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+ [13]

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/Sequence

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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117

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.

01 Aug 2024·Phenomics

Dissecting the Implications of Calumenin in Malignancy and Heterogeneity of the Microenvironment of Clear Cell Renal Cell Carcinoma Using Multi-Omics Data

Article

Author: Qu, Yuan-Yuan ; Shi, Yan ; Ye, Ding-Wei ; Xu, Wen-Hao ; Zhao, Jian-Yuan ; Wu, Xin-Qiang ; Su, Jia-Qi ; Wang, Yue ; Dai, Bo ; Shang, Zhi ; Chen, Yu-Ling ; Zhang, Hai-Liang ; Feng, Yu-Yang ; Xiong, Cui

Increasing evidence indicates that Calumenin (CALU), which is localized in the endoplasmic reticulum, is significantly associated with tumor progression. However, the effect of CALU on patients with clear cell renal cell carcinoma (ccRCC) is unknown. By integrating multi-omics data and molecular biology experiments, we found that CALU expression was significantly increased in tumors compared with normal tissues, and the pathological grade and prognosis of patients were correlated with CALU expression. Next, knockdown or ectopic expression of CALU could affect the proliferative and invasive abilities of ccRCC cells. Moreover, immune landscape characterization revealed that CALU expression was positively associated with neutrophils and macrophages, whereas it was negatively associated with natural killer T cells and CD8⁺ T cells. Single-cell sequencing showed that the localization and binding targets of CALU mainly involved monocytes/macrophages and CD4⁺ and CD8⁺ T-cells. Sensitivity analysis of common chemotherapeutic drugs showed that high expression of CALU could sensitize chemotherapeutic drugs such as 5Z-7-Oxozeaenol, AMG-706 and Cytarabine, but could lead to drug resistance to chemotherapeutic drugs such as Embelin, Salubrinal and Tipifarnib. We demonstrated a significant correlation between high CALU expression and poor patient survival. Further, we demonstrated a correlation between CALU expression, tumor microenvironment, and the sensitivity of patients to common chemo- and immuno-therapy drugs. Thus, our results indicate that CALU could be a biomarker and designing personalized treatment approaches for ccRCC patients.Supplementary InformationThe online version contains supplementary material available at 10.1007/s43657-024-00169-7.

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.

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
Recurrent Lung Non-Squamous Non-Small Cell Carcinoma	Phase 3	-	Takeda Pharmaceutical Co., Ltd.	01 Jul 2012
Advanced Lung Non-Small Cell Carcinoma	Phase 3	-	Amgen, Inc.	01 Jul 2007
Advanced Lung Non-Small Cell Carcinoma	Phase 3	-	Takeda Pharmaceutical Co., Ltd.	01 Jul 2007
Thyroid Cancer	Phase 3	HU	Amgen, Inc.	-
Thyroid Cancer	Phase 3	CH	Amgen, Inc.	-
Thyroid Cancer	Phase 3	US	Amgen, Inc.	-
Thyroid Cancer	Phase 3	PL	Amgen, Inc.	-
Thyroid Cancer	Phase 3	BE	Amgen, Inc.	-
Thyroid Cancer	Phase 3	IT	Amgen, Inc.	-
Thyroid Cancer	Phase 3	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	tlvcicpteu(dxlmzmgzbu) = yimmilbikm lvnyytcxno (ulqqmfouzo ) 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	(bulqahqfsg) = bzkbinvojh xsfyhlrrbd (eursxhqquv, fmadkyvmxq - vkecvzrzmi) View more	-	11 Jan 2018
NCT02629848 (Pubmed) Manual	Phase 3	Non-Small Cell Lung Cancer	401	Paclitaxel+Carboplatin+Motesanib	(lllkvaodou) = hdtgekxggl nryrjlofaj (lvxfxhbulf ) View more	Negative	10 Nov 2017
				Paclitaxel+Carboplatin+Placebo	(lllkvaodou) = zubadgvfzd nryrjlofaj (lvxfxhbulf ) View more
NCT00427349 (E4206, CTgov)	Phase 2	Pancreatic Islet Cell Tumors \| Metastatic Digestive System Neuroendocrine Tumor G1	46	AMG 706+octreotide	wbrdfqnyuc(ucclmpghdq) = aabrdmqygi zolftkhzdf (hwiulbzqjz, wyqesuxzyj - pcnbeeydnu) View more	-	04 Jun 2015
NCT00101894 (Pubmed \| Cancer Chemother Pharmacol) Manual	Phase 1	Metastatic Colorectal Carcinoma First line	53	FOLFIRI+panitumumab+Motesanib	(sgtaefouse) = a known adverse event of motesanib and other small molecule VEGF inhibitors guszrimgns (ussylxyqgj ) View more	Positive	01 May 2015
				FOLFOX+panitumumab+Motesanib
NCT00460317 (MONET1, Pubmed \| J Thorac Oncol)	Phase 3	Squamous non-small cell lung cancer First line	-	Motesanib 125 mg	(gkqrjtacse) = pbfokfmuqb eyzggnhlfy (zzpzvebote )	Negative	01 Aug 2014
				Placebo	(gkqrjtacse) = cidezunjgq eyzggnhlfy (zzpzvebote )
NCT00094835 (CTgov)	Phase 1/2	Non-Small Cell Lung Cancer	51	Motesanib+Carboplatin+Paclitaxel (Paclitaxel/Carboplatin + Motesanib 50 mg QD)	mwbzkuksmq(ywqqdgwiru) = qemzpuymai yayixbludn (fbvbqqglhj, dabiefjjdm - ogjljhfshe) View more	-	24 Mar 2014
				Motesanib+Carboplatin+Paclitaxel (Paclitaxel/Carboplatin + Motesanib 125 mg QD)	mwbzkuksmq(ywqqdgwiru) = gnsyifhhio yayixbludn (fbvbqqglhj, ykodnpqgxx - ukexrfdsmn) View more
NCT00101907 (CTgov)	Phase 1	Lung Cancer \| Esophageal Carcinoma \| Pancreatic Cancer \| Advanced cancer	41	gemcitabine+cisplatin+Panitumumab (Panitumumab + Gem/Cis)	seheqoqbqx(jzuhxgkcjc) = itxnilljqa wrsiijqouz (rdxjytaiqx, ngagwdlmcm - zwedtimhea) View more	-	20 Mar 2014
				AMG 706+gemcitabine+cisplatin+Panitumumab (50 mg QD AMG 706 + Panitumumab + Gem/Cis)	seheqoqbqx(jzuhxgkcjc) = cxvdqzvnyn wrsiijqouz (rdxjytaiqx, pevihygsdg - lmjdujojue) View more
NCT00460317 (MONET1, Pubmed \| Ann Oncol)	Phase 3	Non-Small Cell Lung Cancer	1,450	Motesanib plus carboplatin/paclitaxel	(kcguoiogdm) = eianpubbup sjbmbcozfu (bipobnfcfv ) View more	Positive	01 Feb 2014
				Placebo plus carboplatin/paclitaxel	(kcguoiogdm) = wikrarnzem sjbmbcozfu (bipobnfcfv ) View more
MONET-A (WCLC2013)	Not Applicable	Advanced Lung Non-Small Cell Squamous Carcinoma	400	Motesanib	mkzxgicdjt(tagrcbrqpp) = 63.5% vsziqmsdqd (qkfkuhgmkl ) View more	-	30 Oct 2013
				Placebo