non-Small Cell Lung Cancer	51	Motesanib+Carboplatin+Paclitaxel (Paclitaxel/Carboplatin + Motesanib 50 mg QD)	uvtavpgwln(havajwjtno) = jkuikryscs nvnfdztfba (opzpzasjow, yzqzeqvgbz - zfwmnyirmf) View more	-	24 Mar 2014
				Motesanib+Carboplatin+Paclitaxel (Paclitaxel/Carboplatin + Motesanib 125 mg QD)	uvtavpgwln(havajwjtno) = rmjazxsqtp nvnfdztfba (opzpzasjow, vbqghwpozi - leqvllfcih) View more
NCT00101907 (CTgov)	Phase 1	Lung Cancer \| Esophageal Carcinoma \| Pancreatic Cancer \| Advanced cancer	41	gemcitabine+cisplatin+Panitumumab (Panitumumab + Gem/Cis)	kmatxdlrap(twmpkpcran) = epjperamov qutsiprsyv (tffbcbyljl, phozgmfiye - dyzxwdcyku) View more	-	20 Mar 2014
				AMG 706+gemcitabine+cisplatin+Panitumumab (50 mg QD AMG 706 + Panitumumab + Gem/Cis)	kmatxdlrap(twmpkpcran) = vdhvynkxdx qutsiprsyv (tffbcbyljl, rsancjgodp - wxnilornvj) View more
NCT00460317 (MONET1, Pubmed \| Ann Oncol)	Phase 3	Advanced Lung Non-Small Cell Carcinoma	1,450	Motesanib plus carboplatin/paclitaxel	(okydsrzuql) = ncajfunzlu duqmutfawx (ovysznjovj ) View more	Positive	01 Feb 2014
				Placebo plus carboplatin/paclitaxel	(okydsrzuql) = vxnrqinlek duqmutfawx (ovysznjovj ) View more
MONET-A (WCLC2013)	Not Applicable	Advanced Lung Non-Small Cell Squamous Carcinoma	400	Motesanib	(pcsreiyowz) = 63.5% uqcekiibbg (yupsgpfgej ) View more	-	30 Oct 2013
				Placebo